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Treatment of Older Patients with High-Risk Myelodysplastic Syndromes (MDS): The Emerging Role of Allogeneic Hematopoietic Stem Cell Transplantation (Allo HSCT)

Current Hematologic Malignancy Reports volume 9, pages 57–65 (2014)Cite this article

Abstract

MDS are myeloid clonal hematologic disorders that are most commonly diagnosed in the seventh decade of life. Several treatment options are currently available. However, allo HSCT remains the only curative therapy. Unfortunately, despite the higher incidence of MDS in the older population, less than 10 % of patients undergoing allo HSCT for MDS are > 65 years old. In this paper we discuss the various treatment options in older patients with high-risk MDS with particular emphasis on the role of allo HSCT in older MDS patients.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Raza A, Galili N. The genetic basis of phenotypic heterogeneity in myelodysplastic syndromes. Nat Rev Cancer. 2012;12(12):849–59.

    Article  CAS  PubMed  Google Scholar 

  2. Rollison DE, Howlader N, Smith MT, Strom SS, Merritt WD, Ries LA, et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001–2004, using data from the NAACCR and SEER programs. Blood. 2008;112(1):45–52.

    Article  CAS  PubMed  Google Scholar 

  3. Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004;104(8):2263–8.

    Article  CAS  PubMed  Google Scholar 

  4. Cogle CR, Craig BM, Rollison DE, List AF. Incidence of the myelodysplastic syndromes using a novel claims-based algorithm: high number of uncaptured cases by cancer registries. Blood. 2011;117(26):7121–5.

    Article  CAS  PubMed  Google Scholar 

  5. Goldberg SL, Chen E, Corral M, Guo A, Mody-Patel N, Pecora AL, et al. Incidence and clinical complications of myelodysplastic syndromes among United States Medicare beneficiaries. J Clin Oncol. 2010;28(17):2847–52.

    Article  PubMed  Google Scholar 

  6. Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer. 2007;109(8):1536–42.

    Article  PubMed  Google Scholar 

  7. 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(6):2079–88.

    CAS  PubMed  Google Scholar 

  8. • Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454–65. The revised IPSS score refined the prognostication of patients with MDS.

    Article  CAS  PubMed  Google Scholar 

  9. Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Perez WS, Anasetti C, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood. 2004;104(2):579–85.

    Article  CAS  PubMed  Google Scholar 

  10. Garcia-Manero G, Shan J, Faderl S, Cortes J, Ravandi F, Borthakur G, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia. 2008;22(3):538–43.

    Article  CAS  PubMed  Google Scholar 

  11. Malcovati L, Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005;23(30):7594–603.

    Article  PubMed  Google Scholar 

  12. Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25(23):3503–10.

    Article  PubMed  Google Scholar 

  13. Garcia-Manero G. Myelodysplastic syndromes: 2012 update on diagnosis, risk-stratification, and management. Am J Hematol. 2012;87(7):692–701.

    Article  PubMed  Google Scholar 

  14. Koreth J, Pidala J, Perez WS, Deeg HJ, Garcia-Manero G, Malcovati L, et al. Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis. J Clin Oncol. 2013;31(21):2662–70.

    Article  PubMed  Google Scholar 

  15. Welniak LA, Blazar BR, Murphy WJ. Immunobiology of allogeneic hematopoietic stem cell transplantation. Annu Rev Immunol. 2007;25:139–70.

    Article  CAS  PubMed  Google Scholar 

  16. Greenberg PL, Attar E, Bennett JM, Bloomfield CD, Borate U, De Castro CM, et al. Myelodysplastic syndromes. J Natl Compr Canc Netw. 2013;11(7):838–74.

    CAS  PubMed  Google Scholar 

  17. • 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(3):405–11. EBMTR data showing no difference in post allo-HSCT survival based on age alone.

    Article  PubMed  Google Scholar 

  18. • McClune BL, Weisdorf DJ, Pedersen TL, Tunes da Silva G, Tallman MS, Sierra J, et al. Effect of age on outcome of reduced-intensity hematopoietic cell transplantation for older patients with acute myeloid leukemia in first complete remission or with myelodysplastic syndrome. J Clin Oncol. 2010;28(11):1878–87. CIBMTR data showing no difference in post allo-HSCT survival based on age alone.

    Article  PubMed  Google Scholar 

  19. Atallah E, Pedersen TL, Warlick ED, Dircks A, Weisdorf D, Horowitz MM, et al. The outcome of Hematopoietic Cell Transplantation (HCT) for Myelodysplastic Syndrome (MDS) in adults >=65 years of age: first report of the Coverage with Evidence Development (CED) in medicare beneficiaries. ASH Annual Meeting Abstracts. 2012;120(21):1983.

