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Treatment Options for Myelodysplastic Syndromes
US Oncology & Hematology, 2011;7(2):143-5
AbstractMyelodysplastic syndromes (MDS) are a group of heterogeneous hematopoietic stem cell disorders characterized by peripheral blood cytopenias and a risk of transformation to acute myeloid leukaemia. Until recently, treatment of MDS predominately consisted of supportive care measures. However, three agents for the treatment of MDS have recently been approved: lenalidomide, decitabine, and azacitidine. These agents have dramatically improved the outcomes for patients with MDS. To date, azacitidine is the only agent that has demonstrated a survival advantage when compared with conventional care. Novel agents and combination regimens including lenalidomide, decitabine and azacitidine are being explored in an effort to further improve patient outcomes.
Keywords: Myelodysplastic syndromes, MDS, azacitidine, decitabine, lenalidomide, hypomethlyating agents, supportive care, immunosuppressive therapy
Disclosure: The authors have no conflicts of interest to declare.
Received: March 05, 2010 Accepted September 26, 2010 Citation US Oncology & Hematology, 2011;7(2):143-5
Correspondence: Elias Jabbour, MD, Department of Leukemia, Unit 428, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. E: firstname.lastname@example.org
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders that impair normal hematopoiesis, resulting in a variable number of cytopenias and a potential to evolve into acute myeloid leukaemia (AML).1 With a median age at diagnosis around 70 years, MDS typically affects the elderly.1,2 Hence, there is much morbidity and mortality associated with this patient population, as patients frequently suffer from complications due to cytopenias as well as other comorbidities. The two systems used for classifying MDS are the French American and British (FAB) criteria and the more recently revised World Health Organization (WHO) classification system. A third system, the International Prognostic Scoring System (IPSS), can predict survival based on percentage of bone marrow blasts, karyotype and number of peripheral blood cytopenias3 and is the most widely used prognostic tool for assisting with treatment decisions.
For many years, supportive care with blood products (red blood cell [RBC] and platelet transfusions), hematopoietic growth factors and antibiotics remained the only treatment modality for MDS patients, until the development of three novel agents that may alter the natural history of this disease. Within the past decade, the US Food and Drug Administration (FDA) has approved an immunomodulatory agent, lenalidomide (Revlimid™, Celgene) and two hypomethylating agents, decitabine (Dacogen™, Eisai, Inc.) and azacitidine (Vidaza™, Celgene) for the treatment of patients with MDS. In simple practice, therapy is tailored to IPSS score with an emphasis on supportive care therapies or lenalidomide for lower-risk patients (IPSS low or intermediate [int]-1) and more intensive therapies such as conventional chemotherapy, allogeneic hematopoietic stem cell transplant (HST) and clinical trials, as well as hypomethylating agents, for patients with higher-risk disease (IPSS int-2 or high) or lower-risk patients with progressive disease.3
- Heaney M, Golde D, Myelodysplasia, N Engl J Med, 1999;340:1649–60.
- . 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;100:1542–51.
- Greenberg P, Cox C, LeBeau MM, et al., International scoring system for evaluating prognosis in myelodysplastic syndromes, Blood, 1997;89:2079–88.
- Jadersten 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;26:3607–13.
- Hellstrom-Lindberg E, Efficacy of erythropoietin in the myelodysplastic syndromes: a meta-analysis of 205 patients from 17 studies, Brit J Haemat, 1995;89:67–71.
- . Hellstrom-Lindberg E, Gulbrandsen N, Lindberg G, et al., A validated decision model for treating the anaemia of myelodysplastic syndromes with erythropoietin + granulocyte colony-stimulating factor: significant effects on quality of life, Br J Haematol, 2003;120:1037–46.
- Greenburg PL, Sun Z, Miller KB, et al., Treatment of myelodysplastic syndrome patients with erythropoietin with or without granulocyte colony-stimulating factor: results of a prospective randomized phase 3 trial by Eastern Cooperative Oncology Group (E1996), Blood, 2009;114:2393–400.
- Molldrem JJ, Leifer E, Bahceci E, et al., Antithymocyte globulin for treatment of the bone marrow failure associated with myelodysplastic syndromes, Ann Intern Med, 2002;137:156–63.
- Sloand EM, Wu CO, Greenberg P, et al., Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy, J Clinical Oncol, 2008;26:2505–11.
- Saunthararajah Y, Nakamura R, Wesley R, et al., A simple method to predict response to immunosuppressive therapy in patients with myelodysplastic syndrome, Blood, 2003;102:3025–7.
- . Sloand EM, Olnes MJ, Shenoy A, et al., Alemtuzumab treatment of intermediate-1 myelodysplasia patients is associated with sustained improvement in blood counts and cytogenetic remissions, J Clin Oncol, 2010;28:5166–73.
- List A, Kurtin S, Roe DJ, et al., Efficacy of lenalidomide in myelodysplastic syndromes, N Engl J Med, 2005;352:549–57.
- List A, Dewald G, Bennett J, et al., Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion, New Engl J Med, 2006;355:1456–65.
- 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.
- Cheson BD, Bennett JM, Kantarjian H, et al., Report of an international working group to standardize response criteria for myelodysplastic syndromes, Blood, 2000;96:3671–4.
- 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;24:3895–903.
- Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al., Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomized, open-label, phase III study, Lancet Oncol, 2009;10:223–32.
- Kantarjian H, Issa JP, Rosenfeld CS, et al., Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study, Cancer, 2006;106:1794–803.
- WijerMans P, Suciu S, Liliana Baila L, et al., Low dose decitabine versus best supportive care in elderly patients with intermediate or high risk MDS not eligible for intensive chemotherapy: final results of the randomized phase III study (06011) of the EORTC Leukemia and German MDS Study Groups, Blood, 2008;112:abstract 226.
- Kantarjian H, Oki Y, Garcia-Manero G, 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;109:52–7.
- Cheson BD, Greenberg PL, Bennett JM, et al., Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia, Blood, 2006;108:419–25.
- Steensma DP, Baer MR, Slack JL, 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;27:3842–8.
- Kantarjian HM, O’Brien S, Huang X, et al., Survival advantage with decitabine versus intensive chemotherapy in patients with higher risk myelodysplastic syndrome: comparison with historical experience, Cancer, 2007;109:1133–7.
- Lyons RM, Cosgriff TM, Modi SS, et al., Hematologic response to three alternative dosing schedules of azacitidine in patients with myelodysplastic syndromes, J Clin Oncol, 2009;27:1850–6.
- Martin MG, Walgren RA, Procknow E, et al., A phase II study of 5-day intravenous azacitidine in patients with myelodysplastic syndromes, Am J Hematol, 2009;84:560–4.
- Cutler CS, Lee SJ, Greenberg P, et al., A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for lowrisk myelodysplasia is associated with improved outcome, Blood, 2004;104:579–85.