Bio

Clinical Focus


  • Pediatric Hematology-Oncology
  • Hematology/Oncology/Stem Cell Transplant, Pediatric
  • Oncology (Cancer), Pediatric

Academic Appointments


Professional Education


  • Internship:Children's Memorial Hospital (1988) IL
  • Residency:Children's Memorial Hospital (1990) IL
  • Fellowship:Children's Hospital Boston (1993) MA
  • Board Certification: Pediatric Hematology-Oncology, American Board of Pediatrics (1994)
  • Medical Education:Albany Medical Center (1987) NY
  • Fellowship, Children's Hospital, Boston/DFCI, Pediatric Hematology & Oncology (1993)
  • Residency, Children's Memorial Hospital, Pediatrics (1990)
  • M.D., Albany Medical College, Medicine (1987)
  • M.S., SUNY Buffalo, Immunology (1984)
  • B.S., University of Notre Dame, Pre-professional (1982)

Research & Scholarship

Current Research and Scholarly Interests


My primary research interest is in the study and treatment of neuroblastoma. My clinical interests also include Wilms tumor, hepatoblastoma, post-transplant lymphoproliferative disorders, phase I therapies for hematologic malignancies, as well as palliative and end of life care.

As a clinical investigator in the Children's Oncology Group (COG), I am involved in the clinical trial design of treatment protocols for patients with neuroblastoma, and am the Study Chair for the current COG Phase III Study for the treatment of children with Intermediate Risk Neuroblastoma. I am also the Principal Investigator at Stanford for the New Advances in Neuroblastoma (NANT) Consortium, a limited institution consortium which develops Phase I trials of novel therapies for patients with high risk and recurrent neuroblastoma. I am also interested in new therapies for the treatment of hematologic malignancies and am the Principal Investigator at Stanford for the Therapeutic Advances in Childhood Leukemia (TACL) Consortium, another limited institution consortium specifically dedicated to the development of novel therapies for relapsed leukemias.

Clinical Trials


  • Trial of Nelarabine, Etoposide and Cyclophosphamide in Relapsed T-cell ALL and T-cell LL Not Recruiting

    Nelarabine has shown significant activity in patients with T-cell malignancies. This study will determine the safety and maximum tolerated dose of the combination of nelarabine, cyclophosphamide and etoposide in patients with first bone marrow relapse of T-ALL, or first relapse of T-LL.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • N99-02: Melphalan and Buthionine Sulfoximine Followed by Bone Marrow or Peripheral Stem Cell Transplantation in Treating Children With Resistant or Recurrent Neuroblastoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow or peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more tumor cells. PURPOSE: Phase I trial to study the effectiveness of melphalan and buthionine sulfoximine followed by bone marrow or peripheral stem cell transplantation in treating children who have resistant or recurrent neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Judy Hallagan, (650) 724 - 8811.

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  • Efficacy and Safety of Donepezil Hydrochloride in Preadolescent and Adolescent Children With Attention Impairment Following Cancer Treatment Not Recruiting

    The purpose of this study is to evaluate the efficacy, safety and tolerability of donepezil in children with persistent attention impairment that is present at least 12 months after the completion of cancer treatment.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • T2007-002 Clofarabine, Etoposide, Cyclophosphamide in Relapsed Acute Myelogenous Leukemia (AML) Not Recruiting

    Clofarabine is a drug approved by the FDA (Food and Drug Administration) for treating children (age 1-21) with leukemia. This research study will use clofarabine with two other cancer fighting drugs. Clofarabine will be used together with etoposide (VePesid®, VP-16) and cyclophosphamide (Cytoxan®). Clofarabine, etoposide and cyclophosphamide have been used together in a phase I study to find out the highest doses of these drugs that can be safely given to children with relapsed or refractory leukemia. This study is a phase II study which will use the drugs to study how well these drugs work against AML. This study will also examine the safety of this drug combination.

    Stanford is currently not accepting patients for this trial. For more information, please contact Jennifer Lew, (650) 725 - 4318.

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  • N2001-03: CEP-701 in Treating Young Patients With Recurrent or Refractory High-Risk Neuroblastoma Not Recruiting

    RATIONALE: CEP-701 may stop the growth of tumor cells by blocking the enzymes necessary for their growth. PURPOSE: This phase I trial is studying the side effects and best dose of CEP-701 in treating young patients with recurrent or refractory high-risk neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mario desouza, (650) 724 - 3063.

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  • Study of MLN8237 in Combination With Irinotecan and Temozolomide Recruiting

    The goal of the first part of this clinical trial (Phase I portion) is to study the side effects, drug breakdown (pharmacokinetics), and dosing of the drug MLN8237 when added to standard chemotherapy drugs, irinotecan and temozolomide. The goal of the second part of this clinical trial (Phase II portion) is to learn how many children and young adults show improvements in their neuroblastoma when treated with the combination of MLN8237, irinotecan, and temozolomide.

