Michael Amylon

All Publications

• SAFETY OF HEMATOPOIETIC STEM CELL TRANSPLANTATION IN CHILDREN LESS THAN THREE YEARS OF AGE PEDIATRIC HEMATOLOGY AND ONCOLOGY Dvorak, C. C., Wright, N. B., Wong, W. B., Kristovich, K. M., Matthews, E. W., Weinberg, K. I., Amylon, M. D., Agarwal, R. 2008; 25 (8): 705-722

  Abstract

  Allogeneic hematopoietic stem cell transplantation (HSCT) is a standard treatment for a variety of hematologic conditions. However, very young children may experience different complications of HSCT compared to older patients. The authors retrospectively analyzed the results of 51 transplants performed on children less than 3 years of age between June 1987 and October 2005. Donors were matched-related (n = 21), partially mismatched related (n = 3), and unrelated (n = 27). The majority of patients had one or more grade III organ toxicities, but all nonrelapse deaths were attributable to infection. Perineal dermatitis was found in a large number (73%) of recipients of cyclophosphamide-based conditioning regimens. The 1-year transplant-related mortality (TRM) was 14%, but significantly declined in the more modern period. Grades II-IV acute graft-versus-host-disease (GvHD) was seen in 22% of patients, while chronic extensive GvHD developed in only 7% of patients. Relapse was seen in 40% of transplants performed for a malignant condition, most commonly in those patients not in remission at time of HSCT. The 5-year event-free survival (EFS) and overall survival (OS) were 53 and 64%, respectively. Recipients of fractionated total body irradiation (fTBI) were more likely to have at least one long-term sequelae than patients who received chemotherapy-based regimens (p = .014). These data demonstrate that HSCT can be performed safely in very young children, especially as supportive-care techniques improve. Cyclophosphamide-related perineal dermatitis is a unique complication in very young children. Finally, the incidence of acute and chronic GvHD in this population is low.

  View details for DOI 10.1080/08880010802243524

  View details for Web of Science ID 000261504200001

  View details for PubMedID 19065437

• Projective drawings as measures of psychosocial functioning in siblings of pediatric cancer patients from the Camp Okizu study JOURNAL OF PEDIATRIC ONCOLOGY NURSING Packman, W., Mazaheri, M., Sporri, L., Long, J. K., Chesterman, B., Fine, J., Amylon, M. D. 2008; 25 (1): 44-55

  Abstract

  This research was conducted at a summer camp for siblings of children with cancer. Participants included 77 siblings (ages 6-17 years) and their parents. Before attending camp, 18 of the siblings had experienced the death of their brother or sister with cancer. Projective measures were administered before attending camp and 3 months after camp. These included the Human Figure Drawing (HFD) and the Kinetic Family Drawing-Revised (KFD-R). Siblings were administered both the HFD and KFD-R; parents were given the KFD-R. On the HFD, siblings' emotional distress scores decreased significantly pre- to postcamp. On the KFD-R, nonbereaved siblings and parents showed significant improvement in family environment scores. Bereaved siblings and parents also showed improvement (although nonsignificant). These results support Camp Okizu's effectiveness in increasing siblings' emotional well-being yet underscore the need to implement interventions to address family communication for both bereaved and nonbereaved families.

  View details for DOI 10.1177/1043454207311915

  View details for Web of Science ID 000252001700005

  View details for PubMedID 18187600

• Hematopoietic stem cell transplantation after first marrow relapse of non-T, non-B acute lymphoblastic leukemia - A Pediatric Oncology Group pilot feasibility study JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Sandler, E. S., Homans, A., Mandell, L., Amylon, M., Wall, D. A., Devidas, M., Buchanan, G. R., Lipton, J. M., Billett, A. L. 2006; 28 (4): 210-215

  Abstract

  Relapsed acute lymphoblastic leukemia (ALL) in children is associated with a poor outcome, especially for those patients whose relapse occurs during the first 36 months after diagnosis. The best therapy for these patients is not known. This study was designed to evaluate the feasibility of enrolling children with recurrent ALL in a standardized treatment protocol that included receipt of a hematopoietic stem cell transplant (HSCT).Eligible patients with a bone marrow relapse of non-T, non-B ALL underwent a common induction and consolidation followed by receipt of either an allogeneic HSCT from a human leukocyte antigen (HLA)-identical sibling or an autologous HSCT purged with B-4 blocked ricin. A common conditioning regimen was used for all patients.Twenty-eight patients from eight institutions were enrolled. Fourteen patients did not receive a transplant during the study, because of toxicity (4), relapse (1), inadequate purging (1), and parental or physician preference for an alternative donor transplant (8). Six patients received allogeneic HSCTs. Five of them have remained in remission for a median of 78 months. Eight patients received autologous HSCTs purged with B4-blocked ricin. Four have remained in remission for a median of 94 months. Of the nine patients who received alternative donor transplants, only two remain in remission.We conclude that well designed and controlled prospective studies are necessary to define the role of HSCTs in children with recurrent ALL. In order to be successful, such studies must have the full support of participating centers. Autologous HSC transplantation may have a role in the treatment of relapsed ALL, but further studies are needed.

  View details for Web of Science ID 000237535600004

  View details for PubMedID 16679917

• Siblings of pediatric cancer patients: The quantitative and qualitative nature of quality of life JOURNAL OF PSYCHOSOCIAL ONCOLOGY Packman, W., Greenhalgh, J., Chesterman, B., Shaffer, T., Fine, J., vanZutphen, K., Golan, R., Amylon, M. D. 2005; 23 (1): 87-108

  Abstract

  This study used both quantitative and qualitative methodologies to assess the pediatric health-related quality of life (HRQOL) in siblings (n = 77) of cancer patients attending summer camp. On quantitative measures (Pediatric Quality of Life Inventory (PedsQL) parent and child versions), siblings reported statistically significant improvements in HRQOL from pre-to post camp. The parent sample, as a whole, did not report a statistically significant improvement in the siblings' HRQOL; however, statistically significant improvements were found when the analysis controlled for the responses of bereaved parents. On the qualitative measures (Sibling Qualitative Interview and Camp Okizu Satisfaction Surveys), both children and parents described the positive impact of camp. Using grounded theory, we identified the major themes and found that the positive emotional and social experiences captured by the quotes were paralleled in the quantitative findings of improved HRQOL in psychosocial domains on the PedsQL. These findings suggest the beneficial effects of camp as a psychological intervention and illustrate the value of integrating quantitative and qualitative methodological approaches in research.

  View details for DOI 10.1300/J077v23n01_06

  View details for Web of Science ID 000235052100006

  View details for PubMedID 16492646

• High-dose therapy and autologous hematopoietic stem-cell transplantation for recurrent or refractory pediatric Hodgkin's disease: Results and prognostic indices 45th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) Lieskovsky, Y. E., Donaldson, S. S., Torres, M. A., Wong, R. M., Amylon, M. D., Link, M. P., Agarwal, R. AMER SOC CLINICAL ONCOLOGY. 2004: 4532?40

  Abstract

  To evaluate the outcome of pediatric patients with refractory or relapsed Hodgkin's disease (HD) who undergo high-dose therapy and autologous hematopoietic stem-cell transplantation (AHSCT).From 1989 to 2001, 41 pediatric patients with relapsed or primary refractory HD underwent high-dose therapy followed by AHSCT according to one of four autologous transplantation protocols at Stanford University Medical Center (Stanford, CA). Pretreatment factors were analyzed by univariate and multivariate analysis for prognostic significance for 5-year overall survival (OS), event-free survival (EFS), and progression-free survival (PFS).At a median follow-up of 4.2 years (range, 0.7 to 11.9 years), the 5-year OS, EFS, and PFS rates were 68%, 53%, and 63%, respectively. Multivariate analysis determined the following three factors to be significant predictors of poor OS and EFS: extranodal disease at first relapse, presence of mediastinal mass at time of AHSCT, and primary induction failure. Two of these factors also predicted for poor PFS (extranodal disease at time of first relapse and presence of mediastinal mass at time of transplantation).More than half of children with relapsed or refractory HD can be successfully treated with the combination of high-dose therapy and AHSCT, confirming the efficacy of this approach. Further investigation is now required to determine the optimal timing of AHSCT, as well as to develop alternative regimens for those patients with factors prognostic for poor outcome after AHSCT.

  View details for DOI 10.1200/JCO.2004.02.121

  View details for Web of Science ID 000225175600015

  View details for PubMedID 15542804

• Camp Okizu: Preliminary investigation of a psychological intervention for siblings of pediatric cancer patients CHILDRENS HEALTH CARE Packman, W., Fine, J., Chesterman, B., vanZutphen, K., Golan, R., Amylon, M. D. 2004; 33 (3): 201-215

  View details for Web of Science ID 000223630700003

• Allogeneic hematopoietic cell transplantation for patients with high-risk acute lymphoblastic leukemia in first or second complete remission using fractionated total-body irradiation and high-dose etoposide: A 15-year experience EXPERIMENTAL HEMATOLOGY Jamieson, C. H., Amylon, M. D., Wong, R. M., Blume, K. G. 2003; 31 (10): 981-986

  Abstract

  The rationale for this retrospective study was to identify the long-term overall and event-free survival, relapse, and treatment-related mortality rates of high-risk pediatric and adult first (CR1) and second remission (CR2) patients with acute lymphoblastic leukemia (ALL) who were treated with a single preparatory regimen consisting of fractionated total-body irradiation (FTBI) and high-dose etoposide (VP-16) prior to allogeneic hematopoietic cell transplantation.Over a 15-year period at Stanford University Medical Center, 85 consecutive high-risk pediatric (up to age 17 years; n=41) and adult (age 18-55 years; n=44); patients with leukemia (ALL) in CR1 (n=55) and CR2 (n=30) received HLA-matched sibling allogeneic bone marrow or peripheral blood progenitor grafts after being treated with FTBI (1320 cGy) and high-dose VP-16 (60 mg/kg) as their preparatory regimen. The majority of patients transplanted in CR1 (n=45) had high-risk features, including age above 30 years, white blood cell count at presentation exceeding 25000/microL, extramedullary disease, need for more than 4 weeks of induction chemotherapy to achieve CR, or high-risk chromosomal translocations. Most patients transplanted in CR1 were adults (n=39), whereas patients in CR2 were primarily children or adolescents (n=25).The 10-year Kaplan-Meier estimates of relapse were significantly (p=0.05) lower in CR1 patients (15%+/-10%) than in CR2 patients (33%+/-20%). Relapse was the most common cause of treatment failure in patients transplanted in CR2. There was a significantly (p=0.05) higher rate of chronic graft-vs-host disease in CR1 (32%+/-14%) compared with CR2 (9%+/-11%) patients; however, overall survival for patients transplanted in CR1 (66%+/-14%) was comparable (p=0.67) to that of patients transplanted in CR2 (62%+/-19%). Event-free survival rates also were similar (p=0.53) between CR1 (64%+/-14%) and CR2 (61%+/-18%) patients. Treatment-related mortality rates were equivalent (p=0.51) between CR1 and CR2, as well as between Philadelphia chromosome (Ph) positive (Ph(+))and Ph(-) (p=0.23) ALL patients.Overall, FTBI/VP-16 is a highly effective preparatory regimen that provides durable remissions for patients receiving allogeneic hematopoietic cell transplantation for high-risk ALL in CR1 or CR2.

  View details for DOI 10.1016/S0301-472X(03)00231-5

  View details for Web of Science ID 000220964700018

  View details for PubMedID 14550815

• Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and beta-thalassemia BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Iannone, R., Casella, J. E., Fuchs, E. J., Chen, A. R., Jones, R. J., Woolfrey, A., Amylon, M., Sullivan, K. M., Storb, R. F., Walters, M. C. 2003; 9 (8): 519-528

  Abstract

  We describe previously transfused patients with sickle cell disease (n = 6) and thalassemia (n = 1) who received nonmyeloablative hematopoietic stem cell transplantation (HCT) to induce stable (full or partial) donor engraftment. Patients were 3 to 20 years (median, 9 years) old. All 7 received pretransplantation fludarabine and 200 cGy of total body irradiation; 2 patients also received horse antithymocyte globulin. Patients received bone marrow (n = 6) or peripheral blood stem cells (n = 1) from HLA-identical siblings, followed by a combination of mycophenolate mofetil and cyclosporine or tacrolimus for postgrafting immunosuppression. After nonmyeloablative HCT, absolute neutrophil counts were <0.5 x 10(9)/L and <0.2 x 10(9)/L for a median of 5 days (range, 0-13 days) and 0 days (range 0-13 days), respectively. A median of 0 (range, 0-9) platelet transfusions were administered. No grade IV nonhematologic toxicities were observed. One patient experienced grade II acute graft-versus-host disease. Two months after transplantation, 6 of 7 patients had evidence of donor chimerism (range, 25%-85%). Independent of red blood cell transfusions, these 6 patients initially had increased total hemoglobin and hemoglobin A concentrations and a reduction of reticulocytosis and transfusion requirements. There were no complications attributable to sickle cell disease during the interval of transient mixed chimerism. However, after posttransplantation immunosuppression was tapered, there was loss of the donor graft, and all patients experienced autologous hematopoietic recovery and disease recurrence. One patient did not engraft. The duration of transient mixed chimerism ranged from 97 to 441 days after transplantation in patients 4 and 6, respectively, and persisted until immunosuppressive drugs were discontinued after transplantation. In summary, the nonmyeloablative HCT regimens described here produced minimal toxicity and resulted in transient donor engraftment in 6 of 7 patients with hemoglobinopathies. Although complications from the underlying hemoglobinopathies did not occur during the period of mixed chimerism, these results suggest that stable (full or partial) donor engraftment after nonmyeloablative HCT is more difficult to achieve among immunocompetent pediatric patients with hemoglobinopathies than among adults with hematologic malignancies, perhaps in part because recipients may have been sensitized to minor histocompatibility antigens of their donor by preceding blood transfusions.

  View details for DOI 10.1016/S1083-8791(03)00192-7

  View details for Web of Science ID 000185167400006

  View details for PubMedID 12931121

• High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin's disease: Atopy predicts idiopathic diffuse lung injury syndromes BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Frankovich, J., Donaldson, S. S., Lee, Y. B., Wong, R. M., Amylon, M., Verneris, M. R. 2001; 7 (1): 49-57

  Abstract

  The use of high-dose therapy (HDT) and autologous hematopoietic cell transplantation (AHCT) for children and adolescents with primary refractory and relapsed Hodgkin's disease is increasing. The purpose of this retrospective analysis was to: (1) evaluate the outcome of HDT and AHCT in pediatric patients with Hodgkin's disease, and (2) identify factors that predispose patients to the development of transplantation-related complications. We describe the experiences of 34 pediatric patients from a single institution with primary refractory or relapsed Hodgkin's disease. HDT regimens consisted of cyclophosphamide and etoposide combined with either carmustine, chloroethylcyclohexylnitrosurea, or fractionated total body irradiation. Kaplan-Meier survival predicts that 67% (95% confidence interval [CI] 47%-87%) of patients will be alive and disease-free at 5 years. Nine patients had disease recurrence, of whom 5 relapsed after 1 year (1.5-6.3 years). Five patients succumbed to treatment-related toxicities, of whom 4 died of pulmonary failure. Fifteen patients (44%) developed post-AHCT idiopathic diffuse lung injury syndrome: acute alveolitis (n = 2); diffuse alveolar hemorrhage (n = 2); acute respiratory distress syndrome (n = 2); delayed interstitial pneumonitis (n = 8); and bronchiolitis obliterans (n = 1). The following factors did not predict for the development of a diffuse lung injury syndrome in univariate analysis: prior treatment with bleomycin, pre-HDT pulmonary function tests, and prior thoracic irradiation. Of the patients in our cohort, 44% had a history of atopy (allergic rhinitis and/or asthma). Multivariate logistic analysis revealed that a preexisting history of atopy was highly predictive of idiopathic pulmonary complications (P = .0001, odds ratio = 21, CI 3.6-125). Our experience shows that HDT followed by AHCT results in durable remissions in two thirds of pediatric patients with refractory and relapsed Hodgkin's disease, and a history of atopy is associated with post-AHCT pulmonary complications.

