a References 245 23. Jeha S, Gandhi V, Chan KW, et al. (2004) Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia. Blood 103(3):784–789 24. Jeha S, Razzouk BI, Rytting ME, et al. (2004) Phase II trials of clofarabine in relapsed or refractory pediatric leukemia. Blood 104:196a 25. Kantarjian HM, Gandhi V, Kozuch P, et al. (2003) Phase I clinical and pharmacology study of clofarabine in patients with solid and hematologic cancers. J Clin Oncol 21:1167–1173 26. Kantarjian H, Gandhi V, Cortes J, et al. (2003) Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood 102:2379–2386 27. Santini V, Kantarjian HM, Issa J-P (2001) Changes in DNA methylation in neoplasia: Pathophysiology and therapeutic implications. Ann Intern Med 134:573–586 28. Garcia-Manero G, Bueso-Ramos C, Daniel J, et al. (2002) DNA methylation patterns at relapse in adult acute lymphocytic leukemia. Clin Cancer Res 8:1897–1903 29. Garcia-Manero G, Daniel J, Smith TL, et al. (2002) DNA methylation of multiple promoter-associated CpG islands in adult acute lymphocytic leukemia. Clin Cancer Res 8:2217–2224 30. Roman-Gomez J, Jimenez-Velasco A, Castillejo JA, et al. (2004) Promoter hypermethylation of cancer-related genes: A strong independent prognostic factor in acute lymphoblastic leukemia. Blood 104:2492–2498 31. Shen L, Toyota M, Kondo Y, et al. (2003) Aberrant DNA methylation of p57KIP2 identifies a cell-cycle regulatory pathway with prognostic impact in adult acute lymphocytic leukemia. Blood 101: 4131–4136 32. Faderl S, Kantarjian HM, Thomas DA, et al. (2000) Outcome of Philadelphia chromosome-positive adult acute lymphoblastic leukemia. Leuk Lymphoma 36:263–273 33. Thomas DA, Faderl S, Cortes J, et al. (2004) Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103:4396–4407 34. Thomas DA, Faderl S, Cortes J, et al. (2004) Update of the Hyper- CVAD and imatinib mesylate regimen in Philadelphia (Ph) positive acute lymphocytic leukemia (ALL). Blood 104:748a 35. Towatari M, Yanada M, Usui N, et al. (2004) Combination of intensive chemotherapy and imatinib can rapidly induce high-quality complete remission for a majority of patients with newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia. Blood 104:3507–3512 36. Ottmann OG, Wassmann B, Pfeifer H, et al. (2004) Imatinib given concurrently with induction chemotherapy is superior to imatinib subsequent to induction and consolidation in newly diagnosed Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 104:197a 37. Giles F, Kantarjian H, Wassmann B, et al. (2004) A phase I/II study of AMN107, a novel aminopyrimidine inhibitor of Bcr-Abl, on a continuous daily dosing schedule in adult patients (pts) with imatinib-resistant advanced phase chronic myeloid leukemia (CML) or relapsed/refractory Philadelphia chromosome (Ph+) acute lymphoblastic leukemia (ALL). Blood 104:10a 38. Gögbuget N, Hoelzer D (2004) Treatment with monoclonal antibodies in acute lymphoblastic leukemia: Current knowledge and future prospects. Ann Hematol 83:201–205 39. Thomas DA, Cortes J, O’Brien SM, et al. (2000) Significance of CD20 positivity in de novo acute lymphocytic leukemia (ALL). Blood 96:109a 40. Thomas DA, Cortes J, Faderl S, et al. (2004) Outcome with the Hyper-CVAD and rituximab regimen in Burkitt (BL) and Burkitt-like (BLL) leukemia/lymphoma. Blood 104:901a 41. Ozsahin H, Fluss J, McLin V, et al. (2003) Rituximab with interleukin-2 after autologous bone marrow transplantation for acute lymphocytic leukemia in second remission. Med Pediatr Oncol 38:300–301 42. Tibes R, Keating MJ, Ferrajoli A, et al. (2006) Activity of alemtuzumab in patients with CD52-positive acute leukemia. Cancer 106: 2645–2651 43. Grossbard ML, Freedman AS, Ritz J, et al. (1992) Serotherapy of Bcell neoplasms with anti-B4-blocked ricin: A phase I trial of daily bolus infusion. Blood 79:576–585 44. Szatrowski TP, Dodge RK, Reynolds C, et al. (2003) Lineage specific treatment of adult patients with acute lymphoblastic leukemia in first remission with anti-B4-blocked ricin or high-dose cytarabine: Cancer