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  • N2004-04: Fenretinide LXS in Treating Patients With Recurrent, Refractory, or Persistent Neuroblastoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as fenretinide LXS, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase I trial is studying the side effects and best dose of fenretinide LXS in treating patients with recurrent, refractory, or persistent neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Judy Hallagan, (650) 724 - 8811.

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  • Combination Chemotherapy and Surgery in Treating Young Patients With Wilms Tumor Recruiting

    This phase III clinical trial is studying how well combination chemotherapy and surgery work in treating young patients with Bilateral Wilms tumor and children who are a special risk for forming tumors in both kidneys. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. Giving it after surgery may kill any tumor cells that remain after surgery.

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  • N2001-02: I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma Not Recruiting

    RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine, may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as carboplatin, etoposide, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. An autologous peripheral stem cell or bone marrow transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Giving iodine I 131 metaiodobenzylguanidine and combination chemotherapy with an autologous peripheral stem cell or bone marrow transplant may allow more chemotherapy to be given so that more tumor cells are killed. Giving radiation therapy after an autologous peripheral stem cell or bone marrow transplant may kill any remaining tumor cells. PURPOSE: This phase II trial is studying how well giving iodine I 131 metaiodobenzylguanidine together with combination chemotherapy and radiation therapy works in treating patients who are undergoing an autologous peripheral stem cell or bone marrow transplant for relapsed or refractory neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Hallagan Judy, (650) 724 - 8811.

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  • N2004-06: Irinotecan and Vincristine With 131I-MIBG Therapy for Resistant/Relapsed High-Risk Neuroblastoma Not Recruiting

    RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine (MIGB), may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as irinotecan and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving iodine I 131 MIGB together with irinotecan and vincristine may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of iodine I 131 MIGB when given together with irinotecan and vincristine in treating young patients with resistant or relapsed high-risk neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nadeem Mukhtar, (650) 497 - 8815.

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  • Bortezomib With Chemotherapy for Relapsed Pediatric Acute Lymphoblastic Leukemia (ALL) Not Recruiting

    This is a Phase I/II study of a drug called bortezomib given in combination with chemotherapy drugs used to treat acute lymphoblastic leukemia (ALL) that has come back (recurred). Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) for treating adults with multiple myeloma which is a type of blood cancer. Bortezomib has been shown to cause cancer cells to die in studies done on animals (mice). Studies have been done that have shown that some adults and children with cancer have shown a response to bortezomib when it is used alone. Studies have also been done in adults to evaluate the dose of bortezomib that can be safely given in combination with other chemotherapy drugs. The Phase I portion of this study is complete and the dose for the phase II portion of the study is 1.3mg/m2/day. The phase II portion of the study is open and accruing.

    Stanford is currently not accepting patients for this trial. For more information, please contact Cancer Clinical Trials Office, (650) 498 - 7061.

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  • Zoledronic Acid (ZOMETA) With Cyclophosphamide With Neuroblastoma and Cortical Bone Involvement Not Recruiting

    The purposes of this study are: 1. To find the highest dose of monthly intravenous Zometa that can be given with daily low doses of cyclophosphamide by mouth to children with recurrent or refractory neuroblastoma without causing severe side effects. 2. To find out the side effects seen by giving Zometa and cyclophosphamide on this schedule at different dose levels. 3. To measure blood and urine levels of Zometa during treatment 4. To preliminarily evaluate the antitumor activity of Zometa and concomitant oral cyclophosphamide in children with recurrent and/or refractory neuroblastoma within the confines of a Phase I study. 5. To measure the effects of Zometa on markers of bone breakdown found in urine, blood, and bone marrow 6. To measure the effects of Zometa on the immune system.

    Stanford is currently not accepting patients for this trial. For more information, please contact Judy Hallagan, (650) 724 - 8811.

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  • Interleukin-12 and Interleukin-2 in Treating Patients With Refractory or Recurrent Neuroblastoma Not Recruiting

    Phase I trial to compare the effectiveness of interleukin-12 with or without interleukin-2 in treating young patients who have refractory or recurrent neuroblastoma. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growing. Combining interleukin-2 with interleukin-12 may kill more tumor cells.

    Stanford is currently not accepting patients for this trial. For more information, please contact Judy Hallagan, (650) 724 - 8811.

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  • N2004-03: Intravenous Fenretinide in Treating Young Patients With Recurrent or Resistant Neuroblastoma Not Recruiting

    RATIONALE: Drugs used in chemotherapy, such as fenretinide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. PURPOSE: This phase I trial is studying the side effects and best dose of intravenous fenretinide in treating young patients with recurrent or resistant neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mario Desouza, (650) 724 - 3063.

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  • N2007-03: Vorinostat and 131-I MIBG in Treating Patients With Resistant or Relapsed Neuroblastoma Not Recruiting

    RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radioactive drugs, such as iobenguane I 131, may carry radiation directly to tumor cells and not harm normal cells. Giving vorinostat together with iobenguane I 131 may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of giving vorinostat together with iobenguane I 131 in treating patients with resistant or relapsed neuroblastoma.