  View details for Web of Science ID 000166841300008

  View details for PubMedID 11215699

• Equivalence of 2 effective graft-versus-host disease prophylaxis regimens: Results of a prospective double-blind randomized trial BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Chao, N. J., Snyder, D. S., Jain, M., Wong, R. M., Niland, J. C., Negrin, R. S., Long, G. D., Hu, W. W., Stockerl-Goldstein, K. E., JOHNSTON, L. J., Amylon, M. D., Tierney, D. K., O'Donnell, M. R., Nademanee, A. P., Parker, P., Stein, A., Molina, A., Fung, H., Kashyap, A., Kohler, S., Spielberger, R., Krishnan, A., Rodriguez, R., Forman, S. J., Blume, K. G. 2000; 6 (3): 254-261

  Abstract

  We have previously demonstrated a decrease in the incidence of acute graft-versus-host disease (GVHD) with the addition of methotrexate (MTX) to cyclosporine (CSP) and prednisone (PSE) chemotherapy in patients with leukemia. We have now completed a prospective randomized trial comparing the 3-drug regimen (CSP/MTX/PSE, including 3 doses of MTX) to the standard 2-drug regimen (CSP/MTX, including 4 doses of MTX) to investigate the benefit of PSE used up front for the prevention of acute and chronic GVHD. In the trial, 193 patients were randomized and 186 were included in the final analysis. All patients received a bone marrow graft from a fully histocompatible sibling donor. The preparatory regimen consisted of fractionated total-body irradiation (fTBI) and etoposide in all but 13 patients, who received fTBI and cyclophosphamide. The patients were randomized to receive either CSP/MTX/PSE or CSP/MTX. The 2 groups were well balanced with respect to diagnosis, disease stage, age, donor-recipient sex, and parity. In an intent-to-treat analysis, the incidence of acute GVHD was 18% (95% confidence interval [CI] 12-28) for the CSP/MTX/PSE group compared with 20% (CI 10-26) for the CSP/,MTX group (P = .60), with a median follow up of 2.2 years. Overall survival was 65% for those receiving CSP/MTX/PSE and 72% for those receiving CSP/MTX (P = .10); the relapse rate was 15% for the CSP/MTX/PSE group and 12% for the CSP/MTX group (P = .83). The incidence of chronic GVHD was similar (46% versus 52%; P = .38), with a follow-up of 0.7 to 6.0 years. Of interest, 21 patients went off study due to GVHD (5 in the CSP/MTX/PSE group and 16 in the CSP/MITX group [P = .02]), and 11 patients went off study because of alveolar hemorrhage (3 in the CSP/MTX/PSE group and 8 in the CSP/MTX group [P = .22]). The addition of PSE did not result in a higher incidence of infectious complications, bacterial (66% versus 58%), viral (77% versus 66%), or fungal (20% versus 20%), in those receiving CSP/MTX/PSE versus CSP/MTX, respectively. These data suggest that the addition of PSE was associated with a somewhat lower incidence of early posttransplantation complications but did not have a positive impact on the incidence of acute or chronic GVHD or event-free or overall survival.

  View details for Web of Science ID 000090022300005

  View details for PubMedID 10871150

• Long-term follow-up of 23 patients with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with allogeneic bone marrow transplant in first complete remission LEUKEMIA Snyder, D. S., Nademanee, A. P., O'Donnell, M. R., Parker, P. M., Stein, A. S., Margolin, K., Somlo, G., Molina, A., Spielberger, R., Kashyap, A., Fung, H., Slovak, M. L., Dagis, A., Negrin, R. S., Amylon, M. D., Blume, K. G., Forman, S. J. 1999; 13 (12): 2053-2058

  Abstract

  Between 1984 and 1997, 23 consecutive patients with Philadelphia chromosome-positive acute lymphoblastic leukemia in first complete remission were treated with allogeneic bone marrow transplants from HLA-matched siblings. All patients but one were conditioned with fractionated total body irradiation (1320 cGy) and high-dose etoposide (60 mg/kg). One patient received high-dose cyclophosphamide instead of etoposide, and another patient received both drugs. Nine patients died following BMT, two from relapsed leukemia, and seven from transplant-related causes. The 3-year probabilities of disease-free survival and relapse are 65% and 12%, respectively. For patients transplanted after 1992, these probabilities are 81% (48-95%, 95% confidence interval) and 11% (2-50%), respectively. The relatively low relapse rate in this group of patients compared to published reports may reflect the enhanced anti-leukemic activity of etoposide in combination with FTBI compared to other conditioning regimens. The enhancement in overall survival for patients transplanted after 1992 may reflect improvements in supportive care, in particular, the prophylaxis of serious fungal and viral infections.

  View details for Web of Science ID 000084116700018

  View details for PubMedID 10602428

• Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: a Pediatric Oncology Group study LEUKEMIA Amylon, M. D., Shuster, J., Pullen, J., Berard, C., Link, M. P., Wharam, M., Katz, J., Yu, A., Laver, J., Ravindranath, Y., Kurtzberg, J., Desai, S., Camitta, B., Murphy, S. B. 1999; 13 (3): 335-342

  Abstract

  This study was designed to test the hypothesis that high-dose asparaginase consolidation therapy improves survival in pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma. Five hundred and fifty-two patients (357 patients with T cell acute lymphoblastic leukemia (ALL) and 195 patients with advanced stage lymphoblastic lymphoma) were enrolled in POG study 8704 (T-3). Treatment included rotating combinations of high-dose myelosuppressive chemotherapy agents proven to be effective in T cell ALL in other POG group-wide or local institutional protocols (including vincristine, doxorubicin, cyclophosphamide, prednisone, asparaginase, teniposide, cytarabine and mercaptopurine). After achieving a complete remission (CR), patients were randomized to receive or not receive high-dose intensive asparaginase consolidation (25,000 IU/m2) given weekly for 20 weeks by intramuscular injection. Intrathecal chemotherapy (methotrexate, hydrocortisone and cytarabine) was given to prevent CNS disease, and CNS irradiation was used only for patients with leukemia and an initial WBC of >50,000/microl or patients with active CNS disease at diagnosis. CR was achieved in 96% of patients. The high-dose asparaginase regimen was significantly superior to the control regimen for both the leukemia and lymphoma subgroups. Four-year continuous complete remission rate (CCR) for the leukemia patients was 68% (s.e. 4%) with asparaginase as compared to 55% (s.e. 4%) without. For the lymphoma patients, 4-year CCR was 78% (s.e. 5%) with asparaginase and 64% (s.e. 6%) in the controls. The overall one-sided logrank test had a P value <0.001 favoring asparaginase, while corresponding values were P = 0.002 for ALL and P = 0.048 lymphoblastic lymphoma. Toxicities were tolerable, but there were 18 failures due to secondary malignancies (16 with non-lymphocytic leukemia or myelodysplasia). Neither WBC at diagnosis (leukemia patients) nor lymphoma stage were major prognostic factors. We conclude that when added to a backbone of effective rotating agents, repeated doses of asparaginase during early treatment improve the outcome for patients with T cell leukemia and advanced stage lymphoblastic lymphoma.

  View details for Web of Science ID 000079086000004

  View details for PubMedID 10086723

• Cyclosporine, methotrexate, and prednisone compared with cyclosporine and prednisone for prevention of acute graft-vs.-host disease: effect on chronic graft-vs.-host disease and long-term survival. Biology of blood and marrow transplantation Ross, M., Schmidt, G. M., Niland, J. C., Amylon, M. D., Dagis, A. C., Long, G. D., Nademanee, A. P., Negrin, R. S., O'Donnell, M. R., Parker, P. M., Smith, E. P., Snyder, D. S., Stein, A. S., Wong, R. M., Forman, S. J., Blume, K. G., Chao, N. J. 1999; 5 (5): 285-291

  Abstract

  Graft-vs.-host disease (GVHD) is a major predictor of outcome following allogeneic bone marrow transplantation (BMT). For patients alive at day 100 after BMT, the presence or absence of chronic GVHD is one of the most important determinants of survival and quality of life. We wished to determine the effects on chronic GVHD of two regimens used for the prophylaxis of acute GVHD: cyclosporine, methotrexate, and prednisone (CSA/MTX/PSE) and cyclosporine and prednisone (CSA/PSE). One hundred forty-nine evaluable patients were entered into the acute GVHD study. As of 31 March 1997, 63 months after the last patient underwent BMT, the median survival time was 4.5 years (range 0.09-9.9). The incidence of chronic GVHD was independent of the prophylactic regimen (55 vs. 54%), and extensive chronic GVHD occurred in 25 and 24% of patients receiving CSA/MTX/PSE and CSA/PSE, respectively. Of note, the median Karnofsky performance status of both groups was 100% (range 70-100%), reflecting the low incidence of extensive chronic GVHD. Survival rates free of chronic GVHD were 52 vs. 42% (p = 0.29) for patients receiving CSA/MTX/PSE vs. CSA/PSE. The incidence of relapse was also similar in both groups of patients. These data suggest that the combinations of CSA/MTX/PSE and CSA/PSE result in comparable chronic GVHD-free survival without an increase in leukemic relapse.

  View details for PubMedID 10534058

• Fractionated total-body irradiation, etoposide, and cyclophosphamide followed by allogeneic bone marrow transplantation for patients with high-risk or advanced-stage hematological malignancies. Biology of blood and marrow transplantation Long, G. D., Amylon, M. D., Stockerl-Goldstein, K. E., Negrin, R. S., Chao, N. J., Hu, W. W., Nademanee, A. P., Snyder, D. S., Hoppe, R. T., Vora, N., Wong, R., Niland, J., Reichardt, V. L., Forman, S. J., Blume, K. G. 1997; 3 (6): 324-330

  Abstract

  Myeloablative therapy followed by allogeneic bone marrow transplantation (BMT) has proven to be curative therapy in patients with hematologic malignancies. Relapse, however, remains a major cause of treatment failure for patients with advanced disease. During the past 15 years, we have gained considerable experience with the combination of fractionated total-body irradiation (FTBI) and etoposide followed by allogeneic BMT for hematologic malignancies. In an attempt to decrease post-transplant relapse rates, 67 patients under the age of 50 years with high-risk or advanced-stage hematological malignancies received an intensified regimen of FTBI and etoposide plus cyclophosphamide followed by BMT from a genotypically-matched related donor. The regimen consisted of 1320 cGy of FTBI in 11 fractions, 60 mg/kg of etoposide (VP-16), and 60 mg/kg of cyclophosphamide (CY). Fifty-three patients received cyclosporine and prednisone for graft-vs.-host disease (GVHD) prophylaxis and 14 patients received cyclosporine, methotrexate, and prednisone. Diagnosis at BMT included 45 patients with acute leukemia, 7 patients with chronic leukemia, and 15 patients with high-grade non-Hodgkin's lymphoma (NHL). Actuarial disease-free survival (DFS) at 3 years was 42% +/- 12% for the entire group with a median follow-up of 50 months (range 20-74) for 28 patients who remain alive in continued complete remission (CR). Actuarial 3-year-DFS was 38% +/- 14% in 52 patients with acute or chronic leukemia and 60% +/- 25% in 15 patients with NHL with relapse rates of 45% +/- 16% and 21% +/- 11%, respectively. DFS at 3 years was 40% +/- 18% in 32 patients with acute leukemia in 1st relapse or 2nd CR or chronic myelogenous leukemia in accelerated phase, and was 32% +/- 22% in 20 patients with more advanced disease. Regimen related mortality occurred in 9 patients (4, veno-occlusive disease of the liver; 2, multi-organ failure; 1, diffuse alveolar hemorrhage; 1, central nervous system (CNS) hemorrhage; 1, adult respiratory distress syndrome (ARDS). The combination of FTBI, etoposide, and cyclophosphamide followed by allogeneic BMT is an effective and relatively well-tolerated regimen for patients with advanced hematologic malignancies. The role for this regimen should be further defined by prospective clinical trials.

  View details for PubMedID 9502300

• Allogeneic bone marrow transplant in pediatric patients with high-risk hematopoietic malignancies early in the course of their disease JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Amylon, M. D., Co, J. P., Snyder, D. S., Donaldson, S. S., Blume, K. G., Forman, S. J. 1997; 19 (1): 54-61

  Abstract

  The purpose of this study was to investigate the role of bone marrow transplant (BMT) early in the course of disease for pediatric patients with high-risk leukemia using a preparatory regimen of fractionated total body irradiation (FTBI) and etoposide (VP-16).Those studied were 33 patients aged < or =18 years with either acute leukemia in first complete remission (CR) (n = 29) or chronic myelogenous leukemia (CML) in first chronic phase (n = 4) who received 1,320 cGy FTBI followed by high-dose VP-16 (60 mg/kg) as a preparatory regimen for BMT from matched sibling donors. Patients with acute leukemia included 18 with acute nonlymphocytic leukemia (ANLL), one with biphenotypic acute leukemia (BAL), and 10 with selected "high-risk" acute lymphocytic leukemia (ALL). Patients with ALL were selected for a high risk for recurrence: those who failed standard remission induction chemotherapy, had a t(9;22) or t(4;11) chromosomal translocation, or had certain clinical high-risk features.At the time of analysis, 28 patients are alive, all of them in continued complete remission for 1.1-7.8 years (median, 5.3 years; mean, 4.9 years). The Kaplan-Meier projected event-free survival (EFS) is 84.5% at 7 years, and the actuarial recurrence hazard is 6.5%. All surviving patients have a performance status of >80%.This result of early BMT in a two-institution study of pediatric patients with hematopoietic malignancies suggests that (a) matched sibling allogeneic BMT after conditioning with FTBI and high-dose VP-16 is an excellent treatment for pediatric patients with high-risk leukemia, and (b) children may have a better prognosis than adults treated with allogeneic BMT. Larger multiinstitutional cooperative trials for pediatric patients are needed to confirm this result.

  View details for Web of Science ID A1997WM80700008

  View details for PubMedID 9065720

• Single Institution Experience With Allogeneic Hematopoietic Stem Cell Transplantation for Pediatric and AYA Patients With Acute Leukemia BMT Tandem Meetings Breese, E., Agarwal, R., Kharbanda, S., Breese, M., Amylon, M., Weinberg, K. I., Porteus, M., Dahl, G., Lacayo, N., Schlis, K., Willert, J. R. ELSEVIER SCIENCE INC. 2013: S242?S243

  View details for Web of Science ID 000314441900258

• Hematopoietic Cell Transplantation (HCT) for Treatment of Genetic Lymphohematopoietic Diseases for Patients Lacking a Fully Matched Sibling Donor Using a Novel Conditioning Regimen BMT Tandem Meetings Kharbanda, S., Agarwal, R., Miklos, D. B., Porteus, M., Amylon, M., Willert, J. R., Weinberg, K. I. ELSEVIER SCIENCE INC. 2013: S250?S251

  View details for Web of Science ID 000314441900275

• High Risk Allogeneic Hematopoietic Cell Transplant (HCT) Patients with Any Level of Cytomegalovirus (CMV) Viremia Should Be Treated with Antiviral Therapy to Prevent Serious CMV Disease BMT Tandem Meetings Winestone, L., Agarwal, R., Weinberg, K. L., Porteus, M., Willerts, J. R., Amylon, M., Kharbanda, S. ELSEVIER SCIENCE INC. 2013: S312?S312

  View details for Web of Science ID 000314441900404

• Autologous Transplantation for Hodgkin disease: A Tale of Two Eras BMT Tandem Meetings Garfin, P. M., Luna-Fineman, S., Amylon, M., Kharbanda, S., Weinberg, K. I., Willert, J. R., Porteus, M., Link, M., Agarwal, R. ELSEVIER SCIENCE INC. 2013: S247?S247

  View details for Web of Science ID 000314441900267

• Antimetabolite-based therapy in childhood T-cell acute lymphoblastic leukemia: A report of POG study 9296 PEDIATRIC BLOOD & CANCER Winter, S. S., Holdsworth, M. T., Devidas, M., Raisch, D. W., Chauvenet, A., Ravindranath, Y., Ducore, J. M., Amylon, M. D. 2006; 46 (2): 179-186

  Abstract

  A previous Pediatric Oncology Group (POG) study showed high incidence of secondary acute myelogenous leukemia (AML) in children treated for T-cell acute lymphoblastic leukemia (T-ALL) or higher-stage lymphoblastic lymphoma. To prevent secondary neoplasms, induce prolonged asparagine depletion, and maintain high event-free survival (EFS) in children with newly diagnosed T-ALL or higher-stage non-Hodgkins lymphoma (NHL), we designed this pilot study to determine feasibility and safety of substituting methotrexate/mercaptopurine for teniposide/cytarabine and PEG-asparaginase for native asparaginase.Forty-five patients were entered, 29 with T-ALL and 16 with higher-stage NHL. Forty-two of 45 patients achieved complete remission (CR), and 27 completed the therapy in continuous CR. Treatment consisted of 4-week induction then 6 weeks consolidation and ten 9-week maintenance cycles. Therapy primarily comprised antimetabolites, anthracyclines, alkylating agents, and asparaginase. Expected chemotherapy duration was 100 weeks.Forty-two of 45 patients achieved CR, and 27 completed therapy. The most common toxicities were Grade 3 or 4 myelosuppression after cyclophosphamide/cytarabine and allergic reactions to asparaginase. Two died of sepsis early in maintenance. Five-year EFS was 68.5% (SE 9.1%) for T-ALL and 81.3% (SE 9.8%) for NHL. Five-year EFS was 73.1% (SE 6.8%) for the entire cohort. No patients treated entirely on this study developed secondary neoplasms. One patient taken off study for asparaginase toxicity was treated with multiagent therapy that contained teniposide, and died from secondary myelodysplasia (sMDS)/AML.Substituting methotrexate/mercaptopurine for teniposide/cytarabine and PEG-asparaginase for native asparaginase in a dose-intensive regimen was feasible in children and young adults with newly diagnosed T-ALL or higher-stage NHL. EFS was not compromised and secondary neoplasms were decreased.

