Michael Jeng

All Publications

• Venous malformations. Seminars in pediatric surgery Cooke-Barber, J., Kreimer, S., Patel, M., Dasgupta, R., Jeng, M. 2020; 29 (5): 150976

  Abstract

  Venous malformations include a spectrum of slow-flow malformations that together are the most common forms of vascular anomalies. Care of these patients requires a multi-disciplinary approach. Goals of care are to ameliorate symptoms and to preserve function. Use of therapeutic compression garments remains the mainstay of therapy. There are new and promising therapies over the last few years that will be invaluable tools for optimal care of this complex patient population. Advances in medical therapy through inhibition of the mTOR/PI3K/AKT pathway with Sirolimus and more proximal targeted drugs along with advances in sclerotherapy techniques are promising for the long-term improvement and amelioration of symptoms in patients with venous malformations.

  View details for DOI 10.1016/j.sempedsurg.2020.150976

  View details for PubMedID 33069284

• Hypoferritinemia and iron deficiency in youth with pediatric acute-onset neuropsychiatric syndrome. Pediatric research Chan, A., Karpel, H., Spartz, E., Willett, T., Farhadian, B., Jeng, M., Thienemann, M., Frankovich, J. 2020

  Abstract

  Pediatric acute-onset neuropsychiatric syndrome (PANS) is an abrupt debilitating psychiatric illness. We anecdotally observed hypoferritinemia and iron deficiency in a subset of patients with PANS, prompting this study.In this IRB-approved prospective cohort study, we included patients seen at the Stanford PANS Clinic who met study criteria. The prevalence of hypoferritinemia (using cut-offs of 7 ng/ml in children ≤ 15 years and 18 ng/ml in adolescents > 15 years) and iron deficiency was estimated. Differences in patients with and without hypoferritinemia during PANS flare were explored.Seventy-nine subjects (mean age of PANS onset of 8.7 years) met study criteria. Hypoferritinemia was observed in 27% and three quarters occurred during a PANS flare. Compared to patients without hypoferritinemia during PANS flare, patients with hypoferritinemia had worse global impairment, more comorbid inflammatory diseases, and exhibited a chronic course of PANS illness. The estimated prevalence of iron deficiency was 3-8% in the PANS cohort, 1.4-2.0-fold higher than in the age- and sex-matched U.S.More stringent ferritin level cut-offs than the comparison CDC dataset were used.Hypoferritinemia and iron deficiency appear to be more common in PANS patients. More research is needed to confirm and understand this association.Our study suggests hypoferritinemia and iron deficiency are more common in patients with pediatric acute-onset neuropsychiatric syndrome (PANS) than in the sex- and age-matched US population.Hypoferritinemia was commonly observed during a disease flare but not associated with dietary or demographic factors. In patients with PANS and iron deficiency, clinicians should consider possibility of inflammation as the cause especially if iron deficiency cannot be explained by diet and blood loss.Future research should include larger cohorts to corroborate our study findings and consider examining the iron dynamics on MRI brain imaging in order to better understand the pathophysiology of PANS.

  View details for DOI 10.1038/s41390-020-1103-3

  View details for PubMedID 32746449

• A somatic activating NRAS variant associated with kaposiform lymphangiomatosis GENETICS IN MEDICINE Barclay, S. F., Inman, K. W., Luks, V. L., McIntyre, J. B., Al-Ibraheemi, A., Church, A. J., Perez-Atayde, A. R., Mangray, S., Jeng, M., Kreimer, S. R., Walker, L., Fishman, S. J., Alomari, A. I., Chaudry, G., Trenor, C. C., Adams, D., Kozakewich, H. W., Kurek, K. C. 2019; 21 (7): 1517–24

  View details for DOI 10.1038/s41436-018-0390-0

  View details for Web of Science ID 000473518700009

• Second-line treatments in children with immune thrombocytopenia: Effect on platelet count and patient-centered outcomes AMERICAN JOURNAL OF HEMATOLOGY Grace, R. F., Shimano, K. A., Bhat, R., Neunert, C., Bussel, J. B., Klaassen, R. J., Lambert, M. P., Rothman, J. A., Breakey, V. R., Hege, K., Bennett, C. M., Rose, M. J., Haley, K. M., Buchanan, G. R., Geddis, A., Lorenzana, A., Jeng, M., Pastore, Y. D., Crary, S. E., Neier, M., Neufeld, E. J., Neu, N., Forbes, P. W., Despotovic, J. M. 2019; 94 (7): 741–50

  View details for DOI 10.1002/ajh.25479

  View details for Web of Science ID 000470918600008

• The impact of intraoperative thromboelastography and blood product utilization during pediatric liver transplantation in a single center Ruiz, R., Lee, H., Mendoza, J., Burgis, J. C., Damian, M., Esquivel, C. O., Jeng, M. WILEY. 2019

  View details for Web of Science ID 000485482200047

• STAGE IV EPSTEIN-BARR VIRUS (EBV) CLASSIC HODGKIN LYMPHOMA (CHL) WITH HEPATIC INVOLVEMENT MEETING CRITERIA FOR HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH) AT STANFORD: CLOSE MIMIC VERSUS TRUE HLH? Martin, B., Weiner, H., Lau, E., Jeng, M. WILEY. 2019: S29–S30

  View details for Web of Science ID 000449991100059

• Langerhans Cell Histiocytosis of the Gastrointestinal Tract: Evidence for Risk Organ Status. The Journal of pediatrics Yoon, H. S., Lee, J. H., Michlitsch, J., Garcia-Carega, M., Jeng, M. 2019

  Abstract

  To investigate the "risk status" of Langerhans cell histiocytosis (LCH) of the gastrointestinal tract.Outcomes from 43 published cases of patients with LCH and gastrointestinal tract involvement were matched to 43 patients with LCH without gastrointestinal tract involvement cared for at our institution. Comparisons were made of the 5-year overall survival rates determined from Kaplan-Meier survival curves for the entire cohort of patients, as well as subgroups defined by lack of risk organ involvement and later era of treatment (to control for temporal changes in LCH treatment regimens). In addition, an association between LCH-gastrointestinal tract and risk organ involvement was investigated.The 5-year overall survival for children with LCH-gastrointestinal tract (45.3%) was significantly worse than for those without gastrointestinal tract involvement (94.6%; P = .001). This difference remained significant after we excluded risk organ involvement (53.6%% vs 100%; P = .001), and analyzing subjects diagnosed after 2000 (75% vs 100%; P = .012). A 4-fold increase in risk organ involvement with LCH-gastrointestinal tract was observed (OR 4.359; 95% CI 1.75-10.82, P = .001).This limited retrospective study suggests that patients with LCH-gastrointestinal tract involvement may have decreased survival, independent of risk organ involvement, and provides evidence to support a prospective study to evaluate risk organ status of LCH-gastrointestinal tract. LCH-gastrointestinal tract may be associated with a 4-fold risk for risk organ involvement. Attention to gastrointestinal symptoms and LCH-gastrointestinal tract in young children diagnosed with LCH is warranted.

  View details for DOI 10.1016/j.jpeds.2019.05.003

  View details for PubMedID 31279573

• A multicenter study of patients with multisystem Langerhans cell histiocytosis who develop secondary hemophagocytic lymphohistiocytosis. Cancer Chellapandian, D., Hines, M. R., Zhang, R., Jeng, M., van den Bos, C., Santa-Maria Lopez, V., Lehmberg, K., Sieni, E., Wang, Y., Nakano, T., Williams, J. A., Fustino, N. J., Astigarraga, I., Dunkel, I. J., Abla, O., van Halteren, A. G., Pei, D., Cheng, C., Weitzman, S., Sung, L., Nichols, K. E. 2018

  Abstract

  BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm characterized by the presence of abnormal CD1a-positive (CD1a+ )/CD207+ histiocytes. Hemophagocytic lymphohistiocytosis (HLH) represents a spectrum of hyperinflammatory syndromes typified by the dysregulated activation of the innate and adaptive immune systems. Patients with LCH, particularly those with multisystem (MS) involvement, can develop severe hyperinflammation mimicking that observed in HLH. Nevertheless, to the authors' knowledge, little is known regarding the prevalence, timing, risk factors for development, and outcomes of children and young adults who develop HLH within the context of MS-LCH (hereafter referred to LCH-associated HLH).METHODS: To gain further insights, the authors conducted a retrospective, multicenter study and collected data regarding all patients diagnosed with MS-LCH between 2000 and 2015.RESULTS: Of 384 patients with MS-LCH, 32 were reported by their primary providers to have met the diagnostic criteria for HLH, yielding an estimated 2-year cumulative incidence of 9.3% ± 1.6%. The majority of patients developed HLH at or after the diagnosis of MS-LCH, and nearly one-third (31%) had evidence of an intercurrent infection. Patient age <2 years at the time of diagnosis of LCH; female sex; LCH involvement of the liver, spleen, and hematopoietic system; and a lack of bone involvement each were found to be independently associated with an increased risk of LCH-associated HLH. Patients with MS-LCH who met the criteria for HLH had significantly poorer 5-year survival compared with patients with MS-LCH who did not meet the criteria for HLH (69% vs 97%; P<.0001).CONCLUSIONS: Given its inferior prognosis, further efforts are warranted to enhance the recognition and optimize the treatment of patients with LCH-associated HLH.

  View details for DOI 10.1002/cncr.31893

  View details for PubMedID 30521100

• Management of Complex Arteriovenous Malformations Using a Novel Combination Therapeutic Algorithm. JAMA dermatology Chelliah, M. P., Do, H. M., Zinn, Z., Patel, V., Jeng, M., Khosla, R. K., Truong, M., Marqueling, A., Teng, J. M. 2018; 154 (11): 1316–19

  Abstract

  Importance: Current therapeutic options for patients with extracranial head and neck arteriovenous malformations are limited. Surgical intervention, such as sclerotherapy or resection, often result in rapid recurrence and progression of disease.Objective: To assess the efficacy and tolerability of sirolimus as an adjuvant therapy for endovascular embolization in the management of complicated extracranial head and neck arteriovenous malformations.Design, Setting, and Participants: This case series examined 6 patients with extracranial head and neck arteriovenous malformations treated from January 1, 2013, to December 31, 2017, at a multidisciplinary vascular anomalies clinic within Stanford Hospital and Clinics.Intervention: Initiation of sirolimus at least 1 month prior to endovascular embolization, targeting a trough level of 10 to 15 ng/mL throughout the course of the endovascular embolization series and continued for at least 1 month after the series.Main Outcomes and Measures: Clinical manifestations; disease progression and overall response to treatment were assessed via clinical evaluation and radiographic imaging.Results: All 6 patients (4 male and 2 female patients; mean age, 24.5 years [range, 9-44 years]) responded favorably to the combination of sirolimus therapy followed by endovascular embolization, and 4 patients exhibited a near-complete response. The median duration of follow-up was 19 months (range, 6-40 months). One patient discontinued sirolimus soon after embolization and experienced regrowth of the arteriovenous malformation after 1 year. Sirolimus was resumed, which has stabilized his disease for more than 2 years. Mild adverse effects were noted in 4 patients. The combination therapy was well tolerated in all patients. One patient developed skin ulceration after embolization and required surgical debridement. Another patient developed pulmonary microthrombi after embolization with cyanoacrylate glue that resolved with a brief course of anti-inflammatory therapy.Conclusions and Relevance: Although further prospective trials are needed, this report suggests the benefit of a mammalian target of rapamycin inhibitor as an adjuvant therapy for surgical embolization of complex, extracranial head and neck arteriovenous malformations. The optimal dosing and therapeutic duration of sirolimus treatment before and after embolization remain to be determined.

  View details for PubMedID 30326494

• Physician decision making in selection of second-line treatments in immune thrombocytopenia in children AMERICAN JOURNAL OF HEMATOLOGY Grace, R. F., Despotovic, J. M., Bennett, C. M., Bussel, J. B., Neier, M., Neunert, C., Crary, S. E., Pastore, Y. D., Klaassen, R. J., Rothman, J. A., Hege, K., Breakey, V. R., Rose, M. J., Shimano, K. A., Buchanan, G. R., Geddis, A., Haley, K. M., Lorenzana, A., Thompson, A., Jeng, M., Neufeld, E. J., Brown, T., Forbes, P. W., Lambert, M. P. 2018; 93 (7): 882–88

  Abstract

  Immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder which presents with isolated thrombocytopenia and risk of hemorrhage. While most children with ITP promptly recover with or without drug therapy, ITP is persistent or chronic in others. When needed, how to select second-line therapies is not clear. ICON1, conducted within the Pediatric ITP Consortium of North America (ICON), is a prospective, observational, longitudinal cohort study of 120 children from 21 centers starting second-line treatments for ITP which examined treatment decisions. Treating physicians reported reasons for selecting therapies, ranking the top three. In a propensity weighted model, the most important factors were patient/parental preference (53%) and treatment-related factors: side effect profile (58%), long-term toxicity (54%), ease of administration (46%), possibility of remission (45%), and perceived efficacy (30%). Physician, health system, and clinical factors rarely influenced decision-making. Patient/parent preferences were selected as reasons more often in chronic ITP (85.7%) than in newly diagnosed (0%) or persistent ITP (14.3%, P = .003). Splenectomy and rituximab were chosen for the possibility of inducing long-term remission (P < .001). Oral agents, such as eltrombopag and immunosuppressants, were chosen for ease of administration and expected adherence (P < .001). Physicians chose rituximab in patients with lower expected adherence (P = .017). Treatment choice showed some physician and treatment center bias. This study illustrates the complexity and many factors involved in decision-making in selecting second-line ITP treatments, given the absence of comparative trials. It highlights shared decision-making and the need for well-conducted, comparative effectiveness studies to allow for informed discussion between patients and clinicians.