    Stanford is currently not accepting patients for this trial. For more information, please contact Mario DeSouza, (650) 724 - 3063.

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  • ABT-751 With Chemotherapy for Relapsed Pediatric ALL Not Recruiting

    This is a phase I/II study of an investigational drug called ABT-751, produced by Abbott Laboratories, given in combination with chemotherapy drugs used to treat acute lymphoblastic leukemia (ALL) that has come back (recurred). The phase I portion of this study is being done to find the highest dose of ABT-751 that can be given safely in combination with other chemotherapy drugs. A safe dose is one that does not result in unacceptable side effects. After a safe dose for ABT-751 given with chemotherapy has been found, the study will add additional patients to find out if ABT-751 (given at the maximal safe dose) when given with additional chemotherapy is an effective therapy for the treatment of children with relapsed ALL. It is expected that approximately 15-35 children and young adults will take part in this study.

    Stanford is currently not accepting patients for this trial. For more information, please contact Clare Twist, (650) 723 - 5535.

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  • N2007-02:Bevacizumab,Cyclophosphamide,& Zoledronic Acid in Patients W/ Recurrent or Refractory High-Risk Neuroblastoma Recruiting

    RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Zoledronic acid may stop the growth of tumor cells in bone. Giving bevacizumab together with cyclophosphamide and zoledronic acid may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects of giving bevacizumab together with cyclophosphamide and zoledronic acid in treating patients with recurrent or refractory high-risk neuroblastoma.

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  • Study of HQK-1004 and Valganciclovir to Treat Epstein-Barr Virus (EBV) - Positive Lymphoid Malignancies or Lymphoproliferative Disorders Not Recruiting

    The purpose of this study is to determine if treatment with HQK-1004 and valganciclovir will result in complete or partial responses in patients with EBV-positive lymphoid malignancies or lymphoproliferative disorders.

    Stanford is currently not accepting patients for this trial. For more information, please contact Min Wang, (650) 723 - 5535.

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  • Vorinostat and Isotretinoin in Treating Patients With High-Risk Refractory or Recurrent Neuroblastoma Recruiting

    This phase I trial is studying the side effects and the best dose of vorinostat when given together with isotretinoin to see how well it works in treating patients with high-risk refractory or recurrent neuroblastoma. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Isotretinoin may help vorinostat work better by making tumor cells more sensitive to the drug. Giving vorinostat together with isotretinoin may be an effective treatment for neuroblastoma.

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Teaching

2013-14 Courses


Publications

Journal Articles


  • Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia HAEMATOLOGICA-THE HEMATOLOGY JOURNAL Liedtke, M., Twist, C. J., Medeiros, B. C., Gotlib, J. R., Berube, C., Bieber, M. M., Bhat, N. M., Teng, N. N., Coutre, S. E. 2012; 97 (1): 30-37

    Abstract

    This phase I trial was conducted to determine the safety and pharmacokinetics of monoclonal antibody 216, a human monoclonal Immunoglobulin M antibody targeting a linear B-cell lactosamine antigen, administered alone and in combination with vincristine in patients with relapsed or refractory B-cell acute lymphoblastic leukemia, and to preliminarily assess tumor targeting and efficacy.Three cohorts of patients received escalating doses of monoclonal antibody 216 administered as an intravenous infusion. In the case of poor response to the first dose of monoclonal antibody 216 alone, defined as less than 75% reduction in peripheral blood blast count, a second dose of the antibody with vincristine was given between days 4 and 7. Responses were assessed weekly until day 35. Serum concentration of monoclonal antibody 216 was measured before and after infusion. Monoclonal antibody 216 targeting was determined with an anti-idiotypic antibody to monoclonal antibody 216 and preliminary efficacy was analyzed by changes in peripheral blood blasts.Thirteen patients were enrolled. One episode of grade 3 epistaxis was the only dose-limiting toxicity observed. All patients showed a poor response to the first monoclonal antibody 216 infusion with a decrease in peripheral blasts from 6-65% in 9 patients. In 8 patients, addition of vincristine to monoclonal antibody 216 resulted in an average reduction of the peripheral blasts of 81%. One patient without peripheral blasts achieved a hypoplastic marrow without evidence of leukemia after one infusion of monoclonal antibody 216 and monoclonal antibody 216/vincristine each. Monoclonal antibody 216 was detected on peripheral blasts in all patients.Treatment with monoclonal antibody 216 in combination with vincristine is feasible and well tolerated in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Binding of monoclonal antibody 216 to leukemic blasts was efficient, and favorable early responses were observed.

