Advances in Therapy

, 28:1

Treatment of myelodysplastic syndromes in elderly patients

Review
  • 260 Downloads

Abstract

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal neoplasms with the median age at diagnosis being in the seventh decade. If left untreated, the disease progresses to acute myeloblastic leukemia (AML). There are many options for the management of MDS, but the only potentially curative treatment is allogenic hematopoietic stem cell transplantation (allo-HSCT), which is often not an option because of advanced age or comorbidities at diagnosis or lack of a human leukocyte antigen-identical donor. MDS in the elderly should be managed similar to that in young patients, but the fact that many advanced age patients cannot undergo allo-HSCT precludes any chance of cure. Despite the main objective of prolonging overall survival and the time to progression to AML, the key is to improve quality of life for the longest possible time. To achieve these objectives, supportive care is essential. Likewise, immunomodulatory drugs, such as lenalidomide, can reduce transfusion requirements and reverse cytologic and cytogenetic abnormalities in patients with MDS with chromosome 5q deletion. Elderly patients with high-risk MDS can benefit from 5-azacitidine (5-AZA), with efficacy and safety profiles comparable with those found in patients under 75 years of age. In any patient, predictive drug response scores are required in order to ensure more rational use of these medications.

Keywords

acute myeloblastic leukemia 5-azacitidine elderly myelodysplastic syndromes 

References

  1. 1.
    Nguyen PL. The myelodysplastic syndromes. Hematol Oncol Clin N Am. 2009;23:675–691.CrossRefGoogle Scholar
  2. 2.
    Aul C, Gatterman N, Schneider W. Age related incidence and other epidemiological aspects of myelodysplastic syndromes. Br J Haematol. 1992;82:358–367.PubMedCrossRefGoogle Scholar
  3. 3.
    Benett JM, Catovsky D, Daniel MT, et al: The French-American-British Cooperative Group. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51:189–199.Google Scholar
  4. 4.
    Swerdlow SH, Campo E, Harris NL, et al (eds). WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. 4th Edition. Lyon: IARC Press; 2008.Google Scholar
  5. 5.
    Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–2088.PubMedGoogle Scholar
  6. 6.
    Sierra J, Pérez WS, Rozman C, et al. Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia. Blood. 2002;100:1997–2004.PubMedGoogle Scholar
  7. 7.
    Corey S, Cutler CS, Lee SJ, 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;104:579–585.CrossRefGoogle Scholar
  8. 8.
    List A, Kurtin S, Roe DJ, et al. Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med. 2005;352:549–557.PubMedCrossRefGoogle Scholar
  9. 9.
    List A, Dewald G, Bennett J, et al. Myelodysplastic Syndromes-003 Study Investigators. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006. 355:1456–1465.PubMedCrossRefGoogle Scholar
  10. 10.
    Raza A, Reeves JA, Feldman EJ, 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;111:86–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Silverman LR, Demakos EP, Peterson BL, et al. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukaemia Group B. J Clin Oncol. 2002;20:2429–2440.PubMedCrossRefGoogle Scholar
  12. 12.
    Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. International Vidaza High-Risk MDS Survival Study Group. 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;10:223–232.PubMedCrossRefGoogle Scholar
  13. 13.
    Seymour JF, Fenaux P, Silverman LR, et al. Effects of azacitidine compared with conventional care regimens in elderly (≥75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol. 2010;76:218–227.CrossRefGoogle Scholar
  14. 14.
    Silverman LR, McKenzie DR, Peterson BL, et al. Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B. J Clin Oncol. 2006;20;24:3895–3903.CrossRefGoogle Scholar
  15. 15.
    Garcia JS, Jain N, Godley LA. An update on the safety and efficacy of decitabine in the treatment of myelodysplastic syndromes. Onco Targets Ther. 2010;3:1–13.PubMedGoogle Scholar
  16. 16.
    Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomised study. Cancer. 2006;106:1794–1803.PubMedCrossRefGoogle Scholar
  17. 17.
    Lee JS, Lindquist K, Segal MR, Covinsky KE. Development and validation of a prognostic index for 4-year mortality in older adults. JAMA. 2006;295:801–808.PubMedCrossRefGoogle Scholar
  18. 18.
    Registro Español de SMD (RESMD). Documento consenso sobre el tratamiento de soporte de los pacientes con Síndrome Mielodisplásicos. June 20, 2008.Google Scholar
  19. 19.
    Alessandrino EP, Amadori S, Barosi G, et al. Italian Society of Hematology. Evidence- and consensusbased practice guidelines for the therapy of primary myelodysplastic syndromes. A statement from the Italian Society of Hematology. Haematologica. 2002;87:1286–1306.PubMedGoogle Scholar
  20. 20.
    Bowen D, Culligan D, Jowitt S, et al. UK MDS Guidelines Group. Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br J Haematol. 2003;120:187–200.PubMedCrossRefGoogle Scholar
  21. 21.
    National Comprehensive Cancer Network Practice Guidelines in Oncology. Version 2; 2008. Available at: http://www.nccn.org/professionals/physician_gls/f_guidelines.asp. Accessed February 7, 2011.
  22. 22.
    Rizzo JD, Somerfield MR, Hagerty KL, et al. American Society of Clinical Oncology. American Society of Hematology. Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Clinical Oncology/American Society of Hematology clinical practice guideline update. J Clin Oncol. 2008;26:132–149.PubMedCrossRefGoogle Scholar
  23. 23.
    Hellström-Lindberg E, Malcovati L. Supportive care and use of hematopoietic growth factors in myelodysplastic syndromes. Semin Hematol. 2008;45:14–22.PubMedCrossRefGoogle Scholar
  24. 24.
    Jädersten M, Malcovati L, Dybedal I, et al. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol. 2008;26:3607–3613.PubMedCrossRefGoogle Scholar
  25. 25.
    Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidencebased clinical practice guideline. J Clin Oncol. 2006;24:3187–3205.PubMedCrossRefGoogle Scholar
  26. 26.
    Saunthararajah Y, Nakamura R, Wesley R, Wang QJ, Barrett AJ. A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome. Blood. 2003;102:3025–3027.PubMedCrossRefGoogle Scholar
  27. 27.
    Lim ZY, Killick S, Germing U, et al. Low IPSS score and bone marrow hypocellularity in MDS patients predict hematological responses to antithymocyte globulin. Leukemia. 2007;21:1436–1441.PubMedCrossRefGoogle Scholar
  28. 28.
    Gattermann N. Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload. Int J Hematol. 2008;88:24–29.PubMedCrossRefGoogle Scholar
  29. 29.
    Musto P, Maurillo L, Spagnoli A, et al Ad Hoc Italian Cooperative Study Group on Azacitidine in Myelodysplastic Syndromes Acute Leukemias. Azacitidine for the treatment of lower risk myelodysplastic syndromes. Cancer. 2010;116:1485–1494.PubMedCrossRefGoogle Scholar
  30. 30.
    García-Manero G, Shan J, Faderl S, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia. 2008;22:538–343.PubMedCrossRefGoogle Scholar
  31. 31.
    Aul C, Schneider W. The role of low-dose cytosine arabinoside and aggressive chemotherapy in advanced myelodysplastic syndromes. Cancer. 1989;64:1812–1818.PubMedCrossRefGoogle Scholar
  32. 32.
    Miller KB, Kim K, Morrison FS, et al. The evaluation of low-dose cytarabine in the treatment of myelodysplastic syndromes: a phase-III intergroup study. Ann Hematol. 1992;65:162–168.PubMedCrossRefGoogle Scholar
  33. 33.
    Kantarjian H, O’brien S, Cortes J, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106:1090–1098.PubMedCrossRefGoogle Scholar
  34. 34.
    Sekeres MA, Schoonen WM, Kantarjian H, et al. Characteristics of US patients with myelodysplastic syndromes: results of six cross-sectional physician surveys. J Natl Cancer Inst. 2008;100:1542–1551.PubMedCrossRefGoogle Scholar
  35. 35.
    Itzykson R, Thépot S, Quesnel B, et al. Prognostic factors of response and overall survival in 282 higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117:403–411.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Healthcare 2011

Authors and Affiliations

  1. 1.Hematology and Hemotherapy ServiceHospital San PedroLogroñoSpain

Personalised recommendations