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Perspectives on the treatment of chronic phase and advanced phase CML and Philadelphia chromosome positive ALL

Leukemia volume 17, pages 691–699 (2003)Cite this article

Abstract

Chronic myeloid leukaemia (CML) is a malignant disease of the bone marrow characterised by the presence of the Philadelphia (Ph) chromosome. About 20% of acute lymphoblastic leukaemia (ALL) patients also show this genetic abnormality. A new drug, imatinib (Glivec®, Novartis Pharma AG, Basel, Switzerland, and formerly STI571) is having a profound effect on the treatment and management of all stages of CML and Philadelphia chromosome positive (Ph+) ALL. New treatment algorithms are being developed. Should imatinib replace or be combined with existing therapies? To address this question, we review the pros and cons of therapy with interferon-α (IFN-α), allogeneic transplantation, autologous transplantation, imatinib, and in the case of Ph+ ALL, chemotherapy and experimental approaches. Conservative and aggressive treatments will be discussed and new molecular methods of monitoring cytogenetic response and their significance will also be reviewed.

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References

  1. Nowell PC, Hungerford DA . A minute chromosome in human chronic granulocytic leukemia. Science 1960; 132: 1497–1497.

  2. Rowley JD . Letter: a new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973; 243: 290–293.

    CAS  PubMed  Google Scholar 

  3. Kantarjian HM, Dixon D, Keating MJ, Talpaz M, Walters RS, McCredie KB et al. Characteristics of accelerated disease in chronic myelogenous leukemia. Cancer 1988; 61: 1441–1446.

    Article  CAS  PubMed  Google Scholar 

  4. Gale RP, Hehlmann R, Zhang MJ, Hasford J, Goldman JM, Heimpel H et al. Survival with bone marrow transplantation versus hydroxyurea or interferon for chronic myelogenous leukemia. The German CML Study Group. Blood 1998; 91: 1810–1819.

    CAS  PubMed  Google Scholar 

  5. Anonymous. Hydroxyurea versus busulphan for chronic myeloid leukaemia: an individual patient data meta-analysis of three randomized trials. Chronic myeloid Leukemia Trialists' Collaborative Group. Br J Haematol 2000; 110: 573–576.

  6. Silver RT, Woolf SH, Hehlmann R, Appelbaum FR, Anderson J, Bennett C et al. An evidence-based analysis of the effect of busulfan, hydroxyurea, interferon, and allogeneic bone marrow transplantation in treating the chronic phase of chronic myeloid leukemia: developed for the American Society of Hematology. Blood 1999; 94: 1517–1536.

    CAS  PubMed  Google Scholar 

  7. Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr–abl positive cells. Nat Med 1996; 2: 561–566.

    Article  CAS  PubMed  Google Scholar 

  8. Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002; 346: 645–652.

    Article  CAS  PubMed  Google Scholar 

  9. Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini C, Guilhot F et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 2002; 99: 1928–1937.

    Article  CAS  PubMed  Google Scholar 

  10. Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB, Ottmann OG et al. Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 2002; 99: 3530–3539.

    CAS  PubMed  Google Scholar 

  11. Sokal JE, Cox EB, Baccarani M, Tura S, Gomez GA, Robertson JE et al. Prognostic discrimination in ‘good-risk’ chronic granulocytic leukemia. Blood 1984; 63: 789–799.

    CAS  PubMed  Google Scholar 

  12. Sokal JE, Baccarani M, Russo D, Tura S . Staging and prognosis in chronic myelogenous leukemia. Semin Hematol 1988; 25: 49–61.

    CAS  PubMed  Google Scholar 

  13. Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa. Writing Committee for the Collaborative CML Prognostic Factors Project Group. J Natl Cancer Inst 1998; 90: 850–858.

    Article  CAS  PubMed  Google Scholar 

  14. Huntly BJ, Reid AG, Bench AJ, Campbell LJ, Telford N, Shepherd P et al. Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia. Blood 2001; 98: 1732–1738.

    Article  CAS  PubMed  Google Scholar 

  15. van Rhee F, Szydlo RM, Hermans J, Devergie A, Frassoni F, Arcese W et al. Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1997; 20: 553–560.

