Haematopoietic Stem Cell Transplantation in MDS for Adults

  • Tamás Masszi


Myelodysplastic syndromes comprise a heterogeneous group of stem cell diseases. Different classification systems like the French American and British (FAB), the World Health Organization (WHO) and the International Prognostic Scoring System (IPSS) tried to differentiate the specific entities and envisage the prognosis. The spectrum is wide, including indolent diseases with a probability of survival over 10 years but on the other end patients rapidly progress to acute myeloid leukaemia and will die within a few months. However, most studies include different entities making difficult the clear interpretation of results. Most of the MDS patients are elder than 60 years. As life expectancy is increasing in the developed world the prevalence of MDS is increasing as well. Allogeneic haematopoietic stem cell transplantation is considered to be the only curative treatment for MDS but most patients are too old for myeloablative transplant. Moreover, patients over the age of sixty with the worst IPSS scores have the shortest life expectancy with standard care urging more effective treatment modalities. Younger patients with better IPSS scores may survive 5–10 years even with supportive treatment but these younger patients are those, who have the best transplant results and can be cured too. Unfortunately, with standard conditioning even these younger patients have a high probability of transplant related mortality of approximately 30–40%. Finally, it must be emphasized, that there are no large prospective studies comparing stem cell transplantation versus standard chemotherapy or supportive care in MDS. In consequence, the therapeutic decision making on stem cell transplantation is very difficult and debates are ongoing in the field.


Acute GVHD Chronic GVHD Haematopoietic Stem Cell Transplantation International Prognostic Scoring System Reduce Intensity Conditioning 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Cutler CS, Lee SJ, Greenberg P et al (2004) A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood 104(2):579–585PubMedCrossRefGoogle Scholar
  2. 2.
    Kantarjian H, O’Brien S, Ravandi F et al (2008) Proposal for a new risk model in myelodysplastic syndrome that accounts for events not considered in the original International Prognostic Scoring System. Cancer 113(6):1351–1361PubMedCrossRefGoogle Scholar
  3. 3.
    Alessandrino EP, Della Porta MG, Bacigalupo A et al (2008) WHO classification and WPSS predict post transplant outcome in patients with myelodysplastic syndrome: a study from the GITMO (gruppo italiano trapianto di midollo osseo). Blood 112:895–902PubMedCrossRefGoogle Scholar
  4. 4.
    Chang CK, Storer BE, Scott BL et al (2007) Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novodisease and disease following prior therapy or antecedent hematologic disorders. Blood 110:1379–1387PubMedCrossRefGoogle Scholar
  5. 5.
    Scott BL, Storer BE, Greene JE et al (2007) Marrow fibrosis as a risk factor for posttransplantation outcome in patients with advanced myelodysplastic syndrome or acute myeloid leukemia with multilineage dysplasia. Biol Blood Marrow Transplant 13:345–354PubMedCrossRefGoogle Scholar
  6. 6.
    Wallen H, Gooley TA, Deeg HJ et al (2005) Ablative allogeneic hematopoietic cell transplantation in adults 60 years of age and older. J Clin Oncol 23:3439–3446PubMedCrossRefGoogle Scholar
  7. 7.
    Ditschkowski M, Elmaagaeli AH, Trenschel R et al (2006) Myeloablative allogeneic hematopoietic stem cell transplantation in elderly patients. Clin Transplant 20:127–131PubMedCrossRefGoogle Scholar
  8. 8.
    Sorror ML, Maris MB, Storb R et al (2005) Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 106:2912–2919PubMedCrossRefGoogle Scholar
  9. 9.
    Sorror ML, Sandmaier BM, Storer BE et al (2007) Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol 25:4246–4254PubMedCrossRefGoogle Scholar
  10. 10.
    Martino R, Iacobelli S, Brand R et al (2006) Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood 108:836–846PubMedCrossRefGoogle Scholar
  11. 11.
    Martino R, Valcarcel D, Brunet S et al (2008) Comparable non-relapse mortality and survival after HLA-identical sibling blood stem cell transplantation with reduced or conventional-intensity preparative regimens for high-risk myelodysplasia or acute myeloid leukemia in first remission. Bone Marrow Transplant 41:33–38PubMedCrossRefGoogle Scholar
  12. 12.
