Seminars in Hematology
Volume 46, Issue 1 , Pages 64-75 , January 2009

Treatment of Adult Acute Lymphoblastic Leukemia

  • Nicola Gökbuget

      Affiliations

    • Corresponding Author InformationAddress correspondence to Nicola Gökbuget, MD, J.W. Goethe University Hospital, Medical Department II, Theodor, Stern Kai 7, 60590 Frankfurt am Main, Germany
  • ,
  • Dieter Hoelzer

References 

  1. Thiebaut A, Vernant JP, Degos L, et al. Adult acute lymphocytic leukemia study testing chemotherapy and autologous and allogeneic transplantation (A follow-up report of the French protocol LALA 87). Hematol Oncol Clin North Am. 2000;14:1353–1366
  2. Takeuchi J, Kyo T, Naito K, et al. Induction therapy by frequent administration of doxorubicin with four other drugs, followed by intensive consolidation and maintenance therapy for adult acute lymphoblastic leukemia: the JALSG-ALL93 study. Leukemia. 2002;16:1259–1266
  3. Labar B, Suciu S, Zittoun R, et al. Allogeneic stem cell transplantation in acute lymphoblastic leukemia and non-Hodgkin's lymphoma for patients <or = 50 years old in first complete remission: results of the EORTC ALL-3 trial. Haematologica. 2004;89:809–817
  4. Rowe JM, Buck G, Burnett AK, et al. Induction therapy for adults with acute lymphoblastic leukemia: results of more than 1500 patients from the international ALL trial: MRC UKALL XII/ECOG E2993. Blood. 2005;106:3760–3767
  5. Tobinai K, Takeyama K, Arima F, et al. Phase II study of chemotherapy and stem cell transplantation for adult acute lymphoblastic leukemia or lymphoblastic lymphoma: Japan Clinical Oncology Group study 9004. Cancer Sci. 2007;98:1350–1357
  6. Larson RA, Dodge RK, Linker CA, et al. A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111. Blood. 1998;92:1556–1564
  7. Kantarjian H, Thomas D, O'Brien S, et al. Long-term follow-up results of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD), a dose-intensive regimen, in adult acute lymphocytic leukemia. Cancer. 2004;101:2788–2801
  8. Bassan R, Pogliani E, Casula P, et al. Risk-oriented postremission strategies in adult acute lymphoblastic leukemia: prospective confirmation of anthracycline activity in standard-risk class and role of hematopoietic stem cell transplants in high-risk groups. Hematol J. 2001;2:117–126
  9. Gökbuget N, Arnold R, Buechner T, et al. Intensification of induction and consolidation improves only subgroups of adult ALL: analysis of 1200 patients in GMALL study 05/93 [abstract]. Blood. 2001;98:802a
  10. Linker C, Damon L, Ries C, Navarro W. Intensified and shortened cyclical chemotherapy for adult acute lymphoblastic leukemia. J Clin Oncol. 2002;20:2464–2471
  11. Hallbook H, Simonsson B, Ahlgren T, et al. High-dose cytarabine in upfront therapy for adult patients with acute lymphoblastic leukaemia. Br J Haematol. 2002;118:748–754
  12. Thomas X, Boiron JM, Huguet F, et al. Outcome of treatment in adults with acute lymphoblastic leukemia: analysis of the LALA-94 trial. J Clin Oncol. 2004;22:4075–4086
  13. Annino L, Vegna ML, Camera A, et al. Treatment of adult acute lymphoblastic leukemia (ALL): long-term follow-up of the GIMEMA ALL 0288 randomized study. Blood. 2002;99:863–871
  14. Hunault M, Harousseau JL, Delain M, et al. Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial. Blood. 2004;104:3028–3037
  15. Mancini M. An integrated molecular-cytogenetic classification is highly predictive of outcome in adult acute lymphoblastic leukemia (ALL): analysis of 395 cases enrolled in the GIMEMA 0496 trial [abstract]. Blood. 2001;98:3492a
  16. Ribera JM, Oriol A, Bethencourt C, et al. Comparison of intensive chemotherapy, allogeneic or autologous stem cell transplantation as post-remission treatment for adult patients with high-risk acute lymphoblastic leukemia (Results of the PETHEMA ALL-93 triala). Haematologica. 2005;90:1346–1356