  View details for DOI 10.1002/pbc.20429

  View details for Web of Science ID 000234357500011

  View details for PubMedID 16007607

• PharmGKB update: II. CYP3A5, cytochrome P450, family 3, subfamily A, polypeptide 5. Pharmacological reviews Schuetz, E. G., RELLING, M. V., Kishi, S., Yang, W., Das, S., Chen, P., Cook, E. H., Rosner, G. L., Pui, C. H., Blanco, J. G., Edick, M. J., Hancock, M. L., Winick, N. J., Dervieux, T., Amylon, M. D., Bash, R. O., Behm, F. G., Camitta, B. M., Raimondi, S. C., Goh, B. C., Lee, S. C., Wang, L. Z., Fan, L., Guo, J. Y., Lamba, J., Lim, R., Lim, H. L., Ong, A. B., Lee, H. S., Kuehl, P., Zhang, J., Lin, Y., Assem, M., Schuetz, J., Watkins, P. B., Daly, A., Wrighton, S. A., Hall, S. D., Maurel, P., Brimer, C., Yasuda, K., Venkataramanan, R., Strom, S., Thummel, K., Boguski, M. S. 2004; 56 (2): 159-?

  View details for PubMedID 15169924

• Minimal toxicity using fludarabine and low dose total body irradiation as conditioning for transplantation of HLA matched hematopoietic cells Annual Meeting of the Pediatric-Academic-Societies/Society-for-Pediatric-Research Woolfrey, A. E., Pulsipher, M., Walters, M. C., Amylon, M., Sanders, J. E., STORB, R. NATURE PUBLISHING GROUP. 2003: 281A?281A

  View details for Web of Science ID 000181897901600

• Development and testing of the School Competency Assessment Scale. Journal of pediatric oncology nursing Challinor, J., Moore, I. K., Kramer, R., Pasvogel, A., Leung, K., Amylon, M., Hutter, J., Matthay, K. 2003; 20 (2): 56-64

  View details for PubMedID 12709932

• Bone marrow transplantation in children less than three years of age: Long-term effects on height and hormonal function. 44th Annual Meeting of the American-Society-of-Hematology Jonasdottir, S., Wong, W. B., Agarwal, R., Wilson, D. M., Amylon, M. D., Fechner, P. Y. AMER SOC HEMATOLOGY. 2002: 850A?850A

  View details for Web of Science ID 000179184703359

• A minimal toxicity nonmyeloablative transplant regimen for patients with non-malignant disorders. 44th Annual Meeting of the American-Society-of-Hematology Woolfrey, A., Pulsipher, M. A., Walters, M. C., Amylon, M., Thomson, B., Sanders, J. E., STORB, R. AMER SOC HEMATOLOGY. 2002: 623A?623A

  View details for Web of Science ID 000179184702457

• Genetic polymorphisms in CYP3A5, CYP3A4 and NQO1 in children who developed therapy-related myeloid malignancies PHARMACOGENETICS Blanco, J. G., Edick, M. J., Hancock, M. L., Winick, N. J., Dervieux, T., Amylon, M. D., Bash, R. O., Behm, F. G., Camitta, B. M., Pui, C. H., Raimondi, S. C., Relling, M. V. 2002; 12 (8): 605-611

  Abstract

  Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-ML) are serious complications that affect some patients after acute lymphoblastic leukemia (ALL) treatment. Genetic polymorphisms in the promoter of CYP3A4 (CYP3A4*1B) and in NAD(P)H:quinone oxidoreductase (NQO1609C-->T substitution) have been associated with the risk of t-ML. A polymorphism in CYP3A5 (CYP3A5*3) affects CYP3A activity and the wild-type allele (CYP3A5*1) is in partial linkage with the CYP3A4*1B allele. We compared the genotype frequencies for the CYP3A5*3, the CYP3A4*1B and the NQO1609C-->T substitution in 224 children with ALL who did not develop t-ML (controls) and in 53 children with ALL who did develop the complication. The allele frequencies differed significantly among whites, blacks and Hispanics (P < 0.001 for CYP3A5*3, P < 0.001 for CYP3A4*1B and P = 0.004 for NQO1609), thus we performed the comparisons between ALL controls and t-ML patients after accounting for race. We found no differences in the CYP3A4*1B allele distribution between ALL controls and t-ML patients in whites (P = 0.339, 6.6% vs. 9.8%), blacks (P = 0.498, 93.8% vs. 87.5%) or Hispanics (P = 0.523, 39.1% vs. 25.0%). The frequencies for the NQO1609C-->T allele did not differ between control and t-ML groups in whites (P = 0.191, 35.0% vs. 44.9%), blacks (P = 0.664, 37.5% vs. 37.5%) or Hispanics (P = 0.447, 65.2% vs. 50.0%). We found no differences between the control and t-ML group in the incidence of homozygous CYP3A5*3 genotypes: 82.0% vs. 85.4% in whites (P = 0.403), 6.5% vs. 12.5% in blacks (P = 0.508), and 69.6% vs. 75.0% in Hispanics (P= 0.663). Our data do not support an association between common CYP3A4, NQO1 or CYP3A5 polymorphisms and the risk of t-ML in children treated for ALL.

  View details for Web of Science ID 000179815400004

  View details for PubMedID 12439220

• Bone marrow stroma-supported culture of T-lineage acute lymphoblastic leukemic cells predicts treatment outcome in children: a Pediatric Oncology Group study LEUKEMIA Winter, S. S., Sweatman, J., Shuster, J. J., Link, M. P., Amylon, M. D., Pullen, J., Camitta, B. M., Larson, R. S. 2002; 16 (6): 1121-1126

  Abstract

  Significant predictors of treatment outcome are poorly defined for patients with T-lineage acute lymphoblastic leukemia (T-ALL). A high WBC at diagnosis, which has traditionally been a predictor of poor response in T-ALL, has considerably weakened prognostic significance in the face of modern, more intensive chemotherapy. To test the hypothesis that bone marrow stroma-supported leukemic cell recovery might identify children at high risk for relapse, we measured the ex vivo recovery of T-ALL lymphoblasts from 29 newly diagnosed patients using a stromal cell co-culture assay. In all cases the T-ALL lymphoblasts showed an increase in recovery of T-ALL cells (RTC), ranging from 4 to 343%, in comparison to samples maintained without stroma. Since we were blinded to patient outcome in this case-control study, we then correlated patient outcome with RTC. The RTC for 18 patients in complete continuous remission (CCR) for greater than 4 years was stochastically larger than for the 11 patients who eventually relapsed (P = 0.011, by the two-sided Wilcoxon test). Furthermore, 100% of patients with an RTC of more than 26% had a CCR greater than 4 years while 78% of the patients with an RTC of less than 25% relapsed within 4 years. This is the first report to show that higher lymphoblast recovery may predict a more favorable outcome for children with T-ALL. A prospective study is needed to test whether stroma-supported leukemic cell recovery might serve as a basis for assigning risk-adjusted therapy.

  View details for DOI 10.1038/sj/leu/2402469

  View details for Web of Science ID 000176069600014

  View details for PubMedID 12040442

• Relationship of p15 and p16 gene alterations to elevated dihydrofolate reductase in childhood acute lymphoblastic leukaemia BRITISH JOURNAL OF HAEMATOLOGY Shah, S. J., Taub, J. W., Witt, T. L., Pollock, B. H., Ding, B. C., Moore, D. S., Amylon, M., Pullen, J., Ravindranath, Y., Matherly, L. H. 2001; 113 (3): 746-756

  Abstract

  The downstream effects of p15 and p16 gene deletions and loss of transcripts on dihydrofolate reductase (DHFR) were examined in 63 B-precursor (BP) acute lymphoblastic leukaemia (ALL) samples. p15 and/or p16 gene deletions were seen in 6% and 8%, respectively, of BP-ALL samples; however, losses of p15 and/or p16 transcripts were seen in 26 out of 63 (41%) samples. Loss of p15 transcripts (36.5%) exceeded that for p16 (17.5%). For the 26 BP-ALLs that lacked p15 and/or p16 transcripts, only six (23%) exhibited low levels of DHFR by flow cytometry assay with Pt430, a fluorescent anti-folate. Conversely, 18 out of 37 (49%) BP-ALL samples with intact p15 and/or p16 genes and transcripts showed low levels of DHFR (P = 0.04). In p15- and p16-null K562 cells transfected with a tetracycline-inducible p15 cDNA construct, induction of p15 transcripts and protein was accompanied by decreased growth rates, decreased S-phase fraction, decreased retinoblastoma protein phosphorylation, and markedly reduced levels of DHFR transcripts and protein. Collectively, our results suggest that losses of p15 and/or p16 gene expression result in elevated levels of DHFR in BP-ALL in children. However, additional downstream factors undoubtedly also contribute to elevated levels of this enzyme target.

  View details for Web of Science ID 000169428600029

  View details for PubMedID 11380466

• New recurring cytogenetic abnormalities and association of blast cell karyotypes with prognosis in childhood T-cell acute lymphoblastic leukemia: a Pediatric Oncology Group report of 343 cases BLOOD Schneider, N. R., Carroll, A. J., Shuster, J. J., Pullen, D. J., Link, M. P., Borowitz, M. J., Camitta, B. M., Katz, J. A., Amylon, M. D. 2000; 96 (7): 2543-2549

  Abstract

  To further define the cytogenetic differences between B-cell lineage (B-lineage) acute lymphoblastic leukemia (ALL) and T-cell lineage ALL (T-ALL) and to determine the prognostic value of cytogenetics in childhood T-ALL, the blast cell karyotypes of 343 cases of pediatric T-ALL, the largest series reported to date, were evaluated. Cytogenetics were performed in a single central laboratory, and the children were treated using a single Pediatric Oncology Group protocol. Clear differences between the karyotypic characteristics of B-lineage ALL and T-ALL were confirmed. This study suggests that there may be survival differences associated with some T-ALL blast cell karyotypes. Better survival is associated with only normal karyotypes and with t(10;14) (translocation of chromosomes 10 and 14); worse survival is associated with the presence of any derivative chromosome. Two new recurring chromosome aberrations previously not reported in T-ALL were found: del(1)(p22) and t(8;12)(q13;p13). Ten aberrations found in this series, which were reported only once previously in T-ALL, can now be considered recurring abnormalities in T-ALL. All 12 of these new recurring aberrations are targets for discovery and characterization of new genes that are important in T-cell development and leukemogenesis.

  View details for Web of Science ID 000089552500033

  View details for PubMedID 11001909

• Slow disappearance of peripheral blood blasts is an adverse prognostic factor in childhood T cell acute lymphoblastic leukemia: a Pediatric Oncology Group study LEUKEMIA Griffin, T. C., Shuster, J. J., Buchanan, G. R., Murphy, S. B., Camitta, B. M., Amylon, M. D. 2000; 14 (5): 792-795

  Abstract

  The rapidity of response to induction therapy is emerging as an important prognostic factor in children and adolescents with acute lymphoblastic leukemia (ALL). We studied the relationship between rapidity of reduction in peripheral blood blast count and treatment outcome in children with T cell ALL (T-ALL). Initial systemic chemotherapy included prednisone, vincristine, doxorubicin and cyclophosphamide. A Cox analysis evaluated the correlation between the length of time that the peripheral blood absolute blast count (ABC) remained above 1000/mm3 following the start of treatment and event-free survival (EFS). Data were available for 281 patients. Patients for whom the ABC remained >1000/mm3 for 3 or more days following administration of intensive therapy had an estimated 5-year EFS of 34.2% (s.e. = 7.2) vs 58.3% (3.5) for those whose ABC was <1000/mm3 within 0-2 days, with a hazard ratio (HR) of failure of 2.03 (95% CI = 1.35-3.06, P < 0.001) for the slower responding patients. Pre-treatment of some type (usually with prednisone) occurred in 128 patients (average duration 1.7 days). When this was accounted for, patients with an ABC >1000/mm3 for 5 or more days following the start of treatment of any kind had a HR for failure of 2.27 (95% CI = 1.38-3.72, P < 0.001) compared to those responding within 0-4 days. Inclusion of other clinical and biological factors in a multivariate analysis did not alter the prognostic importance of slower blast clearance. Pediatric patients with T-ALL who have a circulating blast count >1000/mm3 at diagnosis and a relatively slower response to initial treatment are at increased risk of treatment failure. Rapidity of response may therefore be a clinically useful prognostic factor for patients with T-ALL.

  View details for Web of Science ID 000086819400005

  View details for PubMedID 10803508

• Effects of cranial radiation in children with high risk T cell acute lymphoblastic leukemia: a Pediatric Oncology Group report LEUKEMIA Laver, J. H., Barredo, J. C., Amylon, M., Schwenn, M., Kurtzberg, J., Camitta, B. M., Pullen, J., Link, M. P., Borowitz, M., Ravindranath, Y., Murphy, S. B., Shuster, J. 2000; 14 (3): 369-373

  Abstract

  Contemporary chemotherapy has significantly improved event-free survival among patients with T cell-lineage acute lymphoblastic leukemia (T-ALL). Unlike B-precursor ALL, most investigators are still using cranial radiation (CRT) and are hesitant to rely solely on intrathecal therapy for T-ALL. In this study we assessed the effects of CRT upon event-free survival and central nervous system (CNS) relapses in a cohort of children with high risk features of T cell leukemia. In a series of six consecutive studies (1987-1995) patients were non-randomly assigned their CNS prophylaxis per individual protocol. These protocols were based on POG 8704 which relied on rotating drug combinations (cytarabine/cyclophosphamide, teniposide/Ara-C, and vincristine/doxorubicin/6-MP/prednisone) postinduction. Modifications such as high-dose cytarabine, intermediate-dose methotrexate, and the addition of G-CSF, were designed to give higher CNS drug levels (decreasing the need for CRT), to eliminate epidophyllotoxin (decreasing the risk of secondary leukemia), and to reduce therapy-related neutropenia (pilot studies POG 9086, 9295, 9296, 9297, 9398). All patients included in this analysis qualified for POG high risk criteria, WBC >50000/mm3 and/or CNS leukemia. Patients without CNS involvement received 16 doses of age-adjusted triple intra-thecal therapy (TIT = hydrocortisone, MTX, and cytarabine) whereas patients with CNS disease received three more doses of TIT during induction and consolidation. Patients who received CRT were treated with 2400 cGy (POG 8704) or 1800 cGy (POG 9086 and 9295). CNS therapy included CRT in 144 patients while the remaining 78 patients received no radiation by original protocol design. There were 155 males and 57 females with a median age of 8.2 years. The median WBC for the CRT+ and CRT- patients were 186000/mm3 and 200000/mm3, respectively. CNS involvement at diagnosis was seen in 16% of the CRT+ and 23% of the CRT- groups. The complete continuous remission rate (CCR) was not significantly different for the irradiated vs. non-irradiated groups (P = 0.46). The 3-year event-free survival was 65% (s.e. 6%) and 63% (s.e. 4%) for the non-irradiated vs. the radiated group. However, the 3-year CNS relapse rate was significantly higher amongst patients who did not receive CRT; 18% (s.e. 5%) vs. 7% (s.e. 3%) in the irradiated group (P = 0.012). Our analysis in a non-randomized setting, suggests that CRT did not significantly correlate with event-free survival but omitting it had an adverse effect on the CNS involvement at the time of relapse.

  View details for Web of Science ID 000085748400004

  View details for PubMedID 10720128

• Cost analysis of filgrastim for the prevention of neutropenia in pediatric T-cell leukemia and advanced lymphoblastic lymphoma: A case for prospective economic analysis in cooperative group trials MEDICAL AND PEDIATRIC ONCOLOGY Bennett, C. L., Stinson, T. J., Lane, D., Amylon, M., Land, V. J., Laver, J. H. 2000; 34 (2): 92-96

  Abstract

  Growth factor use has been shown to ameliorate chemotherapy-induced neutropenia, leading to shorter hospital stays and lower use of parenteral antibiotics, two costly areas of cancer treatment. Prior reports on pediatric patients have shown evidence of cost savings in some studies, but no such evidence in others. In this study a retrospective analysis compared the costs of inpatient supportive care for pediatric patients with T-cell leukemia and advanced lymphoblastic lymphoma enrolled in a Pediatric Oncology Group trial.Patients 1-22 years of age were randomized to receive either granulocyte colony-stimulating factor (G-CSF; n = 45) or no G-CSF (n = 43) following induction and two cycles of maintenance therapy. There were no significant differences in neutropenia-related outcomes during the induction phase. During maintenance therapy, G-CSF patients had significantly fewer days to an ANC >500 cells/microl and a trend towards fewer days of hospitalization. Data on resource utilization were tabulated from case report forms. Costs were imputed from national data on hospitalization costs, average wholesale prices of pharmaceuticals, and patient billing information from a single institution.Total median costs of supportive care were $34,190 for patients receiving G-CSF and $28,653 for patients not receiving G-CSF (P > 0. 05 for the cost difference). Sensitivity analyses demonstrated that the total cost difference was not statistically significant, even in scenarios that included reasonable variations in estimates of the range of the length of stay, antibiotic regimen, and dosage and cost of G-CSF.In the setting of pediatric leukemia, the cost of growth factor may offset potential savings from shorter hospital stays or lower antibiotic use, a finding consistent with that from the Children's Cancer Study Group.

