Acute Leukemias - Republican Scientific Medical Library

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a References 159 54. Delannoy A, Lhéritier V, Thomas X, Castaigne S, Rigal-Huguet F, Raffoux E, Garban F, Legrand O, Witz F, Dubruille V, et al. (2005) Treatment of Philadelphia-positive acute lymphocytic leukemia (Ph+ ALL) in the elderly with imatinib mesylate (STI571) and chemotherapy. Blood 106(Suppl 1):(abstr 146) 55. Thomas X, Danala C, Le QH, Sebban C, Troncy J, Charrin C, Lhéritier V, Michallet M, Magaud JP, Fiere D (2001) Long-term follow-up of patients with newly diagnosed adult acute lymphoblastic leukemia: A single institution experience of 378 consecutive patients over a 21-year period. Leukemia 15:1811–1822 56. Boissel N, Auclerc MF, Lhéritier V, Perel Y, Thomas X, Leblanc T, Rousselot P, Cayuela JM, Gabert J, Fegueux N, et al. (2003) Should adolescents with acute lymphoblastic leukemia be treated as old children or young adults? Comparison of the French FRALLE-93 and LALA-94 trials. J Clin Oncol 21:774–780 57. Leikin SL, Brubaker C, Hartmann JR, Murphy ML, Wolff JA, Perrin E (1968) Varying prednisone dosage in remission induction of previously untreated childhood leukemia. Cancer 21:346–351 58. Schwartz CL, Thompson EB, Gelber RD, Young ML, Chilton D, Cohen HJ, Sallan SE (2001) Improved response with higher corticosteroid dose in children with acute lymphoblastic leukemia. J Clin Oncol 19:1040–1046 59. Amylon MD, Shuster J, Pullen J, Berard C, Link MP, Wharam M, Katz J, Yu A, Laver J, Ravindranath Y, et al. (1999) Intensive high-dose asparaginase consolidation improves survival for pediatric patients with T cell acute lymphoblastic leukemia and advanced stage lymphoblastic lymphoma: A Pediatric Oncology Group study. Leukemia 13:335–342 60. Riehm H, Gadner H, Henze G, Kornhuber B, Lampert F, Niethammer D, Reiter A, Schelong G (1990) Results and significance of six randomized trials in four consecutive ALL-BFM studies. Hamatol Bluttransfus 33:439–450 61. Tubergen DG, Gilchrist GS, O‘Brien RT, Coccia PF, Sather HN, Waskerwitz MJ, Hammond GD (1993) Improved outcome with delayed intensification for children with acute lymphoblastic leukemia and intermediate presenting features: A Childrens Cancer Group phase III trial. J Clin Oncol 11:527–537 62. Nachman JB, Sather HN, Sensel mg, Trigg ME, Cherlow JM, Lukens JM, Wolff L, Uckun FM, Gaynon PS (1998) Augmented post-induction therapy for children with high-risk acute lymphoblastic leukemia and a slow response to initial therapy. N Engl J Med 338:1663–1671 63. Dombret H, Witz F, de Botton S, Cayuela JM, Delabesse E, Preudhomme C, Huguet-Rigal F, Vekhoff A, Dauriac C, Hayette S, et al. for the Group for Research on Adult <strong>Acute</strong> Lymphoblastic Leukemia (GRAALL) (2004) Imatinib combined with intensive HAM chemotherapy as consolidation of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL). Preliminary results of the AFR03 phase I/II study. Blood 104(Suppl 1):749a 64. Kantarjian HM, O‘Brien S, Smith TL, Cortes J, Giles FJ, Beran M, Pierce S, Huh Y, Andreeff M, Koller C, et al. (2000) Results of treatment with Hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol 18:547–561 65. Thomas DA, Faderl S, Cortes J, O‘Brien S, Giles FJ, Kornblau SM, Garcia-Manero G, Keating MJ, Andreeff M, Jeha S, et al. (2004) Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood 103:4396–4407
ALL Therapy: Review of the MD Anderson Program S. Faderl, D.A. Thomas, Hagop M. Kantarjian Contents 12.1 Introduction ................... 161 12.2 The Hyper-CVAD Regimen in Adult ALL 161 12.2.1 Development and Treatment Outline .................. 161 12.2.2 Modifications of Hyper-CVAD . . . 162 12.3 Subset-Specific Approaches ....... 164 12.3.1 Ph-Positive ALL ............. 164 12.3.2 Mature B ALL (Burkitt Leukemia) 164 12.4 Summary ..................... 166 References ......................... 166 12.1 Introduction Prognosis of adult ALL has improved over the last few decades. Following the lead from the pediatric experience, dose-intense multiagent regimens now achieve remission rates exceeding 80% with 5-year survival probabilities of around 40%. In addition, ALL is more and more recognized as a heterogeneous group of diseases. Definition of subgroups based on cytogenetic-molecular markers has important practical implications including better delineation of prognostic groups, design of risk-adapted therapies, and eventually integration of novel agents into existing therapies that target pathways relevant for ALL pathophysiology. The hyper-CVAD program is one example of a regimen that has been successfully patterned after a previous pediatric regimen and that has developed along advances based on better understanding of ALL biology and availability of new drugs with activity in ALL. This article summarizes the rationale for the development of hyper-CVAD, experience with this regimen in adult ALL, and recent modifications and subtype-specific approaches. 