  17. Gökbuget N, Arnold R, Böhme A, et al. Improved outcome in high risk and very high risk ALL by risk adapted SCT and in standard risk ALL by intensive chemotherapy in 713 adult ALL patients treated according to the prospective GMALL study 07/2003 [abstract]. Blood. 2007;110:12a
  18. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371:1030–1043
  19. Kantarjian HM, O'Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin.Oncol. 2000;18:547–561
  20. Wetzler M, Sanford BL, Kurtzberg J, et al. Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B study 9511. Blood. 2007;109:4164–4167
  21. Conter V, Valsecchi MG, Silvestri D, et al. Pulses of vincristine and dexamethasone in addition to intensive chemotherapy for children with intermediate-risk acute lymphoblastic leukaemia: a multicentre randomised trial. Lancet. 2007;369:123–131
  22. Hoelzer D, Gökbuget N. New approaches in acute lymphoblastic leukemia in adults: where do we go?. Semin Oncol. 2000;27:540–559
  23. Gökbuget N, Hoelzer D. Treatment of adult acute lymphoblastic leukemia. Hematol Am Soc Hematol Educ Program. 2006;133–141
  24. Bachanova V, Weisdorf D. Unrelated donor allogeneic transplantation for adult acute lymphoblastic leukemia: a review. Bone Marrow Transplant. 2008;41:455–464
  25. Chaidos A, Kanfer E, Apperley JF. Risk assessment in haemotopoietic stem cell transplantation: disease and disease stage. Best Pract Res Clin Haematol. 2007;20:125–154
  26. Loberiza F. Summary slides 2003—part III. IMBTR/ABMTR Newsletter. 2006;10:6–9
  27. Goldstone AH, Lazarus HJ, Richards SM, et al. The outcome of 551 1st CR transplants in adult ALL from the UKALL XII/ECOG 2993 study [abstract]. Blood. 2004;104:615a
  28. Arnold R, Beelen D, Bunjes D, et al. Phenotype predicts outcome after allogeneic stem cell transplantation in adult high risk ALL patients [abstract]. Blood. 2003;102:1719a
  29. Goldstone AH, Richards SM, Lazarus HM, et al. In adults with standard-risk acute lymphoblastic leukemia (ALL) the greatest benefit is achieved from a matched sibling allogeneic transplant in first complete remission (CR) and an autologous transplant is less effective than conventional consolidation/maintenance chemotherapy in All patients: final results of the international ALL trial (MRC UKALL XII/ ECOG E2993). Blood. 2008;111:1827–1833
  30. Hahn T, Wall D, Camitta B, et al. The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review. Biol Blood Marrow Transplant. 2006;12:1–30
  31. Yanada M, Matsuo K, Suzuki T, Naoe T. Allogeneic hematopoietic stem cell transplantation as part of postremission therapy improves survival for adult patients with high-risk acute lymphoblastic leukemia: a metaanalysis. Cancer. 2006;106:1657–1663
  32. Hoelzer D, Thiel E, Löffler H, et al. Prognostic factors in a multicenter study for treatment of acute lymphoblastic leukemia in adults. Blood. 1988;71:123–131
  33. Gleissner B, Gökbuget N, Rieder H, et al. CD10-negative pre-B acute lymphoblastic leukemia (ALL): a distinct high-risk subgroup of adult ALL associated with a high frequency of MLL aberrations. Results of the German Multicenter Trials for Adult ALL (GMALL). Blood. 2005;106:4054–4056
  34. Grabher C, von Boehmer H, Look AT. Notch 1 activation in the molecular pathogenesis of T-cell acute lymphoblastic leukaemia. Nat Rev Cancer. 2006;6:347–359
  35. Vitale A, Guarini A, Ariola C, et al. Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol. Blood. 2006;107:473–479
  36. Asnafi V, Buzyn A, Thomas X, et al. Impact of TCR status and genotype on outcome in adult T-cell acute lymphoblastic leukemia: a LALA-94 study. Blood. 2005;105:3072–3078
