memo - Magazine of European Medical Oncology

, Volume 5, Issue 4, pp 277–280

“Stem cell transplantation: its importance today”

Chronic myeloid leukaemia: stem cell transplantation versus new drugs
  • Jiri Pavlu
  • Joydeep Chakrabartty
  • Jane F. Apperley
short review


Allogeneic stem cell transplantation (SCT) had traditionally been the first-line therapy of chronic myeloid leukaemia (CML), but the introduction of tyrosine kinase inhibitors (TKI) has caused a major change to the treatment algorithm. The majority of patients in chronic phase obtain an excellent response to these oral agents with minimal toxicity. SCT is therefore used only in a minority of patients who do not achieve adequate response to first-, second- or even third-generation agents. Patients in accelerated phase are less likely to achieve an optimal response and for patients in blast phase, SCT continues to be the only therapy with curative potential although it is now increasingly used in combination with TKI. This review discusses the place of SCT in the current therapy of CML.


Stem cell transplant Chronic myeloid leukaemia Tyrosine kinase inhibitor Toxicity 


  1. 1.
    Pavlu J, Szydlo RM, Goldman JM, Apperley JF. Three decades of transplantation for chronic myeloid leukemia: what have we learned? Blood. 2011;117:755–7.PubMedCrossRefGoogle Scholar
  2. 2.
    Druker B, Guilhot F, O’Brien S, et al. Five-year follow-up of imatinib therapy for newly diagnosed chronic myelogenous leukemia in chronic-phase shows sustained responses and high overall survival. N Engl J Med. 2006;355:2408–17.PubMedCrossRefGoogle Scholar
  3. 3.
    de Lavallade H, Apperley JF, Khorashad JS, et al. Imatinib for newly diagnosed patients with chronic myeloid leukaemia: incidence of sustained responses in an intention-to-treat analysis. J Clin Oncol. 2008;26:3358–63.PubMedCrossRefGoogle Scholar
  4. 4.
    Milojkovic D, Apperley JF, Gerrard G, et al. Responses to second line tyrosine kinase inhibitors are durable: an intention to treat analysis in chronic myeloid leukemia patients. Blood. 2012;119:1838–43.PubMedCrossRefGoogle Scholar
  5. 5.
    Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362:2251–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362:2260–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Garg RJ, Kantarjian H, O’Brien S, et al. The use of nilotinib or dasatinib after failure to 2 prior tyrosine kinase inhibitors: long-term follow-up. Blood. 2009;114:4361–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Cortes JE, Feldman EJ, Yee K, et al. Subset analysis of response to treatment of chronic phase CML in a phase 1 study of ponatinib in refractory hematologic malignancies. Blood. (ASH Annual Meeting Abstracts) 2011;118:602 (Abstract).CrossRefGoogle Scholar
  9. 9.
    Cortes JE, Talpaz M, Kantarjian HM, et al. A phase 1 study of DCC-2036, a novel oral inhibitor of BCR-ABL kinase, in patients with philadelphia chromosome positive (Ph+) leukemias including patients with T315I mutation. Blood. (ASH Annual Meeting Abstracts) 2011;118:601 (Abstract).CrossRefGoogle Scholar
  10. 10.
    Carella AM, Goldman JM, Martinelli G, et al. Chronic myeloid leukemia: the basis of treatment for tomorrow. Haematologica. 2011;96:1737–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol. 2009;27:6041–51.PubMedCrossRefGoogle Scholar
  12. 12.
    Wang L, Pearson K, Ferguson JE, et al. The early molecular response to imatinib predicts cytogenetic and clinical outcome in chronic myeloid leukaemia. Br J Haematol. 2003;120:990–9.Google Scholar
  13. 13.
    Hanfstein B, Muller MC, Hehlmann R, et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia. doi:10.1038/leu.2012.85.Google Scholar
  14. 14.
    Hughes TP, Hochhaus A, Branford S, et al. Long-term prognostic significance of early molecular response to imatinib in newly diagnosed chronic myeloid leukemia: an analysis from the International Randomized Study of Interferon and STI571 (IRIS). Blood. 2010;116:3758–65.PubMedCrossRefGoogle Scholar