    View details for DOI 10.3324/haematol.2011.045997

    View details for Web of Science ID 000299870500009

    View details for PubMedID 21993685

  • Outcome for Children Treated for Relapsed or Refractory Acute Myelogenous Leukemia (rAML): A Therapeutic Advances in Childhood Leukemia (TACL) Consortium Study PEDIATRIC BLOOD & CANCER Gorman, M. F., Ji, L., Ko, R. H., Barnette, P., Bostrom, B., Hutchinson, R., Raetz, E., Seibel, N. L., Twist, C. J., Eckroth, E., Sposto, R., Gaynon, P. S., Loh, M. L. 2010; 55 (3): 421-429

    Abstract

    Current event-free survival (EFS) rates for children with newly diagnosed acute myeloid leukemia (AML) approach 50-60%. We hypothesize that further improvements in survival are unlikely to be achieved with traditional approaches such as dose intensive chemotherapy or hematopoietic stem cell transplants, since these therapies have been rigorously explored in clinical trials. This report highlights efforts to assess the response rates and survival outcomes after first or greater relapse in children with AML.We performed a retrospective cohort review of pediatric patients with relapsed and refractory AML (rAML) previously treated at TACL institutions between the years of 1995 and 2004. Data regarding disease characteristics at diagnosis and relapse, treatment response, and survival was collected on 99 patients and 164 medullary relapses or treatment failures.The complete response (CR) rate following the second therapeutic attempt was 56 +/- 5%. CR rates following a third treatment attempt was 25 +/- 8% while 17 +/- 7% achieved CR following the fourth through sixth treatments. The 5-year disease-free survival in patients achieving CR following a second therapeutic attempt was 43 +/- 7%. The 5-year EFS and overall survival (OS) rates for all patients receiving a second treatment attempt was 24 +/- 5% and 29 +/- 5%, respectively.This CR rate following a second therapeutic attempt and OS rate in patients with rAML is consistent with the literature. There are limited published data of CR rates for subsequent relapses. Our data can serve as a historical benchmark to compare outcomes of future therapeutic trials in rAML against traditional chemotherapy regimens.

    View details for DOI 10.1002/pbc.22612

    View details for Web of Science ID 000280438600006

    View details for PubMedID 20658611

  • Outcome of Patients Treated for Relapsed or Refractory Acute Lymphoblastic Leukemia: A Therapeutic Advances in Childhood Leukemia Consortium Study JOURNAL OF CLINICAL ONCOLOGY Ko, R. H., Ji, L., Barnette, P., Bostrom, B., Hutchinson, R., Raetz, E., Seibel, N. L., Twist, C. J., Eckroth, E., Sposto, R., Gaynon, P. S., Loh, M. L. 2010; 28 (4): 648-654

    Abstract

    Despite improvements in treatment, approximately 20% of patients with acute lymphoblastic leukemia (ALL) experience relapse and do poorly. The Therapeutic Advances in Childhood Leukemia (TACL) Consortium was assembled to assess novel drugs for children with resistant leukemia. We hypothesize that novel agents and combinations that fail to improve baseline complete remission rates in comparable populations are unlikely to contribute to better outcomes and should be abandoned. We sought to define response rates and disease-free survival (DFS) rates in patients treated at TACL institutions, which could serve as a comparator for future studies.We performed a retrospective cohort review of patients with relapsed and refractory ALL previously treated at TACL institutions between the years of 1995 and 2004. Data regarding initial and relapsed disease characteristics, disease response, and survival were collected and compared with those of published reports.Complete remission (CR) rates (mean +/- SE) were 83% +/- 4% for early first marrow relapse, 93% +/- 3% for late first marrow relapse, 44% +/- 5% for second marrow relapse, and 27% +/- 6% for third marrow relapse. Five-year DFS rates in CR2 and CR3 were 27% +/- 4% and 15% +/- 7% respectively.We generally confirm a 40% CR rate for second and subsequent relapse, but our remission rate for early first relapse seems better than that reported in the literature (83% v approximately 70%). Our data may allow useful modeling of an expected remission rate for any population of patients who experience relapse.

    View details for DOI 10.1200/JCO.2009.22.2950

    View details for Web of Science ID 000274138800021

    View details for PubMedID 19841326

  • Treatment of Recurrent Post-transplant Lymphoproliferative Disorder (PTLD) of the Central Nervous System (CNS) with High-dose Methotrexate (HD-MTX) XI INTERNATIONAL SMALL BOWEL TRANSPLANT SYMPOSIUM Twist, C. J., KJELSON, L., MCKENNEY, A., Bonham, C. A., Esquivel, C., Castillo, R. O. 2009: 116-121
  • Detection of Isolated Tumor Cells in Neuroblastoma by Immunohistochemical Analysis in Bone Marrow Biopsy Specimens Improved Detection With Use of beta-Catenin AMERICAN JOURNAL OF CLINICAL PATHOLOGY Krishnan, C., Twist, C. J., Fu, T., Arber, D. A. 2009; 131 (1): 49-57

