Clinical Focus

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

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 renal tumors, post-transplant lymphoproliferative disorders, 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 COG Phase III Study for the treatment of children with Intermediate Risk Neuroblastoma (ANBL0531). 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.

Clinical Trials

  • Vorinostat and Isotretinoin in Treating Patients With High-Risk Refractory or Recurrent Neuroblastoma Not 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.

    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 Not 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.

    Stanford is currently not accepting patients for this trial. For more information, please contact Pediatric Hematology/Oncology, 650-723-5535.

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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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  • 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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  • SF1126 for Patients With Relapsed or Refractory Neuroblastoma Not Recruiting

    SF1126 is a novel inhibitor of PI3 kinase and mTOR that includes an active moiety (consisting of LY294002) linked to an RGDS tetrapeptide that targets the active agent to integrin expressing tissues. In this first pediatric phase 1 trial of SF1126, dose escalation will follow a 3+3 dose escalation design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 10 patients with tumors with MYCN amplification, Mycn expression, or Myc expression will be treated.

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

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  • N2012-01: Phase 1 Study of Difluoromethylornithine (DFMO) and Celecoxib With Cyclophosphamide/Topotecan Recruiting

    This study will combine an oral drug called DFMO with celecoxib (also oral) and two IV chemotherapy medicines called cyclophosphamide and topotecan. - To find the highest dose of DFMO that can be given with celecoxib, cyclophosphamide and topotecan without causing severe side effects. - To find out the side effects seen by giving DFMO at different dose levels with celecoxib, cyclophosphamide and topotecan. - To measure the levels of DFMO in the blood at different dose levels. - To determine if your tumor gets smaller after treatment with DFMO, celecoxib, cyclophosphamide and topotecan. - To determine if specific gene changes in you or your tumor makes you more prone to side effects or affects your tumor's response to the combination of DFMO, celecoxib, cyclophosphamide and topotecan. - To determine if the amount of normal chemicals in your body called polyamines go down in response to DFMO, celecoxib, cyclophosphamide and topotecan, and whether you are more likely to have a good response to the treatment if they do.

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  • 131I-MIBG Alone VS. 131I-MIBG With Vincristine and Irinotecan VS131I-MIBG With Vorinistat Recruiting

    This study will compare three treatment regimens containing metaiodobenzylguanidine (MIBG) and compare their effects on tumor response and associated side effects, to determine if one therapy is better than the other for people diagnosed with relapsed or persistent neuroblastoma.

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  • Lenalidomide and Dinutuximab With or Without Isotretinoin in Treating Younger Patients With Refractory or Recurrent Neuroblastoma Recruiting

    This phase I trial studies the side effects and best dose of lenalidomide when given together with dinutuximab with or without isotretinoin in treating younger patients with neuroblastoma that does not respond to treatment or that has come back. Drugs used in chemotherapy, such as lenalidomide and isotretinoin, work in different wants to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as dinutuximab, may interfere with the ability of tumor cells to grow and spread. Giving more than one drug (combination chemotherapy) together with dinutuximab therapy may kill more tumor cells.

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  • Neuroblastoma Biology Study Recruiting

    Medical scientists want to find better ways to treat neuroblastoma and to find ways to prevent the tumor from growing back. To do this, they need more information about the characteristics of neuroblastoma cells. Therefore, they want to study samples of neuroblastoma tissues and neuroblastoma and normal cells in the blood and bone marrow that may be related to the growth of neuroblastoma cells. Doctors and other medical scientists also want to find better ways to detect and measure neuroblastoma to improve the ability to follow the response of tumor cells to therapy.

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  • Sorafenib and Cyclophosphamide/Topotecan in Patients With Relapsed and Refractory Neuroblastoma Not Recruiting

    This study will combine three drugs: sorafenib, cyclophosphamide and topotecan. Adding sorafenib to cyclophosphamide and topotecan may increase the effectiveness of this combination. The investigators first need to find out the highest dose of sorafenib that can be given safely together with cyclophosphamide and topotecan. This is the first study to test giving these three drugs together and will help determine the highest dose of sorafenib that can safely be given together with cyclophosphamide and topotecan to patients with resistant/relapsed neuroblastoma.

