Abstract
The choice of primary treatment for patients with chronic myeloid leukaemia diagnosed in chronic phase has become exceedingly difficult. There is little doubt that allogeneic stem cell transplantation (allo-SCT) can eradicate the leukaemia and that a ‘graf-versus-leukaemia’ effect makes a major contribution to this result; conversely only a minority of patients are eligible for transplant, which still carries an appreciable risk of mortality or protracted morbidity. For the majority of patients interferon-alpha prolongs life to some degree in comparison with hydroxyurea but is associated with considerable toxicity. the newly introduced tyrosine kinase inhibitor imatinib mesylate (imatinib, Glivec) induces complete haematologic remission in almost all cases and is associated with a very high incidence of cytogenetic response; its capacity to prolong life in comparison with interferon-alpha is not yet established. Here we review some factors that predict survival after non-transplant therapy and after allografting for CML in chronic phase. We consider two contrasting options for managing the newly diagnosed patient and conclude that for the present allogeneic stem cell transplantation soon after diagnosis should continue to be offered as an option for selected patients. Further experience with the use of imatinib as a single agent or in combination with other anti-leukemic agents may alter the picture in the near future.
Similar content being viewed by others
References
Barrett AJ, Malkovska V. Graft-versus-leukaemia: understanding and using the allo-immune response to treat haematological malignancies.Brit J Haematol. 1996;93:754–761.
Huntly B, Reid AG, Bench AJ, et al. Deletions of the derivative chromosome 9 occur at the time of Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia.Blood. 2001; 98:1732–1738.
Brummendorf TH, Holyoake TL, Rufer N, et al. Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry.Blood. 2000;95:1883–1890.
Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in ‘good risk; chronic granulocytic leukemia.Blood. 1984;63:789–799.
Hasford J, Pfirrmann J, Hehlmann R, et al. A new prognostic score for survival of patients with chronic myeloid leukemia treated with interferon alfa.J Nat Cancer Inst. 1998;90:850–858.
Mahon F, Faberes C, Pueyo S, et al. Response at three months is a good predictive factor for newly diagnosed chronic myeloid leukemia patients treated with recombinant interferon-a.Blood. 1998;92:4059–4065.
Goldman JM, Szydlo R, Horowitz, MM, et al. Choice of pretransplant treatment and timing of transplants for chronic myelogenous leukemia in chronic phase.Blood. 1993;82:2235–2238.
Lee SJ, Kuntz KM, Horowitz MM, et al. Unrelated donor bone marrow transplantation for chronic myeloid leukemia: a decision analysis.Ann Intern Med. 1997;127:1080–1088.
Hehlmann R, Hochhaus A, Kolb H-J, et al. Interferon-a 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.
Gratwohl A, Hermans J, Goldman JM, et al. Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation.Lancet. 1998;352:1087–1092.
McGlave PB, Shu XU, Wen W, et al. Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years experience of the National Marrow Donor Program.Blood. 2000;95:2219–2225.
Craddock C, Szydlo RM, Dazzi F, et al. CMV serostatus is a major determinant of outcome after T-depleted unrelated donor transplant in patients with chronic myeloid leukaemia: the case for tailored GVHD prophylaxis.Brit J Haematol. 2001, 112:228–236.
Barrett AJ, Childs R. Non myeloablative stem cell transplants.Brit J Haematol. 2000;111:6–17.
Champlin RE, Khouri I, Shimoni A, et al. Harnessing graftversus-malignancy: non-myeloablative preparative regimens for allogeneic haematopoietic transplantation, an evolving strategy for adoptive immunotherapy.Brit J Haematol. 2000;111:18–29.
Druker BJ, Tamura S, Buchdunger E, et al. Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of BCR-ABL positive cells.Nature Medicine. 1996;2:561–566.
Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia.New Engl J Med. 2001;344:1031–1037.
Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia.New Engl J Med. 2002;346:645–652.
Hochhaus A, Reiter A, Saussele S, et al. Molecular heterogeneity in complete cytogenetic responders after interferon-a therapy for chronic myelogenous leukemia: low levels of minimal residual disease are associated with continuing remission.Blood. 2000;95:62–66.
Goldman JM, Druker BJ. Chronic myeloid leukemia: current treatment options.Blood. 2001:98:2039–2042.
Author information
Authors and Affiliations
About this article
Cite this article
Goldman, J.M. Treatment of chronic myeloid leukaemia lessons and challenges. Int J Hematol 76 (Suppl 2), 189–192 (2002). https://doi.org/10.1007/BF03165116
Issue Date:
DOI: https://doi.org/10.1007/BF03165116