Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Autografting

Current status of allogeneic HST for chronic myelomonocytic leukemia

Abstract

Allogeneic hematopoietic SCT (HST) offers the only curative potential for patients with chronic myelomonocytic leukemia (CMML). However, there is a paucity of data addressing this approach in CMML. The disease is a relatively under-represented myelodysplastic (MDS)/myeloproliferative subtype among transplant eligible patients. Non-randomized studies suggest that long-term remissions are achievable when using myeloablative or reduced intensity conditioning transplantation. Allogeneic SCT for CMML is often reported as part of MDS registry data. The largest series in adult patients reported a disappointing long-term relapse-free survival (RFS) of 18%. The Fred Hutchinson Cancer and Research Center group reported a 40% long-term RFS for a mixed group of adults and children with CMML who were transplanted over two decades. In this study, we performed a literature search and reviewed available data for adult CMML patients undergoing HST. The dearth of data that span two decades with changing transplant practices prohibited us from performing a formal meta-analysis. However, we elected to present the current status of HST in adult CMML patients. Carefully selected CMML patients may have the most benefit from this curative approach.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Saarni MI, Linman JW . Myelomonocytic leukemia: disorderly proliferation of all marrow cells. Cancer 1971; 27: 1221–1230.

    Article  CAS  PubMed  Google Scholar 

  2. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC: Lyon, France, 2008.

    Google Scholar 

  3. Onida F, Kantarjian HM, Smith TL, Ball G, Keating MJ, Estey EH et al. Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients. Blood 2002; 99: 840–849.

    Article  CAS  PubMed  Google Scholar 

  4. Worsley A, Oscier DG, Stevens J, Darlow S, Figes A, Mufti GJ et al. Prognostic features of chronic myelomonocytic leukaemia: a modified Bournemouth score gives the best prediction of survival. Br J Haematol 1988; 68: 17–21.

    Article  CAS  PubMed  Google Scholar 

  5. Gonzalez-Medina I, Bueno J, Torrequebrada A, Lopez A, Vallespi T, Massague I . Two groups of chronic myelomonocytic leukaemia: myelodysplastic and myeloproliferative. Prognostic implications in a series of a single center. Leuk Res 2002; 26: 821–824.

    Article  CAS  PubMed  Google Scholar 

  6. Germing U, Strupp C, Knipp S, Kuendgen A, Giagounidis A, Hildebrandt B et al. Chronic myelomonocytic leukemia in the light of the WHO proposals. Haematologica 2007; 92: 974–977.

    Article  PubMed  Google Scholar 

  7. Germing U, Strupp C, Aivado M, Gattermann N . New prognostic parameters for chronic myelomonocytic leukemia. Blood 2002; 100: 731–732; author reply 732–733.

    Article  CAS  PubMed  Google Scholar 

  8. Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009; 360: 2289–2301.

    Article  PubMed  Google Scholar 

  9. Grand FH, Hidalgo-Curtis CE, Ernst T, Zoi K, Zoi C, McGuire C et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood 2009; 113: 6182–6192.

    Article  CAS  PubMed  Google Scholar 

  10. Pich A, Riera L, Sismondi F, Godio L, Davico Bonino L, Marmont F et al. JAK2V617F activating mutation is associated with the myeloproliferative type of chronic myelomonocytic leukaemia. J Clin Pathol 2009; 62: 798–801.

    Article  CAS  PubMed  Google Scholar 

  11. Tyner JW, Erickson H, Deininger MW, Willis SG, Eide CA, Levine RL et al. High-throughput sequencing screen reveals novel, transforming RAS mutations in myeloid leukemia patients. Blood 2009; 113: 1749–1755.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kohlmann A, Grossmann V, Klein HU, Schindela S, Weiss T, Kazak B et al. Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1. J Clin Oncol 2010; 28: 3858–3865.

    Article  CAS  PubMed  Google Scholar 

  13. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.

    CAS  PubMed  Google Scholar 

  14. Wattel E, Guerci A, Hecquet B, Economopoulos T, Copplestone A, Mahe B et al. A randomized trial of hydroxyurea versus VP16 in adult chronic myelomonocytic leukemia. Groupe Francais des Myelodysplasies and European CMML Group. Blood 1996; 88: 2480–2487.