  37. Baldus CD, Martus P, Burmeister T, et al. Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favorable outcome. J Clin Oncol. 2007;25:3739–3745
  38. Moorman AV, Harrison CJ, Buck GA, et al. Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007;109:3189–3197
  39. Mancini M, Scappaticci D, Cimino G, et al. A comprehensive genetic classification of adult acute lymphoblastic leukemia (ALL): analysis of the GIMEMA 0496 protocol. Blood. 2005;105:3434–3441
  40. Szczepanski T. Why and how to quantify minimal residual disease in acute lymphoblastic leukemia?. Leukemia. 2007;21:622–626
  41. Wassmann B, Pfeifer H, Gökbuget N, et al. Alternating versus concurrent schedules of Imatinib and chemotherapy as front-line therapy for Philadelphia-positive acute lymphoblastic leukemia (Ph+ALL). Blood. 2006;108:1469–1477
  42. Bruggemann M, Raff T, Flohr T, et al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood. 2006;107:1116–1123
  43. Raff T, Gökbuget N, Luschen S, et al. Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. Blood. 2007;109:910–915
  44. Hagedorn N, Acquaviva C, Fronkova E, et al. Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of “isolated” and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group. Blood. 2007;110:4022–4029
  45. van der Velden V, Cazzaniga G, Schrauder A, et al. Analysis of minimal residual disease by Ig/TCR gene rearrangements: guidelines for interpretation of real-time quantitative PCR data. Leukemia. 2007;21:604–611
  46. Spinelli O, Peruta B, Tosi M, et al. Clearance of minimal residual disease after allogeneic stem cell transplantation and the prediction of the clinical outcome of adult patients with high-risk acute lymphoblastic leukemia. Haematologica. 2007;92:612–618
  47. Wassmann B, Pfeifer H, Stadler M, et al. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2005;106:458–463
  48. Holleman A, Cheok MH, den Boer ML, et al. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. N Engl J Med. 2004;351:533–542
  49. Cheok MH, Evans WE. Acute lymphoblastic leukaemia: a model for the pharmacogenomics of cancer therapy. Nat Rev Cancer. 2006;6:117–129
  50. Stanulla M, Schaeffeler E, Flohr T, et al. Thiopurine methyltransferase (TPMT) genotype and early treatment response to mercaptopurine in childhood acute lymphoblastic leukemia. JAMA. 2005;293:1485–1489
  51. Kishi S, Cheng C, French D, et al. Ancestry and pharmacogenetics of antileukemic drug toxicity. Blood. 2007;109:4151–4157
  52. Arnold R, Massenkeil G, Bornhauser M, et al. Nonmyeloablative stem cell transplantation in adults with high-risk ALL may be effective in early but not in advanced disease. Leukemia. 2002;16:2423–2428
  53. Mohty M, Labopin M, Tabrizzi R, et al. Reduced intensity conditioning allogeneic stem cell transplantation for adult patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation. Haematologica. 2008;93:303–306
  54. Thomas DA, Faderl S, O'Brien S, et al. Chemoimmunotherapy with hyper-CVAD plus rituximab for the treatment of adult Burkitt and Burkitt-type lymphoma or acute lymphoblastic leukemia. Cancer. 2006;106:1569–1580
  55. Hoelzer D, Hiddemann W, Baumann A, et al. High survival rate in adult Burkitts lymphoma/leukemia and diffuse large B-cell lymphoma with mediastinal involvement [abstract]. Blood. 2007;110:518a
  56. Ottmann OG, Wassmann B, Pfeifer H, et al. Imatinib compared with chemotherapy as front-line treatment of elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL). Cancer. 2007;109:2068–2076
  57. Stock W, La M, Sanford B, et al. What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? (A comparison of children's cancer group and Cancer and Leukemia Group B studies). Blood. 2008;112:1646–1654