  15. 15.
    Marin D, Ibrahim AR, Lucas C, et al. Assessment of BCR-ABL1 transcript levels at 3 months is the only requirement for predicting outcome for patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors. J Clin Oncol. 2012;30:232–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Ibrahim AR, Eliasson L, Apperley JF, et al. Poor adherence is the main reason for loss of CCyR and imatinib failure for CML patients on long term therapy. Blood. 2011;117:3733–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Milojkovic D, Nicholson E, Apperley JF, et al. Early prediction of success or failure using second generation tyrosine kinase inhibitors for chronic myeloid leukemia. Haematologica. 2010;92:224–31.CrossRefGoogle Scholar
  18. 18.
    Gratwohl A, Hermans J, Goldman JM, 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;352:1087–92.PubMedCrossRefGoogle Scholar
  19. 19.
    Passweg JR, Walker I, Sobocinski KA, et al. Validation and extension of the EBMT Risk Score for patients with chronic myeloid leukaemia (CML) receiving allogeneic haematopoietic stem cell transplants. Br J Haematol. 2004;125:613–20.PubMedCrossRefGoogle Scholar
  20. 20.
    Pavlu J, Kew A, Taylor-Roberts B, et al. Optimizing patient selection for allogeneic hematopoietic cell transplantation in chronic myeloid leukaemia in chronic phase. Blood. 2010;115:4018–20.PubMedCrossRefGoogle Scholar
  21. 21.
    Lee SJ, Kukreja M, Wang T, et al. Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia. Blood. 2008;112:3500–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Or R, Shapira MY, Resnick I, et al. Nonmyeloablative allogeneic stem cell transplantation for the treatment of chronic myeloid leukemia in first chronic phase. Blood. 2003;101:441–5.PubMedCrossRefGoogle Scholar
  23. 23.
    Crawley C, Szydlo R, Lalancette M, et al. Outcomes of reduced-intensity transplantation for chronic myeloid leukemia: an analysis of prognostic factors from the Chronic Leukemia Working Party of the EBMT. Blood. 2005;106:2969–76.PubMedCrossRefGoogle Scholar
  24. 24.
    Olavarria E, Siddique S, Griffiths MJ, et al. Posttransplantation imatinib as a strategy to postpone the requirement for immunotherapy in patients undergoing reduced-intensity allografts for chronic myeloid leukemia. Blood. 2007;110:4614–7.PubMedCrossRefGoogle Scholar
  25. 25.
    Rea D, Etienne G, Nicolini F, et al. First-line imatinib mesylate in patients with newly diagnosed accelerated phase-chronic myeloid leukemia. Leukemia. doi:10.1038/leu.2012.92.Google Scholar
  26. 26.
    Kantarjian H, Cortes J, Kim DW, et al. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up. Blood. 2009;113:6322–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Le Coutre PD, Giles FJ, Hochhaus A, et al. Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. Leukemia. 2012;26:1189–94.PubMedCrossRefGoogle Scholar
  28. 28.
    Khoury HJ, Kukreja M, Goldman JM, et al. Prognostic factors for outcomes in allogeneic transplantation for CML in the imatinib era: a CIBMTR analysis. Bone Marrow Transplant. 2012;47:810–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Visani G, Rosti G, Bandini G, et al. Second chronic phase before transplantation is crucial for improving survival of blastic phase chronic myeloid leukaemia. Br J Haematol. 2000;109:722–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Fruehauf S, Topaly J, Buss EC, et al. Imatinib combined with mitoxantrone/etoposide and cytarabine is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis. Cancer. 2007;109:1543–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2012

Authors and Affiliations

  • Jiri Pavlu
    • 1
  • Joydeep Chakrabartty
    • 1
  • Jane F. Apperley
    • 1
  1. 1.Centre for HaematologyImperial College London at Hammersmith Hospital, Catherine Lewis CentreLondonUK

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