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Myelodysplastic syndromes: toward a risk-adapted treatment approach

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Pages 611-624 | Published online: 10 Jan 2014

References

  • Greenberg P, Cox C, LeBeau MM et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 89(6), 2079–2088 (1997).
  • Ma X. Epidemiology of myelodysplastic syndromes. Am. J. Med. 125(7 Suppl.), S2–S (2012).
  • Sekeres MA. Epidemiology, natural history, and practice patterns of patients with myelodysplastic syndromes in 2010. J. Natl Compr. Canc Netw. 9(1), 57–63 (2011).
  • Ma X, Does M, Raza A, Mayne ST. Myelodysplastic syndromes: incidence and survival in the United States. Cancer 109(8), 1536–1542 (2007).
  • Germing U, Strupp C, Kundgen A et al. No increase in age-specific incidence of myelodysplastic syndromes. Haematologica 89(8), 905–910 (2004).
  • Matsuda A, Germing U, Jinnai I et al. Difference in clinical features between Japanese and German patients with refractory anemia in myelodysplastic syndromes. Blood 106(8), 2633–2640 (2005).
  • Corey SJ, Minden MD, Barber DL, Kantarjian H, Wang JC, Schimmer AD. Myelodysplastic syndromes: the complexity of stem-cell diseases. Nat. Rev. Cancer 7(2), 118–129 (2007).
  • Cazzola M, Malcovati L. Myelodysplastic syndromes -- coping with ineffective hematopoiesis. N. Engl. J. Med. 352(6), 536–538 (2005).
  • Epling-Burnette PK, Bai F, Painter JS et al. Reduced natural killer (NK) function associated with high-risk myelodysplastic syndrome (MDS) and reduced expression of activating NK receptors. Blood 109(11), 4816–4824 (2007).
  • Claessens Y, Bouscary D, Dupont J et al. In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis. Blood 99(5), 1594–1601 (2002).
  • Fontenay-Roupie M, Bouscary D, Guesnu M et al. Ineffective erythropoiesis in myelodysplastic syndromes: correlation with Fas expression but not with lack of erythropoietin receptor signal transduction. Br. J. Haematol. 106(2), 464–473 (1999).
  • Bouscary D, De Vos J, Guesnu M et al. Fas/Apo-1 (CD95) expression and apoptosis in patients with myelodysplastic syndromes. Leukemia 11(6), 839–845 (1997).
  • Campioni D, Secchiero P, Corallini F et al. Evidence for a role of TNF-related apoptosis-inducing ligand (TRAIL) in the anemia of myelodysplastic syndromes. Am. J. Pathol. 166(2), 557–563 (2005).
  • Hellstrom-Lindberg E, Schmidt-Mende J, Forsblom AM, Christensson B, Fadeel B, Zhivotovsky B. Apoptosis in refractory anaemia with ringed sideroblasts is initiated at the stem cell level and associated with increased activation of caspases. Br. J. Haematol. 112(3), 714–726 (2001).
  • Albitar M, Zhou W, Giles F. Myelodysplastic syndrome: from morphology to biology. Curr. Hematol. Rep. 3(3), 159–164 (2004).
  • Sabattini E, Bacci F, Sagramoso C, Pileri SA. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. Pathologica 102(3), 83–87 (2010).
  • Bennett JM, Catovsky D, Daniel MT et al. Proposals for the classification of the myelodysplastic syndromes. Br. J. Haematol. 51(2), 189–199 (1982).
  • Zeidan AM, Smith BD, Komrokji RS, Gore SD. Prognostication in myelodysplastic syndromes: beyond the International Prognostic Scoring System (IPSS). Am. J. Med. 126(4), e25 (2013).
  • Swerdlow SH, Campo E, Harris NL et al. WHO classification of MDS. In: World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues. IARC, Lyon, France (2008).
  • Campo E, Swerdlow SH, Harris NL, Pileri S, Stein H, Jaffe ES. The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood 117(19), 5019–5032 (2011).
  • Malcovati L, Germing U, Kuendgen A et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J. Clin. Oncol. 25(23), 3503–3510 (2007).
  • Kantarjian H, O'Brien S, Ravandi F et al. 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), 1351–1361 (2008).
  • Komrokji RS, Corrales-Yepez M, Al Ali N et al. Validation of the MD Anderson Prognostic Risk Model for patients with myelodysplastic syndrome. Cancer 118(10), 2659–2664 (2012).
  • Greenberg PL, Tuechler H, Schanz J et al. Revised International Prognostic Scoring System for Myelodysplastic Syndromes. Blood 120(12), 2454–2465 (2012).
  • Bejar R, Levine R, Ebert BL. Unraveling the molecular pathophysiology of myelodysplastic syndromes. J. Clin. Oncol. 29(5), 504–515 (2011).