    Google Scholar 

  20. Pasquini MC, Wang Z. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR Summary Slides, 2010. 2010 [updated 2010; cited 2011 June 16]; Available from: http://www.cibmtr.org.

  21. Nakamura R, Rodriguez R, Palmer J, Stein A, Naing A, Tsai N, et al. Reduced-intensity conditioning for allogeneic hematopoietic stem cell transplantation with fludarabine and melphalan is associated with durable disease control in myelodysplastic syndrome. Bone Marrow Transplant. 2007;40(9):843–50.

    Article  CAS  PubMed  Google Scholar 

  22. Oran B, Giralt S, Saliba R, Hosing C, Popat U, Khouri I, et al. Allogeneic hematopoietic stem cell transplantation for the treatment of high-risk acute myelogenous leukemia and myelodysplastic syndrome using reduced-intensity conditioning with fludarabine and melphalan. Biol Blood Marrow Transplant. 2007;13(4):454–62.

    Article  CAS  PubMed  Google Scholar 

  23. 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(2):246–55.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Allogeneic hematopoietic stem cell transplantation for the treatment of myelodysplastic syndromes. [cited 2013 August 8]; Available from: http://www.cms.gov/Medicare/Coverage/Coverage-with-Evidence-Development/Allogeneic-Hematopoietic-Stem-Cell-Transplantation-for-the-treatment-of-Myelodysplastic-Syndromes-.html.

  25. ClinicalTrials.gov. 5-azacytidine treatment versus 5-azacytidine followed by allogeneic stem cell transplantation in elderly patients with Myelodysplastic Syndrome (MDS). 2011 [updated 2011; cited 2012 December 19]; Available from: http://clinicaltrials.gov/show/NCT01404741.

  26. Rodin MB, Mohile SG. A practical approach to geriatric assessment in oncology. J Clin Oncol. 2007;25(14):1936–44.

    Article  PubMed  Google Scholar 

  27. Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, et al. Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer. 2012;118(13):3377–86.

    Article  PubMed  Google Scholar 

  28. Caillet P, Canoui-Poitrine F, Vouriot J, Berle M, Reinald N, Krypciak S, et al. Comprehensive geriatric assessment in the decision-making process in elderly patients with cancer: ELCAPA study. J Clin Oncol. 2011;29(27):3636–42.

    Article  PubMed  Google Scholar 

  29. Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol. 2011;29(25):3457–65.

    Article  CAS  PubMed  Google Scholar 

  30. Soubeyran P, Fonck M, Blanc-Bisson C, Blanc JF, Ceccaldi J, Mertens C, et al. Predictors of early death risk in older patients treated with first-line chemotherapy for cancer. J Clin Oncol. 2012;30(15):1829–34.

    Article  PubMed  Google Scholar 

  31. Kanesvaran R, Li H, Koo KN, Poon D. Analysis of prognostic factors of comprehensive geriatric assessment and development of a clinical scoring system in elderly Asian patients with cancer. J Clin Oncol. 2011;29(27):3620–7.

    Article  PubMed  Google Scholar 

  32. Naqvi K, Garcia-Manero G, Sardesai S, Oh J, Vigil CE, Pierce S, et al. Association of comorbidities with overall survival in myelodysplastic syndrome: development of a prognostic model. J Clin Oncol. 2011;29(16):2240–6.

    Article  PubMed  Google Scholar 

  33. Deschler B, Ihorst G, Platzbecker U, Germing U, Marz E, de Figuerido M, et al. Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica. 2013;98(2):208–16.

    Article  PubMed  Google Scholar 

  34. Muffly LS, Boulukos M, Swanson K, Kocherginsky M, Cerro PD, Schroeder L, et al. Pilot study of comprehensive geriatric assessment (CGA) in allogeneic transplant: CGA captures a high prevalence of vulnerabilities in older transplant recipients. Biol Blood Marrow Transplant. 2013;19(3):429–34.

    Article  PubMed  Google Scholar 

  35. Scott BL, Deeg HJ. Myelodysplastic syndromes. Annu Rev Med. 2010;61:345–58.

    Article  CAS  PubMed  Google Scholar 

  36. Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol. 2002;20(10):2429–40.

    Article  CAS  PubMed  Google Scholar 

  37. • Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol. 2009;10(3):223–32. First study to show definitive improvement in overall survival with hypomethylating agents.

