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Allogeneic stem cell transplantation for chronic myeloid leukemia in the TKI era: population-based data from the Swedish CML registry

Bone Marrow Transplantation (2019) | Download Citation


Two decades after the introduction of tyrosine kinase inhibitors (TKI), a sizeable portion of patients with chronic myeloid leukemia (CML) in chronic phase (CP) still undergo allogeneic stem cell transplantation (allo-HSCT). We investigated the indications for allo-HSCT, clinical outcome, management of relapse, and post-transplant TKI treatment in a population-based setting using the Swedish CML registry. Of 118 CML patients transplanted between 2002 and 2017, 56 (47.4%) received allo-HSCT in first CP, among whom TKI resistance was the most common transplant indication (62.5%). For patients diagnosed with CML in CP at <65 years of age, the cumulative probability of undergoing allo-HSCT within 5 years was 9.7%. Overall 5-year survival was 96.2%, 70.1% and 36.9% when transplanted in first CP, second or later CP, and in accelerated phase or blast crisis, respectively. Risk factors for relapse were EBMT score >2 and reduced intensity conditioning, and for death, CP > 2 at time point of allo-HSCT only. Non-relapse mortality for patients transplanted in CP was 11.6%. Our data indicate that allo-HSCT still constitutes a reasonable therapeutic option for patients with CML in first CP, especially those resistant to TKI treatment, providing high long-term survival and low non-relapse mortality.

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  1. 1.

    Passweg JR, Baldomero H, Bader P, Bonini C, Duarte RF, Dufour C, et al. Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant. 2017;52:811–7.

  2. 2.

    Hoglund M, Sandin F, Hellstrom K, Bjoreman M, Bjorkholm M, Brune M, et al. Tyrosine kinase inhibitor usage, treatment outcome, and prognostic scores in CML: report from the population-based Swedish CML registry. Blood. 2013;122:1284–92.

  3. 3.

    Hoffmann VS, Baccarani M, Hasford J, Castagnetti F, Di Raimondo F, Casado LF, et al. Treatment and outcome of 2904 CML patients from the EUTOS population-based registry. Leukemia. 2017;31:593–601.

  4. 4.

    Bower H, Bjorkholm M, Dickman PW, Hoglund M, Lambert PC, Andersson TM. Life expectancy of patients with chronic myeloid leukemia approaches the life expectancy of the general population. J Clin Oncol: Off J Am Soc Clin Oncol. 2016;34:2851–7.

  5. 5.

    Sasaki K, Strom SS, O’Brien S, Jabbour E, Ravandi F, Konopleva M, et al. Relative survival in patients with chronic-phase chronic myeloid leukaemia in the tyrosine-kinase inhibitor era: analysis of patient data from six prospective clinical trials. Lancet Haematol. 2015;2:e186–193.

  6. 6.

    Innes AJ, Milojkovic D, Apperley JF. Allogeneic transplantation for CML in the TKI era: striking the right balance. Nature reviews. Clin Oncol. 2016;13:79–91.

  7. 7.

    Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122:872–84.

  8. 8.

    Rezvani K, Kanfer EJ, Marin D, Gabriel I, Rahemtulla A, Taylor A, et al. EBMT risk score predicts outcome of allogeneic hematopoietic stem cell transplantation in patients who have failed a previous transplantation procedure. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 2012;18:235–40.

  9. 9.

    Hehlmann R, Berger U, Pfirrmann M, Heimpel H, Hochhaus A, Hasford J, et al. Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia. Blood. 2007;109:4686–92.

  10. 10.

    Lee SJ, Kukreja M, Wang T, Giralt SA, Szer J, Arora M, et al. Impact of prior imatinib mesylate on the outcome of hematopoietic cell transplantation for chronic myeloid leukemia. Blood. 2008;112:3500–7.

  11. 11.

    Kondo T, Nagamura-Inoue T, Tojo A, Nagamura F, Uchida N, Nakamae H, et al. Clinical impact of pretransplant use of multiple tyrosine kinase inhibitors on the outcome of allogeneic hematopoietic stem cell transplantation for chronic myelogenous leukemia. Am J Hematol. 2017;92:902–8.

  12. 12.