  • Della Porta MG, Malcovati L, Boveri E et al. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J. Clin. Oncol. 27(5), 754–762 (2009).
  • Tiu RV, Visconte V, Traina F, Schwandt A, Maciejewski JP. Updates in cytogenetics and molecular markers in MDS. Curr. Hematol. Malig. Rep. 6(2), 126–135 (2011).
  • Abdel-Wahab O, Figueroa ME. Interpreting new molecular genetics in myelodysplastic syndromes. Hematology Am. Soc. Hematol. Educ. Program 2012, 56–64 (2012).
  • Jerez A, Gondek LP, Jankowska AM et al. Topography, clinical, and genomic correlates of 5q myeloid malignancies revisited. J. Clin. Oncol. 30(12), 1343–1349 (2012).
  • List A, Dewald G, Bennett J et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N. Engl. J. Med. 355(14), 1456–1465 (2006).
  • Haase D, Germing U, Schanz J et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood 110(13), 4385–4395 (2007).
  • Schanz J, Steidl C, Fonatsch C et al. Coalesced multicentric analysis of 2,351 patients with myelodysplastic syndromes indicates an underestimation of poor-risk cytogenetics of myelodysplastic syndromes in the international prognostic scoring system. J. Clin. Oncol. 29(15), 1963–1970 (2011).
  • Schanz J, Tuchler H, Sole F et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J. Clin. Oncol. 30(8), 820–829 (2012).
  • Deeg HJ, Scott BL, Fang M et al. Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS. Blood 120(7), 1398–1408 (2012).
  • Bejar R, Stevenson K, Abdel-Wahab O et al. Clinical effect of point mutations in myelodysplastic syndromes. N. Engl. J. Med. 364(26), 2496–2506 (2011).
  • Papaemmanuil E, Cazzola M, Boultwood J et al. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N. Engl. J. Med. 365(15), 1384–1395 (2011).
  • de Witte T. Allogeneic stem cell transplantation for myelodysplastic syndromes: critical for cure? Clin. Lymphoma Myeloma Leuk. 11( Suppl. 11), S46–S48 (2011).
  • Mitchell M, Gore S, Zeidan A. Iron chelation therapy in myelodysplastic syndromes: where do we stand? Expert Rev Hematol. 6(4), 397–410 (2013).
  • Silva M, Benito A, Sanz C et al. Erythropoietin can induce the expression of bcl-x(L) through Stat5 in erythropoietin-dependent progenitor cell lines. J. Biol. Chem. 274(32), 22165–22169 (1999).
  • Tehranchi R, Fadeel B, Forsblom AM et al. Granulocyte colony-stimulating factor inhibits spontaneous cytochrome c release and mitochondria-dependent apoptosis of myelodysplastic syndrome hematopoietic progenitors. Blood 101(3), 1080–1086 (2003).
  • Zeidan A, Faltas B, Fricke W, Gore S, Ketterling R, Sham R. Sustained Complete Cytogenetic Remission in a Patient with Myelodysplastic Syndrome and Complex Karyotype after Erythropoiesis-Stimulating T herapy followed by Colonic T-cell Lymphoblastic Lymphoma. Leuk. Lymph. 54(7), 1534–1537 (2012)
  • Hellström-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. 120(6), 1037–1046 (2003).
  • Park S, Grabar S, Kelaidi C et al. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood 111(2), 574–582 (2008).
  • Stasi R, Brunetti M, Terzoli E, Abruzzese E, Amadori S. Once-weekly dosing of recombinant human erythropoietin alpha in patients with myelodysplastic syndromes unresponsive to conventional dosing. Ann. Oncol. 15(11), 1684–1690 (2004).
  • Musto P, Lanza F, Balleari E et al. Darbepoetin alpha for the treatment of anaemia in low-intermediate risk myelodysplastic syndromes. Br. J. Haematol. 128(2), 204–209 (2005).
  • Bowen D, Culligan D, Jowitt S et al. Guidelines for the diagnosis and therapy of adult myelodysplastic syndromes. Br. J. Haematol. 120(2), 187–200 (2003).
  • Davidoff A, Smith SW, Baer M et al. Patterns of erythropoiesis-stimulating agent use for myelodysplastic syndromes are not consistent with clinical guidelines Leuk. Res. 37(6), 675–680.
  • Kotla V, Goel S, Nischal S et al. Mechanism of action of lenalidomide in hematological malignancies. J. Hematol. Oncol. 2, 36 (2009).
  • List A, Dewald G, Bennett J et al. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N. Engl. J. Med. 355(14), 1456–1465 (2006).
  • List A, Kurtin S, Roe DJ et al. Efficacy of lenalidomide in myelodysplastic syndromes. N. Engl. J. Med. 352(6), 549–557 (2005).