    Article  CAS  PubMed  Google Scholar 

  38. Itzykson R, Thepot S, Quesnel B, Dreyfus F, Beyne-Rauzy O, Turlure P, et al. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117(2):403–11.

    Article  CAS  PubMed  Google Scholar 

  39. Itzykson R, Thepot S, Quesnel B, Dreyfus F, Recher C, Wattel E, et al. Long-term outcome of higher-risk MDS patients treated with azacitidine: an update of the GFM compassionate program cohort. Blood. 2012;119(25):6172–3.

    Article  CAS  PubMed  Google Scholar 

  40. Kantarjian H, Issa JP, Rosenfeld CS, Bennett JM, Albitar M, DiPersio J, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106(8):1794–803.

    Article  CAS  PubMed  Google Scholar 

  41. Lubbert M, Suciu S, Baila L, Ruter BH, Platzbecker U, Giagounidis A, et al. Low-dose decitabine versus best supportive care in elderly patients with intermediate- or high-risk myelodysplastic syndrome (MDS) ineligible for intensive chemotherapy: final results of the randomized phase III study of the European Organisation for Research and Treatment of Cancer Leukemia Group and the German MDS Study Group. J Clin Oncol. 2011;29(15):1987–96.

    Article  PubMed  Google Scholar 

  42. Steensma DP, Baer MR, Slack JL, Buckstein R, Godley LA, Garcia-Manero G, et al. Multicenter study of decitabine administered daily for 5 days every 4 weeks to adults with myelodysplastic syndromes: the alternative dosing for outpatient treatment (ADOPT) trial. J Clin Oncol. 2009;27(23):3842–8.

    Article  CAS  PubMed  Google Scholar 

  43. List A, Dewald G, Bennett J, Giagounidis A, Raza A, Feldman E, et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006;355(14):1456–65.

    Article  CAS  PubMed  Google Scholar 

  44. Raza A, Reeves JA, Feldman EJ, Dewald GW, Bennett JM, Deeg HJ, et al. Phase 2 study of lenalidomide in transfusion-dependent, low-risk, and intermediate-1 risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008;111(1):86–93.

    Article  CAS  PubMed  Google Scholar 

  45. Ades L, Boehrer S, Prebet T, Beyne-Rauzy O, Legros L, Ravoet C, et al. Efficacy and safety of lenalidomide in intermediate-2 or high-risk myelodysplastic syndromes with 5q deletion: results of a phase 2 study. Blood. 2009;113(17):3947–52.

    Article  CAS  PubMed  Google Scholar 

  46. Itzykson R, Kosmider O, Cluzeau T, Mansat-De Mas V, Dreyfus F, Beyne-Rauzy O, et al. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia. 2011;25(7):1147–52.

    Article  CAS  PubMed  Google Scholar 

  47. Blum W, Garzon R, Klisovic RB, Schwind S, Walker A, Geyer S, et al. Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine. Proc Natl Acad Sci U S A. 2010;107(16):7473–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Platzbecker U, Schetelig J, Finke J, Trenschel R, Scott BL, Kobbe G, et al. Allogeneic hematopoietic cell transplantation in patients age 60–70 years with de novo high-risk myelodysplastic syndrome or secondary acute myelogenous leukemia: comparison with patients lacking donors who received azacitidine. Biol Blood Marrow Transplant. 2012;18(9):1415–21.

    Article  PubMed  Google Scholar 

  49. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51(2):189–99.

    Article  CAS  PubMed  Google Scholar 

  50. Wheatley K, Gray R. Commentary: Mendelian randomization-an update on its use to evaluate allogeneic stem cell transplantation in leukaemia. Int J Epidemiol. 2004;33(1):15–7.

    Article  PubMed  Google Scholar 

  51. Burnett AK, Hills RK, Milligan DW, Goldstone AH, Prentice AG, McMullin MF, et al. Attempts to optimize induction and consolidation treatment in acute myeloid leukemia: results of the MRC AML12 trial. J Clin Oncol. 2010;28(4):586–95.

    Article  CAS  PubMed  Google Scholar 

  52. Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea 3rd E, et al. Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011;12(13):1195–203.

    Article  PubMed Central  PubMed  Google Scholar 

  53. Cassileth PA, Harrington DP, Appelbaum FR, Lazarus HM, Rowe JM, Paietta E, et al. Chemotherapy compared with autologous or allogeneic bone marrow transplantation in the management of acute myeloid leukemia in first remission. N Engl J Med. 1998;339(23):1649–56.

