{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:14:07Z","timestamp":1791051247940,"version":"4.1.0"},"reference-count":23,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"15","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2005,5,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> Nelarabine (compound 506U78), a water soluble prodrug of 9-b-d-arabinofuranosylguanine, is converted to ara-GTP in T lymphoblasts. We sought to define the response rate of nelarabine in children and young adults with refractory or recurrent T-cell disease. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> We performed a phase II study with patients stratified as follows: stratum 1: \u2265 25% bone marrow blasts in first relapse; stratum 2: \u2265 25% bone marrow blasts in \u2265 second relapse; stratum 3: positive CSF; stratum 4: extramedullary (non-CNS) relapse. The initial nelarabine dose was 1.2 g\/m<jats:sup>2<\/jats:sup> daily for 5 consecutive days every 3 weeks. There were two dose de-escalations due to neurotoxicity on this or other studies. The final dose was 650 mg\/m<jats:sup>2<\/jats:sup>\/d for strata 1 and two patients and 400 mg\/m<jats:sup>2<\/jats:sup>\/d for strata 3 and four patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> We enrolled 121 patients (106 assessable for response) at the final dose levels. Complete plus partial response rates at the final dose levels were: 55% in stratum 1; 27% in stratum 2; 33% in stratum 3; and 14% in stratum 4. There were 31 episodes of \u2265 grade 3 neurologic adverse events in 27 patients (18% of patients). <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Nelarabine is active as a single agent in recurrent T-cell leukemia, with a response rate more than 50% in first bone marrow relapse. The most significant adverse events associated with nelarabine administration are neurologic. Further studies are planned to determine whether the addition of nelarabine to front-line therapy for T-cell leukemia in children will improve survival. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2005.03.426","type":"journal-article","created":{"date-parts":[[2005,5,20]],"date-time":"2005-05-20T23:31:45Z","timestamp":1116631905000},"page":"3376-3382","source":"Crossref","is-referenced-by-count":290,"title":["Phase II Study of Nelarabine (compound 506U78) in Children and Young Adults With Refractory T-Cell Malignancies: A Report From the Children\u2019s Oncology Group"],"prefix":"10.1200","volume":"23","author":[{"given":"Stacey L.","family":"Berg","sequence":"first","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Blaney","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Devidas","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom A.","family":"Lampkin","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Murgo","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Bernstein","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Billett","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Kurtzberg","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Reaman","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gaynon","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Whitlock","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Krailo","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Harris","sequence":"additional","affiliation":[{"name":"From the Texas Children\u2019s Cancer Center, Baylor College of Medicine, Houston, TX; Dana Farber Cancer Institute and Children\u2019s Hospital, Boston, MA; Children\u2019s Hospital of Los Angeles, and Keck School of Medicine, University of Southern California, Los Angeles, CA; Children\u2019s National Medical Center, Washington, DC; Children\u2019s Oncology Group, Arcadia, CA, Bethesda, MD, and Gainesville, FL; Duke University Medical Center, Durham, NC; GlaxoSmithKline, Collegeville, PA; Hospital Sainte-Justine, Montreal,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","doi-asserted-by":"crossref","unstructured":"Giblett E, Ammann A, Wara D, et al: Nucleoside-phosphorylase deficiency in a child with severely defective T-cell immunity and normal B-cell immunity. Lancet 1: 1010,1975 -1013,","DOI":"10.1016\/S0140-6736(75)91950-9"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI109058"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V61.4.660.bloodjournal614660"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111514"},{"key":"R5","unstructured":"Rodriguez CO Jr, Mitchell BS, Ayres M, et al: Arabinosylguanine is phosphorylated by both cytoplasmic deoxycytidine kinase and mitochondrial deoxyguanosine kinase. Cancer Res 62: 3100,2002 -3105,"},{"key":"R6","unstructured":"Shewach D, Daddona P, Ashcraft E, et al: Metabolism and selective cytotoxicity of 9-b-D-arabinofuranosylguanine in human lymphoblasts. Cancer Res 45: 1008,1985 -1014,"},{"key":"R7","unstructured":"Shewach D, Mitchell B: Differential metabolism of 9-b-D-arabinofuranosylguanine in human leukemic cells. Cancer Res 49: 6498,1989 -6502,"},{"key":"R8","unstructured":"Lambe C, Averett D, Paff M, et al: 2-Amino-6-methoxypurine arabinoside: An agent for T-cell malignancies. Cancer Res 55: 3352,1995 -3356,"},{"key":"R9","unstructured":"Kurtzberg J, Keating M, Plunkett W, et al: Compound 506 (2-amino-6-methoxypurine arabinoside) is active against T-cell malignancies: Preliminary results of an ongoing phase I trial. Proc Am Soc Clin Oncol 15: 27,1996 ,   (abstr 2022)"},{"key":"R10","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(02)00415-1"},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.3109\/10428199809059234"},{"key":"R12","doi-asserted-by":"publisher","DOI":"10.1007\/BF02780522"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V72.4.1286.1286"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V78.5.1166.1166"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1997.4413253.x"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2000.01891.x"},{"key":"R18","unstructured":"Hirschfeld S, Flowers C, Smith M: Toxicity from intrathecal therapy in pediatric hematologic neoplasms: Is the incidence increasing. Proc Am Soc Clin Oncol 17: 539A,1998 ,   (abstr 2069)"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1991.9.4.679"},{"key":"R20","unstructured":"Kornblau SM, Cortes-Franco J, Estey E: Neurotoxicity associated with fludarabine and cytosine arabinoside chemotherapy for acute leukemia and myelodysplasia. Leukemia 7: 378,1993 -383,"},{"key":"R21","unstructured":"Scherokman B, Filling-Katz M, Tell D: Brachial plexus neuropathy following high-dose cytarabine in acute monoblastic leukemia. Cancer Treat Rep 69: 1005,1985 -1006,"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1703412"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1203\/00006450-198702000-00006"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197703242961203"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.2005.03.426","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T21:08:28Z","timestamp":1653512908000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.2005.03.426"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,5,20]]},"references-count":23,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2005,5,20]]}},"alternative-id":["10.1200\/JCO.2005.03.426"],"URL":"https:\/\/doi.org\/10.1200\/jco.2005.03.426","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,5,20]]}}}