  View details for Web of Science ID 000085165400003

  View details for PubMedID 10657867

• Glutathione S-transferase genotypes in children who develop treatment-related acute myeloid malignancies LEUKEMIA Woo, M. H., Shuster, J. J., Chen, C., Bash, R. O., Behm, F. G., Camitta, B., Felix, C. A., Kamen, B. A., Pui, C. H., Raimondi, S. C., Winick, N. J., Amylon, M. D., RELLING, M. V. 2000; 14 (2): 232-237

  Abstract

  Epipodophyllotoxin-associated secondary myeloid leukemia is a devastating complication of acute lymphoblastic leukemia (ALL) therapy. The risk factors for treatment-related myeloid leukemia remain incompletely defined. Genetic deficiencies in glutathione S-transferase (GST) activities have been linked to higher frequencies of a number of human malignancies. Our objective was to determine whether the null genotype for GSTM1, GSTT1, or both, was more frequent in children with ALL who developed treatment-related myeloid malignancies as compared to those who did not. A PCR technique was used to assay for the null genotype for GSTM1 and GSTT1 in 302 children with ALL, 57 of whom also subsequently developed treatment-related acute myeloid leukemia or myelodysplastic syndrome. Among children with ALL who did not develop treatment-related myeloid malignancies, the frequencies of GSTM1 and GSTT1 wild-type, GSTM1 null-GSTT1 wild-type, GSTM1 wild-type-GSTT1 null, and GSTM1 and GSTT1 null genotypes were 40%, 42%, 9% and 9%, respectively. The corresponding frequencies for patients who developed acute myeloid malignancies were 42%, 32%, 11% and 16%, respectively (P = 0.26). A statistically significant increase in the frequency of the GST null genotype was observed in male patients who developed myeloid malignancies as compared to male ALL control patients (P = 0.036), but was not observed in female patients (P = 0.51). Moreover, a logistic regression analysis of possible predictors for myeloid malignancies, controlling for gender and race, did not reveal an association of GSTM1 or GSTT1 null genotypes (P = 0.62 and 0.11, respectively) with treatment-related malignancies. Our data suggest that GSTM1 and GSTT1 null genotypes may not predispose to epipodophyllotoxin-associated myeloid malignancies.

  View details for Web of Science ID 000085281500003

  View details for PubMedID 10673738

• Multi-lineage chimerism analysis using short or variable number of tandem repeat (STR/VNTR) polymerase chain reaction (PCR) in both bone marrow (BM) and peripheral blood (PB) from patients (PTS) after allogeneic bone marrow transplantation (BMT). Lee, Y. S., Kristovich, K. M., GRUMET, F. C., Amylon, M. D. AMER SOC HEMATOLOGY. 1999: 148A?148A

  View details for Web of Science ID 000083790300699

• Allogeneic bone marrow transplantation (BRIT) for high risk all in first remission (1CR). Fung, H., Jamieson, C., Snyder, D., O'Donnell, M., Chao, N., Stein, A., Nademanee, A., Molina, A., Palmer, M., Negrin, R., Hilger, J., Slovak, M. L., Spielberger, R., Parker, P., Forman, S., Kashyap, A., Vora, N., Krishnan, A., Rodriguez, R., Bhatia, R., Niland, J. C., Senitzer, D., Arber, D., Amylon, M., Arbayo, C., Blume, K. G., Forman, S. J. AMER SOC HEMATOLOGY. 1999: 609A?609A

  View details for Web of Science ID 000083790302758

• Equivalence of two effective GVHD prophylaxis regimens: Results of a prospective blinded randomized trial. Chao, N. J., Snyder, D., Jain, M., Wong, R., Niland, J., Negrin, R. S., Long, G. D., Hu, W. W., Goldstein, K., Johnston, L., Amylon, M., Tierney, D. K., O'Donnell, M., Nademanee, A., Parker, P., Stein, A., Molina, A., Fung, H., Kashyap, A., Spielberger, R., Krishnan, A., Rodriguez, R., Forman, S. J., Blume, K. G. AMER SOC HEMATOLOGY. 1999: 666A?666A

  View details for Web of Science ID 000083790303006

• Significance of commonly used prognostic factors differs for children with T cell acute lymphocytic leukemia (ALL), as compared to those with B-precursor ALL. A Pediatric Oncology Group (POG) study LEUKEMIA Pullen, J., Shuster, J. J., Link, M., Borowitz, M., Amylon, M., Carroll, A. J., Land, V., Look, A. T., McIntyre, B., Camitta, B. 1999; 13 (11): 1696-1707

  Abstract

  T cell acute lymphocytic leukemia (T-ALL) and B-precursor ALL differ significantly in the clinical characteristics of the patients at presentation and in laboratory-defined characteristics of the leukemic cells. We assessed for pediatric patients with T-ALL the relative importance of prognostic factors previously demonstrated to predict outcome in B-precursor ALL. Presenting clinical and laboratory features were correlated with outcome for 441 children 12 months to 21 years of age with previously untreated T-ALL, registered on the Pediatric Oncology Group (POG) T3 protocol between 1986 and 1992. These T-ALL prognostic factor analyses were then compared to similar analyses for 1993 patients with B-precursor ALL enrolled during the same time period on the POG ALinC 14 protocol. Quantitative interaction between phenotype and each prognostic factor was studied to determine the relative importance of the prognostic factor for each of the two major immunophenotypes. We also analyzed the importance of maturational stage as a T-ALL prognostic factor, using a modified Ludwig definition of maturational stage. We conclude that several of the clinical and laboratory prognostic factors, which are used reliably for B-precursor ALL, are much less predictive in T-ALL (ie age, WBC, consensus risk group, hyperdiploidy, presence of trans- locations and CALLA expression). There was no significant difference between the phenotypes in the prognostic importance of race or gender. Our data demonstrate a significant difference in outcome among the three maturational stages of T-cell ALL, with the intermediate group faring best. Using traditional risk group criteria to stratify patients with T-ALL for therapy may not be appropriate.

  View details for Web of Science ID 000083664000005

  View details for PubMedID 10557041

• Comparison of two doses of intravenous immunoglobulin after allogeneic bone marrow transplants BONE MARROW TRANSPLANTATION Abdel-Mageed, A., Graham-Pole, J., del Rosario, M. L., Longmate, J., Ochoa, S., Amylon, M., Elfenbein, G. J., Janiec, J., Jansen, J., Lazarus, H. M. 1999; 23 (9): 929-932

  Abstract

  Intravenous immunoglobulin has been used after bone marrow transplants to prevent infections and acute graft-versus-host disease. However, the minimum dose required for protection is unknown. This may have significant economic implications. A multicenter randomized clinical trial compared the impact of two intravenous immunoglobulin doses on systemic infections and acute graft-versus-host disease in transplant recipients. Either 250 mg/kg or 500 mg/kg was given weekly from day -8 to day +111. Multivariate analysis was used to assess the effect of dose and other risk factors on event-free survival, systemic infection, and acute graft-versus-host disease. The two-dose cohorts had similar event-free survival and infection frequencies. The higher dose was associated with less acute graft-versus-host disease (P = 0.03).

  View details for Web of Science ID 000080097200011

  View details for PubMedID 10338049

• Use of alanosine as a methylthioadenosine phosphorylase-selective therapy for T-cell acute lymphoblastic leukemia in vitro CANCER RESEARCH Batova, A., Diccianni, M. B., Omura-Minamisawa, M., Yu, J., Carrera, C. J., Bridgeman, L. J., Kung, F. H., Pullen, J., Amylon, M. D., Yu, A. L. 1999; 59 (7): 1492-1497

  Abstract

  Methylthioadenosine phosphorylase (MTAP) is an important enzyme for the salvage of adenine and methionine and is deficient in a variety of cancers including T-cell acute lymphocytic leukemia (T-ALL). Previously, we reported that the MTAP gene was deleted in over 30% of T-ALL patients at both diagnosis and relapse. We now report that MTAP-primary T-ALL cells are more sensitive to the toxicity of L-alanosine, an inhibitor of de novo AMP synthesis, than are MTAP+ primary T-ALL cells. As measured by [3H]thymidine incorporation, DNA synthesis in all seven MTAP-primary T-ALL cells was inhibited by L-alanosine with a mean IC50 of 4.8+/-5.3 ILM (range, 0.3-11.3 microM). On the other hand, the IC50 for 60% (12 of 20) of MTAP+ primary T-ALL was 19+/-18 microM (range, 1.7-67 microM; P = 0.02), whereas the remaining 40% (8 of 20) had an IC50 of >80 microM4. Furthermore, normal lymphocytes and MTAP+ primary T-ALL cells were rescued from L-alanosine toxicity by the MTAP substrate 5'-deoxyadenosine, but MTAP-T-ALL cells were not. These results indicate that normal cells, which are intrinsically MTAP+, would be protected from L.-alanosine toxicity, whereas MTAP-tumor cells would be killed. Thus, our results support the use of L-alanosine alone or in combination with a salvage agent as a MTAP-selective therapy and therefore lay the foundation for the initiation of clinical trials for the treatment of T-ALL and other MTAP-deficient malignancies with L-alanosine.

  View details for Web of Science ID 000079527800021

  View details for PubMedID 10197619

• Somatization, anxiety and depression as measures of health-related quality of life of children/adolescents with cancer International Workshop on Assessing Health-Related Quality of Life in Children with Cancer Challinor, J. M., Miaskowski, C. A., Franck, L. S., Slaughter, R. E., Matthay, K. K., Kramer, R. F., Veatch, J. J., Paul, S. M., Amylon, M. D., Moore, I. M. WILEY-BLACKWELL. 1999: 52?57

  Abstract

  This descriptive study of health-related quality of life of children with cancer compared children/adolescents', parents' and teachers' ratings for somatization, depression and anxiety to determine if there were significant correlations among respondent scores. In addition, the percentage of agreement among respondents and significant differences based on age, gender, use of cranial radiation and treatment status were measured. Forty-three children/adolescents with cancer, currently receiving therapy for at least 1 year or who had completed therapy for no more than 3 years (excluding children who had received bone marrow transplants or who had brain tumors), were recruited, with a parent and teacher, from 3 university medical centers. The Behavioral Assessment System for Children questionnaires for children/adolescents, parents and teachers were used. Parents reported a higher level of depression for the children/adolescents with cancer than did the teachers or the children/adolescents themselves. Parents reported a higher level of anxiety for the children/adolescents than did the teachers. High positive correlations were found among scores from parents and teachers and among scores from parents and children/adolescents for the anxiety and depression but not somatization subscales. Children/adolescents and teachers had high, positively correlated scores only for the depression subscale. High, positive correlations were found between somatization, anxiety and depression within each group of respondents. A significant percentage of agreement between all respondents on ratings for at-risk status was obtained only for the depression subscale. Age was the only variable found to have an influence on scores and only for the anxiety subscale.

  View details for Web of Science ID 000084615500010

  View details for PubMedID 10679871

• Randomized trial of r-metHu granulocyte colony-stimulating factor in an intensive treatment for T-cell leukemia and advanced-stage lymphoblastic lymphoma of childhood: A pediatric oncology group pilot study JOURNAL OF CLINICAL ONCOLOGY Laver, J., Amylon, M., Desai, S., Link, M., Schwenn, M., Mahmoud, H., Shuster, J. 1998; 16 (2): 522-526

  Abstract

  Contemporary chemotherapy has significantly improved the event-free survival (EFS) among patients with T-cell disease. However, myelosuppression has been a significant adverse effect of this approach. In this study, we assessed the impact of r-metHu granulocyte colony-stimulating factor (G-CSF) on the period of neutropenia, number of days of hospitalization, and delays in subsequent administration of chemotherapy in a cohort of patients with T-cell leukemia (T-ALL) or advanced stage lymphoblastic lymphoma (ASLL).This open-label, randomized trial incorporated r-metHuG-CSF into the induction and two consecutive continuation-therapy cycles of our intensive program for T-cell malignancies. In the induction phase, r-metHuG-CSF was given after two different combinations of chemotherapy, one of which included vincristine, prednisone, cyclophosphamide, and adriamycin and the other a continuous infusion of high-dose ara-C and L-asparaginase. In the two continuation-therapy cycles, r-metHuG-CSF was given following the combination of vincristine, adriamycin, prednisone, and 6-mercaptopurine (MP) and after continuous infusion of high-dose cytarabine (ara-C).Fifty-six patients with T-ALL and 33 with ASLL were enrolled onto study from April 1994 to December 1995. Our data show no significant difference in number of days of absolute neutrophil count (ANC) less than 500/microL, hospitalizations, or delays in therapy in the induction phase. However, in the continuation-therapy phase the number of days of ANC less than 500/microL was significantly shorter (P = .017) on the G-CSF-arm without significantly affecting the number of days of hospitalizations or delays in therapy.r-metHuG-CSF did not significantly affect the period of neutropenia, hospitalization, or delays in therapy in the induction phase, whereas in the two cycles of continuation therapy, it significantly shortened the period of neutropenia.

  View details for Web of Science ID 000071747900017

  View details for PubMedID 9469336

• Bone marrow transplant in thalassemia - A role for radiation? 7th Cooleys Anemia Symposium Lee, Y. S., Kristovich, K. M., Ducore, J. M., Vichinsky, E., Crouse, V. L., Glader, B. E., Amylon, M. D. NEW YORK ACAD SCIENCES. 1998: 503?505

  View details for Web of Science ID 000074933900078

  View details for PubMedID 9668596

• Economic analysis of G-CSF use with intensive treatment for pediatric lymphoma and T-cell leukemia. Pajeau, T. S., Lane, D., Bennett, C. L., Land, V., Amylon, M., Laver, J. H. AMER SOC HEMATOLOGY. 1997: 316?16

  View details for Web of Science ID A1997YG42400316

• Increased frequency of expression of elevated dihydrofolate reductase in T-cell versus B-precursor acute lymphoblastic leukemia in children BLOOD Matherly, L. H., Taub, J. W., Wong, S. C., Simpson, P. M., Ekizian, R., Buck, S., Williamson, M., Amylon, M., Pullen, J., Camitta, B., Ravindranath, Y. 1997; 90 (2): 578-589

  Abstract

  The relationships between dihydrofolate reductase (DHFR) levels or methotrexate membrane transport and acute lymphoblastic leukemia (ALL) immunophenotype were evaluated on 51 T-cell and 44 B-precursor ALL specimens from 90 pediatric ALL patients at diagnosis and relapse, using a fluorescent methotrexate analog (PT430) and flow cytometry assay (Matherly et al, Blood 85:500, 1995). For T-cell ALL, 35 of 45 (78%) of newly diagnosed patients' specimens exhibited elevated DHFR relative to DHFR levels in ALL blasts from methotrexate-responsive patients. For 30 of 45 diagnostic T-ALL specimens, DHFR expression was heterogeneous, with up to 3 separate subpopulations covering a 44-fold range; the DHFR-overproducing fractions comprised 10% to 88% of the total blasts. Elevated DHFR was less common in B-precursor ALL at diagnosis, being detected in only 17 of 36 specimens (47%); 11 of these samples exhibited DHFR heterogeneity. Median maximal DHFR levels were fourfold higher in T-cell than B-precursor ALL at diagnosis. Within a particular phenotypic group, there were no correlations between DHFR levels and patient prognostic features, including age, sex, chromosomal abnormalities, white blood cell counts (WBCs), and percentage of S-phase. However, for B-precursor ALL, there was a notably higher fraction of African-American than white patients with elevated DHFR. For patients (both phenotypes) with low WBCs (<50,000/ microL), event-free survival times were significantly shorter for those expressing DHFR above a threshold level than for patients expressing DHFR below this level (P < .016); this relationship was not seen for patients with high WBCs (>50,000/microL). Elevated DHFR was detected in 11 of 14 relapse specimens (5 of 6 T-cell and 6 of 8 B-precursor). Two of five paired relapse specimens (both T-cell) from patients treated with methotrexate exhibited increased DHFR levels over those at diagnosis (2.5- to 5-fold); the fraction of DHFR-overproducing blasts was also increased in 4 of 5 paired relapse specimens (2 B-precursor and 2 T-cell). In contrast to the variations in DHFR, highly impaired methotrexate transport was detected in only 6 of 95 ALL specimens, including both diagnosis and relapse. There was no correlation between phenotype and impaired transport. These data provide further rationale for the use of mechanistically based prognostic factors to complement known biologic or disease-based prognostic indicators in the design of ALL therapy including methotrexate, particularly with patients presenting with low WBCs. The finding of a markedly increased frequency of DHFR overexpression in T-cell over B-precursor ALL suggests that this difference is associated with the poorer prognosis of patients with T-cell ALL treated with standard-dose antimetabolite therapy and implies that higher-dose methotrexate (> or = 1 g/m2) during consolidation therapy may be useful in the treatment of this disease.