    Article  CAS  PubMed  Google Scholar 

  54. Reiffers J, Stoppa AM, Attal M, Michallet M, Marit G, Blaise D, et al. Allogeneic vs autologous stem cell transplantation vs chemotherapy in patients with acute myeloid leukemia in first remission: the BGMT 87 study. Leukemia. 1996;10(12):1874–82.

    CAS  PubMed  Google Scholar 

  55. Mohty M, de Lavallade H, Ladaique P, Faucher C, Vey N, Coso D, et al. The role of reduced intensity conditioning allogeneic stem cell transplantation in patients with acute myeloid leukemia: a donor vs no donor comparison. Leukemia. 2005;19(6):916–20.

    Article  CAS  PubMed  Google Scholar 

  56. Logan B, Leifer E, Bredeson C, Horowitz M, Ewell M, Carter S, et al. Use of biological assignment in hematopoietic stem cell transplantation clinical trials. Clin Trials. 2008;5(6):607–16.

    Article  PubMed Central  PubMed  Google Scholar 

  57. Lim ZY, Fiaccadori V, Gandhi S, Hayden J, Kenyon M, Ireland R, et al. Impact of pre-transplant serum ferritin on outcomes of patients with myelodysplastic syndromes or secondary acute myeloid leukaemia receiving reduced intensity conditioning allogeneic haematopoietic stem cell transplantation. Leuk Res. 2010;34(6):723–7.

    Article  CAS  PubMed  Google Scholar 

  58. Armand P, Kim HT, Rhodes J, Sainvil MM, Cutler C, Ho VT, et al. Iron overload in patients with acute leukemia or MDS undergoing myeloablative stem cell transplantation. Biol Blood Marrow Transplant. 2011;17(6):852–60.

    Article  CAS  PubMed  Google Scholar 

  59. Bejar R, Stevenson K, Abdel-Wahab O, Galili N, Nilsson B, Garcia-Manero G, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496–506.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  60. Bejar R, Stevenson KE, Stojanov P, Zaneveld JE, Bar-Natan M, Caughey B, et al. Detection of recurrent mutations by pooled targeted next-generation sequencing in MDS patients prior to treatment with hypomethylating agents or stem cell transplantation. ASH Annual Meeting Abstracts. 2012;120(21):311.

    Google Scholar 

  61. Walter MJ, Shen D, Shao J, Ding L, White BS, Kandoth C, et al. Clonal diversity of recurrently mutated genes in myelodysplastic syndromes. Leukemia. 2013 Feb 27.

  62. Field T, Perkins J, Huang Y, Kharfan-Dabaja MA, Alsina M, Ayala E, et al. 5-Azacitidine for myelodysplasia before allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2010;45(2):255–60.

    Article  CAS  PubMed  Google Scholar 

  63. Scott BL, Storer B, Loken MR, Storb R, Appelbaum FR, Deeg HJ. Pretransplantation induction chemotherapy and posttransplantation relapse in patients with advanced myelodysplastic syndrome. Biol Blood Marrow Transplant. 2005;11(1):65–73.

    Article  PubMed  Google Scholar 

  64. Platzbecker U, Wermke M, Radke J, Oelschlaegel U, Seltmann F, Kiani A, et al. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia. 2012;26(3):381–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  65. Weisdorf D, Spellman S, Haagenson M, Horowitz M, Lee S, Anasetti C, et al. Classification of HLA-matching for retrospective analysis of unrelated donor transplantation: revised definitions to predict survival. Biol Blood Marrow Transplant. 2008;14(7):748–58.

    Article  PubMed Central  PubMed  Google Scholar 

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Conflict of Interest

Dr. Ehab Atallah, Dr. Kathryn Bylow, Dr. Jesse Troy, and Dr. Wael Saber each declare no potential conflict of interest relevant to this article.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Medical College of Wisconsin, Milwaukee, WI, USA

    Ehab Atallah, Kathryn Bylow & Wael Saber

  2. The EMMES Corporation, 401 N. Washington Street, Suite 700, Rockville, MD, 20850, USA

    Jesse Troy

  3. Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Suite C5500, Milwaukee, WI, 53226, USA

    Wael Saber

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  1. Ehab Atallah
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Atallah, E., Bylow, K., Troy, J. et al. Treatment of Older Patients with High-Risk Myelodysplastic Syndromes (MDS): The Emerging Role of Allogeneic Hematopoietic Stem Cell Transplantation (Allo HSCT). Curr Hematol Malig Rep 9, 57–65 (2014). https://doi.org/10.1007/s11899-013-0195-9

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Keywords

  • MDS
  • Allogeneic hematopoietic stem cell transplantation
  • Age
  • Comprehensive geriatric assessment
  • Hypomethylating agents