    Stem Cell Trialists’ Collaborative Group (2005) Allogeneic peripheral blood stem cell compared with bone marrow transplantation in the management of hematologic maligfnancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol 23:5074–5087CrossRefGoogle Scholar
  13. 13.
    Cutler C, Giri S, Jeyapalan S et al (2001) Acute and chronic graft-versus-host disease after allogeneic peripheral-blood stem cell and bone marrow transplantation: a meta-analysis. J Clin Oncol 19:3685–3691PubMedGoogle Scholar
  14. 14.
    Dey BR, Shaffer J, Yee AJ et al (2007) Comparison of outcomes after transplantation of peripheral blood stem cells versus bone marrow following an identical nonmyeloablative conditioning regimen. Bone Marrow Transplant 40:19–27PubMedCrossRefGoogle Scholar
  15. 15.
    Guardiola P, Runde V, Bacigalupo A et al (2002) Retrospective comparison of bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes. Blood 99:4370–4378PubMedCrossRefGoogle Scholar
  16. 16.
    del Canizo MC, Martinez C, Conde E et al (2003) Peripheral blood is safer than bone marrow as a source of hematopoietic progenitors in patients with myelodysplastic syndromes who receive an allogeneic transplantation. Results from the Spanish registry. Bone Marrow Transplant 32:987–992PubMedCrossRefGoogle Scholar
  17. 17.
    de Witte T, Hagemeijer A, Suciu S et al (2010) Value of allogeneic stem cell transplantation (SCT) versus autologous SCT and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergoup Trial. Hematologica. doi:103324/haematol.2009.019182Google Scholar
  18. 18.
    Ducastelle S, Ades L, Gardin C et al (2006) Long-term follow up of autologous stem cell transplantation after intensive chemotherapy in patients with myelodysplastic syndrome or secondary acute myeloid leukemia. Haematologica 91:373–376PubMedGoogle Scholar
  19. 19.
    de Witte T, Brand R, van Biezen A et al (2006) The role of stem cell source in autologous hematopoietic stem cell transplantation for patients with myelodysplastic syndromes. Haematologica 91:750–756PubMedGoogle Scholar
  20. 20.
    de Witte T, Suciu S, Verhoef G et al (2001) Intensive chemotherapy followed by allogeneic or autologous stem cell transplantation for patients with myelodysplastic syndromes (MDSs) and acute myeloid leukemia following MDS. Blood 98:2326–2331PubMedCrossRefGoogle Scholar
  21. 21.
    Kroger N, Brand R, van Biezen A et al (2006) Autologous stem cell transplantation for therapy-related acute myeloid leukemia and myelodysplastic syndrome. Bone Marrow Transplant 37:183–189PubMedCrossRefGoogle Scholar
  22. 22.
    De Witte T, Hermans J, Vossen J et al (2000) Haematopoietic stem cell transplantation for patients with myelodysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the chronic leukemia working party of the European Group for Blood and Marrow Transplantation. Br J Haematol 110:620–630PubMedCrossRefGoogle Scholar
  23. 23.
    Al-Ali HK, Brand R, van Biezen A et al (2007) A retrospective comparison of autologous and unrelated donor hematopoietic cell transplantation in myelodysplastic syndrome and secondary acute myeloid leukemia: a report on behalf of the Chronic Leukemia Working Party of the European Group for Blood and Mararow Transplantation (EBMT). Leukemia 21:1945–1951PubMedCrossRefGoogle Scholar
  24. 24.
    Sierra J, Perez WS, Rozman C et al (2002) Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia. Blood 100:1997–2004PubMedGoogle Scholar
  25. 25.
    Fujimaki K, Taguchi J, Fujita H et al (2004) Thiotepa/cyclophosphamide/TBI as a conditioning regimen for allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome. Bone Marrow Transplant 33:789PubMedCrossRefGoogle Scholar
  26. 26.
    Deeg HJ, Storer B, Slattery J et al (2002) Conditioning with targeted busulfan and cyclophsophamide for hemopoietic stem cell transplantation from related and unrelated donors in patients with myelodysplastic syndrome. Blood 100:1201–1207PubMedCrossRefGoogle Scholar
  27. 27.