    Abstract

    Evaluation of the bone marrow is a critical component of accurate staging and surveillance for recurrent disease in neuroblastoma. The value of routine immunohistochemical analysis of otherwise histologically negative bone marrow biopsy specimens has not been adequately evaluated. By using synaptophysin, chromogranin, and beta-catenin, immunohistochemical analysis performed on otherwise histologically negative bone marrow specimens identified isolated tumor cells (ITCs) in 9.1%, 5.0%, and 10.0% of 220 biopsy specimens, respectively. Overall survival, as estimated by the Kaplan-Meier method, was not significantly different between patients with and without ITCs (P = .357). Of the immunohistochemical markers evaluated, beta-catenin showed the greatest sensitivity for identifying ITCs in the bone marrow and showed reactivity in primary tumor samples. We found that the presence of ITCs identified by immunohistochemical analysis may predict the persistence of disease but does not show significant overall survival differences. We also identified beta-catenin as a sensitive immunohistochemical marker of primary and metastatic neuroblastoma.

    View details for DOI 10.1309/AJCPAJODRJYD3OB2

    View details for Web of Science ID 000262314500007

    View details for PubMedID 19095565

  • 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 Web of Science ID 000252006000044

    View details for PubMedID 16856156

  • I-123 MIBG mapping with intraoperative gamma probe for recurrent neuroblastoma MOLECULAR IMAGING AND BIOLOGY Iagaru, A., Peterson, D., Quon, A., Dutta, S., Twist, C., Daghighian, F., Gambhir, S. S., Albanese, C. 2008; 10 (1): 19-23

    Abstract

    Intraoperative gamma probe guidance has become widely utilized for sentinel lymph node dissection in patients with breast cancer and melanoma, using (99m)Tc sulfur colloid. However, new indications are possible and need to continue to be investigated. We report the use during a wedge liver biopsy of a new hand-held gamma probe designed for (123)I intraoperative guidance. The patient studied is a 5-year-old boy with history of stage 4 high-risk neuroblastoma. Anatomic imaging (CT, MRI), (99m)Tc bone scintigraphy and 2-deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) were negative, but the (123)I MIBG scintigraphy suggested recurrent liver disease. A decision was made to biopsy these lesions to obtain histopathological confirmation. Intraoperative gamma probe mapping of the liver identified areas with signal above the background, but these were prove to be hemosiderin deposits on histo-pathology examination.

    View details for DOI 10.1007/s11307-007-0116-1

    View details for Web of Science ID 000252107800002

    View details for PubMedID 17975716

  • Effects of human monoclonal antibody 216 on B-progenitor acute lymphoblastic leukemia in vitro PEDIATRIC BLOOD & CANCER Bieber, M. M., Twist, C. J., Bhat, N. M., Teng, N. N. 2007; 48 (4): 380-386

    Abstract

    Human monoclonal antibody (mAb) 216 is a naturally occurring IgM cytotoxic mAb that binds to a glycosylated epitope on the surface of B-lymphocytes. This study investigated if this mAb could bind and kill acute lymphoblastic leukemia (ALL) B-progenitor lymphoblasts in vitro. ALL cell lines were used to determine if combining mAb 216 with chemotherapeutic drugs would enhance killing and cell lines were used to measure cytotoxicity by mAb 216 with human complement.Expression of cell surface markers and mAb 216 epitope on fresh and banked ALL bone marrow samples was determined by flow cytometry. Fresh lymphoblasts were incubated for 20 hr with mAb 216 without complement to measure cytotoxicity. Cytotoxicity of ALL cell lines incubated with mAb 216 and vincristine (VCR) or human complement was determined using flow cytometry.Pre-B-ALL cells but not T-ALL cells are bound and killed by mAb 216. The combination of mAb 216 and VCR at sub-therapeutic levels demonstrated enhanced cytotoxicity beyond that observed for either agent alone. Incubation of mAb 216 with human complement increased cytotoxicity of ALL cell lines.This increased cytotoxicity with chemotherapy and the functional ability of mAb 216 to use multiple pathways to induce cell death identify mAb 216 as a potentially novel therapeutic tool in the treatment of B-progenitor ALL. Based on the results from this preclinical study, a Phase I clinical trial with mAb 216 for the treatment of patients with relapsed or refractory B-lineage ALL is ongoing.

    View details for DOI 10.1002/pbc.20770

    View details for Web of Science ID 000244611500004

    View details for PubMedID 16421902

  • A phase I clinical trial of the hu14.18-IL2 (EMD 273063) as a treatment for children with refractory or recurrent neuroblastoma and melanoma: A study of the Children's Oncology Group CLINICAL CANCER RESEARCH Osenga, K. L., Hank, J. A., Albertini, M. R., Gan, J., Sternberg, A. G., Eickhoff, J., Seeger, R. C., Matthay, K. K., Reynolds, C. P., Twist, C., Krailo, M., Adamson, P. C., Reisfeld, R. A., Gillies, S. D., Sondel, P. M. 2006; 12 (6): 1750-1759