    Article  CAS  PubMed  Google Scholar 

  16. Kantarjian HM, Smith TL, O'Brien S, Beran M, Pierce S, Talpaz M . Prolonged survival in chronic myelogenous leukemia after cytogenetic response to interferon-alpha therapy. The Leukemia Service. Ann Intern Med 1995; 122: 254–261.

    Article  CAS  PubMed  Google Scholar 

  17. Guilhot F, Chastang C, Michallet M, Guerci A, Harousseau JL, Maloisel F et al. Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group. N Engl J Med 1997; 337: 223–229.

    Article  CAS  PubMed  Google Scholar 

  18. Bonifazi F, de Vivo A, Rosti G, Guilhot F, Guilhot J, Trabacchi E et al. Chronic myeloid leukemia and interferon-α: a study of complete cytogenetic responders. Blood 2001; 98: 3074–3081.

    Article  CAS  PubMed  Google Scholar 

  19. Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM et al. Activity of a specific inhibitor of the BCR–ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001; 344: 1038–1042.

    Article  CAS  PubMed  Google Scholar 

  20. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM et al. Efficacy and safety of a specific inhibitor of the BCR–ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001; 344: 1031–1037.

    Article  CAS  PubMed  Google Scholar 

  21. Hochhaus A, Weisser A, La Rosee P, Emig M, Muller MC, Saussele S et al. Detection and quantification of residual disease in chronic myelogenous leukemia. Leukemia 2000; 14: 998–1005.

    Article  CAS  PubMed  Google Scholar 

  22. Le Gouill S, Talmant P, Milpied N, Daviet A, Ancelot M, Moreau P et al. Fluorescence in situ hybridization on peripheral-blood specimens is a reliable method to evaluate cytogenetic response in chronic myeloid leukemia. J Clin Oncol 2000; 18: 1533–1538.

    Article  CAS  PubMed  Google Scholar 

  23. Duba HC, Hilbe W, Mehringer A, Erdel M, Thaler J, Utermann G . Hypermetaphase and interphase fluorescence in situ hybridisation for monitoring of remission status in Philadelphia chromosome positive chronic myeloid leukaemia. Int J Oncol 2000; 17: 1245–1249.

    CAS  PubMed  Google Scholar 

  24. Tamura S, Saheki K, Takatsuka H, Wada H, Fujimori Y, Okamoto T et al. Early detection of relapse and evaluation of treatment for mixed chimerism using fluorescence in situ hybridization following allogeneic hematopoietic cell transplant for hematological malignancies. Ann Hematol 2000; 79: 622–626.

    Article  CAS  PubMed  Google Scholar 

  25. Schoch C, Schnittger S, Bursch S, Gerstner D, Hochhaus A, Berger U et al. Comparison of chromosome banding analysis, interphase- and hypermetaphase-FISH, qualitative and quantitative PCR for diagnosis and for follow-up in chronic myeloid leukemia: a study on 350 cases. Leukemia 2002; 16: 53–59.

    Article  CAS  PubMed  Google Scholar 

  26. Cross NC, Feng L, Chase A, Bungey J, Hughes TP, Goldman JM . Competitive polymerase chain reaction to estimate the number of BCR–ABL transcripts in chronic myeloid leukemia patients after bone marrow transplantation. Blood 1993; 82: 1929–1936.

    CAS  PubMed  Google Scholar 

  27. Hochhaus A, Lin F, Reiter A, Skladny H, Hehlmann R, Goldman JM et al. Quantitative molecular methods to monitor the response of CML patients to interferon-alpha. Bone Marrow Transplant 1996; 17 (Suppl 3): S41–S44.

    PubMed  Google Scholar 

  28. Mensink E, van de Locht A, Schattenberg A, Linders E, Schaap N, Geurts vK et al. Quantitation of minimal residual disease in Philadelphia chromosome positive chronic myeloid leukaemia patients using real-time quantitative RT-PCR. Br J Haematol 1998; 102: 768–774.

    Article  CAS  PubMed  Google Scholar 

  29. Preudhomme C, Revillion F, Merlat A, Hornez L, Roumier C, Duflos-Grardel N et al. Detection of BCR–ABL transcripts in chronic myeloid leukemia (CML) using a'real time' quantitative RT-PCR assay. Leukemia 1999; 13: 957.