  View details for PubMedID 29659042

• CNS Langerhans Cell Histiocytosis: Common Hematopoietic Origin for LCH-Associated Neurodegeneration and Mass Lesions CANCER McClain, K. L., Picarsic, J., Chakraborty, R., Zinn, D., Lin, H., Abhyankar, H., Scull, B., Shih, A., Lim, K., Eckstein, O., Lubega, J., Peters, T. L., Olea, W., Burke, T., Ahmed, N., Hicks, M., Tran, B., Jones, J., Dauser, R., Jeng, M., Baiocchi, R., Schiff, D., Goldman, S., Heym, K. M., Wilson, H., Carcamo, B., Kumar, A., Rodriguez-Galindo, C., Whipple, N. S., Campbell, P., Murdoch, G., Kofler, J., Heales, S., Malone, M., Woltjer, R., Quinn, J. F., Orchard, P., Kruer, M. C., Jaffe, R., Manz, M. G., Lira, S. A., Parsons, D., Merad, M., Man, T., Allen, C. E. 2018; 124 (12): 2607–20

  Abstract

  Central nervous system Langerhans cell histiocytosis (CNS-LCH) brain involvement may include mass lesions and/or a neurodegenerative disease (LCH-ND) of unknown etiology. The goal of this study was to define the mechanisms of pathogenesis that drive CNS-LCH.Cerebrospinal fluid (CSF) biomarkers including CSF proteins and extracellular BRAFV600E DNA were analyzed in CSF from patients with CNS-LCH lesions compared with patients with brain tumors and other neurodegenerative conditions. Additionally, the presence of BRAFV600E was tested in peripheral mononuclear blood cells (PBMCs) as well as brain biopsies from LCH-ND patients, and the response to BRAF-V600E inhibitor was evaluated in 4 patients with progressive disease.Osteopontin was the only consistently elevated CSF protein in patients with CNS-LCH compared with patients with other brain pathologies. BRAFV600E DNA was detected in CSF of only 2/20 (10%) cases, both with LCH-ND and active lesions outside the CNS. However, BRAFV600E+ PBMCs were detected with significantly higher frequency at all stages of therapy in LCH patients who developed LCH-ND. Brain biopsies of patients with LCH-ND demonstrated diffuse perivascular infiltration by BRAFV600E+ cells with monocyte phenotype (CD14+ CD33+ CD163+ P2RY12- ) and associated osteopontin expression. Three of 4 patients with LCH-ND treated with BRAF-V600E inhibitor experienced significant clinical and radiologic improvement.In LCH-ND patients, BRAFV600E+ cells in PBMCs and infiltrating myeloid/monocytic cells in the brain is consistent with LCH-ND as an active demyelinating process arising from a mutated hematopoietic precursor from which LCH lesion CD207+ cells are also derived. Therapy directed against myeloid precursors with activated MAPK signaling may be effective for LCH-ND. Cancer 2018;124:2607-20. © 2018 American Cancer Society.

  View details for PubMedID 29624648

• Leukocyte and plasma activation profiles in chronically transfused patients with a history of allergic reactions TRANSFUSION Fontaine, M. J., Shih, H., Schubert, R., Wong, W., Andrews, J., Jeng, M., Tirouvanziam, R. 2017; 57 (11): 2639–48

  Abstract

  Allergic transfusion reactions are drawbacks to the benefits of transfusion. Classically, allergic transfusion reactions depend on histamine release from mast cells or basophils, but other leukocyte subsets may also be important. Thus, we propose to better define the exact leukocyte subsets involved in allergic transfusion reactions.The overall objective of the current study was to compare the activation of specific peripheral blood leukocyte subsets (monocytes, neutrophils, eosinophils, and basophils) in a cohort of 13 patients who received chronic transfusions and had a history of allergic transfusion reactions compared with a control group of patients who received chronic transfusions and had no history of allergic transfusion reactions. Leukocyte subsets were analyzed by flow cytometry at baseline and after red blood cell transfusion, and cytokine levels in platelet-free plasma collected at the same time points were measured by Luminex assay.Flow cytometry and cytokine profiles before and after transfusion did not differ significantly between patients who did and did not have a history of allergic transfusion reactions (p > 0.05). However, post-transfusion samples from both groups showed a decrease in CD63 expression in basophils, monocytes, and eosinophils and a decrease in CD45 expression in all leukocyte subsets compared with pretransfusion samples. Interleukin 10 levels increased after transfusion in the group with a history of allergic transfusion reactions (p = 0.0469), and RANTES (regulated upon activation, normal T-cell expressed and secreted) was significantly decreased post-transfusion in all patients (p = 0.0122).None of the leukocyte subsets from patients who had a history of allergic transfusion reactions significantly increased in activation either before or after transfusion. All leukocyte subsets from patients who did and did not have a history of allergic transfusion reactions decreased in their activation profile upon transfusion challenge.

  View details for DOI 10.1111/trf.14275

  View details for Web of Science ID 000414611800014

  View details for PubMedID 28880378

• Development and Initial Validation of the Macrophage Activation Syndrome/Primary Hemophagocytic Lymphohistiocytosis Score, a Diagnostic Tool that Differentiates Primary Hemophagocytic Lymphohistiocytosis from Macrophage Activation Syndrome JOURNAL OF PEDIATRICS Minoia, F., Bovis, F., Davi, S., Insalaco, A., Lehmberg, K., Shenoi, S., Weitzman, S., Espada, G., Gao, Y., Anton, J., Kitoh, T., Kasapcopur, O., Sanner, H., Merino, R., Astigarraga, I., Alessio, M., Jeng, M., Chasnyk, V., Nichols, K. E., Zeng Huasong, Li, C., Micalizzi, C., Ruperto, N., Martini, A., Cron, R. Q., Ravelli, A., Horne, A., Pediat Rheumatology Int Trials Org, Childhood Arthritis Rheumatology, Pediat Rheumatology Collaborative, Histiocyte Soc 2017; 189: 72-+

  Abstract

  To develop and validate a diagnostic score that assists in discriminating primary hemophagocytic lymphohistiocytosis (pHLH) from macrophage activation syndrome (MAS) related to systemic juvenile idiopathic arthritis.The clinical, laboratory, and histopathologic features of 362 patients with MAS and 258 patients with pHLH were collected in a multinational collaborative study. Eighty percent of the population was assessed to develop the score and the remaining 20% constituted the validation sample. Variables that entered the best fitted model of logistic regression were assigned a score, based on their statistical weight. The MAS/HLH (MH) score was made up with the individual scores of selected variables. The cutoff in the MH score that discriminated pHLH from MAS best was calculated by means of receiver operating characteristic curve analysis. Score performance was examined in both developmental and validation samples.Six variables composed the MH score: age at onset, neutrophil count, fibrinogen, splenomegaly, platelet count, and hemoglobin. The MH score ranged from 0 to 123, and its median value was 97 (1st-3rd quartile 75-123) and 12 (1st-3rd quartile 11-34) in pHLH and MAS, respectively. The probability of a diagnosis of pHLH ranged from <1% for a score of <11 to >99% for a score of  ≥123. A cutoff value of ≥60 revealed the best performance in discriminating pHLH from MAS.The MH score is a powerful tool that may aid practitioners to identify patients who are more likely to have pHLH and, thus, could be prioritized for functional and genetic testing.

  View details for DOI 10.1016/j.jpeds.2017.06.005

  View details for Web of Science ID 000417154100019

  View details for PubMedID 28807357

• Long-Term Follow-Up of Lymphatic Malformations in Children Treated with Sildenafil PEDIATRIC DERMATOLOGY Tu, J. H., Tafoya, E., Jeng, M., Teng, J. M. 2017; 34 (5): 559–65

  Abstract

  Lymphatic malformations (LMs) are challenging to treat. Reports on the benefits of sildenafil for LM management have been mixed. This study evaluated long-term clinical outcomes of pediatric LM patients after sildenafil treatment.A retrospective chart review was performed on pediatric LM patients treated with sildenafil in the past 5 years. Patients were also contacted to complete a survey of comprehensive questions about their LM after sildenafil and subsequent interventions.Of 12 patients identified, 10 (83.3%) participated in the follow-up survey. The average age was 8 years (range 4-16 yrs), median treatment duration was 9 months, and the average time of follow-up after sildenafil was 4 years; one patient is still taking sildenafil. Ten patients surveyed (83.3%) reported positive therapeutic response, with improvement in the size and compressibility of their LM during posttreatment clinical visits. Six received additional interventions (four sirolimus, one sclerotherapy, one surgery) after sildenafil was discontinued, with all but one reporting a positive response to subsequent interventions. Minor side effects at the time of sildenafil treatment included mild flushing, dizziness, and transient nausea, but no adverse effects were reported at the long-term follow-up.This is the first report of long-term follow-up of pediatric LM patients treated with sildenafil. Our findings suggest that sildenafil is beneficial for the symptomatic treatment of LMs. Additional analysis on the role of sildenafil as adjuvant therapy is necessary to optimize the use of this medication in the management of complex LMs.

  View details for PubMedID 28884903

• Multisite external validation of a risk prediction model for the diagnosis of blood stream infections in febrile pediatric oncology patients without severe neutropenia. Cancer Esbenshade, A. J., Zhao, Z., Aftandilian, C., Saab, R., Wattier, R. L., Beauchemin, M., Miller, T. P., Wilkes, J. J., Kelly, M. J., Fernbach, A., Jeng, M., Schwartz, C. L., Dvorak, C. C., Shyr, Y., Moons, K. G., Sulis, M., Friedman, D. L. 2017

  Abstract

  Pediatric oncology patients are at an increased risk of invasive bacterial infection due to immunosuppression. The risk of such infection in the absence of severe neutropenia (absolute neutrophil count ≥ 500/μL) is not well established and a validated prediction model for blood stream infection (BSI) risk offers clinical usefulness.A 6-site retrospective external validation was conducted using a previously published risk prediction model for BSI in febrile pediatric oncology patients without severe neutropenia: the Esbenshade/Vanderbilt (EsVan) model. A reduced model (EsVan2) excluding 2 less clinically reliable variables also was created using the initial EsVan model derivative cohort, and was validated using all 5 external validation cohorts. One data set was used only in sensitivity analyses due to missing some variables.From the 5 primary data sets, there were a total of 1197 febrile episodes and 76 episodes of bacteremia. The overall C statistic for predicting bacteremia was 0.695, with a calibration slope of 0.50 for the original model and a calibration slope of 1.0 when recalibration was applied to the model. The model performed better in predicting high-risk bacteremia (gram-negative or Staphylococcus aureus infection) versus BSI alone, with a C statistic of 0.801 and a calibration slope of 0.65. The EsVan2 model outperformed the EsVan model across data sets with a C statistic of 0.733 for predicting BSI and a C statistic of 0.841 for high-risk BSI.The results of this external validation demonstrated that the EsVan and EsVan2 models are able to predict BSI across multiple performance sites and, once validated and implemented prospectively, could assist in decision making in clinical practice. Cancer 2017. © 2017 American Cancer Society.

  View details for DOI 10.1002/cncr.30792

  View details for PubMedID 28542918

• Case Report: Clinical Variation in Children With Thrombopoietin Receptor (C-MPL) Mutations: Report of 2 Cases. Journal of pediatric hematology/oncology Lo, C., Alvarez, E., Ohgami, R. S., Jeng, M. 2017

  Abstract

  Congenital amegakaryocytic thrombocytopenia (CAMT, MIM# 604498) is a rare congenital bone marrow failure syndrome which presents early in life with abnormal bleeding because of thrombocytopenia. Classically, megakaryocytes are decreased to absent in the bone marrow. The development of aplastic anemia early in childhood has led to the recommendation for early stem cell transplantation. Quantitative or loss-of-function mutations in the myeloproliferative leukemia gene (c-mpl), whose gene product functions as the thrombopoietin receptor, have been identified as causative for CAMT. Approximately 100 cases of CAMT are published in the medical literature. We describe 2 cases of CAMT who demonstrate disparate clinical courses, thereby highlighting phenotypic differences and increasing awareness of this clinical entity.

  View details for PubMedID 28859041

• Clinical Characteristics and Quality of Life of Children with ITP Starting Second Line Treatments: Data from the ITP Consortium of North America ICON1 Study Grace, R. F., Klaassen, R. J., Rothman, J. A., Hege, K., Neufeld, E. J., Bennett, C. M., Lambert, M., Breakey, V. R., Bussel, J. B., Buchanan, G. R., Rose, M. J., Geddis, A., Shimano, K., Haley, K. M., Lorenzana, A., Neunert, C., Thompson, A. A., Pastore, Y. D., Jeng, M., Crary, S. E., Neier, M., Brown, T., Forbes, P., Despotovic, J. M. AMER SOC HEMATOLOGY. 2016

  View details for Web of Science ID 000394446807088

• Hemophagocytic Lymphohistiocytosis in Langerhans Cell Histiocytosis: A Multicenter Retrospective Descriptional Study Chellapandian, D., Zhang, R., Jeng, M., van den Bos, C., Lopez, V., Lehmberg, K., Sieni, E., Wang, Y., Nakano, T., Williams, J., Fustino, N., Astigarraga, I., Dunkel, I., An, Q., Cheng, C., Weitzman, S., Sung, L., Nichols, K. E. WILEY-BLACKWELL. 2016: S38–S39

  View details for Web of Science ID 000383581100067

• Elevated CSF Osteopontin and Peripheral Blood Cells with BRAF Mutations in Patients with Langerhans Cell Histiocytosis-Associated Neurodegeneration Zinn, D., Picarsic, J., Chakraborty, R., Lin, H., Abhyankar, H., Scull, B., Shih, A., Lim, K., Simko, S., Eckstein, O., Peters, T. L., Olea, W., Burke, T., Ahmed, N., Parsons, D., Hicks, M., Tran, H. D., Jones, J., Dauser, R., Jeng, M., Baiocchi, R., Schiff, D., Goldman, S., Heym, K., Kumar, A., Rodriguez-Galindo, C., Whipple, N., Campbell, P., Murdoch, G., Heales, S., Malone, M., Woltjer, R., Quinn, J., Orchard, P., Kruer, M., Jaffe, R., Lira, S., Merad, M., Man, T., McClain, K. L., Allen, C. E. WILEY-BLACKWELL. 2016: S37–S38

  View details for Web of Science ID 000383581100064

• Pregnancy Complicated by Gorham-Stout Disease and Refractory Chylothorax. AJP reports Hellyer, J., Oliver-Allen, H., Shafiq, M., Tolani, A., Druzin, M., Jeng, M., Rockson, S., Lowsky, R. 2016; 6 (4): e355-e358

  Abstract

  Introduction Gorham-Stout Disease (GSD) is a rare disorder of bony destruction due to lymphangiomatosis, and is often triggered by hormones. One complication of GSD is the development of chylothorax, which carries a high mortality rate. Very little experience has been published to guide management in GSD during pregnancy to optimize both fetal and maternal health. Case Study A 20-year-old woman with known GSD presented with shortness of breath at 18 weeks of pregnancy, due to bilateral chylothoraces which required daily drainage. To minimize chylous fluid formation, she was placed on bowel rest with total parenteral nutrition (limiting lipid intake) and received octreotide to decrease splanchnic blood flow and chylous fluid drainage. Treatment options were limited due to her pregnancy. Twice daily home chest tube drainage of a single lung cavity, total parenteral nutrition, octreotide, and albumin infusions allowed successful delivery of a healthy 37 weeks' gestation infant by cesarean delivery. Discussion This case illustrates the management of a rare clinical disease of bone resorption and lymphangiomatosis complicated by bilateral, refractory chylothoraces, triggered by pregnancy, in whom treatment options are limited, and the need for a multidisciplinary health care team to ensure successful maternal and fetal outcomes.