    Abstract

    Evaluate the clinical safety, toxicity, immune activation/modulation, and maximal tolerated dose of hu14.18-IL2 (EMD 273063) in pediatric patients with recurrent/refractory neuroblastoma and other GD2-positive solid tumors.Twenty-seven pediatric patients with recurrent/refractory neuroblastoma and one with melanoma were treated with a humanized anti-GD2 monoclonal antibody linked to human interleukin 2 (IL-2). Cohorts of patients received hu14.18-IL2, administered i.v. over 4 hours for three consecutive days, at varying doses. Patients with stable disease, partial, or complete responses were eligible to receive up to three additional courses of therapy.Most of the clinical toxicities were anticipated and similar to those reported with IL-2 and anti-GD2 monoclonal antibody therapy and to those noted in the initial phase I study of hu14.18-IL2 in adults with metastatic melanoma. The maximal tolerated dose was determined to be 12 mg/m2/d, with agent-related dose-limiting toxicities of hypotension, allergic reaction, blurred vision, neutropenia, thrombocytopenia, and leukopenia. Three patients developed dose-limiting toxicity during course 1; seven patients in courses 2 to 4. Two patients required dopamine for hypotension. There were no treatment-related deaths, and all toxicity was reversible. Treatment with hu14.18-IL2 led to immune activation/modulation as evidenced by elevated serum levels of soluble IL-2 receptor alpha (sIL2Ralpha) and lymphocytosis. The median half-life of hu14.18-IL2 was 3.1 hours. There were no measurable complete or partial responses to hu14.18-IL2 in this study; however, three patients did show evidence of antitumor activity.Hu14.18-IL2 (EMD 273063) can be administered safely with reversible toxicities in pediatric patients at doses that induce immune activation. A phase II clinical trial of hu14.18-IL2, administered at a dose of 12 mg/m2/d x 3 days repeated every 28 days, will be done in pediatric patients with recurrent/refractory neuroblastoma.

    View details for DOI 10.1158/1078-0432.CCR-05-2000

    View details for Web of Science ID 000236458800016

    View details for PubMedID 16551859

  • The role of age in neuroblastoma risk stratification: the German, Italian, and children's oncology group perspectives CANCER LETTERS London, W. B., Boni, L., Simon, T., Berthold, F., Twist, C., Schmidt, M. L., Castleberry, R. P., Matthay, K. K., Cohn, S. L., De Bernardi, B. 2005; 228 (1-2): 257-266

    Abstract

    Recent evidence suggests that the cut-off for age utilized in neuroblastoma risk groups should be increased from the 365-day cut-off currently in use. Separate cooperative group analyses were performed by German and Italian groups and two analyses by the Children's Oncology Group (North America, Australia, New Zealand, Switzerland, Netherlands). In general, the results are in agreement regarding the prognostic contribution of age. There is strong evidence to support an increase in the age cut-off to a value in the range of 15-18 months based on the results from the German analysis and two COG analyses. However, Italian results in INSS stage 4 patients show that outcome in patients 12-17 months is not better than that of older patients. Further analyses are warrented.

    View details for DOI 10.1016/j.canlet.2004.12.054

    View details for Web of Science ID 000232241100034

    View details for PubMedID 16024170

  • Assessment of lymphadenopathy in children PEDIATRIC CLINICS OF NORTH AMERICA Twist, C. J., Link, M. P. 2002; 49 (5): 1009-?

    Abstract

    The assessment of lymphadenopathy in children is a common diagnostic problem in pediatrics. An understanding of the wide variety of diseases and conditions that may present as lymphadenopathy is essential to determining the most appropriate work up for an individual patient. Although the majority of these children will prove to have a benign disorder, it is important that the pediatrician also have an appreciation for the malignant diseases that may present with lymphadenopathy, so that in such cases the diagnosis of a serious or life-threatening disease can be made in a timely manner.

    View details for Web of Science ID 000178952200008

    View details for PubMedID 12430623

  • A case from Stanford University. Neuroblastoma with diffuse bone marrow involvement. Nuclear medicine review. Central & Eastern Europe Durski, J. M., Twist, C. J., Goris, M. 2001; 4 (1): 61-62

    View details for PubMedID 14600970

  • The mouse Cd83 gene: structure, domain organization, and chromosome localization IMMUNOGENETICS Twist, C. J., Beier, D. R., Disteche, C. M., Edelhoff, S., Tedder, T. F. 1998; 48 (6): 383-393