    Article  CAS  PubMed  Google Scholar 

  30. Emig M, Saussele S, Wittor H, Weisser A, Reiter A, Willer A et al. Accurate and rapid analysis of residual disease in patients with CML using specific fluorescent hybridization probes for real time quantitative RT-PCR. Leukemia 1999; 13: 1825–1832.

    Article  CAS  PubMed  Google Scholar 

  31. Hochhaus A, Reiter A, Skladny H, Reichert A, Saussele S, Hehlmann R . Molecular monitoring of residual disease in chronic myelogenous leukemia patients after therapy. Recent Results Cancer Res 1998; 144: 36–45.

    Article  CAS  PubMed  Google Scholar 

  32. Hochhaus A, Reiter A, Saussele S, Reichert A, Emig M, Kaeda J et al. Molecular heterogeneity in complete cytogenetic responders after interferon-alpha therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission. German CML Study Group and the UK MRC CML Study Group. Blood 2000; 95: 62–66.

    CAS  PubMed  Google Scholar 

  33. Goldman JM, Druker BJ . Chronic myeloid leukemia: current treatment options. Blood 2001; 98: 2039–2042.

    Article  CAS  PubMed  Google Scholar 

  34. Druker B for the IRIS (International Randomized IFN vs STI571) Study Group. STI571 (Gleevec/Glivec, imatinib) versus interferon (IFN)+cytarabine as initial therapy for patients with CML: results of a randomized study. Proc Am Soc Clin Oncol 2002; 21: 1a (Abstract).

  35. Chronic Myeloid Leukemia Trialists' Collaborative Group. Interferon alfa versus chemotherapy for chronic myeloid leukemia: a meta-analysis of seven randomized trials: Chronic Myeloid Leukemia Trialists' Collaborative Group. J Natl Cancer Inst 1997; 89: 1616.

  36. The Italian Cooperative Study Group on Myeloid Leukemia. Long-term follow-up of the italian trial of interferon-alpha versus conventional chemotherapy in chronic myeloid leukemia The Italian The Italian Cooperative Study Group on Chronic Myeloid Leukemia. Blood 1998; 92: 1541–1548.

  37. Kantarjian HM, Giles FJ, O'Brien SM, Talpaz M . Clinical course and therapy of chronic myelogenous leukemia with interferon-alpha and chemotherapy. Hematol Oncol Clin North Am 1998; 12: 31–80.

    Article  CAS  PubMed  Google Scholar 

  38. Mughal TI, Goldman JM . Chronic myeloid leukaemia: a therapeutic challenge. Ann Oncol 1995; 6: 637.

    Article  CAS  PubMed  Google Scholar 

  39. Sawyers CL . Chronic myeloid leukemia. N Engl J Med 1999; 340: 1330–1340.

    Article  CAS  PubMed  Google Scholar 

  40. Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Lancet 1998; 352: 1087.

    Article  CAS  PubMed  Google Scholar 

  41. Hehlmann R, Hochhaus A, Kolb HJ, Hasford J, Gratwohl A, Heimpel H et al. Interferon-alpha before allogeneic bone marrow transplantation in chronic myelogenous leukemia does not affect outcome adversely, provided it is discontinued at least 90 days before the Procedure. Blood 1999; 94: 3668–3677.

    CAS  PubMed  Google Scholar 

  42. Brunstein CG, McGlave PB . The biology and treatment of chronic myelogenous leukemia. Oncology (Huntingt) 2001; 15: 23–31.

    Google Scholar 

  43. Baron F, Frere P, Fillet G, Beguin Y . Treatment of leukemia relapse after allogeneic hematopoietic stem cell transplantation by donor lymphocyte infusion and STI-571. Haematologica 2001; 86: 993–994.

    CAS  PubMed  Google Scholar 

  44. Wassmann B, Klein SA, Scheuring U, Pfeifer H, Martin H, Gschaidmeier H et al. Hematologic and cytogenetic remission by STI571 (Glivec) in a patient relapsing with accelerated phase CML after second allogeneic stem cell transplantation. Bone Marrow Transplant 2001; 28: 721–724.

    Article  CAS  PubMed  Google Scholar 

  45. Kantarjian H, O'Brien S, Cortes J, Giralt S, Rios M, Shan J et al. Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia. Blood 2002; 299: 100.