    Breccia M, Palandri F, Iori AP, Colaci E, Latagliata R, Castagnetti F, et al. Second-generation tyrosine kinase inhibitors before allogeneic stem cell transplantation in patients with chronic myeloid leukemia resistant to imatinib. Leuk Res. 2010;34:143–7.

  13. 13.

    Höglund M, Olsson K, Sandin F. Kronisk Myeloisk Leukemi. Nationell kvalitetsrapport för 2016. Regional Cancer Centre (RCC) 2017.

  14. 14.

    Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM. et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.

  15. 15.

    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;352:1087–92.

  16. 16.

    Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.

  17. 17.

    Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 2005;11:945–56.

  18. 18.

    Team RCR: A language and environment for statistical computing. R Foundation for Statistical Computing. 2018.

  19. 19.

    Passweg JR, Baldomero H, Bader P, Bonini C, Cesaro S, Dreger P, et al. Impact of drug development on the use of stem cell transplantation: a report by the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2017;52:191–6.

  20. 20.

    Oyekunle A, Zander AR, Binder M, Ayuk F, Zabelina T, Christopeit M, et al. Outcome of allogeneic SCT in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy. Ann Hematol. 2013;92:487–96.

  21. 21.

    Saussele S, Lauseker M, Gratwohl A, Beelen DW, Bunjes D, Schwerdtfeger R, et al. Allogeneic hematopoietic stem cell transplantation (allo SCT) for chronic myeloid leukemia in the imatinib era: evaluation of its impact within a subgroup of the randomized German CML Study IV. Blood. 2010;115:1880–5.

  22. 22.

    Piekarska A, Gil L, Prejzner W, Wisniewski P, Leszczynska A, Gniot M, et al. Pretransplantation use of the second-generation tyrosine kinase inhibitors has no negative impact on the HCT outcome. Ann Hematol. 2015;94:1891–7.

  23. 23.

    Carvalho FR, Zuckermann J, Paz A, Fischer G, Daudt LE, Rigoni LD, et al. Characterization of patients with chronic myeloid leukemia unresponsive to tyrosine kinase inhibitors who underwent allogeneic hematopoietic stem cell transplantation. Int J Hematol-Oncol stem Cell Res. 2017;11:30–36

  24. 24.

    Hehlmann R, Saussele S, Voskanyan A, Silver RT. Management of CML-blast crisis. Best Pract Res Clin Haematol. 2016;29:295–307.

  25. 25.

    Visani G, Rosti G, Bandini G, Tosi P, Isidori A, Malagola M, 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.

  26. 26.

    Khoury HJ, Kukreja M, Goldman JM, Wang T, Halter J, Arora M, 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.

  27. 27.

    Jiang Q, Xu LP, Liu DH, Liu KY, Chen SS, Jiang B, et al. Imatinib mesylate versus allogeneic hematopoietic stem cell transplantation for patients with chronic myelogenous leukemia in the accelerated phase. Blood. 2011;117:3032–40.

  28. 28.

    Rea D, Etienne G, Nicolini F, Cony-Makhoul P, Johnson-Ansah H, Legros L, et al. First-line imatinib mesylate in patients with newly diagnosed accelerated phase-chronic myeloid leukemia. Leukemia. 2012;26:2254–9.

  29. 29.

    Ohanian M, Kantarjian HM, Quintas-Cardama A, Jabbour E, Abruzzo L, Verstovsek S, et al. Tyrosine kinase inhibitors as initial therapy for patients with chronic myeloid leukemia in accelerated phase. Clin Lymphoma, Myeloma & Leuk. 2014;14:155–.e151.

  30. 30.

    Gratwohl A, Pfirrmann M, Zander A, Kroger N, Beelen D, Novotny J, et al. Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment. Leukemia. 2016;30:562–9.

  31. 31.

    Chhabra S, Ahn KW, Hu ZH, Jain S, Assal A, Cerny J, et al. Myeloablative vs reduced-intensity conditioning allogeneic hematopoietic cell transplantation for chronic myeloid leukemia. Blood Adv. 2018;2:2922–36.

  32. 32.

    Liu QF, Xu XJ, Chen YK, Sun J, Zhang Y, Fan ZP, et al. Long-term outcomes of HLA-matched sibling compared with mismatched related and unrelated donor hematopoietic stem cell transplantation for chronic phase chronic myelogenous leukemia: a single institution experience in China. Ann Hematol. 2011;90:331–41.