  View details for PubMedID 27708981

• Erratum: Pregnancy Complicated by Gorham-Stout Disease and Refractory Chylothorax. AJP reports Hellyer, J., Oliver-Allen, H., Shafiq, M., Tolani, A., Druzin, M., Jeng, M., Rockson, S., Lowsky, R. 2016; 6 (4)

  Abstract

  [This corrects the article DOI: 10.1055/s-0036-1593443.].

  View details for PubMedID 27822433

• Langerhans Cell Histiocytosis Enters the Genomics Age ONCOLOGY-NEW YORK Jeng, M. 2016; 30 (2): 140-141

  View details for Web of Science ID 000370987600003

  View details for PubMedID 26888791

• Updated analysis: central venous access device infection rates in an expanded cohort of paediatric patients with severe haemophilia receiving prophylactic recombinant tissue plasminogen activator. Haemophilia McCarthy, C. E., O'Brien, M., Andrews, J., Zoland, J. M., Macasiray, E., Wong, W., Lo, C., Glader, B., TAMARESIS, J., Jeng, M. 2016; 22 (1): 81-86

  Abstract

  Central venous access devices (CVADs) are used in the care of paediatric haemophilic patients with difficult peripheral access, but their use is limited by complications such as infection. We previously published our experience with monthly recombinant tissue plasminogen activator (r-tPA) administration to CVADs of haemophilic patients as an intervention for infection prophylaxis, which suggested a 10-fold decrease in infection rate compared to published rates without r-tPA.This study was conducted to assess the CVAD infection rate in an expanded haemophilia cohort receiving r-tPA over an extended period.A retrospective review was performed on patients with haemophilia who received monthly r-tPA to CVADs, with data collected from January 1, 2008 to December 31, 2012. The data were merged with the previously reported data set (collected from June 1, 1998 to December 31, 2007).Over the entire observation period, there were 46 350 CVAD days among 32 patients [26 severe factor VIII (FVIII) deficiency, six severe FIX deficiency]. Eight patients received immune tolerance therapy for inhibitors and 24 patients received prophylactic factor administration. No patients were HIV positive. Three infections were observed, with an overall infection rate of 0.06 infections per 1000 CVAD days.A low CVAD infection rate, similar to that observed in our previous study (0.04 per 1000 CVAD days), was observed in this expanded haemophilia cohort treated with prophylactic r-tPA, supporting the use of monthly r-tPA as CVAD infection prophylaxis in haemophilia patients.

  View details for DOI 10.1111/hae.12772

  View details for PubMedID 26248602

• Genes Influencing the Development and Severity of Chronic ITP Identified through Whole Exome Sequencing Despotovic, J. M., Polfus, L. M., Flanagan, J. M., Bennett, C. M., Lambert, M. P., Neunert, C., Kumar, M., Klaassen, R. J., Thornburg, C., Jeng, M., Recht, M., Kirk, S. E., Thompson, A. A., Nugent, D. J., Neufeld, E. J., Bussel, J. B., Boerwinkle, E., Grace, R. F. AMER SOC HEMATOLOGY. 2015

  View details for Web of Science ID 000368019000137

• Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY Holzinger, D., Fassl, S. K., de Jager, W., Lohse, P., Roehrig, U. F., Gattorno, M., Omenetti, A., Chiesa, S., Schena, F., Austermann, J., Vogl, T., Kuhns, D. B., Holland, S. M., Rodriguez-Gallego, C., Lopez-Almaraz, R., Arostegui, J. I., Colino, E., Roldan, R., Fessatou, S., Isidor, B., Poignant, S., Ito, K., Epple, H., Bernstein, J. A., Jeng, M., Frankovich, J., Lionetti, G., Church, J. A., Ong, P. Y., LaPlant, M., Abinun, M., Skinner, R., Bigley, V., Sachs, U. J., Hinze, C., Hoppenreijs, E., Ehrchen, J., Foell, D., Chae, J. J., Ombrello, A., Aksentijevich, I., Sunderkoetter, C., Roth, J. 2015; 136 (5): 1337-1345

  Abstract

  Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin).We sought to characterize the genetic cause and clinical spectrum of Hz/Hc.Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA.Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 ± 1300 μg/mL) compared with those with PAPA syndrome (116 ± 74 μg/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1.Mutations resulting in charge reversal in the y-domain of PSTPIP1 (E→K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.

  View details for DOI 10.1016/j.jaci.2015.04.016

  View details for PubMedID 26025129

• The ASPHO 2015 Distinguished Career Award goes to Dr. Winfred C. Wang, MD. Pediatric blood & cancer Hankins, J., Reiss, U., Jeng, M. 2015; 62: 19-20

  View details for DOI 10.1002/pbc.25489

  View details for PubMedID 25773264

• Dissecting the Heterogeneity of Macrophage Activation Syndrome Complicating Systemic Juvenile Idiopathic Arthritis JOURNAL OF RHEUMATOLOGY Minoia, F., Davi, S., Horne, A., Bovis, F., Demirkaya, E., Akikusa, J., Ayaz, N. A., Al-Mayouf, S. M., Barone, P., Bica, B., Bolt, I., Breda, L., De Cunto, C., Enciso, S., Gallizzi, R., Griffin, T., Hennon, T., Horneff, G., Jeng, M., Kapovic, A. M., Lipton, J. M., Manzoni, S. M., Rumba-Rozenfelde, I., Magalhaes, C. S., Sewairi, W. M., Stine, K. C., Vougiouka, O., Weaver, L. K., Davidsone, Z., de Inocencio, J., Ioseliani, M., Lattanzi, B., Tezer, H., Buoncompagni, A., Picco, P., Ruperto, N., Martini, A., Cron, R. Q., Ravelli, A. 2015; 42 (6): 994-1001

  Abstract

  To seek insights into the heterogeneity of macrophage activation syndrome (MAS) complicating systemic juvenile idiopathic arthritis (sJIA) through the analysis of a large patient sample collected in a multinational survey.International pediatric rheumatologists and hemato-oncologists entered their patient data, collected retrospectively, in a Web-based database. The demographic, clinical, laboratory, histopathologic, therapeutic, and outcome data were analyzed in relation to (1) geographic location of caring hospital, (2) subspecialty of attending physician, (3) demonstration of hemophagocytosis, and (4) severity of clinical course.A total of 362 patients were included by 95 investigators from 33 countries. Demographic, clinical, laboratory, and histopathologic features were comparable among patients seen in diverse geographic areas or by different pediatric specialists. Patients seen in North America were given biologics more frequently. Patients entered by pediatric hemato-oncologists were treated more commonly with biologics and etoposide, whereas patients seen by pediatric rheumatologists more frequently received cyclosporine. Patients with demonstration of hemophagocytosis had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen, and were more frequently administered cyclosporine, intravenous immunoglobulin (IVIG), and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, had more full-blown clinical picture, and were more commonly given cyclosporine, IVIG, and etoposide.The clinical spectrum of MAS is comparable across patients seen in different geographic settings or by diverse pediatric subspecialists. There was a disparity in the therapeutic choices among physicians that underscores the need to establish uniform therapeutic protocols.

  View details for DOI 10.3899/jrheum.141261

  View details for Web of Science ID 000355543300016

  View details for PubMedID 25877504

• Evaluation of Febrile, Nonneutropenic Pediatric Oncology Patients with Central Venous Catheters Who Are Not Given Empiric Antibiotics JOURNAL OF PEDIATRICS Bartholomew, F., Aftandilian, C., Andrews, J., Gutierrez, K., Luna-Fineman, S., Jeng, M. 2015; 166 (1): 157-162

  Abstract

  To evaluate the practice of empiric antibiotics for febrile, nonneutropenic pediatric oncology patients with a central venous catheter (CVC) in place.Episodes of fever without neutropenia (absolute neutrophil count [ANC] ≥500 cells/mm(3)) were reviewed retrospectively in pediatric oncology patients with a CVC undergoing chemotherapy. Characteristics and symptoms were compared between patients with bacteremia and patients without bacteremia.A total of 392 episodes of nonneutropenic fever in 138 subjects (52 females; 38%) were reviewed. In this cohort, the median age at an episode was 7 years, and the majority of patients had a diagnosis of acute leukemia (54%). Median ANC was 3100 cells/mm(3) (IQR, 1570-5980 cells/mm(3)). Median temperature was 38.7°C (IQR, 38.3-39.2°C). Twenty-four infectious episodes (6%) occurred in 18 subjects, and 5 CVCs required removal; all patients requiring removal admitted and received antibiotics owing to chills. There were no significant difference in age, sex, or ANC between patients with bacteremia and those without bacteremia; however, mean temperature was higher in the patients with bacteremia (39.4°C vs 38.7°C; P = .003). No deaths due to sepsis occurred, and no CVCs were removed because antibiotics were not administered empirically.Our practice of observing pediatric oncology patients undergoing chemotherapy with CVCs who are not neutropenic does not appear to lead to increased serious adverse outcomes and avoids antibiotic exposure for >90% of patients without a bacterial infection.

  View details for DOI 10.1016/j.jpeds.2014.09.008

  View details for PubMedID 25444524

• Genomic analysis of bone marrow failure and myelodysplastic syndromes reveals phenotypic and diagnostic complexity. Haematologica Zhang, M. Y., Keel, S. B., Walsh, T., Lee, M. K., Gulsuner, S., Watts, A. C., Pritchard, C. C., Salipante, S. J., Jeng, M. R., Hofmann, I., Williams, D. A., Fleming, M. D., Abkowitz, J. L., King, M., Shimamura, A. 2015; 100 (1): 42-48

  Abstract

  Accurate and timely diagnosis of inherited bone marrow failure and inherited myelodysplastic syndromes is essential to guide clinical management. Distinguishing inherited from acquired bone marrow failure/myelodysplastic syndrome poses a significant clinical challenge. At present, diagnostic genetic testing for inherited bone marrow failure/myelodysplastic syndrome is performed gene-by-gene, guided by clinical and laboratory evaluation. We hypothesized that standard clinically-directed genetic testing misses patients with cryptic or atypical presentations of inherited bone marrow failure/myelodysplastic syndrome. In order to screen simultaneously for mutations of all classes in bone marrow failure/myelodysplastic syndrome genes, we developed and validated a panel of 85 genes for targeted capture and multiplexed massively parallel sequencing. In patients with clinical diagnoses of Fanconi anemia, genomic analysis resolved subtype assignment, including those of patients with inconclusive complementation test results. Eight out of 71 patients with idiopathic bone marrow failure or myelodysplastic syndrome were found to harbor damaging germline mutations in GATA2, RUNX1, DKC1, or LIG4. All 8 of these patients lacked classical clinical stigmata or laboratory findings of these syndromes and only 4 had a family history suggestive of inherited disease. These results reflect the extensive genetic heterogeneity and phenotypic complexity of bone marrow failure/myelodysplastic syndrome phenotypes. This study supports the integration of broad unbiased genetic screening into the diagnostic workup of children and young adults with bone marrow failure and myelodysplastic syndromes.

  View details for DOI 10.3324/haematol.2014.113456

  View details for PubMedID 25239263

• Malignant Transformation of Infantile Hemangioma to Angiosarcoma: Response to Chemotherapy With Bevacizumab PEDIATRIC BLOOD & CANCER Jeng, M. R., Fuh, B., Blatt, J., Gupta, A., Merrow, A. C., Hammill, A., Adams, D. 2014; 61 (11): 2115-2117

  Abstract

  We describe a child initially diagnosed with multi-focal infantile hemangioma (cutaneous, hepatic, pulmonary), a benign vascular lesion, which underwent malignant transformation to angiosarcoma. The use of anti-angiogenic agents, such as bevacizumab, an anti-vascular endothelial growth factor (VEGF) antibody, has been reported in adults with angiosarcoma. Treatment with chemotherapy (gemcitabine and docetaxel) and bevacizumab resulted in disease response with progression free survival of 12 months. This report describes the response to chemotherapy and bevacizumab in a child with angiosarcoma and highlights the potential for malignant transformation of benign vascular lesions and the need for careful monitoring.

  View details for DOI 10.1002/pbc.25067

  View details for PubMedID 24740626

• Mediastinal Kaposiform Hemangioendothelioma and Kasabach-Merritt Phenomenon in a Patient with no Skin Changes and a Normal Chest CT. Pediatric hematology and oncology Wallenstein, M. B., Hole, M. K., McCarthy, C., Fijalkowski, N., Jeng, M., Wong, W. B. 2014; 31 (6): 563-567

  Abstract

  A 16-month-old previously healthy boy was admitted to the hospital with respiratory distress and thrombocytopenia. Initial workup demonstrated large pleural and pericardial effusions. The patient had no cutaneous abnormality on physical examination, and his initial chest CT (computed tomography) was nondiagnostic. He required multiple platelet transfusions, chest tube placement, and pericardiocentesis. Sixteen days after admission, a chest MRI (magnetic resonance imaging) revealed a large infiltrative mass of the superior mediastinum, consistent with kaposiform hemangioendothelioma (KHE). The patient's thrombocytopenia was due to associated Kasabach-Merritt phenomenon (KMP). The patient now has complete resolution of KMP after medical treatment with prednisolone, aminocaproic acid, vincristine, and aspirin.