    Google Scholar 

  46. Barrett J, Childs R . Non-myeloablative stem cell transplants. Br J Haematol 2000; 111: 6–17.

    Article  CAS  PubMed  Google Scholar 

  47. Hansen JA, Gooley TA, Martin PJ, Appelbaum F, Chauncey TR, Clift RA et al. Bone marrow transplants from unrelated donors for patients with chronic myeloid leukemia. N Engl J Med 1998; 338: 962–968.

    Article  CAS  PubMed  Google Scholar 

  48. McGlave PB, Shu XO, Wen W, Anasetti C, Nademanee A, Champlin R et al. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the national marrow donor program. Blood 2000; 95: 2219–2225.

    CAS  PubMed  Google Scholar 

  49. Lee SJ, Klein JP, Anasetti C, Antin JH, Loberiza FR, Bolwell BJ et al. The effect of pretransplant interferon therapy on the outcome of unrelated donor hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in first chronic phase. Blood 2001; 98: 3205–3211.

    Article  CAS  PubMed  Google Scholar 

  50. Margolis J, Borrello I, Flinn IW . New approaches to treating malignances with stem cell transplantation. Semin Oncol 2000; 27: 524–530.

    CAS  PubMed  Google Scholar 

  51. Merx K, Muller MC, Kreil S, Lahaye T, Paschka P, Schoch C et al. Early reduction of BCR–ABL mRNA transcript levels predicts cytogenetic response in chronic phase CML patients treated with imatinib after failure of interferon alpha. Leukemia 2002; 16: 1579.

    Article  CAS  PubMed  Google Scholar 

  52. Stentoft J, Pallisgaard N, Kjeldsen E, Holm MS, Nielsen JL et al. Kinetics of BCR–ABL fusion transcript levels in chronic myeloid leukemia patients treated with STI571 measured by quantitative real-time polymerase chain reaction. Eur J Haematol 2001; 67: 302.

    Article  CAS  PubMed  Google Scholar 

  53. Graham SM, Jorgensen HG, Allan E, Pearson C, Alcorn MJ, Richmond L et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 2002; 99: 319.

    Article  CAS  PubMed  Google Scholar 

  54. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN et al. Clinical resistance to STI-571cancer therapy caused by BCR–ABL gene mutation or amplification. Science 2001; 293: 876–880.

    Article  CAS  PubMed  Google Scholar 

  55. Hochhaus A, Kreil S, Corbin AS, La Rosee P, Muller MC, Lahaye T et al. Molecular and chromosomal mechanisms of resistance to imatinib (STI571) therapy. Leukemia 2002; 16: 2190.

    Article  CAS  PubMed  Google Scholar 

  56. Branford S, Rudzki Z, Walsh S, Grigg A, Arthur C, Taylor K et al. High frequency of point mutations clustered within the adenosinetriphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemiaor Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance. Blood 2002; 99: 3472.

    Article  CAS  PubMed  Google Scholar 

  57. Roumiantsev S, Shah NP, Gorre ME, Nicoll J, Brasher BB, Sawyers CL et al. Clinical resistance to the kinase inhibitor STI-571 in chronic myeloid leukemia by mutation of Tyr-253 in the Abl kinase domain P-loop. Proc Natl Acad Sci USA 2002; 99: 10700.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. von Bubnoff N, Schneller F, Peschel C, Duyster J . BCR–ABL gene mutations in relation to clinical resistance of Philadelphia-chromosome-positive leukaemia to STI571: a prospective study. Lancet 2002; 359: 487–91.

  59. Sawyers CL . Research on resistance to cancer drug Gleevec. Science 2001; 294: 1834.

    Article  CAS  PubMed  Google Scholar 

  60. Cortes JE, Talpaz M, Kantarjian H . Chronic myelogenous leukemia: a review. Am J Med 1996; 100: 555–570.

    Article  CAS  PubMed  Google Scholar 

  61. Schiffer CA . Acute myeloid leukemia in adults: where do we go from here. Cancer Chemother Pharmacol 2001; 48 (Suppl 1): S45–S52.

    Article  PubMed  Google Scholar 

  62. Dann EJ, Anastasi J, Larson RA . High-dose cladribine therapy for chronic myelogenous leukemia in the accelerated or blast phase. J Clin Oncol 1998; 16: 1498–1504.