    Castro-Malaspina H, Harris RE, Gajewski J et al (2002) Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood 99:1943–1951PubMedCrossRefGoogle Scholar
  28. 28.
    Yakoub-Agha I, de La Salmoniere P, Ribaud P et al (2000) Allogeneic bone marrow transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients—Report of the French Society of Bone Marrow Transplantation. J Clin Oncol 18:963–971PubMedGoogle Scholar
  29. 29.
    Kojima R, Kami M, Kanda Y et al (2005) Comparison between reduced intensity and conventional myeloablative allogeneic stem-cell transplantation in patients with hematologic malignancies aged between 50 and 59 years. Bone Marrow Transplant 36:667–674PubMedCrossRefGoogle Scholar
  30. 30.
    Scott BL, Sandmaier BM, Storer B et al (2006) Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia 20:128–135PubMedCrossRefGoogle Scholar
  31. 31.
    Yakoub Agha I, Mesnil F, Kuentz M et al (2006) Allogeneic marrow stem cell transplantation from human leukocyte antigen-identical siblings versus human leukocyte antigen-allelic-matched unrelated donors (10/10) in patients with standard-risk hematologic malignancy: a prospective study from the French Society of Bone Marrow Transplantation and Cell Therapy. J Clin Oncol 24:5695–5702CrossRefGoogle Scholar
  32. 32.
    de Lima M, Anagnostopoulos A, Munsell M et al (2004) Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 104:865–872PubMedCrossRefGoogle Scholar
  33. 33.
    Tauro S, Craddock C, Peggs K et al (2005) Allogeneic stem cell transplantation used a reduced intensity conditioning regimen has the capacity to produce durable remission and long-term disease free survival in patient with high-risk acute myeloid leukemia and myelodysplasia. J Clin Oncol 23:9387–9393PubMedCrossRefGoogle Scholar
  34. 34.
    Lim ZY, Ho AYL, Ingram W et al (2006) Outcomes of alemtuzumab-based reduced intensity conditioning stem cell transplantation using unrelated donors for myelodysplastic syndromes. Br J Haematol 135:201–209PubMedCrossRefGoogle Scholar
  35. 35.
    Lim ZY, Pearce L, HO AYL et al (2007) Delayed attainment of full donor chimaerism following alemtuzumab-based reduced-intensity conditioning haematopoeitic stem cell transplantation for acute myeloid leukaemia and myelodysplastic syndromes i8s associated with improved outcomes. Br J Haematol 138:517–526Google Scholar
  36. 36.
    Laport GG, Sandmaier BM, Storer BE et al (2008) Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation for adult patients with myelodysplastic syndrome and myeloproliferative disorders. Biol Blood Marrow Transplant 14:246–255PubMedCrossRefGoogle Scholar
  37. 37.
    Valcarcel D, Martino R, Caballero D et al (2008) Sustained remission of high-risk acute myeloid leukemia and myelodysplastic syndrome after reduced intensity conditioning allogeneic hematopoietic transplantation. Chronic graft-versus-host disease is the strongest factor improving survival. J Clin Oncol 26:577–584PubMedCrossRefGoogle Scholar
  38. 38.
    Laughlin M, Eapen M, Rubinstein M et al (2004) Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 351:2265–2275PubMedCrossRefGoogle Scholar
  39. 39.
    Sato A, Ooi J, Takahashi S et al (2010) Unrelated cord blood transplantation after myeloablative conditioning in adults with advanced myeloblastic syndromes. Bone Marrow Transplant. [Epub ahead of print] (9 April 2010; doi: 10.1038/bmt.2010.9).Google Scholar
  40. 40.
    Majhal N, Brunstein C, Toblyn M et al (2008) Reduced-intensity allogeneic transplant in patients older than 55 years: unrelated umbilical cord blood is safe and effective for patients without a matched related donor. Biol Blood Marrow Transplant 14(3):282–289CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Department of Haematology and Stem Cell TransplantationSt. István and St. László Hospital of BudapestBudapestHungary

Personalised recommendations