  View details for DOI 10.3109/08880018.2013.825356

  View details for PubMedID 24047193

• Elevated tricuspid regurgitant jet velocity in subgroups of thalassemia patients: insight into pathophysiology and the effect of splenectomy ANNALS OF HEMATOLOGY Singer, S. T., Kuypers, F., Fineman, J., Gildengorin, G., Larkin, S., Sweeters, N., Rosenfeld, H., Kurio, G., Higa, A., Jeng, M., Huang, J., Vichinsky, E. P. 2014; 93 (7): 1139-1148

  Abstract

  A high tricuspid regurgitant jet velocity (TRV) signifies a risk for or established pulmonary hypertension (PH), which is a serious complication in thalassemia patients. The underlying pathophysiology in thalassemia subgroups and potential biomarkers for early detection and monitoring are not well defined, in particular as they relate to spleen removal. To better understand some of these unresolved aspects, we examined 76 thalassemia patients (35 non-transfused), 25 splenectomized non-thalassemia patients (15 with hereditary spherocytosis), and 12 healthy controls. An elevated TRV (>2.5 m/s) was found in 25/76 (33 %) of the patients, confined to non-transfused or those with a late start of transfusions, including patients with hemoglobin H-constant spring, a finding not previously described. These non or late-transfused patients (76 % splenectomized) had significantly increased platelet activation (sCD40L), high platelet count, endothelial activation (endothelin-1), and hemolysis (LDH, plasma-free Hb), while hypercoagulable and inflammatory markers were not significantly increased. The same markers were increased in the seven patients with confirmed PH on cardiac catheterization, suggesting their possible role for screening patients at risk for PH. A combination of hemolysis and absence of spleen is necessary for developing a high TRV, as neither chronic hemolysis in the non-splenectomized thalassemia patients nor splenectomy without hemolysis, in the non-thalassemia patients, resulted in an increase in TRV.

  View details for DOI 10.1007/s00277-014-2037-9

  View details for Web of Science ID 000337144900006

  View details for PubMedCentralID PMC4467727

• Oxandrolone for the treatment of bone marrow failure in Fanconi anemia. Pediatric blood & cancer Rose, S. R., Kim, M., Korbee, L., Wilson, K. A., Douglas Ris, M., Eyal, O., Sherafat-Kazemzadeh, R., Bollepalli, S., Harris, R., Jeng, M. R., Williams, D. A., Smith, F. O. 2014; 61 (1): 11-19

  Abstract

  A majority of Fanconi anemia (FA) patients will experience bone marrow failure (BMF) and androgen therapy (most often oxymetholone) may be utilized as a treatment to improve BMF-related cytopenias. However, oxymetholone is associated with toxicities making identification of other agents of interest. In this study we aimed to evaluate the toxicity profile and hematologic response in patients with FA who are treated with low-dose oxandrolone, a synthetic non-fluorinated anabolic steroid, similar to oxymetholone, with known dosing thresholds for virilization.A single arm, Phase I/II study was designed to treat patients on low-dose oxandrolone. If no toxicity or hematologic response was noted at 16 weeks, a single dose escalation was offered. Subjects were regularly assessed for toxicity, including determinations of virilization, behavioral changes, and liver and kidney function. At 32 weeks, those who demonstrated hematologic response were allowed to continue study treatment, and those without improvement were deemed non-responsive.Nine subjects completed the study and were followed for a median of 99 weeks (46-136 weeks). Three (33.3%) subjects developed mild sub-clinical virilization and continued treatment with a dose reduction. None (0%) had adverse behavioral changes. Two (22.2%) developed elevated liver function tests at 42 and 105 weeks. Seven (77.8%) subjects had a hematologic response.Oxandrolone appears to be well-tolerated, has limited toxicities at the administered doses in FA with patients, and may be an alternative androgen for the treatment of BMF in FA.

  View details for DOI 10.1002/pbc.24617

  View details for PubMedID 24019220

• Immune Thrombocytopenia in Children Less Than 1 Year of Age: A Single-institution 10-year Experience. Journal of pediatric hematology/oncology Lo, C., Wong, W., Glader, B., Jeng, M. 2013; 35 (5): 406-408

  Abstract

  Immune thrombocytopenia (ITP) in children less than one year of age is less well characterized compared to ITP in toddlers and school-age children. We performed a 10-year retrospective review of ITP patients in this age-cohort at our institution. Diagnosis and classification were made according to the 2009 International Working Group criteria. Fourteen infants were identified. Their bleeding scores were Grades 1 to 2 (79%), Grade 3 (22%), Grades 4 to 5 (0%). Eight patients received treatment with a 75% response rate. Three patients (21%) developed chronic ITP. These observations suggest that ITP in very young patients is similar to typical childhood ITP.

  View details for DOI 10.1097/MPH.0b013e3182580ab4

  View details for PubMedID 22767132

• Clofarabine salvage therapy for refractory high-risk langerhans cell histiocytosis. Pediatric blood & cancer Abraham, A., Alsultan, A., Jeng, M., Rodriguez-Galindo, C., Campbell, P. K. 2013; 60 (6): E19-22

  Abstract

  Pediatric patients with refractory multisystem Langerhans cell histiocytosis (LCH) have a poor prognosis despite aggressive chemotherapy. Salvage therapy with cytarabine and cladribine has shown promise as an effective treatment but is associated with significant toxicity. A previous report described two patients with refractory LCH who had a rapid response to single-agent clofarabine with minimal toxicity. In this report, we describe four children with refractory, risk-organ-positive LCH who were treated with clofarabine and provide follow-up for the two previously reported cases. The results support development of a formal trial evaluating clofarabine as front-line salvage for refractory LCH.

  View details for DOI 10.1002/pbc.24436

  View details for PubMedID 23255383

• MONTHLY RECOMBINANT TISSUE PLASMINOGEN ACTIVATOR ADMINISTRATION TO IMPLANTABLE CENTRAL VENOUS ACCESS DEVICES DECREASES INFECTIONS IN CHILDREN WITH HEMOPHILIA: UPDATED ANALYSIS FROM AN EXPANDED COHORT McCarthy, C., Zoland, J., Macasiray, E., Wong, W., Glader, B., Jeng, M. WILEY-BLACKWELL. 2013: S17–S17

  View details for Web of Science ID 000317984800057

• An exploratory epidemiological study of Langerhans cell histiocytosis PEDIATRIC BLOOD & CANCER Venkatramani, R., Rosenberg, S., Indramohan, G., Jeng, M., Jubran, R. 2012; 59 (7): 1324-1326

  Abstract

  We explored potential risk factors associated with Langerhans cell histiocytosis (LCH) in a predominantly Hispanic population in Los Angeles. Sixty children with LCH (cases) and, 150 randomly selected patients (controls) were interviewed. There was no statistically significant difference between cases and controls in the following: Family history of thyroid disease, smokers in the family, maternal problems during pregnancy, and pesticide exposure. Cases were more likely to report a family history of cancer (OR 2.5), infection during infancy (OR 2.76), and parental occupational exposure to metal, granites, or wood dust (OR 2.48).

  View details for DOI 10.1002/pbc.24136

  View details for Web of Science ID 000309752400035

  View details for PubMedID 22434707

• Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia PEDIATRIC BLOOD & CANCER Grace, R. F., Bennett, C. M., Ritchey, A. K., Jeng, M., Thornburg, C. D., Lambert, M. P., Neier, M., Recht, M., Kumar, M., Blanchette, V., Klaassen, R. J., Buchanan, G. R., Kurth, M. H., Nugent, D. J., Thompson, A. A., Stine, K., Kalish, L. A., Neufeld, E. J. 2012; 58 (2): 221-225

  Abstract

  Treatment choice in pediatric immune thrombocytopenia (ITP) is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies.The objective of this study was to evaluate univariate and multivariable predictors of platelet count response to rituximab. After local IRB approval, 565 patients with chronic ITP enrolled and met criteria for this study in the longitudinal, North American Chronic ITP Registry (NACIR) between January 2004 and October 2010. Treatment response was defined as a post-treatment platelet count ≥ 50,000/µl within 16 weeks of rituximab and 14 days of steroids. Treatment response data were captured both retrospectively at enrollment and then prospectively.Eighty (14.2%) patients were treated with rituximab with an overall response rate of 63.8% (51/80). Univariate correlates of response to rituximab included the presence of secondary ITP and a positive response to steroids. In multivariable analysis, response to steroids remained a strong correlate of response to rituximab, OR 6.8 (95% CI 2.0-23.0, P = 0.002). Secondary ITP also remained a strong predictor of response to rituximab, OR 5.6 (95% CI 1.1-28.6, P = 0.04). Although 87.5% of patients who responded to steroids responded to rituximab, 48% with a negative response to steroids did respond to rituximab.In the NACIR, response to steroids and presence of secondary ITP were strong correlates of response to rituximab, a finding not previously reported in children or adults.

  View details for DOI 10.1002/pbc.23130

  View details for Web of Science ID 000298259000012

  View details for PubMedID 21674758

• Estimation of liver T*2 in transfusion-related iron overload in patients with weighted least squares T*2 IDEAL MAGNETIC RESONANCE IN MEDICINE Vasanawala, S. S., Yu, H., Shimakawa, A., Jeng, M., Brittain, J. H. 2012; 67 (1): 183-190

  Abstract

  MRI imaging of hepatic iron overload can be achieved by estimating T(2) values using multiple-echo sequences. The purpose of this work is to develop and clinically evaluate a weighted least squares algorithm based on T(2) Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) technique for volumetric estimation of hepatic T(2) in the setting of iron overload. The weighted least squares T(2) IDEAL technique improves T(2) estimation by automatically decreasing the impact of later, noise-dominated echoes. The technique was evaluated in 37 patients with iron overload. Each patient underwent (i) a standard 2D multiple-echo gradient echo sequence for T(2) assessment with nonlinear exponential fitting, and (ii) a 3D T(2) IDEAL technique, with and without a weighted least squares fit. Regression and Bland-Altman analysis demonstrated strong correlation between conventional 2D and T(2) IDEAL estimation. In cases of severe iron overload, T(2) IDEAL without weighted least squares reconstruction resulted in a relative overestimation of T(2) compared with weighted least squares.

  View details for DOI 10.1002/mrm.22986

  View details for PubMedID 21574184

• Disseminated Intravascular Coagulation Due to IgM-Mediated Autoimmune Hemolytic Anemia PEDIATRIC BLOOD & CANCER Bleakly, N. T., Fontaine, M. J., Pate, L. L., Sutherland, S. M., Jeng, M. 2011; 57 (2): 329-331

  Abstract

  Disseminated intravascular coagulation (DIC) due to red cell hemolysis has been previously attributed to transfusion-related hemolytic reactions, but not to autoimmune hemolytic anemia. We report a case of DIC in a child with complement-fixing IgM-mediated cold-agglutinin autoimmune hemolysis, which resulted in arterial thrombosis and gangrene of the upper and lower extremities.

  View details for DOI 10.1002/pbc.23024

  View details for PubMedID 21671368

• IMMUNE-MEDIATED THROMBOCYTOPENIA IN CHILDREN LESS THAN 1 YEAR OF AGE: A SINGLE-INSTITUTION 10-YEAR EXPERIENCE Lo, C., Newman, A., Wong, W., Glader, B., Jeng, M. WILEY-BLACKWELL. 2011: 915–15

  View details for Web of Science ID 000288463100067

• Diffuse Infantile Hepatic Hemangiomas: A Report of Four Cases Successfully Managed with Medical Therapy PEDIATRIC DERMATOLOGY Yeh, I., Bruckner, A. L., Sanchez, R., Jeng, M. R., Newell, B. D., Frieden, I. J. 2011; 28 (3): 267-275

  Abstract

  We report four cases of diffuse infantile hepatic hemangioma, a rare but potentially life-threatening subset of hepatic hemangiomas. All patients demonstrated distinctive dome-shaped red-purple cutaneous hemangiomas. Two patients responded to steroids and propranolol (one in combination with vincristine), and two responded to steroids and vincristine. After a systematic literature review, we identified 26 previously reported cases of diffuse infantile hepatic hemangioma. Diffuse infantile hepatic hemangioma had a mortality rate of 17% and a >70% incidence of hypothyroidism, often severe (n = 30). More than one-third of patients developed heart failure (high output in half the cases). Based on our experience, early aggressive medical management, as well as thyroid replacement when indicated, should be initiated early in the course of diffuse infantile hepatic hemangioma pending evaluation for liver transplant.

  View details for DOI 10.1111/j.1525-1470.2011.01421.x

  View details for Web of Science ID 000291034400008

  View details for PubMedID 21517953

• The role of vanin-1 and oxidative stress-related pathways in distinguishing acute and chronic pediatric ITP BLOOD Zhang, B., Lo, C., Shen, L., Sood, R., Jones, C., Cusmano-Ozog, K., Park-Snyder, S., Wong, W., Jeng, M., Cowan, T., Engleman, E. G., Zehnder, J. L. 2011; 117 (17): 4569-4579

  Abstract

  Pediatric immune thrombocytopenia (ITP) is usually self-limited. However, approximately 20% of children develop chronic ITP, which can be associated with significant morbidity because of long-term immunosuppression and splenectomy in refractory cases. To explore the molecular mechanism of chronic ITP compared with acute ITP, we studied 63 pediatric patients with ITP. Gene expression analysis of whole blood revealed distinct signatures for acute and chronic ITP. Oxidative stress-related pathways were among the most significant chronic ITP-associated pathways. Overexpression of VNN1, an oxidative stress sensor in epithelial cells, was most strongly associated with progression to chronic ITP. Studies of normal persons demonstrated VNN1 expression in a variety of blood cells. Exposure of blood mononuclear cells to oxidative stress inducers elicited dramatic up-regulation of VNN1 and down-regulation of PPARγ, indicating a role for VNN1 as a peripheral blood oxidative stress sensor. Assessment of redox state by tandem mass spectrometry demonstrated statistically significant lower glutathione ratios in patients with ITP versus healthy controls; lower glutathione ratios were also seen in untreated patients with ITP compared with recently treated patients. Our work demonstrates distinct patterns of gene expression in acute and chronic ITP and implicates oxidative stress pathways in the pathogenesis of chronic pediatric ITP.