    Article  CAS  PubMed  Google Scholar 

  63. Sacchi S, Kantarjian HM, O'Brien S, Cortes J, Rios MB, Giles FJ et al. Chronic myelogenous leukemia in nonlymphoid blastic phase: analysis of the results of first salvage therapy with three different treatment approaches for 162 patients. Cancer 1999; 86: 2632.

    CAS  PubMed  Google Scholar 

  64. Giles FJ, Cortes JE, Baker SD, Thomas DA, O'Brien S, Smith TL et al. Troxacitabine, a novel dioxolane nucleoside analog, has activity in patients with advanced leukemia. J Clin Oncol 2001; 19: 762–771.

    Article  CAS  PubMed  Google Scholar 

  65. Giles FJ, Kantarjian HM, Kornblau SM, Thomas DA, Garcia-Manero G, Waddelow TA et al. Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Cancer 2001; 92: 406–413.

    Article  CAS  PubMed  Google Scholar 

  66. Karp JE, Kaufmann SH, Adjei AA, Lancet JE, Wright JJ, End DW . Current status of clinical trials of farnesyl transferase inhibitors. Curr Opin Oncol 2001; 13: 470–476.

    Article  CAS  PubMed  Google Scholar 

  67. Hoover RR, Mahon FX, Melo JV, Daley GQ . Overcoming STI571 resistance with the farnesyl transferase inhibitor SCH66336. Blood 2002; 100: 1068.

    Article  CAS  PubMed  Google Scholar 

  68. Czuczman MS, Dodge RK, Stewart CC, Frankel SR, Davey FR, Powell BL et al. Value of immunophenotype in intensively treated adult acute lymphoblastic leukemia: cancer and leukemia Group B study 8364. Blood 1999; 93: 3931–3939.

    CAS  PubMed  Google Scholar 

  69. Westbrook CA, Hooberman AL, Spino C, Dodge RK, Larson RA, Davey F et al. Clinical significance of the BCR–ABL fusion gene in adult acute lymphoblastic leukemia: a Cancer and Leukemia Group B Study (8762). Blood 1992; 80: 2983–2990.

    CAS  PubMed  Google Scholar 

  70. Secker-Walker LM, Craig JM, Hawkins JM, Hoffbrand AV . Philadelphia positive acute lymphoblastic leukemia in adults: age distribution, BCR breakpoint and prognostic significance. Leukemia 1991; 5: 196–199.

    CAS  PubMed  Google Scholar 

  71. Kantarjian HM, O'Brien S, Smith TL, Cortes J, Giles FJ, Beran M et al. Results of treatment with hyper-CVAD, a dose-intensive regimen in, adult acute lymphocytic leukemia. J Clin Oncol 2000; 18: 547.

    Article  CAS  PubMed  Google Scholar 

  72. Snyder DS . Allogeneic stem cell transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. Biol Blood Marrow Transplant 2000; 6: 597.

    Article  CAS  PubMed  Google Scholar 

  73. Ottmann OG, Druker Bj, Sawyers CL, Goldman JM, Reiffers J, Silver RT, Tura S, Fischer T, Deininger M, Schiffer CA, Baccarini M, Gratwohl A, Hochhaus A, Hoelzer D, Fernandes-Reese S, Gathmann I, Capdeville R, O'Brien S . A phase II trial of imatinib in patients with relapsed or refractory Philadelphia chromosome positive acute lymphoid leukemias. Blood 2002; 100: 1965.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Harper Hospital, Detroit, MI, USA

    C A Schiffer

  2. III. Medizinische Klinik, Universitätsklinikum Mannheim, Universität Heidelberg, Mannheim, Germany

    R Hehlmann

  3. Department of Medicine and Cancer Research Center, Section of Hematology/Oncology, University of Chicago, Chicago, IL, USA

    R Larson

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  1. C A Schiffer
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Additional information

These topics were discussed at the annual meeting of the American Society of Hematology, Orlando, FL, 7–11 December, 2001 in a CME session titled ‘Controversies in the management of CML’ (Moderator: SD Nimer).

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Schiffer, C., Hehlmann, R. & Larson, R. Perspectives on the treatment of chronic phase and advanced phase CML and Philadelphia chromosome positive ALL. Leukemia 17, 691–699 (2003). https://doi.org/10.1038/sj.leu.2402879

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