    CAS  PubMed  Google Scholar 

  15. Beran M, Estey E, O’Brien SM, Giles FJ, Koller CA, Kornblau S et al. Results of topotecan single-agent therapy in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia. Leuk Lymphoma 1998; 31: 521–531.

    Article  CAS  PubMed  Google Scholar 

  16. Kantarjian H, Beran M, Cortes J, O’Brien S, Giles F, Pierce S et al. Long-term follow-up results of the combination of topotecan and cytarabine and other intensive chemotherapy regimens in myelodysplastic syndrome. Cancer 2006; 106: 1099–1109.

    Article  CAS  PubMed  Google Scholar 

  17. Fenaux P, Raza A, Mufti GJ, Aul C, Germing U, Kantarjian H et al. A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome. Blood 2007; 109: 4158–4163.

    Article  CAS  PubMed  Google Scholar 

  18. Tessema M, Langer F, Dingemann J, Ganser A, Kreipe H, Lehmann U . Aberrant methylation and impaired expression of the p15(INK4b) cell cycle regulatory gene in chronic myelomonocytic leukemia (CMML). Leukemia 2003; 17: 910–918.

    Article  CAS  PubMed  Google Scholar 

  19. Wijermans PW, Ruter B, Baer MR, Slack JL, Saba HI, Lubbert M . Efficacy of decitabine in the treatment of patients with chronic myelomonocytic leukemia (CMML). Leuk Res 2008; 32: 587–591.

    Article  CAS  PubMed  Google Scholar 

  20. Kantarjian H, Oki Y, Garcia-Manero G, Huang X, O’Brien S, Cortes J et al. Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 2007; 109: 52–57.

    Article  CAS  PubMed  Google Scholar 

  21. Silverman LR, McKenzie DR, Peterson BL, Holland JF, Backstrom JT, Beach CL et al. Cancer and Leukemia Group B. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921 and 9221 by the Cancer and Leukemia Group. Br J Clin Oncol 2006; 24: 3895–3903.

    Article  CAS  Google Scholar 

  22. Aribi A, Borthakur G, Ravandi F, Shan J, Davisson J, Cortes J et al. Activity of decitabine, a hypomethylating agent, in chronic myelomonocytic leukemia. Cancer 2007; 109: 713–717.

    Article  CAS  PubMed  Google Scholar 

  23. Arnold R, de Witte T, van Biezen A, Hermans J, Jacobsen N, Runde V et al. Unrelated bone marrow transplantation in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: an EBMT survey. European Blood and Marrow Transplantation Group. Bone Marrow Transplant 1998; 21: 1213–1216.

    Article  CAS  PubMed  Google Scholar 

  24. Chang KL, O’Donnell MR, Slovak ML, Dagis AC, Arber DA, Niland JC et al. Primary myelodysplasia occurring in adults under 50 years old: a clinicopathologic study of 52 patients. Leukemia 2002; 16: 623–631.

    Article  CAS  PubMed  Google Scholar 

  25. Deeg HJ, Shulman HM, Anderson JE, Bryant EM, Gooley TA, Slattery JT et al. Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age. Blood 2000; 95: 1188–1194.

    CAS  PubMed  Google Scholar 

  26. Elliott MA, Tefferi A, Hogan WJ, Letendre L, Gastineau DA, Ansell SM et al. Allogeneic stem cell transplantation and donor lymphocyte infusions for chronic myelomonocytic leukemia. Bone Marrow Transplant 2006; 37: 1003–1008.

    Article  CAS  PubMed  Google Scholar 

  27. Gergis U, Wissa U . High-risk myelodysplastic syndromes: chemotherapy, transplantation, and beyond. Curr Hematol Malig Rep 2010; 5: 1–8.

    Article  PubMed  Google Scholar 

  28. Kerbauy DM, Chyou F, Gooley T, Sorror ML, Scott B, Pagel JM et al. Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia. Biol Blood Marrow Transplant 2005; 11: 713–720.