  View details for DOI 10.1182/blood-2010-09-304931

  View details for PubMedID 21325602

• Effect of chronic red cell transfusion therapy on vasculopathies and silent infarcts in patients with sickle cell disease AMERICAN JOURNAL OF HEMATOLOGY Gyang, E., Yeom, K., Hoppe, C., Partap, S., Jeng, M. 2011; 86 (1): 104-106

  Abstract

  Regular, chronic red cell transfusions (CTX) have been shown to be effective prophylaxis against stroke in sickle cell disease (SCD) in those at risk. Because serial brain imaging is not routinely performed, little is known about the impact of CTX on silent infarcts (SI) and cerebral vascular pathology. Thus, we retrospectively evaluated the magnetic resonance imaging reports of a cohort of SCD patients who were prescribed CTX for either primary or secondary stroke prophylaxis. Seventeen patients with Hb SS were included (mean age 15 years, mean follow-up 4.3 years). Eight patients were on CTX for primary prophylaxis. New SI occurred in 17.6% of patients corresponding to an SI rate of 5.42 per 100 patient-years. Vasculopathy of the cerebral arteries was present in 65% of patients and progressed in 63% of these patients. Those who developed progressive vasculopathy were on CTX for an average of 8 years before lesions progressed. Patients on CTX for secondary prophylaxis had more SIs and evidence of progressive vascular disease than patients on CTX for primary prophylaxis. We conclude that adherence to CTX does not necessarily prevent SI or halt cerebral vasculopathy progression, especially in those with a history of overt stroke.

  View details for DOI 10.1002/ajh.21901

  View details for PubMedID 21117059

• Apoptosis and Pediatric Idiopathic Neutropenia CURRENT PEDIATRIC REVIEWS Garcia, M., Jeng, M., Nadeau, K. 2011; 7 (4): 321–28

  View details for DOI 10.2174/157339611796892337

  View details for Web of Science ID 000434515500010

• Response to Steroids Predicts Response to Rituximab In Pediatric Chronic Immune Thrombocytopenia Grace, R. F., Bennett, C. M., Ritchey, A., Jeng, M. R., Thornburg, C., Lambert, M., Neier, M., Recht, M., Kumar, M., Blanchette, V., Klaassen, R., Buchanan, G. R., Kurth, M., Nugent, D. J., Thompson, A. A., Stine, K., Kalish, L. A., Neufeld, E. J. AMER SOC HEMATOLOGY. 2010: 1510

  View details for Web of Science ID 000289662204101

• Adherence to Study Medication and Visits: Data From the BABY HUG Trial PEDIATRIC BLOOD & CANCER Thornburg, C. D., Rogers, Z. R., Jeng, M. R., Rana, S. R., Iyer, R. V., Faughnan, L., Hassen, L., Marshall, J., McDonald, R. P., Wang, W. C., Huang, X., Rees, R. C. 2010; 54 (2): 260-264

  Abstract

  Subject retention and adherence are essential to maintain the power and validity of the Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG). We designed a study to assess adherence with study medication administration and study visits and to evaluate socioeconomic factors (SES) that may influence these measurements of adherence. These data are important for assessing impact of adherence on BABY HUG trial outcome and defining impact of SES on adherence.Each subject's median study medication (MedAd) and mean visit adherence (VAd) were evaluated. We examined associations of adherence with SES of participating families.MedAd data were available on 153 of the 191 subjects who started randomized study medication. MedAd was 101.7% of volume prescribed, with 88.9% of subjects taking at least 80% of doses. VAd data were available on 185 of the 191 subjects who started randomized study medication. VAd was 97.3%, with 82.2% of subjects having no missed visits. During dose titration, subjects had on average 12.9% higher medication adherence than subjects who were on a stable dose and had less frequent study visits. MedAd and VAd were not significantly associated with SES.Subjects in the BABY HUG trial have had excellent adherence. SES was not associated with adherence, suggesting that SES should not be used as a criterion for enrolment in clinical trials. Additional efforts are needed to maintain medication adherence, particularly when the interval between scheduled visits increases. (ClinicalTrials.gov number, NCT00006400).

  View details for DOI 10.1002/pbc.22324

  View details for Web of Science ID 000273206700016

  View details for PubMedID 19856395

  View details for PubMedCentralID PMC2795096

• Fusion of PDGFRB to two distinct loci at 3p21 and a third at 12q13 in imatinib-responsive myeloproliferative neoplasms BRITISH JOURNAL OF HAEMATOLOGY Hidalgo-Curtis, C., Apperley, J. F., Stark, A., Jeng, M., Gotlib, J., Chase, A., Cross, N. C., Grand, F. H. 2010; 148 (2): 268-273

  Abstract

  We identified four patients who presented with BCR-ABL1 negative myeloproliferative neoplasms and cytogenetically visible abnormalities of chromosome band 5q31-35. Fluorescence in situ hybridization indicated that the platelet-derived growth factor receptor beta gene (PDGFRB) was disrupted in all four cases and 5' rapid amplification of cDNA ends identified in-frame mRNA fusions between PDGFRB and WDR48 (3p21), GOLGA4 (3p21) and BIN2 (12q13). Strikingly, all three genes encode proteins involving intracellular trafficking. Imatinib, a known inhibitor of PDGFRbeta, selectively blocked the growth of t(3;5) myeloid colonies and produced clinically significant responses in all patients. We conclude that PDGFRB fuses to diverse partner genes in atypical myeloproliferative neoplasms (MPNs). Although very rare, identification of these fusions is critical for proper management of affected individuals.

  View details for DOI 10.1111/j.1365-2141.2009.07955.x

  View details for Web of Science ID 000272884100009

  View details for PubMedID 20085582

• Monthly recombinant tissue plasminogen activator administration to implantable central venous access devices decreases infections in children with haemophilia HAEMOPHILIA Jeng, M. R., O'Brien, M., Wong, W., Zoland, J., Lea, J., Tang, N., Glader, B. 2009; 15 (6): 1272-1280

  Abstract

  Central venous access devices (CVAD) have been effectively used in the care of haemophilia patients. This is particularly true in children, who often have difficult venous access. CVAD complications (infection and thrombosis), risk factors, and complication rates, have been well-documented. However, effective interventions which decrease complication rates have not been identified. In this study, we review our experience with the use of monthly recombinant tissue plasminogen activator (rtPA) administration in haemophilia patients with fully implanted CVADs. Data on 19 haemophilia patients with 24 CVADs were available for analysis, with a total of 24 520 CVAD days. An infection rate of 0.04 infections per 1000 CVAD days and a thrombosis rate of 0.04 thrombi per 1000 CVAD days was observed. The observed infectious complication rate is at least one logarithm lower than many published CVAD infection rates in haemophilia patients who have not received rtPA administration. No bleeding complications were noted. Monthly rtPA is safe and appears to be effective in decreasing CVAD infection rates. Larger, randomized controlled studies are indicated to validate this finding.

  View details for DOI 10.1111/j.1365-2516.2009.02063.x

  View details for PubMedID 19601989

• Neonatal Alloimmune Thrombocytopenia and Neutropenia Associated With Maternal Human Leukocyte Antigen Antibodies PEDIATRIC BLOOD & CANCER Gramatges, M. M., Fani, P., Nadeau, K., Pereira, S., Jeng, M. R. 2009; 53 (1): 97-99

  Abstract

  Neonatal thrombocytopenia or neutropenia may result from passive transfusion of maternally derived antibodies. Antibodies against platelet antigens are commonly associated with neonatal alloimmune thrombocytopenia (NAIT), and anti-neutrophil antibodies are frequently identified in alloimmune neonatal neutropenia (ANN). Combined alloimmune cytopenias in the newborn are rarely reported; even fewer reports document human leukocyte antigen (HLA) antibodies as a potential cause of neonatal thrombocytopenia or neutropenia. We describe neutropenia and thrombocytopenia in a newborn associated with markedly elevated maternal HLA antibodies in the absence of anti-neutrophil or anti-platelet antibodies to highlight consideration of HLA antibodies in the pathogenesis of ANN and NAIT.

  View details for DOI 10.1002/pbc.21979

  View details for PubMedID 19229975

• Idiopathic neutropenia of childhood is associated with Fas/FasL expression CLINICAL IMMUNOLOGY Nadeau, K. C., Callejas, A., Wong, W. B., Joh, J. W., Cohen, H. J., Jeng, M. R. 2008; 129 (3): 438-447

  Abstract

  Idiopathic neutropenia (IN) in children is characterized by decreased neutrophil counts (<1500/microl), can be acute or chronic (greater than 6 months duration). The pathophysiology is not well understood; therefore, potential mechanisms of pediatric IN were investigated. An increase in Fas transcripts in neutrophils of IN patients compared to age-matched healthy control (HC) neutrophils was observed (p<0.005). Increased expression of Fas protein was found in IN neutrophils, while Fas surface expression on other immune cells was similar. Plasma from acute IN patients had higher protein levels of soluble FasL than chronic IN patients. When HC neutrophils were incubated in plasma from IN patients, greater rates of apoptosis were observed. Biochemical studies suggest the apoptotic factor(s) in plasma is heat-sensitive, non-IgG, and 12-50 kD protein. Addition of anti-sFasL blocking antibodies to patient plasma caused a statistically significant decrease in neutrophil apoptosis. These studies show that the Fas/FasL pathway could be associated with neutrophil apoptosis in childhood IN.

  View details for DOI 10.1016/j.clim.2008.08.006

  View details for PubMedID 18819843

• Study Drug and Visit Adherence: Data from the BABY HUG Trial 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium Thornburg, C. D., Rogers, Z. R., Wang, W., Jeng, M., Rana, S. R., Iyer, R. V., Faughnan, L., Marshall, J., Hassen, L., McDonald, R., Rees, R. C. AMER SOC HEMATOLOGY. 2008: 461–61

  View details for Web of Science ID 000262104701497

• Clofarabine in refractory Langerhans cell histiocytosis PEDIATRIC BLOOD & CANCER Rodriguez-Galindo, C., Jeng, M., Khuu, P., McCarville, M. B. 2008; 51 (5): 703-706

  Abstract

  Patients with multi-system Langerhans cell histiocytosis (LCH) who progress on frontline therapy have a dismal outcome. Responses to cladribine have been reported in relapsed LCH, but there are no well defined salvage regimens for LCH is refractory to therapy. The next generation deoxyadenosine analog, clofarabine, has demonstrated activity in patients with leukemia that is refractory to salvage regimens, including other nucleotide congeners; however, no experience exist on the use of clofarabine in LCH. In this report we describe significant single agent activity of clofarabine in disseminated LCH refractory to salvage regimens, including cladribine.

  View details for DOI 10.1002/pbc.21668

  View details for Web of Science ID 000259465400033

  View details for PubMedID 18623218

• Neonatal heparin overdose-a multidisciplinary team approach to medication error prevention. The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG Arimura, J., Poole, R. L., Jeng, M., Rhine, W., Sharek, P. 2008; 13 (2): 96-98

  Abstract

  Despite the efforts of many hospitals, system failures can result in medication errors that may be life threatening. During 2006 and 2007, nine neonates received potentially fatal doses of heparin. This paper will review contributing factors to the heparin medication errors and ways to minimize the risk of heparin overdose.

  View details for DOI 10.5863/1551-6776-13.2.96

  View details for PubMedID 23055872

  View details for PubMedCentralID PMC3462065

• Relative response of patients with myelodysplastic syndromes and other transfusion-dependent anaemias to deferasirox (ICL670): a 1-yr prospective study EUROPEAN JOURNAL OF HAEMATOLOGY Porter, J., Galanello, R., Saglio, G., Neufeld, E. J., Vichinsky, E., Cappellini, M. D., Olivieri, N., Piga, A., Cunningham, M. J., Soulieres, D., Gattermann, N., Tchernia, G., Maertens, J., Giardina, P., Kwiatkowski, J., Quarta, G., Jeng, M., Forni, G. L., Stadler, M., Cario, H., Debusscher, L., Della Porta, M., Cazzola, M., Greenberg, P., Alimena, G., Rabault, B., Gathmann, I., Ford, J. M., Alberti, D., Rose, C. 2008; 80 (2): 168-176

  Abstract

  This 1-yr prospective phase II trial evaluated the efficacy of deferasirox in regularly transfused patients aged 3-81 yrs with myelodysplastic syndromes (MDS; n = 47), Diamond-Blackfan anaemia (DBA; n = 30), other rare anaemias (n = 22) or beta-thalassaemia (n = 85). Dosage was determined by baseline liver iron concentration (LIC).In patients with baseline LIC > or = 7 mg Fe/g dry weight, deferasirox initiated at 20 or 30 mg/kg/d produced statistically significant decreases in LIC (P < 0.001); these decreases were greatest in MDS and least in DBA. As chelation efficiency and iron excretion did not differ significantly between disease groups, the differences in LIC changes are consistent with mean transfusional iron intake (least in MDS: 0.28 +/- 0.14 mg/kg/d; greatest in DBA: 0.4 +/- 0.11 mg/kg/d). Overall, LIC changes were dependent on dose (P < 0.001) and transfusional iron intake (P < 0.01), but not statistically different between disease groups. Changes in serum ferritin and LIC were correlated irrespective of disease group (r = 0.59), supporting the potential use of serum ferritin for monitoring deferasirox therapy. Deferasirox had a safety profile compatible with long-term use. There were no disease-specific safety/tolerability effects: the most common adverse events were gastrointestinal disturbances, skin rash and non-progressive serum creatinine increases.Deferasirox is effective for reducing iron burden with a defined, clinically manageable safety profile in patients with various transfusion-dependent anaemias. There were no disease-specific adverse events. Once differences in transfusional iron intake are accounted for, dose-dependent changes in LIC or serum ferritin are similar in MDS and other disease groups.