  58. Ribera JM, Oriol A, Sanz MA, et al. Comparison of the results of the treatment of adolescents and young adults with standard-risk acute lymphoblastic leukemia with the Programa Espanol de Tratamiento en Hematologia pediatric-based protocol ALL-96. J Clin Oncol. 2008;26:1843–1849
  59. Gökbuget N, Arnold R, Böhme A, et al. Risk adapted treatment of adolescents with acute lymphoblastic leukemia (ALL) according to the German Multicenter Study Group (GMALL) studies 06/99 and 07/03 yields significantly different outcome for subgroups. Haematologica. 2007;92(suppl 1):135
  60. Vignetti Ma, Fazi P, Cimino G, et al. Imatinib plus steroids induces complete remissions and prolonged survival in elderly Philadelphia chromosome-positive acute lymphoblastic leukemia patients without additional chemotherapy: results of the GIMEMA LAL0201-B protocol. Blood. 2007;109:3676–3678
  61. Thomas DA, Faderl S, Cortes J, et al. Treatment of Philadelphia chromosome-positive acute lymphocytic leukemia with hyper-CVAD and imatinib mesylate. Blood. 2004;103:4396–4407
  62. Yanada M, Takeuchi J, Sugiura I, et al. High complete remission rate and promising outcome by combination of imatinib and chemotherapy for newly diagnosed BCR-ABL-positive acute lymphoblastic leukemia: a phase II study by the Japan Adult Leukemia Study Group. J Clin Oncol. 2006;24:460–466
  63. Fielding AK, Goldstone AH. Allogeneic haematopoietic stem cell transplant in Philadelphia-positive acute lymphoblastic leukaemia. Bone Marrow Transplant. 2007;41:447–453
  64. Pfeifer H, Wassmann B, Pavlova A, et al. Kinase domain mutations of BCR-ABL frequently precede imatinib-based therapy and give rise to relapse in patients with de novo Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood. 2007;110:727–734
  65. Ravandi F, Thomas D, Kantarjian H, et al. Phase II study of combination of the HyperCVAD regimen with dasatinib in patients with Philadelphia chromosome (Ph) or BCR-ABL positive acute lymphoblastic leukemia (ALL) and lymphoid blast phase chronic myeloid leukemia (CML-LB) [abstract]. Blood. 2007;110:2814a
  66. Foa R, Vignetti M, Vitale A, et al. Dasatinib as front-line monotherapy for the induction treatment of adult and elderly Ph+ acute lymphoblastic leukemia (ALL) patients: interim analysis of the GIMEMA prospective study LAL1205 [abstract]. Blood. 2007;110:7a
  67. Thomas DA, O'Brien S, Jorgensen JL, et al. Prognostic significance of CD20 expression in adults with de novo precursor B-lineage acute lymphoblastic leukemia. Blood. 2008;Aug 14 [Epub ahead of print]
  68. Thomas D, Kantarjian H, Faderl S, et al. Update of the modified hyper-CVAD regimen with or without rituximab as frontline therapy of adults with acute lymphocytic leukemia (ALL) or lymphoblastic lymphoma (LL) [abstract]. Blood. 2007;110:2824a
  69. Gökbuget N, Hoelzer D. Rituximab in the treatment of adult ALL. Ann Hematol. 2006;85:117–119
  70. Appelbaum FR, Rosenblum D, Arceci RJ, et al. End points to establish the efficacy of new agents in the treatment of acute leukemia. Blood. 2007;109:1810–1816
  71. Gökbuget N, Bassan R, Dekker A, et al. Developing a European network for adult ALL. Hematol J. 2004;3(5):S46–S52
  72. Apostolidou E, Swords R, Alvarado Y, Giles FJ. Treatment of acute lymphoblastic leukaemia: a new era. Drugs. 2007;67:2153–2171
  73. Pui CH, Jeha S. New therapeutic strategies for the treatment of acute lymphoblastic leukaemia. Nat Rev Drug Discov. 2007;6:149–165
  74. Tavernier E, Boiron JM, Huguet F, et al. Outcome of treatment after first relapse in adults with acute lymphoblastic leukemia initially treated by the LALA-94 trial. Leukemia. 2007;21:1907–1914
  75. Fielding AK, Richards SM, Chopra R, et al. Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007;109:944–950

PII: S0037-1963(08)00145-5

doi: 10.1053/j.seminhematol.2008.09.003

Seminars in Hematology
Volume 46, Issue 1 , Pages 64-75 , January 2009