    Abstract

    Human CD83 (hCD83) is a 45 000 Mr cell-surface protein expressed predominantly by dendritic lineage cells. In this report, the genomic locus encoding mouse CD83 (Cd83) was isolated and the gene structure determined. The Cd83 gene spans approximately 19 kilobases (kb) and is composed of five exons, with two exons encoding a single extracellular immunoglobulin (Ig)-like domain. Mouse CD83 (mCD83) cDNAs were isolated by reverse transcriptase polymerase chain reaction of mouse RNA. Sequence determination revealed substantial conservation, with mCD83 and hCD83 sharing 63% amino acid identity. The transmembrane and cytoplasmic regions of CD83 were most highly conserved. Mouse CD83 mRNA of 2.4 kb was abundantly expressed in spleen and brain, but could also be detected in most tissues analyzed. These results suggest that in the mouse, as in humans, widely distributed dendritic cells may express mCD83. Chromosome localization revealed that the Cd83 gene is present on mouse chromosome 13 band A5, while the locus for the human gene (CD83) is located within a homologous region of human chromosome 6p23. Thus, the CD83 protein and gene appear to be well conserved during recent mammalian evolution. The isolation and characterization of the mCD83 cDNA and gene provides important information and tools that will facilitate the study of CD83 and dendritic cell function in a mouse model system.

    View details for Web of Science ID 000076754500003

    View details for PubMedID 9799334

  • Hurler syndrome: II. Outcome of HLA genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children BLOOD Peters, C., Shapiro, E. G., Anderson, J., Henslee-Downey, P. J., Klemperer, M. R., Cowan, M. J., Saunders, E. F., deAlarcon, P. A., Twist, C., Nachman, J. B., Hale, G. A., Harris, R. E., Rozans, M. K., Kurtzberg, J., Grayson, G. H., Wiliams, T. E., Lenarsky, C., Wagner, J. E., Krivit, W. 1998; 91 (7): 2601-2608

    Abstract

    Untreated patients with Hurler syndrome (MPSIH) experience progressive neurologic deterioration and early death. Allogeneic bone marrow transplantation (BMT) ameliorates or halts this course. The Storage Disease Collaborative Study Group was formed to evaluate the effectiveness and toxicity of BMT. Effectiveness was defined as engrafted survival with continuing cognitive development. Fifty-four patients deficient in leukocyte alpha-L-iduronidase enzyme activity (median age, 1.8 years; range, 0.4 to 7.9) received high-dose chemotherapy with or without irradiation and BMT from HLA-genotypically identical sibling (GIS) or HLA-haploidentical related (HIR) donors between September 16, 1983 and July 14, 1995; all children were included in this report. Thirty-nine of 54 patients (72%) engrafted following the first BMT. The probability of grade II to IV acute graft-versus-host disease (GVHD) at 100 days was 32% for GIS and 55% for HIR patients. The probability of extensive chronic GVHD was 0% for GIS and 24% for HIR patients. The actuarial probability of survival at 5 years was 64% for all patients, 75% for GIS patients, 53% for HIR patients, and 53% for patients with donor marrow engraftment. The baseline Mental Developmental Index (MDI) was examined both for children less than and greater than 24 months of age at BMT. Children transplanted before 24 months had a mean baseline MDI of 78, while those transplanted after 24 months had a mean baseline MDI of 63 (P = . 0002). Both baseline and post-BMT neuropsychologic data were available for 26 of 30 engrafted survivors. Of 14 patients transplanted before 24 months of age, nine demonstrated developmental trajectories that were normal or somewhat slower than normal. In contrast, of 12 patients transplanted after 24 months of age, only three showed developmental trajectories that were normal or somewhat slower than normal (P = .01). For children with a baseline MDI greater than 70, there was a significant correlation between the MDI at follow-up study and leukocyte alpha-L-iduronidase enzyme activity (P = .02). Children were more likely to maintain normal cognitive development if they were fully engrafted following BMT from a donor with homozygous normal leukocyte alpha-L-iduronidase enzyme activity. Children who developed acute GVHD of grade II or worse had significantly poorer cognitive outcomes (P < .009). No difference in the post-BMT MDI was observed between patients whose preparative therapies did (n = 10; radiation dose, 300 to 1,400 cGy) or did not (n = 16) include radiation. We conclude that MPSIH patients, particularly those less than 24 months of age with a baseline MDI greater than 70, can achieve a favorable long-term outcome with continuing cognitive development and prolonged survival after successful BMT from a related donor with homozygous normal enzyme activity.

    View details for Web of Science ID 000072671900045

    View details for PubMedID 9516162

  • ISOLATION OF MOUSE T-CELL LYMPHOMA LINES FROM DIFFERENT LONG-TERM INTERLEUKIN 2-DEPENDENT CULTURES CANCER RESEARCH Giglia, J. S., OVAK, G. M., Yoshida, M. A., Twist, C. J., Jeffery, A. R., Pauly, J. L. 1985; 45 (10): 5027-5034