and Leukemia Group B study 9311. Cancer 97:1471–1480 45. Graham ML (2003) Pegaspargase: A review of clinical studies. Adv Drug Delivery Rev 55:1293–1302 46. Abshire TC, Pollock BH, Billett AL, et al. (2000) Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: A pediatric oncology group study. Blood 96:1709–1715 47. Avramis VI, Sencer S, Periclou AP, et al. (2002) A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: A Children’s Cancer Group study. Blood 99:1986–1994 48. Hawkins D, Park JR, Thomson BG, et al. (2004) Asparaginase pharmacokinetics after intensive polyethylene glycol-conjugated L-asparaginase therapy for children with relapsed acute lymphoblastic leukemia. Clin Cancer Res 10:5335–5341 49. Furman RR, Gandhi V, Bennett JC, et al. (2004) Intravenous forodesine (BCX-1777), a novel purine nucleoside phosphorylase (PNP) inhibitor, demonstrates clinical activity in phase I/II studies in patients with B-cell acute lymphoblastic leukemia. Blood 104:750a 50. Duvic M, Foss FM, Olsen EA, et al. (2004) Intravenous forodesine (BCX-1777), a novel purine nucleoside phosphorylase (PNP) inhibitor, demonstrates clinical activity in patients with refractory cutaneous T-cell lymphoma. Blood 104:683a 51. Pui CH, Relling MV, Evans WE (2003) Role of pharmacogenomics and pharmacodynamics in the treatment of acute lymphoblastic leukemia. Best Pract Res Clin Haematol 15:741–756 52. Krajinovic M, Costea I, Chiasson S (2002) Polymorphism of the thymidylate synthas gene and outcome of acute lymphoblastic leukemia. Lancet 359:1033–1034 53. Ulrich CM, Yasui Y, Storb R, et al. (2001) Pharmacogenetics of methotrexate: Toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood 98:231–234 54. Taub JW, Matherly LH, Ravindranath Y, et al. (2002) Polymorphisms in methylenetetrahydrofolate reductase and methotrexate sensi
246 Chapter 19 · Novel Therapies in <strong>Acute</strong> Lymphoblastic Leukemia tivity in childhood acute lymphoblastic leukemia. Leukemia 16: 764–765 55. Evans WE, Crom WR, Abromowitch M, et al. (1986) Clinical pharmacodynamics of high-dose methotrexate in acute lymphocytic leukemia. Identification of a relation between concentration and effect. N Engl J Med 14:471–477 56. Relling MV, Hancock ML, Rivera GK, et al. (1999) Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyl-transferase gene locus. J Natl Cancer Inst 91:2001– 2008 57. Belkow VM, Krynetski EY, Schuetz JD, et al. (1999) Reduced folate carrier expression in acute lymphoblastic leukemia: A mechanism for ploidy but not lineage differences in methotrexate accumulation. Blood 93:1643–1650 58. Ramakers-van Woerden NL, Pieters R, Loonen AH, et al. (2000) TEL- AML1 gene fusion is related to in vitro drug sensitivity for L-asparaginase in childhood acute lymphoblastic leukemia. Blood 96:1094–1099 59. Stam RW, den Boer ML, Meijerink JP, et al. (2003) Differential mRNA expression of ara-C-metabolizing enzymes explains ara-C sensitivity in MLL gene-rearranged infant acute lymphoblastic leukemia. Blood 101:1270–1276
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E.H. Estey · S.H. Faderl · H. M.
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E. H. Estey Department of Leukemia
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VI Table of Contents 14 Philadelphi
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VIII Contributors S. H. Faderl Depa
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X Contributors D. Wartenberg Depart
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Therapy of AML Elihu Estey Contents
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a 1.2 · Standard Therapy 3 Table 1
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a 1.2 · Standard Therapy 9 Fig. 1.
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a 3.2 · Etiology 51 part of the in
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Relapsed and Refractory Acute Myelo
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ALL Therapy: Review of the MD Ander
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