  View details for Web of Science ID A1997XL77400010

  View details for PubMedID 9226157

• Shortened survival after relapse in T-cell acute lymphoblastic leukemia patients with P16/P15 deletions LEUKEMIA RESEARCH Diccianni, M. B., Batova, A., Yu, J., Vu, T., Pullen, J., Amylon, M., Pollock, B. H., Yu, A. L. 1997; 21 (6): 549-558

  Abstract

  p16 Alterations were detected in > 60% of 103 primary T-ALL samples. In paired diagnosis-relapse patient samples, 80% of the relapse samples with p16 deletion were deleted at diagnosis. When p16 was homozygously deleted, p15 gene alterations were found in 72% of the diagnosis T-ALL patient samples, increasing significantly to 100% at relapse. Alterations of p18 were not detected. No clinical significance of p15/p16 gene deletion in diagnosis T-ALL was found with respect to white blood cell (WBC) count, incidence of mediastinal mass, rate of relapse, duration of first remission or event-free survival. In relapse T-ALL, however, patients with p16 deletion experienced a significantly shorter duration of post-relapse survival, demonstrating that p16 deletion is clinically significant in T-ALL.

  View details for Web of Science ID A1997XR42800008

  View details for PubMedID 9279366

• Influence of age on the outcome of 500 autologous bone marrow transplant procedures for hematologic malignancies Annual Meeting of the German-and-Austrian-Society-of-Hematology-and-Oncology KUSNIERZGLAZ, C. R., Schlegel, P. G., Wong, R. M., Schriber, J. R., Chao, N. J., Amylon, M. D., Hu, W. W., Negrin, R. S., Lee, Y. S., Blume, K. G., Long, G. D. AMER SOC CLINICAL ONCOLOGY. 1997: 18?25

  Abstract

  To determine the effect of age on the outcome of autologous bone marrow transplantation (ABMT) and/or peripheral-blood progenitor-cell (PBPC) transplantation.A retrospective analysis was performed on 500 consecutive patients who ranged in age from 1 to 65 years (median, 40) with non-Hodgkin's lymphoma (NHL), Hodgkin's disease (HD), multiple myeloma (MM), or acute nonlymphoblastic leukemia (AML) who underwent autologous hematopoietic-cell transplant procedures at Stanford University Medical Center.The actuarial 5-year event-free survival (EFS) rate was 44%, the relapse rate 47%, and the regimen-related mortality (RRM) rate 8.6%. Disease status at time of transplantation, categorized as either minimal or advanced disease, was the strongest predictive factor for EFS (relative risk (RR) for advanced-disease group, 1.8; P < .0003) and relapse rate (RR for advanced-disease group, 1.9; P < .0004). Patients with minimal or advanced disease had an EFS rate of 48% and 30% and relapse rates of 43% and 72%, respectively. The EFS rate of patients less than 50 years verus > or = 50 years of age was 46% versus 34% (P = .03). Cox regression analysis showed that age was predictive for EFS (RR for patients 50 to 65 years, 1.4; P = .03). The actuarial RRM rate for these age groups was 7.4% versus 12.7% (P = .07), respectively. Multivariate analysis demonstrated that age (odds ratio [OR] for patients 50 to 65 years, 1.9; P < .05) and period of transplantation (OR for most recent years [1991 to 1995], 0.6; P = .06) were the most predictive factors for RRM.Although age greater than 50 years is associated with an inferior outcome following autologous hematopoietic-cell transplantation, it does not appear to be warranted to limit this potentially curative procedure based solely on age. The upper age limit of high-dose therapy with autologous progenitor-cell and/ or bone marrow support remains to be defined.

  View details for Web of Science ID A1997WB90700005

  View details for PubMedID 8996120

• Bone marrow transplant in thalassemia at Stanford University: A role for radiation? Lee, Y. S., Kristovich, K. M., Ducore, J. M., Vichinsky, E., Crouse, V. L., Glader, B. E., Amylon, M. D. AMER SOC HEMATOLOGY. 1996: 2467?67

  View details for Web of Science ID A1996VT98302467

• Influence of preparatory regimen and source of hematopoietic cells on outcome of autotransplantation for non-Hodgkin's lymphoma. Biology of blood and marrow transplantation Stockerl-Goldstein, K. E., Horning, S. J., Negrin, R. S., Chao, N. J., Hu, W. W., Long, G. D., Hoppe, R. T., Amylon, M. D., BROWN, B. W., Wong, R. M., Blume, K. G. 1996; 2 (2): 76-85

  Abstract

  The use of high-dose chemotherapy with or without total-body irradiation (TBI) followed by autologous hematopoietic cell transplantation is associated with improved survival for relapsed or refractory non-Hodgkin's lymphoma (NHL). Previous reports comparing preparatory regimens with or without TBI followed by autologous bone marrow transplantation (ABMT) or peripheral blood progenitor cell transplantation (PBPCT) for these patients did not demonstrate any survival difference between the different modalities. No randomized studies comparing survival for patients with NHL transplanted with radiochemotherapy vs. chemotherapy alone have been reported. We treated 221 patients with high-risk, relapsed or refractory NHL with either chemotherapy alone or radiochemotherapy followed by ABMT or PBPCT. The patients were assigned preparatory regimens in a non-randomized manner and this analysis was performed to evaluate differences in outcome with the two preparatory regimens. Actuarial five-year event-free survival (EFS) was similar in patients receiving fractionated total-body irradiation (FTBI) plus etoposide (VP-16) and cyclophosphamide (Cy) compared with chemotherapy alone consisting of carmustine (BCNU) plus identical doses of VP-16 and Cy (52% vs. 46%, p = 0.08). Overall survival (OS) favored radiochemotherapy (61%) compared with chemotherapy alone (53%, p = 0.02). The relapse rate was the same in both groups (41%), whereas the transplantation-related mortality (TRM) was similar in patients receiving chemotherapy alone and those receiving radiochemotherapy (13% vs. 7% respectively, p = 0.30). Proportional hazards analysis of significant variables including preparatory regimen found only the number of prior relapses to be predictive of EFS. Fewer number of prior relapses, radiochemotherapy and PBPCT were significant predictors of favorable OS. In additional analyses, the improved OS of the radiochemotherapy regimen was confirmed only for patients receiving ABMT but was not a significant predictor of outcome in patients transplanted with PBPCT. From these retrospective data we conclude: 1) PBPCT resulted in survival superior to that of ABMT; 2) the risk of relapse is similar with either preparatory regimen; 3) patients with fewer prior relapses enjoyed superior overall and event-free survival as well as fewer relapses; and 4) there were no significant differences in the two preparatory regimens when combined with PBPCT in relapsed or refractory NHL.

  View details for PubMedID 9118302

• Pleuropulmonary blastoma: A marker for familial disease JOURNAL OF PEDIATRICS Priest, J. R., Watterson, J., Strong, L., Woods, W. G., Byrd, R. L., Friend, S. H., Newsham, I., Amylon, M. D., Pappo, A., Mahoney, D. H., Langston, C., Heyn, R., Kohut, G., Freyer, D. R., Bostrom, B., Richardson, M. S., Barredo, J., DEHNER, L. P. 1996; 128 (2): 220-224

  Abstract

  To catalog and evaluate patterns of disease in families of children with pleuropulmonary blastoma (PPB).Data have been collected since 1988 on 45 children with PPB and their families. All pathologic materials were centrally reviewed. Preliminary molecular genetic analyses were performed when possible.In 12 of 45 patients, an association was found between PPB and other dysplasias, neoplasias, or malignancies in the patients with or in their young relatives. The diseases found to be associated with PPB include other cases of PPB, pulmonary cysts, cystic nephromas, sarcomas, medulloblastomas, thyroid dysplasias and neoplasias, malignant germ cell tumors, Hodgkin disease, leukemia, and Langerhans cell histiocytosis. Abnormalities of the p53 tumor suppressor gene, Wilms tumor suppressor gene (WT1), and the putative second genetic locus for Wilms tumor (WT2) were not found in preliminary investigations.The occurrence of PPB appears to herald a constitutional and heritable predisposition to dysplastic or neoplastic disease in approximately 25% of cases. All patients with PPB and their families should be investigated carefully. Further research of this new family cancer syndrome may provide insight into the genetic basis of these diseases.

  View details for Web of Science ID A1996TW05400010

  View details for PubMedID 8636815

• Identifying early predictors of mortality in pediatric patients with acute leukemia and pneumonia CHEST RANDLE, C. J., Frankel, L. R., Amylon, M. D. 1996; 109 (2): 457-461

  Abstract

  To identify clinical variables of pneumonia in children with acute leukemia that predicted respiratory failure and mortality.A retrospective chart review of children with acute leukemia admitted to the hospital with the diagnosis of pneumonia or ARDS from March 1991 to April 1994.Lucile Salter Packard Children's Hospital at Stanford, a 168-bed teaching hospital and regional tertiary referral center for children in northern California.During this study period, 20% of the 174 admissions of children with acute leukemia had pneumonia at the time of admission or during the course of the hospitalization for a total of 36 admissions. The mean age of these children was 9.2 +/- 1.1 years.Eleven percent of the children with pulmonary infiltrates in one quadrant on the chest x-ray film at the onset of pneumonia and 53% of the children with pulmonary infiltrates in more than one quadrant at the onset of pneumonia died. Fifteen percent of the children without sepsis at the onset of pneumonia and 70% of the children with sepsis at onset died. Eighteen percent of the children without shock at the onset of pneumonia and 75% of the children with shock at the onset died. None of the children died who required < or = 3L/min of O2 to maintain SO2 > or = 95%, but 79% of the children who required > 3L/min O2 died. Using the criteria "> 3 L/min O2 by nasal cannula to maintain SO2 > or = 95%" to identify the nonsurvivors had a sensitivity of 100% and specificity of 88%. This specificity was not increased by combining the criteria "O2 requirements at any time" and "the extent of pulmonary infiltrates at the onset of pneumonia." All children who required mechanical ventilatory support for respiratory failure had previously received > 3 L/min O2 by nasal cannula to maintain SO2 > or = 95% for 37.8 +/- 12.9 h (range 3 to 96 h). Nine of the 10 children in our study who received mechanical ventilation died.In children with acute leukemia and pneumonia, the amount of O2 required to maintain SO2 > or = 95% may identify those who are likely to develop respiratory failure hours before mechanical ventilatory support is needed. The ability to identify children at risk for respiratory failure is not increased by combining the risk factors "oxygen requirements" and "extent of pulmonary infiltrates at the onset of pneumonia". Finally, only 10% of the children who required mechanical ventilatory support survived.

  View details for Web of Science ID A1996TV42900033

  View details for PubMedID 8620722

• BUSULFAN/CYCLOPHOSPHAMIDE AS CONDITIONING REGIMEN FOR ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR MYELODYSPLASIA JOURNAL OF CLINICAL ONCOLOGY ODONNELL, M. R., Long, G. D., Parker, P. M., Niland, J., Nademanee, A., Amylon, M., Chao, N., Negrin, R. S., Schmidt, G. M., Slovak, M. L., Smith, E. P., Snyder, D. S., Stein, A. S., Traweek, T., Blume, K. G., Forman, S. J. 1995; 13 (12): 2973-2979

  Abstract

  A non-radiation-containing regimen of busulfan and cyclophosphamide (BU/CY) was evaluated for toxicity, relapse, and long-term survival in patients who received allogeneic bone marrow transplantation (BMT) for myelodysplasia (MDS).Thirty-eight patients with MDS, including eight with therapy-related MDS, were prepared for BMT using BU/CY.Fourteen patients remain in first remission 18 to 60 months posttransplant. Five patients relapsed after BMT, and four of these patients died. Eight additional patients died of acute or chronic graft-versus-host disease (GVHD), and 11 died of regimen-related toxicity, primarily systemic mycoses. Overall survival rate at 2 years was 45% (95% confidence interval [CI], 0.30 to 0.61), with a 24% probability of relapse (95% CI, 0.10 to 0.49). Regimen-related toxicity was manifested primarily as hepatic dysfunction in 72% of patients, with 16% developing overt venoocclusive disease (VOD).Non-radiation-containing preparative regimens offer long-term survival in allogeneic BMT for MDS that is comparable to that of radiation-containing regimens, and are useful in patients with therapy-related MDS. Monitoring BU levels may reduce regimen-related mortality and improve survival.

  View details for Web of Science ID A1995TK25600017

  View details for PubMedID 8523063

• High frequency alterations of the p16 and p15, but not p18, CDK inhibitors in T cell acute lymphoblastic leukemia Yu, A. L., Diccianni, M. B., Batova, A., Vu, T., Pullen, J., Amylon, M., Pollock, B., Yu, J. AMER SOC HEMATOLOGY. 1995: 1057?57

  View details for Web of Science ID A1995TH91001059

• DOES ACTIVATION OF THE TAL1 GENE OCCUR IN A MAJORITY OF PATIENTS WITH T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA - A PEDIATRIC-ONCOLOGY-GROUP STUDY BLOOD Bash, R. O., Hall, S., Timmons, C. F., Crist, W. M., Amylon, M., SMITH, R. G., Baer, R. 1995; 86 (2): 666-676

  Abstract

  Almost 25% of patients with T-cell acute lymphoblastic leukemia (T-ALL) have tumor-specific rearrangements of the TAL1 gene. Although TAL1 expression has not been observed in normal lymphocytes, TAL1 gene products are readily detected in leukemic cells that harbor a rearranged TAL1 allele. Hence, it has been proposed that ectopic expression of TAL1 promotes the development of T-ALL. In this report, we show that TAL1 is expressed in the leukemic cells of most patients with T-ALL, including many that do not display an apparent TAL1 gene alteration. A polymorphic dinucleotide repeat in the transcribed sequences of TAL1 was used to determine the allele specificity of TAL1 transcription in primary T-ALL cells. Monoallelic expression of TAL1 was observed in the leukemic cells of all patients (8 of 8) bearing a TAL1 gene rearrangement. In the leukemic cells of patients without detectable TAL1 rearrangements, TAL1 transcription occurred in either a monoallelic (3 of 7 patients) or a biallelic (4 of 7 patients) fashion. Thus, TAL1 activation in these patients may result from subtle alterations in cis-acting regulatory sequences (affecting expression of a single TAL1 allele) or changes in trans-acting factors that control TAL1 transcription (affecting expression of both TAL1 alleles).

  View details for Web of Science ID A1995RH80100029

  View details for PubMedID 7605997

• EVALUATION OF HIGH-DOSE ARA-C (HDA) IN TREATMENT OF CHILDHOOD T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA (T-ALL) AND ADVANCED-STAGE LYMPHOBLASTIC NON-GROUP (POG) STUDY Katz, J. A., AMYLON, M. A., Ravindranath, Y., Shuster, J. J. AMER SOC HEMATOLOGY. 1994: A145?A145

  View details for Web of Science ID A1994PR75400565

• FRACTIONATED TOTAL-BODY IRRADIATION AND HIGH-DOSE ETOPOSIDE AS A PREPARATORY REGIMEN FOR BONE-MARROW TRANSPLANTATION FOR 94 PATIENTS WITH CHRONIC MYELOGENOUS LEUKEMIA IN CHRONIC PHASE BLOOD Snyder, D. S., Negrin, R. S., ODONNELL, M. R., Chao, N. J., Amylon, M. D., Long, G. D., Nademanee, A. P., Stein, A. S., Parker, P. M., Smith, E. P., Somlo, G., Margolin, K., Molina, A., Stepan, D. E., LIPSETT, J. A., Hoppe, R. T., Slovak, M. L., Niland, J. C., Dagis, A. C., Wong, R. M., Forman, S. J., Blume, K. G. 1994; 84 (5): 1672-1679

  Abstract

  Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event-free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus-associated interstitial pneumonitis, and years from diagnosis to BMT.