    Abstract

    A number of different biological properties have been ascribed to the hormone-like protein interleukin 2 (IL-2). However, the most salient feature of this lymphokine is its ability to sustain the long-term proliferation of T-cells from humans and mice. Reported herein are the results of studies demonstrating the isolation of growth factor-independent cell lines from the long-term IL-2-dependent murine T-cell line CTLL-2 that is used frequently as the source of target cells in IL-2 bioassays. Sustained log-phase growth of these T-cells in vitro has been achieved using Petri dishes of polymethylpentene; growth could not be sustained in similar dishes of glass, untreated polystyrene, polystyrene that had been treated for cell culture, or polycarbonate. The IL-2-independent line grew as a T-cell lymphoma when injected i.p. into pristane-treated, but not untreated, syngeneic C57BL/6 mice. In contrast, cells from the IL-2 parental line CTLL-2 did not grow in vivo. Characterization of the IL-2-independent lines propagated in vitro (denoted as line CEC) or in vivo (denoted as line CEP) demonstrated that they retained their dependency for 2-mercaptoethanol and expressed phenotypic profiles of their parental line CTLL-2 (Thy 1.2+, Lyt-1-; Lyt-2-). Isolation of an IL-2-independent T-cell lymphoma from a CTLL-2 line obtained from another investigator using a protocol that has proven reproducible under carefully controlled laboratory conditions and defined phenotypic traits of the syngeneic T-cell isolates provided evidence that the tumors were not a cross-culture contaminant arising as a result of a laboratory accident. Moreover, karyotypic analysis using a quinacrine:Hoechst banding technique revealed similar marker chromosomes in the IL-2-dependent and -independent lines. IL-2-independent lines have also been established from the IL-2-dependent murine T-cell line CT-6. Accordingly, the results of these studies suggest that, during prolonged cultivation that has included exposure to crude IL-2 preparations known to contain phorbol ester, possibly viruses, and other contaminants, the IL-2-dependent lines have developed subpopulations that are thought to have undergone malignant transformation of unknown etiology to generate IL-2-independent murine T-cell lymphomas that can be passaged repetitively either in vitro or in vivo.

    View details for Web of Science ID A1985ARH6200053

    View details for PubMedID 3875403

  • STUDIES OF CULTURED HUMAN LYMPHOCYTES-T .2. INITIATION OF PAIRED T-CELL AND B-CELL LINES FROM HEALTHY DONORS PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE Pauly, J., Russell, C. W., PIRELA, D. L., Twist, C. J., REINERTSON, R., Callahan, J., Minowada, J. 1983; 172 (3): 283-290

    Abstract

    We report the sustained cultivation of both B- and T-lymphoblastoid cell lines from randomly selected healthy donors, and the results of studies defining the frequency with which these cell lines can be established. B-cell lines were initiated using the Epstein-Barr virus. Of 52 attempts, 40 B-cell lines (77% success) were obtained from 24 different donors. T-cell lines were started and propagated in long-term (greater than 100 days) cultures using the T-cell growth factor interleukin-2 (IL-2). Of 55 attempts, 54 (98%) were successful in initiating IL-2-dependent T-cell lines, and these were derived from 28 healthy adults. Likewise, of 45 attempts, 32 (71%) were successful in producing paired lines in which both the B-cell line and T-cell line were cultivated from a single blood collection (N = 22 donors). Phenotypic profiles of these lines were defined using multiple marker assays, including rosette formation, surface immunoglobulins, cytochemistry, karyotype, as well as xenoantisera and monoclonal antibodies defining different membrane antigens. This work demonstrates the feasibility of propagating paired human B and T lymphoblastoid lines suitable for many comparative immunobiological studies.

    View details for Web of Science ID A1983QG04100002

    View details for PubMedID 6189130

  • STUDIES OF CULTURED HUMAN LYMPHOCYTES-T .4. PRODUCTION OF SERUM-FREE AND MITOGEN-FREE SUPERNATANTS HAVING HIGH-LEVELS OF THE HUMAN T-CELL GROWTH-PROMOTER INTERLEUKIN-2 IRCS MEDICAL SCIENCE-BIOCHEMISTRY Pauly, J. L., Twist, C. J., PIRELA, D. L., REINERTSON, R. R., Callahan, J. J., Russell, C. W. 1983; 11 (1): 77-78
  • STUDIES OF CULTURED HUMAN LYMPHOCYTES-T .6. CULTURE FLASK COMPOSITION MARKEDLY AFFECTS IL-2-DEPENDENT T-CELL PROLIFERATION AS DEFINED IN COMPARATIVE STUDIES OF GLASS, POLYSTYRENE AND POLYMETHYLPENTENE VESSELS IRCS MEDICAL SCIENCE-BIOCHEMISTRY Pauly, J. L., OVAK, G. M., Twist, C. J., RUSSEL, C. W. 1983; 11 (6): 534-535
  • STUDIES OF CULTURED HUMAN LYMPHOCYTES-T .3. A QUANTITATIVE ASSAY OF THE HUMAN T-CELL GROWTH-PROMOTING LYMPHOKINE INTERLEUKIN-2 IRCS MEDICAL SCIENCE-BIOCHEMISTRY Pauly, J. L., Twist, C. J., PIRELA, D. L., REINERTSON, R. R., Callahan, J. J., Russell, C. W. 1982; 10 (11): 899-900

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