12.2 The Hyper-CVAD Regimen in Adult ALL 12.2.1 Development and Treatment Outline To address the problem of poor prognosis in children with mature B-cell ALL (Burkitt’s leukemia/lymphoma), Murphy, et al. developed a short-term dose-intense chemotherapy regimen that consisted of a combination of fractionated cyclophosphamide, followed by vincristine and adriamycin in combination with CNS prophylaxis of intrathecal methotrexate and cytarabine [1]. Following hematologic recovery, patients would receive a second cycle, this time with a noncross-resistant combination of high-dose intravenous methotrexate and cytarabine. This sequence was repeated four times for a total of eight courses. The rationale of the combination was based on the cell cycle characteristics of the rapidly proliferating mature B ALL cells. Given a generation time of the ALL cells of about 25 h and a plasma half-life of cyclophosphamide of around 6 h, fractionation of cyclophosphamide every 12 h would indicate that the leukemic blasts are exposed to the active metabolite at least twice during their doubling time and thus exert a more powerful effect than would be possible with once daily dosing [2, 3]. Of 29 children treated, 27 (93%) achieved complete remission (CR) with an estimated 2-year disease-free survival of 81%. Although highly effective, sig-
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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 5 Table 1
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a 1.2 · Standard Therapy 7 tween G
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a 1.2 · Standard Therapy 9 Fig. 1.
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a 1.2 · Standard Therapy 11 of tre
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a 1.2 · Standard Therapy 13 Table
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a 1.2 · Standard Therapy 15 permit
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a References 17 19. Care RS, Valk P
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a References 19 6-thioguanine in th
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Acute Myeloid Leukemia: Epidemiolog
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a 3.1 · Epidemiology 49 3.1.4 Gend
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a 3.2 · Etiology 51 part of the in
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a 3.2 · Etiology 53 for the develo
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a References 55 38. Crane MM, Stom
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Relapsed and Refractory Acute Myelo
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a 4.2 · Prognostic Factors in Pati
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a 4.3 · Treatment of Relapsed and
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a 4.4 · Hematopoietic Stem Cell Tr
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a 4.6 · Gemtuzumab Ozogamicin 65 T
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a 4.7 · Relapsed and Refractory Ac
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a 4.7 · Relapsed and Refractory Ac
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a References 71 The ability of immu
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a References 73 39. Vogler WR, McCa
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a References 75 95. Sievers EL, Lar
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Part II - Acute Lymphoblastic Leuke
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78 Chapter 5 · Acute Lymphoblastic
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Molecular Biology and Genetics Meir
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a 6.3 · Structural Aberrations 97
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a 6.3 · Structural Aberrations 99
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a 6.5 · Molecular Aberrations 101
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a References 103 clear that homozyg
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a References 105 53. Chim CS, Tam C
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Page 93 and 94: Diagnosis of Acute Lymphoblastic Le
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Page 103 and 104: a References 129 47. Kita K, Shirak
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212 Chapter 16 · Treatment of Lymp
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214 Chapter 16 · Treatment of Lymp
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216 Chapter 17 · The Role of Allog
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230 Chapter 18 · The Role of Autol
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238 Chapter 19 · Novel Therapies i
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248 Chapter 20 · Minimal Residual
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264 Chapter 21 · Central Nervous S
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276 Chapter 22 · Relapsed Acute Ly
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278 Chapter 22 · Relapsed Acute Ly
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Emergencies in Acute Lymphoblastic
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a 23.5 · Hyperleukocytosis 283 LA
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a 23.9 · Neurological Complication
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a References 287 29. Hingorani AD,
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Subject Index A aberrant methylatio
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a Subject Index 291 CREB, see enhan
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a Subject Index 293 MUD, see matche
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