  View details for Web of Science ID A1994PE38700040

  View details for PubMedID 8068956

• BONE-MARROW TRANSPLANTATION FOR THALASSEMIA - THE USA EXPERIENCE Workshop on Bone Marrow Transplantation for Hemoglobinopathies Walters, M. C., Thomas, E. D. LIPPINCOTT-RAVEN PUBL. 1994: 11?17

  Abstract

  We have reviewed the results of bone marrow transplantation in 30 patients with thalassemia major who were treated in the United States.Ten patients who underwent transplantation in Seattle and 20 patients from five other U.S. centers were identified through a survey of the International Bone Marrow Transplant Registry. These transplants were performed between November 1981 and April 1992 in patients with diverse ethnic backgrounds and ranged in age from 6 months to 14 years (median 4.0 years). Twenty-seven of the 30 patients received marrow from a human leukocyte antigen (HLA)-identical sibling or other family member, one patient received HLA-matched marrow from an unrelated donor, and two patients were given haploidentical but HLA-mismatched marrow from a related donor. Cytoreductive (preparative) therapy varied among institutions and pretransplant risk categories. In general, patients were given busulfan (12-24 mg/kg) or dimethylmyleran (5 mg/kg) in combination with cyclophosphamide (120-240 mg/kg). A subset of patients were given total body irradiation (TBI) at a dose of 720 cGy followed by cyclophosphamide (120 mg/kg).Sixteen of 27 patients (59%) who received marrow from an HLA-identical family member are event-free survivors, with a duration of follow-up ranging from 2 months to > 10 years after transplantation. Six of these 27 patients (22%) had recurrence of thalassemia and five (19%) died. The estimated actuarial rate of thalassemia recurrence was 24% and the rate of event-free survival was 57%. Only one of the three patients who received marrow from HLA-nonidentical or unrelated donors survives event-free. Liver biopsies were not routinely performed before transplant. Thus, classification of patients into Lucarelli risk groups was not possible. A modified risk classification was devised by using liver size and iron status assessed by the regularity of chelation and the serum ferritin level. With use of this classification, there was no significant difference in event-free survival between transplant risk groups.The findings observed in this small series of patients confirms that thalassemia can be cured with bone marrow transplantation. Although most patients are event-free survivors, a significant number experienced recurrence of their disease. A cooperative multicenter trial of U.S. transplant centers may be necessary to evaluate the use of marrow transplantation for thalassemia and to determine optimal treatment.

  View details for Web of Science ID A1994MV00200004

  View details for PubMedID 8311166

• ROLE OF ETOPOSIDE (VP-16) IN PREPARATORY REGIMENS FOR PATIENTS WITH LEUKEMIA OR LYMPHOMA UNDERGOING ALLOGENEIC BONE-MARROW TRANSPLANTATION Symposium on Allogeneic Bone Marrow Transplantation - State of the Art and Future Directions Blume, K. G., Long, G. D., Negrin, R. S., Chao, N. J., KUSNIERZGLAZ, C., Amylon, M. D. STOCKTON PRESS. 1994: S9?S10

  Abstract

  In 1983, we began a series of clinical trials with the goal of reducing the relapse rate following allogeneic BMT for hematologic malignancies. Because of its anti-leukemic activity, the drug VP-16 was chosen and combined with total body irradiation (TBI). The first series (trial I) consisted of patients who had advanced leukemia. This trial showed a relapse rate of 32% and a disease-free survival rate of 43%. Thereafter, this regimen was tested in a randomized trial (trial II) under the auspices of the Southwest Oncology Group (SWOG study 8612). The FTBI/VP-16 regimen was compared with the combination of busulfan and cyclophosphamide (BU/CY). A recent analysis indicates a disease-free advantage for patients prepared with FTBI/VP-16; however this difference is not statistically significant. In another trial (trial III), patients in their first remission of leukemia were prepared with the FTBI/VP-16 regimen and long-term disease-free survival was found to be 60-70% with a relapse rate of approximately 10%. These results compare favorably with data obtained with alternative preparatory regimens. The FTBI/VP-16 regimen is currently being compared to the 'standard' regimen, FTBI/CY, in a prospective trial (trial IV). Since the regimen-related toxicity has been relatively low, we have added one dose of CY 60 mg/kg to the FTBI/VP-16 combination. This regimen (trial V) is currently being tested in patients with advanced leukemia. The preliminary results of this ongoing trial indicate further improvement in disease-free survival through a reduction of the post-transplant relapse rate.

  View details for Web of Science ID A1994QE92500004

  View details for PubMedID 7728133

• FRACTIONATED TOTAL-BODY IRRADIATION AND HIGH-DOSE ETOPOSIDE AS A PREPARATORY REGIMEN FOR BONE-MARROW TRANSPLANTATION FOR 99 PATIENTS WITH ACUTE-LEUKEMIA IN 1ST COMPLETE REMISSION BLOOD Snyder, D. S., Chao, N. J., Amylon, M. D., Taguchi, J., Long, G. D., Negrin, R. S., Nademanee, A. P., ODONNELL, M. R., Schmidt, G. M., Stein, A. S., Parker, P. M., Smith, E. P., Stepan, D. E., Molina, A., LIPSETT, J. A., Hoppe, R. T., Niland, J. C., Dagis, A. C., Wong, R. M., Forman, S. J., Blume, K. G. 1993; 82 (9): 2920-2928

  View details for Web of Science ID A1993ME65700039

• Fractionated total body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 99 patients with acute leukemia in first complete remission. Blood Snyder, D. S., Chao, N. J., Amylon, M. D., Taguchi, J., Long, G. D., Negrin, R. S., Nademanee, A. P., O'Donnell, M. R., Schmidt, G. M., Stein, A. S. 1993; 82 (9): 2920-2928

  Abstract

  Ninety-nine consecutive patients with acute leukemia in first complete remission under age 50 (median age 27 years; age range 1 to 47 years) with a histocompatible sibling donor were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation. Sixty-one patients were diagnosed with acute myelogenous leukemia (AML), 34 patients with acute lymphoblastic leukemia (ALL), 3 patients with biphenotypic acute leukemia, and 1 patient with acute undifferentiated leukemia. Thirty of the 34 patients with ALL had at least one of the following high-risk factors: age greater than 30, white blood cell count at presentation > 25,000/microL, extramedullary disease, certain chromosomal translocations, or the need for greater than 4 weeks of induction chemotherapy to achieve first complete remission. Cumulative probabilities of disease-free survival and relapse at 3 years were 61% and 12%, respectively, for the 61 patients with AML and 64% and 12%, respectively, for the 34 patients with ALL. By stepwise Cox regression analysis, significant prognostic variables for patients with acute myelogenous leukemia were the presence of acute graft-versus-host disease and increasing age, whereas for patients with acute lymphoblastic leukemia, significant variables were age and the development of cytomegalovirus-associated interstitial pneumonia. Complications related to graft-versus-host disease and relapse of leukemia were the major causes of death.

  View details for PubMedID 8219241

• CYCLOSPORINE, METHOTREXATE, AND PREDNISONE COMPARED WITH CYCLOSPORINE AND PREDNISONE FOR PROPHYLAXIS OF ACUTE GRAFT-VERSUS-HOST DISEASE NEW ENGLAND JOURNAL OF MEDICINE Chao, N. J., Schmidt, G. M., Niland, J. C., Amylon, M. D., Dagis, A. C., Long, G. D., Nademanee, A. P., Negrin, R. S., ODONNELL, M. R., Parker, P. M., Smith, E. P., Snyder, D. S., Stein, A. S., Wong, R. M., Blume, K. G., Forman, S. J. 1993; 329 (17): 1225-1230

  Abstract

  Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation remains a serious problem. In a clinical trial, we tested the combination of cyclosporine and prednisone with and without methotrexate for the prevention of GVHD.One hundred fifty patients with either acute leukemia in first complete remission, chronic myelogenous leukemia in first chronic phase, or lymphoblastic lymphoma in first complete remission were enrolled in the study. All the patients were given fractionated total-body irradiation (1320 cGy) and etoposide (60 mg per kilogram of body weight) in preparation for transplantation, and received bone marrow from genotypically histocompatible donors. To prevent GVHD, they were randomly assigned to prophylactic treatment with either cyclosporine, methotrexate, and prednisone or cyclosporine and prednisone without methotrexate. All the patients received standardized supportive care after transplantation, including intravenous gamma globulin.Patients receiving cyclosporine, methotrexate, and prednisone had a significantly lower incidence of acute GVHD of grades II to IV (9 percent) than those receiving cyclosporine and prednisone (23 percent, P = 0.02). Multivariate regression analysis demonstrated that an increased risk of acute GVHD was associated with an elevated serum creatinine concentration (P = 0.006) and treatment with cyclosporine and prednisone alone (P = 0.02). The lower incidence of acute GVHD was not associated with a higher rate of relapse of leukemia or lymphoma. There was no significant difference in disease-free survival at three years between the two treatment groups (64 percent with the three-drug regimen vs. 59 percent with the two-drug regimen, P = 0.57).The combination of cyclosporine, methotrexate, and prednisone was more effective in preventing acute GVHD of grades II to IV than was the combination of cyclosporine and prednisone without methotrexate.

  View details for Web of Science ID A1993MB98800003

  View details for PubMedID 8413388

• HRX INVOLVEMENT IN DENOVO AND SECONDARY LEUKEMIAS WITH DIVERSE CHROMOSOME 11Q23 ABNORMALITIES BLOOD Hunger, S. P., Tkachuk, D. C., Amylon, M. D., Link, M. P., Carroll, A. J., WELBORN, J. L., Willman, C. L., Cleary, M. L. 1993; 81 (12): 3197-3203

  Abstract

  Chromosome band 11q23 is a site of recurrent translocations and interstitial deletions in human leukemias. Recent studies have shown that the 11q23 gene HRX is fused to heterologous genes from chromosomes 4 or 19 after t(4;11)(q21;q23) and t(11;19)(q23;p13) translocations to create fusion genes encoding proteins with structural features of chimeric transcription factors. In this report, we show structural alterations of HRX by conventional Southern blot analyses in 26 of 27 de novo leukemias with cytogenetically diverse 11q23 abnormalities. The sole case that lacked HRX rearrangements was a t(11;17)-acute myeloid leukemia with French-American-British M3-like morphology. We also analyzed 10 secondary leukemias that arose after therapy with topoisomerase II inhibitors and found HRX rearrangements in 7 of 7 with 11q23 translocations, and in 2 of 2 with unsuccessful karyotypes. In total, we observed HRX rearrangements in 35 leukemias involving at least nine distinct donor loci (1q32, 4q21, 6q27, 7p15, 9p21-24, 15q15, 16p13, and two 19p13 sites). All breakpoints localized to an 8-kb region that encompassed exons 5-11 of HRX, suggesting that fusion proteins containing similar portions of HRX may be consistently created in leukemias with 11q23 abnormalities. We conclude that alteration of HRX is a recurrent pathogenetic event in leukemias with 11q23 aberrations involving many potential partners in a variety of settings including acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia in blast crisis, and topoisomerase II inhibitor-induced secondary leukemias of both the myeloid and lymphoid lineages.

  View details for Web of Science ID A1993LG65900005

  View details for PubMedID 8389614

• MULTIFOCAL LEUKOENCEPHALITIS CAUSED BY VARICELLA-ZOSTER VIRUS IN A CHILD WITH LEUKEMIA - SUCCESSFUL TREATMENT WITH ACYCLOVIR PEDIATRIC INFECTIOUS DISEASE JOURNAL CARMACK, M. A., Twiss, J., Enzmann, D. R., Amylon, M. D., Arvin, A. M. 1993; 12 (5): 402-406

  View details for Web of Science ID A1993LC78200011

  View details for PubMedID 8392165

• CLINICAL-FEATURES AND OUTCOME OF T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA IN CHILDHOOD WITH RESPECT TO ALTERATIONS AT THE TAL1 LOCUS - A PEDIATRIC ONCOLOGY GROUP-STUDY BLOOD Bash, R. O., Crist, W. M., Shuster, J. J., Link, M. P., Amylon, M., Pullen, J., Carroll, A. J., Buchanan, G. R., SMITH, R. G., Baer, R. 1993; 81 (8): 2110-2117

  Abstract

  Alteration of the TAL1 locus is the most common nonrandom genetic defect in childhood T-cell acute lymphoblastic leukemia (T-ALL). To determine if rearrangements of the TAL1 proto-oncogene confer a distinct leukemic phenotype, we studied leukemic peripheral blood or bone marrow samples from 182 children with newly diagnosed T-ALL enrolled on Pediatric Oncology Group treatment protocols. Forty-eight (26%) of the samples had a local rearrangement of the TAL1 locus. Demographic and clinical features were compared for patient subgroups with and without TAL1 rearrangements. The only clinical correlates that were significantly associated with TAL1 gene rearrangements were higher white blood cell count (P = .017) and higher hemoglobin (P = .007) at diagnosis. Immunophenotypically, samples with altered TAL1 were more likely to be CD2+ (P = .001) and lack CD10 (cALLa) expression (P = .007) than those without the rearrangement. There was a trend toward improved event-free survival (EFS) in patients with TAL1 rearrangements (4-year EFS was 44% +/- 7% for patients without the rearrangements v 59% +/- 11% for those with rearrangements), but the difference was not significant (P = .34). The role of TAL1 in leukemogenesis has yet to be clearly defined, and the prognostic significance of TAL1 gene rearrangements in T-ALL deserves further study.

  View details for Web of Science ID A1993KY00500018

  View details for PubMedID 8471769

• BUSULFAN ETOPOSIDE - INITIAL EXPERIENCE WITH A NEW PREPARATORY REGIMEN FOR AUTOLOGOUS BONE-MARROW TRANSPLANTATION IN PATIENTS WITH ACUTE NONLYMPHOBLASTIC LEUKEMIA BLOOD Chao, N. J., Stein, A. S., Long, G. D., Negrin, R. S., Amylon, M. D., Wong, R. M., Forman, S. J., Blume, K. G. 1993; 81 (2): 319-323

  Abstract

  Current intensive chemotherapy for acute nonlymphoblastic leukemia (ANLL) results in a complete remission in the majority of patients. Unfortunately, the duration of remission is short and most of the patients will experience a relapse of their underlying disease. Autologous bone marrow (BM) transplantation is being explored as a treatment modality designed to improve relapse-free survival. We have conducted a phase II trial exploring the combination of busulfan (16 mg/kg) and etoposide (60 mg/kg) in an attempt to improve antitumor efficacy using this novel preparative regimen. To date, 50 patients (48 with ANLL and 2 patients with biphenotypic acute leukemia) have been treated. The first 20 patients received unmanipulated BM; 28 patients subsequently received 4-hydroperoxycyclophosphamide (4-HC) (60 micrograms/mL)-purged bone marrow, and 2 patients with biphenotypic acute leukemia received both 4-HC (60 micrograms/mL) and etoposide (5 micrograms/mL)-purged BM. Thirty-four patients were in first complete remission (CR1), 12 patients in second complete remission (CR2), and 4 patients in relapse. The median time from first complete remission to BM harvest was 3 months (range, 0.8 to 4) compared with median time of 2 months (range, 1.5 to 5.0) for patients in second complete remission. The median time from harvest to transplant was 1 month for both groups (range, 0.4 to 36). A median of 0.7 x 10(8) (range, 0.2 to 1.4) mononuclear cells were infused. Patients achieved an absolute neutrophil count of > or = 500/microL at a median of 26 days (range, 13 to 96), an untransfused platelet count > or = 20,000/microL at a median of 56 days (range, 15 to 278) and a sustained hematocrit > or = 30% at a median of 50 days (range, 19 to 116). Twenty-six patients are alive and in continued CR. Follow-up of the surviving patients ranged from 6 months to 66 months with a median follow-up of 31 months. Patients receiving purged BM have an actuarial disease-free survival of 57% with a relapse rate of 28% compared with patients receiving unpurged BM whose actuarial disease-free survival is 32% with a relapse rate of 62% (P = .06 for relapse rate). The most significant extramedullary toxicities for this regimen are hepatic and cutaneous (including mucositis). The BU/VP-16 regimen is associated with a significant proportion of patients surviving disease free, especially in the group receiving purged BM. Whether this regimen offers a substantial improvement in disease-free survival over currently used regimens will require a prospective randomized study.

  View details for Web of Science ID A1993KH51200006

  View details for PubMedID 8422458

• LANGERHANS CELL HISTIOCYTOSIS PRESENTING WITH THE SUPERIOR VENA-CAVA SYNDROME - A CASE-REPORT MEDICAL AND PEDIATRIC ONCOLOGY Mogul, M., HARTMAN, G., Donaldson, S., Gelb, A., Link, M., Amylon, M., Glader, B. 1993; 21 (6): 456-459

  Abstract

  A case of Langerhans' cell histiocytosis confined to the mediastinum and presenting with de novo superior cava syndrome is reported. The causes of superior vena cava syndrome in childhood are discussed as is the importance of obtaining pathologic diagnosis prior to initiating therapy.