  33. 33.

    Ma YR, Huang XJ, Xu ZL, Liu KY, Chen H, Zhang XH, et al. Transplantation from haploidentical donor is not inferior to that from identical sibling donor for patients with chronic myeloid leukemia in blast crisis or chronic phase from blast crisis. Clin Transplant. 2016;30:994–1001.

  34. 34.

    Jiang H, Xu LP, Liu DH, Liu KY, Chen SS, Jiang B, et al. Allogeneic hematopoietic SCT in combination with tyrosine kinase inhibitor treatment compared with TKI treatment alone in CML blast crisis. Bone Marrow Transplant. 2014;49:1146–54.

  35. 35.

    Jain NA, Ito S, Tian X, Kurlander R, Battiwalla M, Lu K, et al. Clinical and biological predictors of outcome following relapse of CML post-allo-SCT. Bone Marrow Transplant. 2015;50:189–96.

  36. 36.

    Savani BN, Montero A, Kurlander R, Childs R, Hensel N, Barrett AJ. Imatinib synergizes with donor lymphocyte infusions to achieve rapid molecular remission of CML relapsing after allogeneic stem cell transplantation. Bone Marrow Transplant. 2005;36:1009–15.

  37. 37.

    Xu LP, Xu ZL, Zhang XH, Chen H, Chen YH, Han W, et al. Allogeneic stem cell transplantation for patients with T315I BCR-ABL mutated chronic myeloid leukemia. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 2016;22:1080–6.

  38. 38.

    Miyamoto T, Fukuda T, Nakashima M, Henzan T, Kusakabe S, Kobayashi N, et al. Donor lymphocyte infusion for relapsed hematological malignancies after unrelated allogeneic bone marrow transplantation facilitated by the Japan Marrow Donor Program. Biol Blood Marrow Transplant: J Am Soc Blood Marrow Transplant. 2017;23:938–44.

  39. 39.

    Chalandon Y, Passweg JR, Schmid C, Olavarria E, Dazzi F, Simula MP, et al. Outcome of patients developing GVHD after DLI given to treat CML relapse: a study by the Chronic Leukemia Working Party of the EBMT. Bone Marrow Transplant. 2010;45:558–64.

  40. 40.

    Olavarria E, Siddique S, Griffiths MJ, Avery S, Byrne JL, Piper KP, 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.

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We thank all Swedish hematologists and study nurses who have reported patients to the Swedish CML registry. We also appreciate the work of data managers at the respective Regional Cancer Centers.

Author information


  1. Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Lund, Sweden

    • Anna Lübking
    • , Stig Lenhoff
    •  & Johan Richter
  2. Department of Hematology, Linköping University Hospital, Linköping, Sweden

    • Arta Dreimane
  3. Regional Cancer Centre, Uppsala University Hospital, Uppsala, Sweden

    • Fredrik Sandin
  4. Department of Hematology, Umeå University Hospital, Umeå, Sweden

    • Cecilia Isaksson
    •  & Berit Märkevärn
  5. Department of Hematology and Coagulation, Sahlgrenska University Hospital, Gothenburg, Sweden

    • Mats Brune
  6. Department of Cellular Therapy and Allogeneic Stem Cell Transplantation, Karolinska University Hospital and Section of Hematology, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden

    • Per Ljungman
  7. Department of Medicine, Division of Hematology, Karolinska University Hospital Solna, Stockholm, Sweden

    • Leif Stenke
  8. Department of Medical Sciences, Division of Hematology, Uppsala University Hospital, Uppsala, Sweden

    • Martin Höglund
    •  & Ulla Olsson-Strömberg


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UOS, AL, AD, JR, LS, MH and SL contributed to the conception and design of the study. UOS and AL coordinated the project, analyzed the data and wrote the manuscript. UOS, AL, AD, CI, BM, MB, and PL contributed to the collection and assembly of data. FS contributed to analysis, statistical methodology and manuscript writing. All authors contributed to critical revision of the manuscript. All authors read and approved the final manuscript.

Conflict of interest

UOS has received honoraria from Ariad. JR has received honoraria and research funding from Novartis and Bristol-Myers Squibb, and honoraria from Ariad. AL, AD, BM, CI, LS, FS, MB, MH, PL and SL report no disclosures.

Corresponding author

Correspondence to Anna Lübking.

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