    Stanford is currently not accepting patients for this trial.

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2015-16 Courses


All Publications

  • Successful Treatment of Systemic and Central Nervous System Post-Transplant Lymphoproliferative Disorder Without the Use of High-Dose Methotrexate or Radiation PEDIATRIC BLOOD & CANCER Mahapatra, S., Chin, C. C., Iagaru, A., Heerema-McKenney, A., Twist, C. J. 2014; 61 (11): 2107-2109

    View details for DOI 10.1002/pbc.25129

    View details for Web of Science ID 000342723300041

  • F-18-FDG PET/CT in the management of patients with post-transplant lymphoproliferative disorder NUCLEAR MEDICINE COMMUNICATIONS Takehana, C. S., Twist, C. J., Mosci, C., Quon, A., Mittra, E., Iagaru, A. 2014; 35 (3): 276-281


    Post-transplant lymphoproliferative disorder (PTLD) is a rare but serious complication in transplant patients. Although fluorine-18 2-fluoro-2-deoxyglucose PET and computed tomography (F-FDG PET/CT) has been used for the evaluation and management of patients with PTLD, its utility has yet to be documented. We were therefore prompted to review our experience with F-FDG PET/CT in PTLD.We retrospectively reviewed the records of consecutive patients who had undergone F-FDG PET/CT for evaluation of PTLD from January 2004 to June 2012 at our institution. F-FDG PET/CT scans were compared with other imaging modalities performed concurrently. A chart review of pertinent clinical information was also conducted.A total of 30 patients were identified (14 female and 16 male; 1.7-76.7 years of age, average: 23.8 years). Twenty-seven participants had biopsy-proven PTLD and another three had been treated for PTLD because of high clinical suspicion of disease and positive F-FDG PET/CT findings in the absence of histological diagnosis. Eighty-three percent of these PTLD patients had extranodal involvement. In 57% of the cases, F-FDG PET/CT detected occult lesions not identified on other imaging modalities or suggested PTLD in equivocal lesions. The more aggressive PTLD histological subtypes demonstrated higher SUVmax compared with the less aggressive subtypes.F-FDG PET/CT is beneficial in the diagnostic evaluation of patients with PTLD. F-FDG PET/CT has the ability to detect occult lesions not identified on other imaging modalities, particularly extranodal lesions. In addition, F-FDG PET/CT may predict the PTLD subtype, as the lesions with higher pathologic grade presented with significantly higher SUVmax compared with the less aggressive forms.

    View details for DOI 10.1097/MNM.0000000000000050

    View details for Web of Science ID 000331291000008

  • Angioimmunoblastic T Cell Lymphoma: An Unusual Presentation of Posttransplant Lymphoproliferative Disorder in a Pediatric Patient ACTA HAEMATOLOGICA Kraus, T. S., Twist, C. J., Tan, B. T. 2014; 131 (2): 95-101


    Posttransplant lymphoproliferative disorders (PTLD) are a potentially life-threatening complication of immunosuppression in transplant recipients. The majority of cases are Epstein-Barr virus-associated lesions of B cell origin. T cell PTLD is rare, particularly in pediatric patients. We present an unusual case of monomorphic T cell PTLD with features of angioimmunoblastic T cell lymphoma in an 8-year-old heart transplant patient, presenting with cranial nerve palsy. © 2013 S. Karger AG, Basel.

    View details for DOI 10.1159/000353783

    View details for Web of Science ID 000331488500006

    View details for PubMedID 24157860

  • 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


    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


    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


    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


    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


    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


    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


    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


    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


    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-?


    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


    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


    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



    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



    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