  View details for Web of Science ID A1993LK60200013

  View details for PubMedID 8515729

• PROGRESS AGAINST CHILDHOOD-CANCER - THE PEDIATRIC ONCOLOGY GROUP EXPERIENCE PEDIATRICS Vietti, T. J., Land, V., Shuster, J. J., Amylon, M., Link, M., Berard, C., Crist, W., Borowitz, M., FALLETTA, J., Bowman, W. P., Brecher, M., Castleberry, R., Frankel, L., Goorin, A., Hayes, F. A., Hvizdala, E., Krischer, J. P., Pollock, B. H., McWilliams, N., Murphy, S., Pick, T., Pullen, J., Ravindranath, Y., Smith, E. I., Steuber, C. P., Sullivan, M., VANEYS, J., Wharam, M. 1992; 89 (4): 597-600

  Abstract

  The sequential outcome was evaluated for all childhood cancers in which the Pediatric Oncology Group has conducted a series of clinical trials, with constant eligibility, on patients with newly diagnosed cancer. The analysis was applied to more than 7000 patients with cancer diagnosed between 1976 and 1989. These include acute leukemia (4 subgroups), non-Hodgkins lymphoma (4 subgroups), osteogenic sarcoma, and advanced neuroblastoma. In 8 of these 10 disease areas, significant improvement in outcome has occurred. In rare diseases such as pediatric cancer, collaborative studies may be the only way to conduct therapeutic trials of sufficient statistical power. A cooperative group has distinct advantages over a series of ad hoc collaborative studies in that it can maintain a unified data base, study its history with minimal confounding effects of changing institutional participants, and develop long-term research relationships among its participants.

  View details for Web of Science ID A1992HM25100004

  View details for PubMedID 1557237

• CURRENT RESULTS OF STUDIES OF IMMUNOPHENOTYPE-BASED, AGE-BASED AND LEUKOCYTE-BASED THERAPY FOR CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA 5TH INTERNATIONAL SYMP ON THERAPY OF ACUTE LEUKEMIAS Crist, W., Shuster, J., Look, T., Borowitz, M., Behm, F., Bowman, P., Frankel, L., Pullen, J., Krance, R., Steuber, P., Camitta, B., Amylon, M., Link, M., Land, V. NATURE PUBLISHING GROUP. 1992: 162?166

  Abstract

  From February 1986 to January 1991 the Pediatric Oncology Group (POG) treated 2404 children or adolescents with acute lymphoblastic leukemia (ALL) on immunophenotype (T-, B-, Pre-B, or Early pre-B-cell), age, and leukocyte count based treatment protocols (ALinC 14, T-cell 3, B-cell and infant leukemia studies). The immunophenotypic subgroups comprised 78.9% B-precursor cell, 15.1% T-cell, 2.0% B-cell, and 4% infant ALL. Patients with B-progenitor cell ALL were stratified by age and leukocyte count and randomized to receive induction therapy comprised of vincristine, prednisone, and asparaginase with triple intrathecal chemotherapy (methotrexate, hydrocortisone, cytarabine), followed by intensification with moderate-dose MTX (Regimen A), moderate-dose MTX plus asparaginase (Regimen B), moderate-dose MTX plus cytarabine given early (Regimen C), or moderate-dose MTX plus cytarabine given over the first 16 months of therapy (Regimen D). Continuation therapy comprised mercaptopurine and methotrexate with vincristine plus prednisone pulses. Central nervous system preventive treatment was continued for two years. Patients with T-cell or B-cell ALL or infants less than 1 yr old were treated on individual very intensive multiagent therapy protocols. The 4-year event-free survival for all patients was 66.4% +/- 2.4%; B-precursor ALL approximately 72%, T-ALL approximately 50%, B-ALL approximately 60%, and infants less than 1 yr old approximately 16.5%. We conclude that about two-thirds of newly diagnosed children with ALL can be cured with this approach which spares the majority of children exposure to alkylating agents, anthracyclines, epipodophylotoxins, and irradiation, diminishing the risks of serious acute and late effects.

  View details for Web of Science ID A1992HX75100043

• T(2-14)(P13-Q32) - A RECURRING ABNORMALITY IN LYMPHOCYTIC-LEUKEMIA - A PEDIATRIC-ONCOLOGY-GROUP STUDY CANCER GENETICS AND CYTOGENETICS Watson, M. S., Land, V. J., Carroll, A. J., Pullen, J., Borowitz, M. J., Link, M. P., Amylon, M., Behm, F. G. 1992; 58 (2): 121-124

  Abstract

  Chromosome banding studies of 1,411 children with newly diagnosed acute lymphocytic leukemia (ALL) identified two patients with the t(2;14)(p13;q32) chromosome abnormality and a third patient with a complex three-way translocation involving the same breakpoints on chromosomes 2 and 14 but also involving chromosome 12 at band q11. The three cases demonstrated variability of immunophenotypes: one was a T-cell ALL, and two were early pre-B ALLs. All three patients achieved complete remissions and have remained in remission for 14-19 months.

  View details for Web of Science ID A1992HK76700002

  View details for PubMedID 1551073

• ALLOGENEIC BONE-MARROW TRANSPLANTATION FOR HIGH-RISK ACUTE LYMPHOBLASTIC-LEUKEMIA DURING 1ST COMPLETE REMISSION BLOOD Chao, N. J., Forman, S. J., Schmidt, G. M., Snyder, D. S., Amylon, M. D., KONRAD, P. N., Nademanee, A. P., ODONNELL, M. R., Parker, P. M., Stein, A. S., Smith, E., Wong, R. M., Hoppe, R. T., Blume, K. G. 1991; 78 (8): 1923-1927

  View details for Web of Science ID A1991GK54200004

• Allogeneic bone marrow transplantation for high-risk acute lymphoblastic leukemia during first complete remission. Blood Chao, N. J., Forman, S. J., Schmidt, G. M., Snyder, D. S., Amylon, M. D., KONRAD, P. N., Nademanee, A. P., O'Donnell, M. R., Parker, P. M., Stein, A. S. 1991; 78 (8): 1923-1927

  Abstract

  Fifty-three patients with high-risk acute lymphoblastic leukemia (ALL) under age 50 with a histocompatible sibling donor received high-dose radiochemotherapy followed by allogeneic bone marrow transplantation (BMT). The high-risk factors used to identify the patients were: white blood cell count at initial presentation, cytogenetic abnormalities, age, extramedullary leukemic infiltration, and time from initial therapy to complete remission. Patients with one or more of the above risk factors who received BMT have a disease-free survival of 61% with a median follow-up of 66 months (range 11 months to 10.6 years), and an actuarial relapse rate of 10%. This study demonstrates that patients with high-risk ALL achieve a significant disease-free survival and cure rate with the use of allogeneic fully matched sibling BMT. However, a properly designed prospective study comparing the outcome of BMT with the best currently available chemotherapy data is required to define the ultimate role of BMT in this group of patients.

  View details for PubMedID 1912575

• ALLOGENEIC BONE-MARROW TRANSPLANTATION AS THERAPY FOR PRIMARY INDUCTION FAILURE FOR PATIENTS WITH ACUTE-LEUKEMIA JOURNAL OF CLINICAL ONCOLOGY Forman, S. J., Schmidt, G. M., Nademanee, A. P., Amylon, M. D., Chao, N. J., FAHEY, J. L., KONRAD, P. N., Margolin, K. A., Niland, J. C., ODONNELL, M. R., Parker, P. M., Smith, E. P., Snyder, D. S., Somlo, G., Stein, A. S., Blume, K. G. 1991; 9 (9): 1570-1574

  Abstract

  The survival of patients with acute leukemia who do not achieve a remission with primary therapy is very poor. High-dose chemoradiotherapy followed by allogeneic bone marrow transplantation (BMT) has been shown to be effective therapy for patients with acute and chronic leukemia. Therefore, we determined the long-term disease-free survival of patients who did not achieve a remission and were then treated with high-dose therapy and bone marrow allografting from matched sibling donors. Twenty-one patients (median age, 28 years) who did not achieve a remission with induction chemotherapy were subsequently treated with allogeneic BMT. After BMT, 90% achieved a complete remission. Six died of complications of the therapy, and six patients relapsed between 27 and 448 days after BMT. Nine patients (43%; median age, 25 years) are alive between 556 and 4,174 days after BMT. The cumulative probability of disease-free survival at 10 years is 43%. This study suggests that allogeneic BMT can be an effective therapy to achieve long-term control of acute leukemia, even in those patients who do not achieve a remission with primary therapy.

  View details for Web of Science ID A1991GD39800009

  View details for PubMedID 1875218

• PHILADELPHIA-CHROMOSOME AND MONOSOMY-7 IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA - A PEDIATRIC ONCOLOGY GROUP-STUDY BLOOD Russo, C., Carroll, A., Kohler, S., Borowitz, M., Amylon, M., Homans, A., Kedar, A., Shuster, J., Land, V., Crist, W., Pullen, J., Link, M. 1991; 77 (5): 1050-1056

  Abstract

  During an 8-year period, 3,638 children from institutions of the Pediatric Oncology Group (POG) were diagnosed with acute lymphoblastic leukemia (ALL). Fifty-seven patients had Philadelphia chromosome-positive (Ph1) ALL. Blast cells obtained at diagnosis from 13 of these 57 cases (23%) were also found to have partial or complete monosomy 7 (-7). This subgroup of children with Ph1/-7 ALL was comprised primarily of older males with early B-lineage ALL. Bone marrow specimens from six Ph1/-7 patients were studied further using the polymerase chain reaction and primers that flank the ALL, and chronic myelogenous leukemia breakpoints to determine the molecular characteristic of the 9;22 translocation. Rearrangements were detected in RNA from bone marrow and/or peripheral blood cells of six patients, although four were in hematologic remission at the time of the analysis. Five cases showed the ALL breakpoint, while one child with Ph1/-7 showed the chronic myelogenous leukemia breakpoint. The induction failure rate was much higher in this subgroup (31%) as compared with Ph1-negative cases, and the projected duration of event-free survival reflected the aggressive nature of this subgroup because no children are projected to remain in remission at 2 years. ALL with both the 9;22 translocation and -7 appears to represent a unique and previously undescribed subgroup of childhood ALL associated with a particularly adverse outcome. Leukemic transformation in such patients may involve the interaction of a dominant oncogene (Ph1) and a tumor suppressor gene (-7).

  View details for Web of Science ID A1991EZ33000019

  View details for PubMedID 1995090

• LACK OF TRANSMISSION OF THE LIVE ATTENUATED VARICELLA VACCINE VIRUS TO IMMUNOCOMPROMISED CHILDREN AFTER IMMUNIZATION OF THEIR SIBLINGS PEDIATRICS Diaz, P. S., Au, D., Smith, S., Amylon, M., Link, M., Smith, S., Arvin, A. M. 1991; 87 (2): 166-170

  Abstract

  The safety of administering the live attenuated Oka/Merck varicella vaccine to the well siblings of children with malignancy was evaluated as a strategy for reducing the risk of household exposure to varicella among immunocompromised children. Susceptible well children were eligible for vaccination if the child with malignancy had leukemia, lymphoma, or solid tumor in remission for 3 months or longer. No evidence of vaccine virus transmission was found among 30 children with malignancy whose 37 healthy susceptible siblings were immunized with varicella vaccine. Varicella-zoster virus was not isolated from the oropharyngeal secretions taken from 17 vaccinees or their 14 immunocompromised siblings. None of the 30 immunocompromised children had vaccine-related rashes or showed immunologic evidence of subclinical varicella-zoster virus infection based on testing for varicella-zoster virus IgG antibodies and T-lymphocyte proliferation to varicella-zoster virus. Four healthy vaccinees eventually had mild breakthrough cases of varicella, with transmission to the high-risk sibling in 3 cases. However, even in these families, the immunocompromised children had been protected from household exposure varicella for at least 20 months early in the course of their immunosuppressive treatment.

  View details for Web of Science ID A1991EW34200008

  View details for PubMedID 1846236

• Dermatoglyphics and acute lymphocytic leukemia in children. Journal of pediatric oncology nursing Edelstein, J., Amylon, M., Walsh, J. A. 1991; 8 (1): 30-38

  Abstract

  Cellular features of acute lymphocytic leukemia (ALL) in children suggest that it originates in abnormal embryogenesis. Because palmar flexion creases develop in the embryo at the same time as the blood-forming cells, and because both arise from mesodermal tissue, insults to the embryo that may lead to leukemic changes in the blood-forming cells may also result in aberrant palmar crease patterns. This study investigated the relationship between aberrant palmar creases and ALL in children who developed leukemia at age 6 years or younger. Odds ratios and chi squares demonstrated significant differences in bilateral aberrant palmar creases between ALL children and relatives (P less than .025). Differences were not explained by familial clustering of aberrant creases. These results support the theory that the insult occurred during pregnancy, probably in the first trimester. There were no significant differences in either bilateral or unilateral aberrant palmar creases between ALL children and their siblings. All children with bilateral aberrant creases had a higher incidence of central nervous system involvement (50%) than those without bilateral aberrant creases (6%). This may reflect a preleukemic change in utero before the time the blood-brain barrier has been established.

  View details for PubMedID 2012691

• TREATMENT OF T-LINEAGE ACUTE LYMPHOBLASTIC-LEUKEMIA HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Amylon, M. D. 1990; 4 (5): 937-949

  Abstract

  T-cell acute lymphoblastic leukemia is an aggressive disease that responds poorly to "standard" therapy designed for the more common B-lineage ALLs in childhood. The principles of this "standard" therapy were derived from empiric clinical trials. Thus, it is not surprising that the therapy that had the greatest impact on survival in the group as a whole would be found to be most successful for the most common subset of patients. T-cell malignant lymphoblasts share many biologic features that set them apart from the more common B-lineage lymphoblasts. Some of these biologic features suggest therapeutic approaches that should be particularly successful in treating patients with T-cell leukemia. The use of aggressive, multiple-agent "pulse" chemotherapy has been shown through empiric trials to have relative efficacy in T-cell lymphoblastic leukemia, presumably because of the rapid generation time and high growth fraction. Future studies will (1) determine the optimal dose and schedule of cytosine arabinoside needed to exploit the increased Ara-CTP accumulation in T-cell blasts, (2) determine the efficacy of a new agent, deoxycoformycin, an inhibitor of adenosine deaminase, to exploit the biochemical phenotype of T-cell blasts, and (3) assess the ability of conjugated anti-T monoclonal antibodies to deliver a cytotoxic agent, thus exploiting unique antigenic determinants at the cell surface. As more is learned about the biology of T-cell malignancies, further treatment strategies may be suggested to exploit the new features that are discovered. Similarly, it is hoped that the unique features of the B-lineage leukemias will suggest treatment strategies that will improve survival in those patients as well. Certainly, improved survival has already been achieved in the case of the B-cell leukemias and Burkitt's lymphomas, and improvement may also be possible for the pre-B and early pre-B phenotypes of lymphoblastic leukemia.

  View details for Web of Science ID A1990ED91700006

  View details for PubMedID 2262486

• THE T(1-14)(P34-Q11) IS NONRANDOM AND RESTRICTED TO T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA - A PEDIATRIC ONCOLOGY GROUP-STUDY BLOOD Carroll, A. J., Crist, W. M., Link, M. P., Amylon, M. D., Pullen, D. J., Ragab, A. H., Buchanan, G. R., Wimmer, R. S., Vietti, T. J. 1990; 76 (6): 1220-1224

  Abstract

  We report the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;14)(p34;q11) in children with acute lymphoblastic leukemia (ALL). This chromosomal abnormality occurred in leukemia cells from 5 of 1,630 (0.3%) consecutive children with newly diagnosed ALL who were entered on a single Pediatric Oncology Group classification study (POG 8600) between January 1986 and February 1989. The frequency of the t(1;14) was 3% (5 of 168 cases) in children with T-cell ALL. All five cases had pseudodiploid karyotypes, and in 3 cases the t(1;14) was accompanied by a deletion of the long arm of chromosome 6. This translocation is of special interest because the breakpoint on chromosome 14 in band q11 corresponds to the assigned locus of the T-cell receptor alpha/delta chain gene. All five of our patients and three cases reported previously have had T-cell ALL. These findings, considered together, suggest that this translocation is specific for T-cell ALL and that a gene in the 1p34 region may play an important role in malignant transformation of thymocytes.