    Article  PubMed  Google Scholar 

  29. Krishnamurthy P, Lim ZY, Nagi W, Kenyon M, Mijovic A, Ireland R et al. Allogeneic haematopoietic SCT for chronic myelomonocytic leukaemia: a single-centre experience. Bone Marrow Transplant 2010; 45: 1502–1507.

    Article  CAS  PubMed  Google Scholar 

  30. Kroger N, Bornhauser M, Ehninger G, Schwerdtfeger R, Biersack H, Sayer HG et al. Allogeneic stem cell transplantation after a fludarabine/busulfan-based reduced-intensity conditioning in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Ann Hematol 2003; 82: 336–342.

    Article  CAS  PubMed  Google Scholar 

  31. Kroger N, Zabelina T, Guardiola P, Runde V, Sierra J, Van Biezen A et al. Allogeneic stem cell transplantation of adult chronic myelomonocytic leukaemia. A report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 2002; 118: 67–73.

    Article  PubMed  Google Scholar 

  32. Laport GG, Sandmaier BM, Storer BE, Scott BL, Stuart MJ, Lange T et al. Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol Blood Marrow Transplant 2008; 14: 246–255.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lim Z, Brand R, Martino R, van Biezen A, Finke J, Bacigalupo A et al. Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol 2010; 28: 405–411.

    Article  PubMed  Google Scholar 

  34. Mittal P, Saliba RM, Giralt SA, Shahjahan M, Cohen AI, Karandish S et al. Allogeneic transplantation: a therapeutic option for myelofibrosis, chronic myelomonocytic leukemia and Philadelphia-negative/BCR-ABL-negative chronic myelogenous leukemia. Bone Marrow Transplant 2004; 33: 1005–1009.

    Article  CAS  PubMed  Google Scholar 

  35. Nelson Jr RP, Yu M, Schwartz JE, Robertson MJ, Hromas R, Fausel CA et al. Long-term disease-free survival after nonmyeloablative cyclophosphamide/fludarabine conditioning and related/unrelated allotransplantation for acute myeloid leukemia/myelodysplasia. Bone Marrow Transplant 2010; 45: 1300–1308.

    Article  CAS  PubMed  Google Scholar 

  36. Ocheni S, Kroger N, Zabelina T, Zander AR, Bacher U . Outcome of allo-SCT for chronic myelomonocytic leukemia. Bone Marrow Transplant 2009; 43: 659–661.

    Article  CAS  PubMed  Google Scholar 

  37. Runde V, de Witte T, Arnold R, Gratwohl A, Hermans J, van Biezen A et al. Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant 1998; 21: 255–261.

    Article  CAS  PubMed  Google Scholar 

  38. Tse W, Deeg HJ . Hematopoietic cell transplantation for chronic myeloproliferative disorders. Arch Immunol Ther Exp (Warsz) 2006; 54: 375–380.

    Article  Google Scholar 

  39. Zang DY, Deeg HJ, Gooley T, Anderson JE, Anasetti C, Sanders J et al. Treatment of chronic myelomonocytic leukaemia by allogeneic marrow transplantation. Br J Haematol 2000; 110: 217–222.

    Article  CAS  PubMed  Google Scholar 

  40. Eissa H, Gooley TA, Sorror ML, Nguyen F, Scott BL, Doney K et al. Allogeneic hematopoietic cell transplantation for chronic myelomonocytic leukemia: relapse-free survival is determined by karyotype and comorbidities. Biol Blood Marrow Transplant 2010; 17: 908–915.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Sorror M, Storer B, Sandmaier BM, Maloney DG, Chauncey TR, Langston A et al. Hematopoietic cell transplantation–comorbidity index and Karnofsky performance status are independent predictors of morbidity and mortality after allogeneic nonmyeloablative hematopoietic cell transplantation. Cancer 2008; 112: 1992–2001.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to U Gergis.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheng, H., Kirtani, V. & Gergis, U. Current status of allogeneic HST for chronic myelomonocytic leukemia. Bone Marrow Transplant 47, 535–541 (2012). https://doi.org/10.1038/bmt.2011.141

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/bmt.2011.141

Keywords

This article is cited by

Search

Quick links