  View details for DOI 10.1111/j.1600-0609.2007.00985.x

  View details for Web of Science ID 000252320600010

  View details for PubMedID 18028431

  View details for PubMedCentralID PMC2268958

• Precursor B-Cell acute lymphoblastic leukemia presenting with hemophagocytic lymphohistiocytosis PEDIATRIC BLOOD & CANCER O'Brien, M. M., Lee-Kim, Y., George, T. I., McClain, K. L., Twist, C. J., Jeng, M. 2008; 50 (2): 381-383

  Abstract

  Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome which can be an inherited congenital disorder or can develop secondary to malignancy, infection, or autoimmune disease. Secondary HLH due to malignancy occurs most commonly with T or NK-cell lymphoid neoplasms. HLH with B-cell malignancies is less common and HLH has rarely been described in association with precursor B-cell acute lymphoblastic leukemia (B-ALL). We report three cases of HLH associated with B-ALL and review 17 cases of ALL-associated HLH previously reported in the literature.

  View details for DOI 10.1002/pbc.20950

  View details for PubMedID 16856156

• Gene expression and pathway analysis of immune thrombocytopenic purpura BRITISH JOURNAL OF HAEMATOLOGY Sood, R., Wong, W., Gotlib, J., Jeng, M., Zehnder, J. L. 2008; 140 (1): 99-103

  Abstract

  A global expression profile of peripheral blood from patients with immune thrombocytopenic purpura (ITP) was performed that identified an ITP-specific signature, which also included interferon (IFN)-induced genes. Several genes correlated with ITP have been shown to be associated with expression signatures in systemic lupus erythematosis and rheumatoid arthritis, indicating an overlap with other autoimmune disorders. Pathway analysis demonstrated that IFN signalling, death receptor and protein ubiquitination pathways were associated with ITP. These results provide the first glimpse of the genes and pathways consistently aberrant in ITP, identifying new targets for investigations of pathogenesis and treatment of ITP.

  View details for DOI 10.1111/j.1365-2141.2007.06881.x

  View details for PubMedID 18005267

• Cold agglutinin syndrome in pediatric liver transplant recipients PEDIATRIC TRANSPLANTATION Wong, W., Merker, J. D., Nguyen, C., Berquist, W., Jeng, M., Viele, M., Glader, B., Fontaine, M. J. 2007; 11 (8): 931-936

  Abstract

  Anemia is a common finding in post-liver transplant patients. Causes for the anemia include nutritional deficiencies, red cell aplasia as well as immune-mediated hemolysis. One of the immunologic causes of hemolytic anemia is drug-induced hemolysis. Tacrolimus is a common immunosuppressant used in post-liver transplant patients to prevent graft rejection. There have been reports of tacrolimus-associated hemolytic anemia secondary to hemolytic uremic syndrome as well as autoimmune hemolysis. There are also case-reports of severe hemolytic anemia related to cold agglutinin production in post-liver transplant patients. We described in this paper three cases of severe cold agglutinin hemolytic anemia in three pediatric liver transplant patients. Steroid therapy, plasmapheresis and withdrawal of tacrolimus led to resolution of the severe hemolytic process in each case. Whether the immune-mediated hemolysis is related to tacrolimus is not clear and needs to be characterized further.

  View details for DOI 10.1111/j.1399-3046.2007.00795.x

  View details for PubMedID 17976131

• Phase Ib clinical trial of starch-conjugated deferoxamine (40SD02): a novel long-acting iron chelator BRITISH JOURNAL OF HAEMATOLOGY Harmatz, P., Grady, R. W., Dragsten, P., Vichinsky, E., Giardina, P., Madden, J., Jeng, M., Miller, B., Hanson, G., Hedlund, B. 2007; 138 (3): 374-381

  Abstract

  The most widely used drug for iron chelation is deferoxamine (DFO) mesylate. While effective in promoting iron excretion, it requires prolonged daily infusions, often resulting in poor compliance. A clinical trial was conducted using starch-conjugated DFO (S-DFO; 40SD02), a high-molecular-weight iron chelator possessing prolonged vascular retention. Single doses of S-DFO were infused intravenously into groups of four transfusion-dependent patients with beta-thalassaemia at doses of 150, 300, 600 and 900 mg/kg. Urinary iron excretion and various pharmacologic parameters were evaluated for 1 week and safety for 3 weeks. No drug-related effects were observed on clinical chemistries, haematological and coagulation parameters, urinalyses, vital signs or electrocardiograms. Drug-related adverse events were limited to four urticarial reactions, none requiring termination of the infusion. The drug stimulated clinically significant urinary iron excretion, with the highest dose (900 mg/kg) inducing excretion of 1.31 mg of iron/kg (range 0.79-1.90 mg/kg) over 1 week, with residual iron-binding capacity present in the plasma for over 6 d. In summary, treatment with S-DFO, administered weekly, has the potential to achieve iron balance in the poorly compliant patient.

  View details for DOI 10.1111/j.1365-2141.2007.06651.x

  View details for Web of Science ID 000247753500013

  View details for PubMedID 17614825

• Prospective evaluation of patient-reported outcomes during treatment with deferasirox or deferoxamine for iron overload in patients with beta-thalassemia CLINICAL THERAPEUTICS Cappellini, M. D., Bejaoui, M., Agaoglu, L., Porter, J., Coates, T., Jeng, M., Lai, M. E., Mangiagli, A., Strauss, G., Girot, R., Watman, N., Ferster, A., Loggetto, S., Abish, S., Cario, H., Zoumbos, N., Vichinsky, E., Opitz, H., Ressayre-Djaffer, C., Abetz, L., Rofail, D., Baladi, J. 2007; 29 (5): 909-917

  Abstract

  Iron chelation therapy (ICT) with deferoxamine (DFO), the current standard for the treatment of iron overload in patients with transfusion-dependent disorders such as beta-thalassemia, requires regular subcutaneous or intravenous infusions. This can lead to reduced quality of life and poor adherence, resulting in increased morbidity and mortality in iron-overloaded patients with beta-thalassemia. Deferasirox is an orally administered iron chelator that has been approved for use in the United States, Switzerland, and other countries.This analysis was conducted to compare patient-reported outcomes (PROs) during receipt of DFO infusions or once-daily oral therapy with deferasirox (ICL670).PROs were prospectively evaluated as part of a randomized, Phase III study comparing the efficacy and safety profile of DFO 20 to 60 mg/kg per day with those of deferasirox 5 to 30 mg/kg per day in patients (age > or =2 years) with beta-thalassemia who were receiving regular transfusions and had a liver iron concentration of > or =2 mg/g dry weight. PRO questionnaires were completed by patients or a parent or legal guardian at baseline, week 4, week 24, and end of study (EOS). Patients assessed their level of satisfaction with study treatment (very satisfied, satisfied, neutral, dissatisfied, or very dissatisfied) and rated its convenience (very convenient, convenient, neutral, inconvenient, or very inconvenient). Time lost from normal activities due to ICT in the previous 4 weeks was recorded using a single global assessment. At week 4, patients who had previous experience with DFO were asked to indicate their preference for treatment (ICT received before the study, ICT received during the study, no preference, or no response) and the reason for that preference. At EOS, all patients were asked if they would be willing to continue using the ICT they had received during the study. All study analyses were performed in all patients who received at least 1 dose of study medication.Five hundred eighty-six patients (304 females, 282 males; age range, 2-53 years) received treatment with DFO (n = 290) or deferasirox (n = 296). Significantly more patients treated with deferasirox reported being very satisfied or satisfied with treatment compared with those treated with DFO (week 4: 92.0% vs 50.4%, respectively; week 24: 89.6% vs 44.0%; EOS: 85.1% vs 38.7%; all, P < 0.001). At the same time points, the majority of those treated with deferasirox reported that treatment was very convenient or convenient compared with those treated with DFO (95.5% vs 21.3%, 91.7% vs 17.4%, and 92.7% vs 11.3%, respectively; all, P < 0.001). Among patients who had previously taken DFO and were randomized to receive deferasirox during the study, 96.9% reported a preference for deferasirox over DFO. At EOS, the proportion of patients indicating a willingness to continue study therapy was significantly greater in those receiving deferasirox than in those receiving DFO (85.8% vs 13.8%; P < 0.001).In this study, patient-reported satisfaction and convenience were significantly higher for the once-daily, oral ICT deferasirox than for DFO infusions. Among patients who had received DFO before the study, the majority indicated a preference for deferasirox over DFO. Most patients receiving deferasirox indicated that they would be willing to continue taking it. These results suggest that deferasirox had a positive impact on patients' daily lives.

  View details for DOI 10.1016/j.clinthera.2007.05.007

  View details for Web of Science ID 000247335600012

  View details for PubMedID 17697909

• Gene expression profile of idiopathic thrombocytopenic purpura (ITP) reveals elevated expression of interferon regulated genes. 48th Annual Meeting of the American-Society-of-Hematology Sood, R., Wong, W., Gotlib, J., Jeng, M., Zehnder, J. L. AMER SOC HEMATOLOGY. 2006: 211A–211A

  View details for Web of Science ID 000242440000703

• Darbepoetin alfa and ferric gluconate ameliorate the anemia associated with recessive dystrophic epidermolysis bullosa PEDIATRIC DERMATOLOGY Kuo, D. J., Bruckner, A. L., Jeng, M. R. 2006; 23 (6): 580-585

  Abstract

  Our objective was to describe the efficacy of darbepoetin alfa and ferric gluconate complex in the treatment of the anemia associated with recessive dystrophic epidermolysis bullosa. To accomplish this aim, we retrospectively reviewed a series of patients with this disease treated in a single institution with darbepoetin alfa and parenteral iron for anemia. Four patients with recessive dystrophic epidermolysis bullosa were treated for a mean length of treatment of 14.5 months (4-18 months). Three patients received parenteral iron in the form of ferric gluconate complex and one received iron dextran. The mean pretreatment hemoglobin was 6.8 g/dL (4.9-9.6 g/dL). All four had improvements in their hemoglobin levels and energy levels with a mean increase in hemoglobin level of 2.8 g/dL (p = 0.003). We found darbepoetin alfa and ferric gluconate complex to be effective in the treatment of anemia associated with recessive dystrophic epidermolysis bullosa and to have distinct advantages over previously described formulations, and we concluded that they should be considered in the supportive care of this disease. We recommend the development of a standardized protocol for the evaluation and management of recessive dystrophic epidermolysis bullosa-associated anemia.

  View details for PubMedID 17156003

• Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease BRITISH JOURNAL OF HAEMATOLOGY Fung, E. B., Harmatz, P. R., Lee, P. D., Milet, M., Bellevue, R., Jeng, M. R., Kalinyak, K. A., Hudes, M., Bhatia, S., Vichinsky, E. P. 2006; 135 (4): 574-582

  Abstract

  Iron-overload associated endocrinopathy is the most frequently reported complication of chronic transfusion therapy in patients with thalassaemia (Thal). This study compared iron-overloaded subjects with Thal (n = 142; 54%M; age 25.8 +/- 8.1 years) and transfused sickle-cell disease (Tx-SCD; n = 199; 43%M, 24.9 +/- 13.2 years) to non-transfused SCD subjects (non-Tx-SCD; n = 64, 50%M, 25.3 +/- 11.3 years), to explore whether the underlying haemoglobinopathy influences the development of endocrinopathy. Subjects were recruited from 31 centres in the USA, Canada and the UK. Subjects with Thal had more evidence of diabetes (13% vs. 2%, P < 0.001), hypogonadism (40% vs. 4%, P < 0.001), hypothyroidism (10% vs. 2%, P = <0.001) and growth failure (33% vs. 7%, P < 0.001), versus Tx-SCD. Fifty-six per cent of Thal had more than one endocrinopathy compared with only 13% of Tx-SCD (P < 0.001). In contrast, Tx-SCD was not different from non-Tx-SCD. Multivariate analysis indicated that endocrinopathy was more likely in Thal than SCD [Odds Ratio (OR) = 9.4, P < 0.001], with duration of chronic transfusion a significant predictor (OR = 1.4 per 10 years of transfusion, P = 0.04). Despite iron overload, endocrinopathy was not increased in Tx-SCD versus non-Tx-SCD, suggesting that the underlying disease may modulate iron-related endocrine injury. However, because transfusion duration remained a significant predictor of endocrinopathy, these data should be confirmed in SCD subjects that have been chronically transfused for longer periods of time.

  View details for DOI 10.1111/j.1365-2141.2006.06332.x

  View details for Web of Science ID 000241342900019

  View details for PubMedID 17054676

• Gene expression profile of idiopathic thrombocytopenic purpura (ITP) 2nd Expert Meeting of the Intercontinental-Childhood-ITP-Study-Group (ICIS) Sood, R., Wong, W., Jeng, M., Zehnder, J. L. WILEY PERIODICALS, INC. 2006: 675–77

  Abstract

  To search for novel mechanisms that contribute to the pathophysiology of idiopathic thrombocytopenic purpura (ITP), we determined the whole blood gene expression profile in five ITP patients and five control samples. Using DNA microarrays that contained 24,473 unique putative genes, we found 176 cDNAs that were strongly correlated with ITP. These included a cluster of interferon-regulated genes and TLR7, as well many less-well characterized genes which are candidates for further study. We believe this approach is likely to yield new insights into our understanding of the molecular pathophysiology of ITP.

  View details for DOI 10.1002/pbc.20981

  View details for Web of Science ID 000240405600010

  View details for PubMedID 16933260

• Application of a geographic information system to explore associations between air pollution and micronucleus frequencies in African American children and adults ENVIRONMENTAL AND MOLECULAR MUTAGENESIS Huen, K., Gunn, L., Duramad, P., Jeng, M., Scalf, R., Holland, N. 2006; 47 (4): 236-246

  Abstract

  Exposure to air pollution has been associated with adverse respiratory and cardiovascular health outcomes in both children and adults. In this study, we used geographic information systems (GISs) to explore possible associations between chromosomal damage in 65 African American children and their mothers from Oakland, California, and both proximity to traffic and regional ozone levels. Study participants were interviewed at the Healthy Child Clinic of Children's Hospital, Oakland, and their blood and buccal cells were collected for assessment of chromosomal damage by the micronucleus (MN) assay. Regional ozone levels, which decreased from April to November with a secondary peak in late summer, were highly correlated with season by month (r=-0.84, P=0.02) and strongly associated with MN frequency (frequency ratio (FR): 3.37, 95% confidence interval (CI): 1.30-8.72) in both cell types of children and adults. Additionally, MN frequencies were modestly associated with individual measures of traffic density in children (FR=2.45, 95% CI=0.86-7.10), but not in adults; this suggests a greater vulnerability to traffic-related air pollution in children. Smoking in the household also increased MN frequency in the lymphocytes of children (FR: 1.13, 95%CI: 1.01-1.24) and adults (FR: 1.06, 95%CI: 0.99-1.13), whereas vitamin use in adults decreased MN frequency in both lymphocytes and buccal cells (FR: 0.17, 95%CI: 0.02-1.31; FR: 0.18, 95%CI: 0.03-1.18, respectively). Our data indicate that GIS-generated measures of traffic density for individual households augment regional ozone monitoring data used to assess effects of air pollution. This approach helped to demonstrate elevated cytogenetic damage in exposed minority children.

