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      Role of nelarabine in the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma

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          Abstract

          T-cell malignancies have distinct biochemical, immunologic, and clinical features which set them apart from non-T-cell malignancies. In the past, T-cell leukemia portended a worse prognosis than leukemia of B-cell origin. Cure rates have improved with intensification of therapy and advanced understanding of the molecular genetics of T-cell malignancies. Further advances in the treatment of T-cell leukemia will require the development of novel agents that can target specific malignancies without a significant increase in toxicity. Nelarabine (2-amino-9β-D-arabinosyl-6-methoxy-9H-guanine), a synthesized guanosine nucleoside prodrug of ara-G (9-β-D-arabinofuranosylguanine), recently received accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of relapsed/refractory T-ALL and T-LBL in adults and children. Nelarabine is water soluble and rapidly converted to ara-G, which is specifically cytotoxic to T-lymphocytes and T-lymphoblastoid cells. Clinical and pharmacokinetic investigations have established that nelarabine is active as a single agent which has led to exploration of an expanded role in the treatment of T-cell hematologic malignances.

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          Most cited references 47

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          Acute lymphoblastic leukemia.

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              Uniform approach to risk classification and treatment assignment for children with acute lymphoblastic leukemia.

               G Reamon,  S Sallan,  P Gaynon (1995)
              To define more uniform criteria for risk-based treatment assignment for children with acute lymphoblastic leukemia (ALL), the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) sponsored a workshop in September 1993. Participants included representatives from the Childrens Cancer Group (CCG), Pediatric Oncology Group (POG), Dana-Farber Cancer Institute (DFCI), St Jude Children's Research Hospital (SJCRH), and the CTEP. Workshop participants presented and reviewed data from ALL clinical trials, using weighted averages to combine outcome data from different groups. For patients with B-precursor (ie, non-T, non-B) ALL, the standard-risk category (4-year event-free survival [EFS] rate, approximately 80%) will include patients 1 to 9 years of age with a WBC count at diagnosis less than 50,000/microL. The remaining patients will be classified as having high-risk ALL (4-year EFS rate, approximately 65%). For patients with T-cell ALL, different treatment strategies have yielded different conclusions concerning the prognostic significance of T-cell immunophenotype. Therefore, some groups/institutions will classify patients with T-cell ALL as high risk, while others will assign risk for patients with T-cell ALL based on the uniform age/WBC count criteria. Workshop participants agreed that the risk category of a patient may be modified by prognostic factors in addition to age and WBC count criteria, and that a common set of prognostic factors should be uniformly obtained, including DNA index (DI), cytogenetics, early response to treatment (eg, day-14 bone marrow), immunophenotype, and CNS status. The more uniform approach to risk-based treatment assignment and to collection of specific prognostic factors should increase the efficiency of future ALL clinical research.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                December 2007
                December 2007
                : 3
                : 6
                : 1135-1141
                Affiliations
                Department of Pediatrics, Division of Pediatric Hematology/Oncology, University of Alabama at Birmingham Birmingham, Alabama, USA
                Author notes
                Correspondence: Todd Cooper Department of Pediatrics, Division of Pediatric Hematology/Oncology, Children’s Hospital of Alabama, 1600 7th Avenue South, ACC 512, Birmingham, AL. 35233 Tel +1 205 939 9285 Fax +1 205 975 1941 Email tcooper@ 123456peds.uab.edu
                Article
                2387290
                18516261
                © 2007 Dove Medical Press Limited. All rights reserved
                Categories
                Review

                Medicine

                t-cell acute lymphoblastic leukemia, 9-β-d-arabinofuranosylguanine, nelarabine

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