  View details for Web of Science ID A1990DZ19200022

  View details for PubMedID 2400810

• REPOPULATION OF MARROW AFTER TRANSPLANTATION - MR IMAGING WITH PATHOLOGICAL CORRELATION RADIOLOGY Stevens, S. K., Moore, S. G., Amylon, M. D. 1990; 175 (1): 213-218

  Abstract

  Sixty-seven magnetic resonance (MR) studies of the lumbar spine were performed in 15 patients with bone marrow transplants, and the appearance of marrow regeneration on MR images was correlated with results of bone marrow biopsy and pathologic examination. After transplantation, T1-weighted MR images of vertebral marrow showed a characteristic band pattern consisting of a peripheral zone of intermediate signal intensity and a central zone of bright signal intensity. Reciprocal changes were identified on short inversion time inversion recovery images. At histologic examination the central zone corresponded to fatty marrow; the peripheral zone corresponded to a zone of regenerating hematopoietic cells. Posttransplantation T1 and T2 relaxation times of the entire vertebral marrow were calculated from the spin-echo images; no statistically significant trends in relaxation times were noted. Knowledge of the normal MR pattern of marrow regeneration after transplantation may be useful in screening for residual marrow disease, determining marrow engraftment, and differentiating marrow repopulation with normal versus malignant cells.

  View details for Web of Science ID A1990CV27100038

  View details for PubMedID 2315483

• Bone marrow transplantation for hematologic malignancies: the Stanford experience. Clinical transplants Chao, N. J., Amylon, M. D., Long, G. D., Negrin, R. S., Hoppe, R. T., Horning, S. J., Blume, K. G. 1990: 157-163

  Abstract

  Allogeneic and autologous BMTs are highly effective and successful treatment modalities for selected patients. Use of BMT earlier in the course of disease yields better results when compared to patients with more advanced disease. Recent advances such as use of cloned growth factors, cytokines, etc..., will continue to contribute to lessen morbidity and mortality. Finally, as investigators understand, prevent, and treat expected side effects from BMTs, the patients' burden in terms of physical, psychological, and financial costs should lessen substantially.

  View details for PubMedID 2103141

• BONE-MARROW TRANSPLANTATION FOR ACUTE LYMPHOBLASTIC-LEUKEMIA WORKSHOP ON ACUTE LYMPHOBLASTIC LEUKEMIA Blume, K. G., Schmidt, G. M., Chao, N. J., Amylon, M. D., KONRAD, P. N., Forman, S. J. JOHN WILEY & SONS. 1990: 279?283

  View details for Web of Science ID A1990BQ12T00023

• REDUCED NEUTROPHIL COUNTS IN CHILDREN WITH TRANSIENT ERYTHROBLASTOPENIA OF CHILDHOOD JOURNAL OF PEDIATRICS Rogers, Z. R., Bergstrom, S. K., Amylon, M. D., Buchanan, G. R., Glader, B. E. 1989; 115 (5): 746-748

  View details for Web of Science ID A1989AY22300015

  View details for PubMedID 2809908

• AFTER TREATMENT ENDS - PSYCHOSOCIAL SEQUELAE IN PEDIATRIC CANCER SURVIVORS AMERICAN JOURNAL OF ORTHOPSYCHIATRY Fritz, G. K., Williams, J. R., Amylon, M. 1988; 58 (4): 552-561

  Abstract

  Fifty-two survivors of childhood cancer and their families were assessed by questionnaire and interview to determine survivors' psychosocial status two years or more after treatment. Most were functioning well and serious psychosocial problems were relatively rare. Communication patterns during treatment were most predictive of psychosocial outcome whereas indicators of medical severity were least predictive. The heterogeneity of effective coping styles, appropriate to varied personality types, was noted.

  View details for Web of Science ID A1988Q705400008

  View details for PubMedID 3228162

• IDIOTYPE AS A TUMOR-SPECIFIC MARKER IN CHILDHOOD B-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA BLOOD Carroll, W. L., Link, M. P., Cleary, M. L., Bologna, S., CARSWELL, C., Amylon, M. D., Smith, S. D., Levy, R. 1988; 71 (4): 1068-1073

  Abstract

  Immunoglobulin (Ig) or idiotype (Id) is a tumor-specific target in those B cell malignancies that express this molecule on their surface. We explored the biology of B cell acute lymphoblastic leukemia (B cell ALL) using Id as a tumor marker. In this report we describe the development of anti-Id monoclonal antibodies (MAB) for two children with B cell ALL. These reagents were used retrospectively to study tumor kinetics and to detect residual disease after chemotherapy. In both cases serum Id values were strikingly high at diagnosis (1.2 mg/mL and 10.8 mg/mL), suggesting that the tumor cells were relatively mature B cells capable of significant antibody production. In both patients the serum Id levels fell with the institution of therapy and confirmed that the patients were in remission. Increasing serum Id predicted relapse four months before conventional methods in patient 1, and Id proved to be a more sensitive measure of tumor burden than Southern blot analysis of rearranged Ig genes in bone marrow samples. Surprisingly, low levels of Id were redetected in the second patient just before completing therapy and have persisted for over a year despite the absence of clinical evidence of recurrent disease. Thus, serum Id levels reflect tumor burden during initial therapy but may not necessarily predict tumor progression after a complete clinical remission.

  View details for Web of Science ID A1988M985300037

  View details for PubMedID 3128346

• CLINICAL AND BIOLOGIC CHARACTERIZATION OF T-CELL NEOPLASIAS WITH REARRANGEMENTS OF CHROMOSOME-7 BAND Q34 BLOOD Smith, S. D., Morgan, R., Gemmell, R., Amylon, M. D., Link, M. P., Linker, C., Hecht, B. K., Warnke, R., Glader, B. E., Hecht, F. 1988; 71 (2): 395-402

  Abstract

  In T cell malignancy, rearrangements of chromosome 14 have been observed with a break in the band that contains the alpha chain gene for the T cell receptor (TCR). Because the beta chain TCR gene is in chromosome band 7q34, we searched for and report finding specific rearrangements of 7q34 exclusively in T cell malignancies. The rearrangements were reciprocal translocations between 7q34 and other points: 1p34, 9q32, 9q34, 15q22, and 19p13. The malignancies containing a 7q34 translocation were either T cell acute lymphoblastic leukemias or T cell lymphoblastic lymphomas that had similarities in clinical, enzyme, immunologic, and cellular characteristics. Hybridization using a probe to the beta-TCR gene disclosed unique rearrangements consistent with clonality in every case. A common pattern with chromosome breakpoints involving TCR genes may be emerging in T cell neoplasia.

  View details for Web of Science ID A1988L922400019

  View details for PubMedID 2962650

• ESTABLISHMENT AND CHARACTERIZATION OF A COMMON ACUTE LYMPHOBLASTIC-LEUKEMIA CELL-LINE WITH A DELETION OF CHROMOSOME-3 BAND Q26 CANCER RESEARCH Smith, S. D., Morgan, R., Galili, N., Amylon, M. D., Link, M. P., Hecht, F., Sklar, J., Glader, B. E. 1987; 47 (6): 1652-1656

  Abstract

  This paper describes the establishment and characterization of a new cell line (SUP-B7) which was established from a child with "common" acute lymphoblastic leukemia. The SUP-B7 cells (and the patient's tumor) have been characterized by cytochemical staining, monoclonal antibodies, enzyme analyses, gene rearrangement studies, and karyotype analysis. The SUP-B7 cells are periodic acid-Schiff positive, common acute lymphoblastic leukemia antigen positive, and terminal deoxynucleotidyl transferase positive, and they lack the Epstein-Barr virus genome. In addition, the SUP-B7 cells lack cytoplasmic and surface immunoglobulins, and the immunoglobulin gene rearrangement studies showed rearranged heavy chain genes with germ line light chain genes. Concordance between the cell line and the patient's tumor was established by the immunoglobulin gene rearrangement studies. Using Southern blot analysis of the DNA from the patient's tumor and the SUP-B7 cells, there was comigration of the bands representing the rearranged immunoglobulin heavy chain gene. In addition, the SUP-B7 cells possess a single chromosome abnormality: del(3)(q26q28), with the chromosome breakpoint at or near the transferrin receptor gene. Since the SUP-B7 cell line is concordant with the patient's malignancy and since these cells possess a single chromosomal abnormality, the SUP-B7 cell line may be a useful tool in determining the biological significance of the chromosome deletion: del(3)(q26q28).

  View details for Web of Science ID A1987G548300030

  View details for PubMedID 3469019

• PREDNISONE STIMULATION OF ERYTHROPOIESIS IN LEUKEMIC CHILDREN DURING REMISSION AMERICAN JOURNAL OF HEMATOLOGY Amylon, M. D., Perrine, S. P., Glader, B. E. 1986; 23 (2): 179-181

  Abstract

  Children with acute leukemia in remission manifest reticulocytosis and a significant increase in hemoglobin concentration (mean increment of 2.3 +/- 1.1 g/dl) following prednisone pulse therapy. This hemoglobin increment is not associated with changes in serum erythropoietin activity. It is speculated that this stimulation of red cell production may be a direct effect of steroids on erythroid progenitor cells.

  View details for Web of Science ID A1986E046700012

  View details for PubMedID 3463202

• INTENSIVE RETREATMENT OF CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA IN 1ST BONE-MARROW RELAPSE - A PEDIATRIC ONCOLOGY GROUP-STUDY NEW ENGLAND JOURNAL OF MEDICINE Rivera, G. K., Buchanan, G., Boyett, J. M., Camitta, B., Ochs, J., Kalwinsky, D., Amylon, M., Vietti, T. J., Crist, W. M. 1986; 315 (5): 273-278

  Abstract

  We devised a plan of intensive chemotherapy to address the problem of inadequate results of treatment in children with acute lymphoblastic leukemia in first bone marrow relapse. Immediately after remission was induced with four conventional drugs, a two-week intensification course of teniposide and cytarabine was given to eradicate subclinical leukemia. Patients in remission were then treated for two years with rapid rotation of pairs of drugs that were not cross-resistant and periodic courses of the same agents used to induce remission. A second complete remission was induced in 31 of the 39 patients in whom response to chemotherapy could be assessed. The probability of maintaining bone marrow remission in these patients for one year was 0.38 +/- 0.19 (95 percent confidence interval); the two-year probability was 0.29 +/- 0.17. Seven patients completed the treatment program, five of whom have been in continuous second complete remission 17 to 20 months after the cessation of therapy. Children whose initial bone marrow remission lasted less than 18 months had significantly poorer responses to retreatment than did those with a longer first remission (P = 0.004). Intensive chemotherapy, as described here, may save half of the children with acute lymphoblastic leukemia in whom bone marrow relapse occurs after a relatively long initial remission.

  View details for Web of Science ID A1986D401700001

  View details for PubMedID 3523250

• CHROMOSOME-9 ABNORMALITIES IN CHILDHOOD T-CELL LEUKEMIA NEW ENGLAND JOURNAL OF MEDICINE Smith, S. D., Link, M. P., Trela, M., Amylon, M., Sklar, J., Morgan, R., Hecht, F. 1986; 315 (3): 195-196

  View details for Web of Science ID A1986D192800023

  View details for PubMedID 3487732

• NEURO-BLASTOMA IN INFANTS - WHEN IS THERAPY NECESSARY Amylon, M. D., Link, M. P., Perrine, S. P., Shochat, S. J., Donaldson, S. S., Glader, B. E. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1985: A257?A257

  View details for Web of Science ID A1985AEU1800880

• VARICELLA ZOSTER ANTIBODY-TITERS AFTER THE ADMINISTRATION OF INTRAVENOUS IMMUNE SERUM GLOBULIN OR VARICELLA ZOSTER IMMUNE GLOBULIN AMERICAN JOURNAL OF MEDICINE PARYANI, S. G., Arvin, A. M., Koropchak, C. M., Wittek, A. E., Amylon, M. D., DOBKIN, M. B., BUDINGER, M. D. 1984; 76 (3A): 124-127

  Abstract

  Varicella is a serious infection in the immunocompromised patient. Prophylaxis with varicella zoster immune globulin is known to decrease the incidence of severe varicella infection. The titers of antibody to varicella zoster virus were compared in patients who received either varicella zoster immune globulin or intravenous immune globulin, 4 ml or 6 ml/kg per dose. The titers of antibody to varicella zoster virus were comparable in each group.

  View details for Web of Science ID A1984SL72400018

  View details for PubMedID 6324585

• IMMUNE THROMBOCYTOPENIA ASSOCIATED WITH ACUTE NONLYMPHOCYTIC LEUKEMIA JOURNAL OF PEDIATRICS Amylon, M. D., Link, M. P., Glader, B. E. 1984; 105 (5): 776-778

  View details for Web of Science ID A1984TR54000020

  View details for PubMedID 6502309

• COMPARISON OF VARICELLA ZOSTER ANTIBODY-TITERS IN PATIENTS GIVEN INTRAVENOUS IMMUNE SERUM GLOBULIN OR VARICELLA ZOSTER IMMUNE GLOBULIN JOURNAL OF PEDIATRICS PARYANI, S. G., Arvin, A. M., Koropchak, C. M., DOBKIN, M. B., Wittek, A. E., Amylon, M. D., BUDINGER, M. D. 1984; 105 (2): 200-205

  Abstract

  We compared the VZV IgG antibody titers after administration of varicella zoster immune globulin and serum immune globulin intravenously (IGIV) in VZV seronegative pediatric patients with cancer. Four patients received VZIG at standard doses; four received IGIV at 4 ml/kg every 4 weeks for four doses; and five received IGIV at 6 ml/kg every 6 weeks for two to four doses. VZV antibody titers were measured by radiommunoassay (RIA), enzyme-linked immunosorbent assay (ELISA), indirect fluorescent antibody assay (IFA), and neutralizing antibody assay. The mean peak and trough VZV titers by RIA were comparable in all three groups: 1:724 at 4 weeks after VZIG, 1:2048 at 4 weeks after 4 ml/kg IGIV, and 1:776 at 6 weeks after 6 ml/kg IGIV. The titers measured by ELISA, IFA, and neutralizing antibody were comparable after VZIG or IGIV. The VZV titers by RIA were maintained at greater than or equal to 1:1024 after subsequent doses of 4 ml/kg IGIV, and at greater than or equal to 1:256 after subsequent doses of 6 ml/kg IGIV. Adverse effects were rare. The VZV antibody titers assessed 4 to 6 weeks after IGIV administration were equivalent to the titers measured 4 weeks after administration of VZIG.

  View details for Web of Science ID A1984TE14400004

  View details for PubMedID 6086866

• A SINGLE MONOCLONAL-ANTIBODY IDENTIFIES T-CELL LINEAGE OF CHILDHOOD LYMPHOID MALIGNANCIES BLOOD Link, M., Warnke, R., Finlay, J., Amylon, M., Miller, R., Dilley, J., Levy, R. 1983; 62 (4): 722-728

  Abstract

  Immunophenotyping studies with monoclonal antibodies have revealed the heterogeneity of childhood acute lymphoblastic leukemia (ALL) and non-Hodgkin's lymphoma (NHL). The lymphoid malignancies of T-cell lineage are particularly heterogeneous and, until now, no single monoclonal antibody has been found to identify all cases of T-ALL and T-NHL. A monoclonal antibody, 4H9, recognizes an antigen of 40,000 molecular weight on normal and malignant T cells. Thirty-six cases of childhood T-ALL and T-NHL were tested, and in all cases, the malignant blast cells were reactive with 4H9, whereas malignant cells from 61 cases of non-T ALL and NHL were not reactive with 4H9. Monoclonal antibody 4H9 is a sensitive and specific reagent for the identification of childhood T-cell ALL and NHL and should be extremely useful in immunophenotyping studies of lymphoid malignancies.

  View details for Web of Science ID A1983RK80600002

  View details for PubMedID 6603882

• CRANIAL NERVE INVOLVEMENT IN CHILDREN WITH LEUKEMIA AND LYMPHOMA JOURNAL OF CLINICAL ONCOLOGY PARYANI, S. B., Donaldson, S. S., Amylon, M. D., Link, M. P. 1983; 1 (9): 542-545

  Abstract

  Between 1965 and 1982, 52 children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma were found to have central nervous system involvement of their disease. Of this group, 20 developed clinically apparent cranial nerve paresis or palsy. The cranial nerve most frequently affected was No. VII. With therapy, 16 of the patients had objective control of their central nervous system disease. Among these 16 patients, cranial nerve palsies resolved completely in 14, and only two children were left with residual cranial nerve dysfunction. Seven patients received intrathecal chemotherapy before radiation therapy was instituted in an attempt to control their cranial nerve palsies. Cranial nerve palsy resolved in only two of these seven patients. However, the addition of whole-brain irradiation in the remaining five patients reversed cranial nerve dysfunction in four of them. The combination of intrathecal chemotherapy and central nervous system irradiation was successful in reversing cranial nerve dysfunction in 11 of 13 patients in whom central nervous system disease was ultimately controlled. As cranial nerve dysfunction is associated with distressing signs and symptoms, the combination of central nervous system irradiation and intrathecal chemotherapy is important palliative therapy to initiate promptly. Intrathecal therapy alone appears to be inadequate therapy for prompt and durable reversal of symptoms in this group of patients.

  View details for Web of Science ID A1983RK55800005

  View details for PubMedID 6583324