  View details for DOI 10.1002/em.20193

  View details for Web of Science ID 000236929900003

  View details for PubMedID 16416421

• Granulocyte-macrophage colony stimulating factor and immunosuppression in the treatment of pediatric acquired severe aplastic anemia PEDIATRIC BLOOD & CANCER Jeng, M. R., Naidu, P. E., Rieman, M. D., Rodriguez-Galindo, C., Nottage, K. A., Thornton, D. T., Li, C. S., Wiang, W. C. 2005; 45 (2): 170-175

  Abstract

  Immunosuppressive therapy (IS) is effective in the treatment of patients with acquired severe aplastic anemia (SAA). An enhanced myeloid response and decreased infection risk may be possible with the addition of a hematopoietic cytokine. Published data on the combination of cytokines and IS in patients with SAA are limited. The addition of G-CSF to IS shortens the time to neutrophil count recovery, but may not improve overall survival. Because GM-CSF acts differently than G-CSF, its use in combination with IS may be different.A retrospective chart review was performed on patients diagnosed with SAA and treated with IS and GM-CSF at St. Jude Children's Research Hospital. Hematologic recovery, prognostic factors, and infection data were collected.Eighteen patients were included in this study. The median age at diagnosis was 7.2 years (range 1.8-17.0). Ten patients (56%) had a complete response, four (22%) a partial response, and four (22%) no response. Median time to erythrocyte and platelet transfusion independence were 90 (18,243) and 64 days (18-243), and to discontinuation of treatment 287 days (90-730). Median time to partial (ANC > 500) and full (ANC > 1,500) neutrophil recovery were 41 and 51 days, respectively. Seventeen documented discrete infections occurred in six patients over 36 patient years.GM-CSF, in addition to IS, may shorten time to neutrophil count recovery, may be beneficial in decreasing infection rates, and may improve platelet response in patients with SAA. However, consistent with studies utilizing G-CSF, GM-CSF probably does not affect overall response rate. To fully answer whether or not cytokine therapy is of added value to IS in pediatric patients, a multi-institutional randomized trial is needed.

  View details for DOI 10.1002/pbc.20278

  View details for PubMedID 15593082

• Frequency of Fanconi anemia in Brazil and efficacy of screening for the FANCA 3788-3790del mutation BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH Magdalena, N., Pilonetto, D. V., Bitencourt, M. A., Pereira, N. F., Ribeiro, R. C., Jeng, M., Pasquini, R. 2005; 38 (5): 669-673

  Abstract

  Fanconi anemia (FA) is an autosomal recessive genetic disease characterized by progressive bone marrow failure, susceptibility to cancer and multiple congenital anomalies. There is important clinical variability among patients and the knowledge of factors which might predict outcome would greatly help the decision making regarding the choices of treatment and the appropriate time to start it. Future studies of the possible correlation between specific mutations with specific clinical presentations will provide the answer to one of these factors. At our Center we standardized a rapid and precise screening test using a mismatch PCR assay for a specific mutation (3788-3790del in exon 38 of gene FANCA) in Brazilian FA patients. We present the results obtained after screening 80 non-consanguineous FA patients referred from all regions of Brazil with a clinical diagnosis of FA supported by cellular hypersensitivity to diepoxybutane. We were able to detect the 3788-3790del allele in 24 of the 80 (30%) FA patients studied. Thirteen of the 80 (16.25%) were homozygotes and 11 of the 80 (13.75%) were compound heterozygotes, thus confirming the high frequency of the FANCA 3788-3790del mutation in Brazilian FA patients. The identification of patients with specific mutations in the FA genes may lead to a better clinical description of this condition, also providing data for genotype-phenotype correlations, to a better understanding of the interaction of this specific mutation with other mutations in compound heterozygote patients, and ultimately to the right choices of treatment for each patient with improvement of the prognosis on future studies.

  View details for Web of Science ID 000229605000003

  View details for PubMedID 15917947

• Epstein-Barr virus-associated peripheral T-cell lymphoma and hemophagocytic syndrome arising after liver transplantation: Case report and review of the literature PEDIATRIC BLOOD & CANCER George, T. I., Jeng, M., Berquist, W., Cherry, A. M., Link, M. P., Arber, D. A. 2005; 44 (3): 270-276

  Abstract

  Post-transplantation lymphoproliferative disorders (PTLD) are a well-recognized complication of solid organ transplantation. The vast majority of PTLD are Epstein-Barr virus (EBV)-related infections that manifest as B-cell malignancies. We report an unusual case of an EBV-associated T-cell lymphoma in a 10-year-old boy who had previously undergone liver transplantation at age 4 years. He presented with hemophagocytic syndrome (HPS) and active EBV infection, with positive serum titers and polymerase chain reaction (PCR) for EBV in blood, colon, and antral samples.

  View details for DOI 10.1002/pbc.20231

  View details for PubMedID 15468305

• Chronic transfusion therapy for children with sickle cell disease and recurrent acute chest syndrome 44th Annual Meeting of the American-Society-of-Hematology Hankins, J., Jeng, M., Harris, S., Li, C. S., Liu, T. B., Wang, W. LIPPINCOTT WILLIAMS & WILKINS. 2005: 158–61

  Abstract

  The objective was to study the effects of chronic transfusion therapy (CTX) on the prevention of new episodes of acute chest syndrome (ACS) in children with sickle cell disease (SCD) and recurrent or unusually severe ACS. A retrospective chart review was performed of patients given CTX for recurrent or severe ACS. Frequency, median severity score, and median hospital stay for ACS episodes were determined. Differences in these values before and during CTX were analyzed. Twenty-seven patients were identified. Before treatment, the ACS incidence was 1.3 episodes per patient-year; during treatment, it decreased to 0.1 episodes per patient-year (P < 0.0001). The median severity score for ACS episodes was 0.8 (range 0-5) before CTX and 0.5 (0-3) during CTX (P = 0.84). The median hospital stay was 5 days (range 3-15 days) before CTX and 3 days (2-7 days) during CTX (P = 0.38). CTX significantly reduces the incidence of ACS events among patients with a history of recurrent or severe episodes but does not significantly decrease their severity. The effectiveness of CTX should be prospectively compared with that of hydroxyurea and stem cell transplantation.

  View details for Web of Science ID 000227690900010

  View details for PubMedID 15750449

• Hematologic problems in immigrants from Ssutheast Asia HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA Jeng, M. R., Vichinsky, E. 2004; 18 (6): 1405-?

  Abstract

  An increasing number of Southeast Asian immigrants have come to North America. Physicians who care for this population should be aware of the high prevalence of hematologic disorders and develop an approach to their diagnosis and management. Malaria and the hematologic sequelae, glucose-6-phophate dehydrogenase deficiency, the thalassemia syndromes, Southeast Asian ovalocytosis, visceral leishmaniasis, HIV infection, and iron-deficiency anemia, all of which may pertain to these patients, are reviewed in this article.

  View details for DOI 10.1016/j.hoc.2004.06.014

  View details for PubMedID 15511622

• Natural history of moderate aplastic anemia in children PEDIATRIC BLOOD & CANCER Howard, S. C., Naidu, P. E., Hu, X. J., Jeng, M. R., Rodriguez-Gallindo, C., Rieman, M. D., Wang, W. C. 2004; 43 (5): 545-551

  Abstract

  Moderate aplastic anemia (MAA) in children is a rare, idiopathic condition of bone marrow insufficiency that can resolve spontaneously, persist for months or years, or progress to severe aplastic anemia (SAA). We evaluated the rate of progression to SAA.We reviewed the records of 136 children referred for evaluation of bone marrow failure from 1978 to 2002 at St. Jude Children's Research Hospital. MAA was defined by a hypocellular bone marrow (<50%) and 2 or 3 cytopenias (absolute neutrophil count <1,500/mm(3), absolute reticulocyte count <40,000/mm(3), platelet count <100,000/mm(3)) lasting at least 6 weeks.Twenty-four patients met the criteria for MAA. At a median follow-up of 66 months (range, 10-293), 16 patients (67%) progressed to SAA, 5 (21%) had persistent MAA, and 3 (12%) had complete resolution of MAA. No risk factors for progression could be identified.When childhood MAA is treated with supportive care alone, 2/3 of patients progress to SAA.

  View details for DOI 10.1002/pbc.20131

  View details for Web of Science ID 000224191300006

  View details for PubMedID 15382271

• Cow's milk allergy in a patient with hyper-IgE syndrome ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY Hernandez-Trujillo, V. P., Nguyen, W. T., Belleau, J. T., Jeng, M., Conley, M. E., Lew, D. B. 2004; 92 (4): 469-474

  Abstract

  Both hyper-IgE syndrome and food allergies can result in the early onset of skin rash, eosinophilia, and markedly elevated serum IgE. Occasionally, it can be difficult to distinguish the 2 disorders. Most patients with hyper-IgE syndrome do not have food allergy.To describe a child with cow's milk allergy associated with hyper-IgE syndrome manifesting as failure to thrive (FTT).Epicutaneous skin prick test to cow's milk, CAP radioallergosorbent test, atopy patch tests, and double-blind, placebo-controlled milk challenge (DBPCMC) were performed.During initial presentation at 3 weeks of age, the circulating eosinophil count increased from 13,800/mm3 to 44,254/mm3 within 2 weeks while taking cephalexin. Despite treatment, he had worsening rash and FTT at 10 weeks of age with an IgE level of 8,454 U/mL. After changing from an infant milk formula with whey protein to an amino acid-based formula in combination with oral antibiotic treatment, his rash and growth velocity improved markedly within 2 months. IgE decreased to 2,747 U/mL. He remained clinically well for 12 months. He subsequently developed additional food and inhalant allergies with an increase in IgE to 12,150 U/mL. Cow's milk allergy was confirmed by epicutaneous skin prick test, atopy patch test, and DBPCMC.Traditional prophylactic antistaphylococcal antibiotics, in combination with Neocate formula, were effective in treating the early skin manifestations of hyper-IgE syndrome and FTT in this infant. Cow's milk protein allergy should be considered in patients with hyper-IgE syndrome and FTT.

  View details for Web of Science ID 000220877000014

  View details for PubMedID 15104201

• Extranodal Rosai-Dorfman disease in children JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Rodriguez-Galindo, C., Helton, K. J., Sanchez, N. D., Rieman, M., Jeng, M., Wang, W. 2004; 26 (1): 19-24

  Abstract

  Sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease (RDD), is a histiocytic disorder that usually presents with painless massive cervical lymphadenopathy. The course is usually self-limited, but treatment may be required in cases with compression of vital organs. Patients may present with extranodal involvement only, and in these cases the clinical and histologic diagnosis may be difficult. The authors describe three patients with RDD who had exclusive extranodal disease in the head and neck area, in whom the clinical presentation mimicked other more common conditions.

  View details for Web of Science ID 000187885600007

  View details for PubMedID 14707706

• Effects of erythrocytapheresis transfusion on the viscoelasticity of sickle cell blood CLINICAL HEMORHEOLOGY AND MICROCIRCULATION Thurston, G. B., Henderson, N. M., Jeng, M. 2004; 30 (2): 83-?

  Abstract

  Red blood cells containing hemoglobin S are less deformable than normal erythrocytes and have a major effect on the viscoelasticity of blood. This alteration in rheology increases the impedance to flow, leading to an increase in RBC aggregation and reduction in oxygen saturation, which induces further sickling and occlusions in the microcirculation. Patients with sickle cell disease (SCD) can experience severe complications, such as acute pain and stroke. Automated red blood cell exchange transfusion, or erythrocytapheresis, is used with homozygous SCD (Hb SS) to replace sickled cells with normal cells, thereby decreasing the percentage of sickle hemoglobin (%Hb S) and maintaining a net balance in iron accumulation. These patients received monthly erythrocytapheresis with a goal to maintain a pre-pheresis %Hb S at less than 30%. In this study, viscoelastic parameters were used to quantify the effectiveness of this therapy for six patients undergoing chronic erythrocytapheresis. Whole blood viscosity, elasticity and relaxation time at oscillatory strains of 0.2, 1 and 5, and hematocrit and %Hb S were measured prior to erythrocytapheresis and 15 minutes after completion and compared with normal reference values at the patient's hematocrit. This study confirms the beneficial effects on viscosity, elasticity, and relaxation time of erythrocytapheresis.

  View details for Web of Science ID 000220566900002

• Effects of erythrocytapheresis transfusion on the viscoelasticity of sickle cell blood. Clinical hemorheology and microcirculation Thurston, G. B., Henderson, N. M., Jeng, M. 2004; 30 (2): 83-97

  Abstract

  Red blood cells containing hemoglobin S are less deformable than normal erythrocytes and have a major effect on the viscoelasticity of blood. This alteration in rheology increases the impedance to flow, leading to an increase in RBC aggregation and reduction in oxygen saturation, which induces further sickling and occlusions in the microcirculation. Patients with sickle cell disease (SCD) can experience severe complications, such as acute pain and stroke. Automated red blood cell exchange transfusion, or erythrocytapheresis, is used with homozygous SCD (Hb SS) to replace sickled cells with normal cells, thereby decreasing the percentage of sickle hemoglobin (%Hb S) and maintaining a net balance in iron accumulation. These patients received monthly erythrocytapheresis with a goal to maintain a pre-pheresis %Hb S at less than 30%. In this study, viscoelastic parameters were used to quantify the effectiveness of this therapy for six patients undergoing chronic erythrocytapheresis. Whole blood viscosity, elasticity and relaxation time at oscillatory strains of 0.2, 1 and 5, and hematocrit and %Hb S were measured prior to erythrocytapheresis and 15 minutes after completion and compared with normal reference values at the patient's hematocrit. This study confirms the beneficial effects on viscosity, elasticity, and relaxation time of erythrocytapheresis.

  View details for PubMedID 15004333

• Effects of erythrocytapheresis transfusion on the viscoelasticity of sickle cell blood CLINICAL HEMORHEOLOGY AND MICROCIRCULATION Thurston, G. B., Henderson, N. M., Jeng, M. 2004; 30 (1): 61-75

  Abstract

  Red blood cells containing hemoglobin S are less deformable than normal erythrocytes and have a major effect on the viscoelasticity of blood. This alteration in rheology increases the impedance to flow, leading to an increase in RBC aggregation and reduction in oxygen saturation, which induces further sickling and occlusions in the microcirculation. Patients with sickle cell disease (SCD) can experience severe complications, such as acute pain and stroke. Automated red blood cell exchange transfusion, or erythrocytapheresis, is used in homozygous SCD (Hb SS) to replace sickled cells with normal cells, thereby decreasing the percentage of sickle hemoglobin (%Hb S) and maintaining a net balance in iron accumulation. These patients received monthly erythrocytapheresis with a goal to maintain a pre-pheresis %Hb S at less than 30%. In this study, viscoelastic parameters were used to quantify the effectiveness of this therapy for six patients undergoing chronic erythrocytapheresis. Whole blood viscosity, elasticity and relaxation time at oscillatory strains of 0.2, 1 and 5, and hematocrit and %Hb S were measured prior to erythrocytapheresis and 15 minutes after completion and compared with normal reference values at the patient's hematocrit. This study confirms the beneficial effects on viscosity, elasticity, and relaxation time of erythrocytapheresis.

  View details for Web of Science ID 000188948100009

  View details for PubMedID 14967885

• Identification of hemochromatosis gene polymorphisms in chronically transfused patients with sickle cell disease AMERICAN JOURNAL OF HEMATOLOGY Jeng, M. R., Adams-Graves, P., Howard, T. A., Whorton, M. R., Li, C. S., Ware, R. E. 2003; 74 (4): 243-248

  Abstract

  Three polymorphic gene mutations in the human hemochromatosis (HFE) gene (C282Y, H63D, S65C) are associated with non-transfusion-related iron overload in Caucasians. More recently, these mutations have also been identified in African-Americans. However, the prevalence of HFE gene mutations in African-Americans with sickle cell disease (SCD) has not been described. The presence of these mutations in this population is particularly important, because patients with SCD may be placed on chronic red cell transfusion therapy and are thus at further risk for iron overload. Thus, we attempted to establish the gene mutation prevalence in African-Americans with SCD, to compare this frequency with published gene frequencies in African-Americans, and to evaluate their significance with regard to transfusion-related iron overload. Eighty-nine African-American patients with SCD, all of whom were receiving chronic red cell transfusion therapy, were screened by DNA analysis for the three HFE gene mutations. Two patients were heterozygous for the C282Y HFE mutation (2.3%), six were heterozygous for the H63D mutation (6.8%), none carried the S65C mutation (0.0%), and no homozygous or compound heterozygous subjects were identified. The prevalence of C282Y and H63D in the SCD population was similar to that observed in the general African-American population. In addition, there was no increased mutation prevalence when comparing those SCD patients on chronic transfusion therapy who had ferritin levels greater than 2,500 ng/mL and those less than 2,500 ng/mL. This study represents the first identification of the known HFE gene mutations by DNA analysis in the SCD population. We conclude that the presence of recognized HFE coding region mutations do not seem to have an impact on the degree of iron overload in patients with SCD receiving chronic transfusion therapy.

  View details for PubMedID 14635204

• A phase 1b study of the safety, pharmacokinetics, acute tolerability, and efficacy of ascending single doses of 40SDO2 (CHF5140, GS 460) in iron-loaded patients. Harmatz, P., Grady, R. W., Vichinsky, E., Giardina, P. J., Jeng, M., Madden, J., Nugent, K. A., Dragsten, P., Hedlund, B. AMER SOC HEMATOLOGY. 2003: 121A

  View details for Web of Science ID 000186536700413

• Liver transplantation for acute Budd-Chiari syndrome in identical twin sisters with factor V leiden mutation TRANSPLANTATION Nezakatgoo, N., Shokouh-Amiri, M. H., Gaber, A. O., Grewal, H. P., Vera, S. R., Chamsuddin, A. A., Eshun, J. K., Jeng, M. 2003; 76 (1): 195-198

  Abstract

  Budd-Chiari syndrome (BCS) is uncommon in the children. The cause of BCS comprises several diseases leading to thrombophilia. Activated protein C resistance as a result of a single gene mutation in factor V, the so called factor V Leiden (FVL), is the most common cause of thrombophilia.We report a simultaneous occurrence of BCS in identical twin sisters of 13 years of age with heterozygous FVL mutation.One sister presented with acute BCS leading to fulminant hepatic failure. She underwent liver transplantation with subsequent normalization of activated protein C resistance. The other twin sister, who was diagnosed with extensive thromboses of the inferior vena cava, portal vein, and hepatic veins, was successfully managed by aggressive chemical and mechanical thrombolysis followed by therapeutic anticoagulation. Genomic DNA studies confirmed heterozygosity of FVL mutation in the sisters' father and older brother.The exact cause of the BCS in children should be thoroughly and rapidly investigated, and, if necessary, immediate family members should also be tested for genetic defects in factor V or concomitant thrombophilia.

  View details for DOI 10.1097/01.TP.0000073977.83480.B1

  View details for Web of Science ID 000184261000033

  View details for PubMedID 12865809

• Resolution of chronic hepatic sequestration in a patient with homozygous sickle cell disease receiving hydroxyurea JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Jeng, M. R., Rieman, M. D., Naidu, P. E., Kaste, S. C., Jenkins, J. J., Serjeant, G., Wang, W. C. 2003; 25 (3): 257-260

  Abstract

  Hepatic sequestration is an uncommon complication in patients with homozygous sickle cell disease. Although transfusion therapy has been effective for the acute condition, no definitive treatment of chronic hepatic sequestration has been identified. We describe a 17-year-old male patient with hemoglobin SS and chronic hepatic sequestration who was treated with long-term (60 months) hydroxyurea. After 36 months of HU therapy, the patient had both an excellent hematologic response and a resolution of hepatic sequestration, as evidenced by disappearance of clinical hepatomegaly, normalization of liver volume on serial computed tomography scans, as well as decreased sinusoidal dilatation and congestion and red blood cell sickling on liver biopsy. The findings in this case suggest that hydroxyurea may benefit patients who have unusual complications of sickle cell disease, such as chronic erythrocyte sickling in the liver.

  View details for Web of Science ID 000181416800013

  View details for PubMedID 12621248

• Pseudotumor cerebri in two adolescents with acquired aplastic anemia JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY Jeng, M. R., Rieman, M., Bhakta, M., Helton, K., Wang, W. C. 2002; 24 (9): 765-768

  Abstract

  A 13-year-old boy and a 16-year-old girl both presented with headaches and nausea after they were diagnosed with severe acquired aplastic anemia. Both patients had symptoms and signs consistent with the clinical syndrome of pseudotumor cerebri including headaches, nausea, papilledema, and elevated intracranial pressure. Both patients were treated with therapeutic lumbar puncture and acetazolamide, which relieved their symptoms. Acetazolamide dosage was given while the patients underwent an immunosuppressive regimen. We hypothesize that the pseudotumor cerebri in these two pediatric patients was the result of an increased production of cerebrospinal fluid in response to anemia and that the removal of fluid and treatment with acetazolamide appear to be helpful in such cases.

  View details for Web of Science ID 000179764700018

  View details for PubMedID 12468922

• Summary of symposium: the future of stem cell transplantation for sickle cell disease. Journal of pediatric hematology/oncology Woodard, P., Jeng, M., Handgretinger, R., Wang, W., Cunningham, J. 2002; 24 (7): 512-514

  View details for PubMedID 12368684

• Treatment of children with Langerhans cell histiocytosis with 2-chlorodeoxyadenosine AMERICAN JOURNAL OF HEMATOLOGY Rodriguez-Galindo, C., Kelly, P., Jeng, M., Presbury, G. G., Rieman, M., Wang, W. 2002; 69 (3): 179-184

  Abstract

  Langerhans cell histiocytosis (LCH) is a disorder characterized by proliferation of activated Langerhans cells. Immune dysregulation is believed to be part of the pathogenesis. Although current therapies are very effective at inducing remission, multiple recurrences and long-term sequelae are common for patients with low-risk disease, and a significant proportion of young patients die of their disease. More effective therapies based on the pathogenesis of LCH are needed. We investigated the use of 2-chloro-deoxyadenosine (2-CdA), a purine analogue with an antiproliferative effect on histiocytes and lymphocytes, in patients with recurrent or high-risk LCH. Six patients with recurrent LCH received 2-CdA (5-7 mg/m(2)/day for 5 days, repeated every 21-28 days). All patients achieved remission. With a median follow-up of 15 months (range, 3-25 months), 5 patients remain in remission. A patient with multisystem disease who recurred after 13 months, achieved a second remission with 2-CdA. Hematologic toxicity was minimal, and no infectious complications were documented. 2-CdA is among the most effective drugs for the treatment of LCH, and this is probably due to both its anti-proliferative and immunomodulatory effects. 2-CdA needs to be considered for the treatment of recurrent LCH. However, its incorporation into front-line treatment of patients with multi-system LCH needs further study.

  View details for DOI 10.1002/ajh.10053

  View details for Web of Science ID 000174133800004

  View details for PubMedID 11891804

• Central venous catheter complications in sickle cell disease AMERICAN JOURNAL OF HEMATOLOGY Jeng, M. R., Feusner, J., Skibola, C., Vichinsky, E. 2002; 69 (2): 103-108

  Abstract

  A review of patients with sickle cell disease (SCD) and central venous catheters (CVCs) was performed to evaluate the frequency of catheter complications (infections, thrombotic events, and premature CVC removal. Fifteen evaluable patients were identified during our review of a 7.5-year period. The median age was 18 years (range, 1.5-30 years); 14 were African American, and 1 was Latino; 5 were male, and 10 were female. Forty-one CVCs were placed (36 Mediport and 5 Broviac catheters) for a total of 12,120 CVC days. We observed a median of 2 CVCs per patient (range, 1-8 CVCs per patient) with 67 discrete episodes of CVC-associated infection (range, 0-18 per patient) involving 10 patients. The rate of CVC-associated infection for patients with SCD at our institution was 5.5 infections per 1,000 CVC days; this rate was significantly higher than the rate of CVC-associated infection in our patients with cancer (P < 0.001). We also determined that the rate of CVC-associated thrombosis was 0.99 events per 1,000 CVC days and involved 33% of the patients with SCD; the rate of premature CVC removal was 3.15 per 1,000 CVC days, and 78% of CVCs were removed prematurely. We conclude that patients with SCD are at high risk for CVC-related complications, and improved care and close monitoring of CVCs should be encouraged to decrease morbidity in these chronically ill patients.

  View details for Web of Science ID 000173581300003

  View details for PubMedID 11835345

• Itraconazole-enhanced vincristine neurotoxicity in a child with acute lymphoblastic leukemia PEDIATRIC HEMATOLOGY AND ONCOLOGY Jeng, M. R., Feusner, J. 2001; 18 (2): 137-142

  Abstract

  A boy with acute lymphoblastic leukemia (ALL) experienced life-threatening vincristine neurotoxicity while simultaneously exposed to itraconazole. Five pediatric and six adult cases of itraconazole-enhanced vincristine toxicity have been reported, all with ALL. Upon cessation of the itraconazole, the patient's symptoms resolved, which is similar to the outcome of the previously reported cases: 10 of 11 patients had complete resolution of symptoms.

  View details for Web of Science ID 000167123900008

  View details for PubMedID 11255732

• Hydroquinone, a benzene metabolite, increases the level of aneusomy of chromosomes 7 and 8 in human CD34-positive blood progenitor cells CARCINOGENESIS Smith, M. T., Zhang, L. P., Jeng, M., Wang, Y. X., Guo, W. H., Duramad, P., Hubbard, A. E., Hofstadler, G., Holland, N. T. 2000; 21 (8): 1485-1490

  Abstract

  Benzene is an established human carcinogen, producing leukemia, hematotoxicity and perhaps lymphoma. Its carcinogenicity is most likely dependent upon its conversion to phenol and hydroquinone, the latter being oxidized to the highly toxic 1,4-benzoquinone in the bone marrow. Exposure of human lymphocytes and cell lines to hydroquinone has previously been shown to cause various forms of genetic damage, including aneusomy and the loss and gain of chromosomes. However, the target cells for leukemogenesis are the pluripotent stem cells or early progenitor cells which carry the CD34 antigen (CD34(+) cells). In this study, human cord blood, which is particularly rich in CD34(+) cells, was exposed to hydroquinone for 72 h in a medium that favored CD34(+) cell survival and growth. CD34(+) and CD34(-) cells were then isolated. Fluorescence in situ hybridization was employed to determine the level of aneusomy of chromosomes 7 and 8 in both cell types. CD34(+) cells were generally more susceptible to aneusomy induction by hydroquinone than CD34(-) cells. Increased trisomy and monosomy of chromosomes 7 and 8 were observed in CD34(+) cells (P(trend) < 0.001), whereas in CD34(-) cells only an increased level of monosomy 7 was detected (P(trend) = 0.002). Particularly striking effects of hydroquinone were observed in CD34(+) cells on monosomy 7 and trisomy 8, two common clonal aberrations found in myeloid leukemias, suggesting that these aneusomies produced by hydroquinone in CD34(+) cells play a role in benzene-induced leukemogenesis.

  View details for Web of Science ID 000088561800004

  View details for PubMedID 10910948