  • 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 111(1), 86–93 (2008).
  • Pellagatti A, Jadersten M, Forsblom AM et al. Lenalidomide inhibits the malignant clone and up-regulates the SPARC gene mapping to the commonly deleted region in 5q- syndrome patients. Proc. Natl Acad. Sci. USA 104(27), 11406–11411 (2007).
  • Sokol L, List AF. Immunomodulatory therapy for myelodysplastic syndromes. Int. J. Hematol. 86(4), 301–305 (2007).
  • Fenaux P, Giagounidis A, Selleslag D et al. A randomized phase 3 study of lenalidomide versus placebo in RBC transfusion-dependent patients with low-/intermediate-1-risk myelodysplastic syndromes with del5q. Blood 118(14), 3765–3776 (2011).
  • Padron E, Komrokji R, List AF. The 5q- syndrome: biology and treatment. Curr. Treat. Options Oncol. 12(4), 354–368 (2011).
  • Wlodarski MW, Gondek LP, Nearman ZP et al. Molecular strategies for detection and quantitation of clonal cytotoxic T-cell responses in aplastic anemia and myelodysplastic syndrome. Blood 108(8), 2632–2641 (2006).
  • Barrett AJ, Sloand E. Autoimmune mechanisms in the pathophysiology of myelodysplastic syndromes and their clinical relevance. Haematologica 94(4), 449–451 (2009).
  • Fozza C, Contini S, Galleu A et al. Patients with myelodysplastic syndromes display several T-cell expansions, which are mostly polyclonal in the CD4(+) subset and oligoclonal in the CD8(+) subset. Exp. Hematol. 37(8), 947–955 (2009).
  • Sloand EM, Melenhorst JJ, Tucker ZC et al. T-cell immune responses to Wilms tumor 1 protein in myelodysplasia responsive to immunosuppressive therapy. Blood 117(9), 2691–2699 (2011).
  • Molldrem JJ, Jiang YZ, Stetler-Stevenson M, Mavroudis D, Hensel N, Barrett AJ. Haematological response of patients with myelodysplastic syndrome to antithymocyte globulin is associated with a loss of lymphocyte-mediated inhibition of CFU-GM and alterations in T-cell receptor Vbeta profiles. Br. J. Haematol. 102(5), 1314–1322 (1998).
  • Scott BL, Ramakrishnan A, Fosdal M et al. Anti-thymocyte globulin plus etanercept as therapy for myelodysplastic syndromes (MDS): a phase II study. Br. J. Haematol. 149(5), 706–710 (2010).
  • Sloand EM, Pfannes L, Chen G et al. CD34 cells from patients with trisomy 8 myelodysplastic syndrome (MDS) express early apoptotic markers but avoid programmed cell death by up-regulation of antiapoptotic proteins. Blood 109(6), 2399–2405 (2007).
  • Sloand EM, Wu CO, Greenberg P, Young N, Barrett J. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J. Clin. Oncol. 26(15), 2505–2511 (2008).
  • Saunthararajah Y, Nakamura R, Nam J et al. HLA-DR15 (DR2) is overrepresented in myelodysplastic syndrome and aplastic anemia and predicts a response to immunosuppression in myelodysplastic syndrome. Blood 100(5), 1570–1574 (2002).
  • Passweg JR, Giagounidis AAN, Simcock M et al. Immunosuppressive therapy for patients with myelodysplastic syndrome: a prospective randomized multicenter phase III trial comparing antithymocyte globulin plus cyclosporine with best supportive care – SAKK 33/99. J. Clin. Oncol. 29(3), 303–309 (2011).
  • 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. 28(35), 5166–5173 (2010).
  • Jones PA, Baylin SB. The epigenomics of cancer. Cell 128(4), 683–692 (2007).
  • Schecter J, Galili N, Raza A. MDS: Refining existing therapy through improved biologic insights. Blood Rev. 26(2), 73–80 (2012).
  • Muller A, Florek M. 5-Azacytidine/Azacitidine. Recent Results Cancer Res. 184, 159–170 (2010).
  • 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 leukemia group B. J. Clin. Oncol. 20(10), 2429–2440 (2002).
  • 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. 24(24), 3895–3903 (2006).
  • 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 randomised, open-label, phase III study. Lancet Oncol. 10(3), 223–232 (2009).
  • 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. 27(11), 1850–1856 (2009).
  • Leone G, D'Alo F, Zardo G, Voso MT, Nervi C. Epigenetic treatment of myelodysplastic syndromes and acute myeloid leukemias. Curr. Med. Chem. 15(13), 1274–1287 (2008).
  • Kantarjian H, Issa JJ, Rosenfeld CS et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer 106(8), 1794–1803 (2006).
  • 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 109(1), 52–57 (2007).
  • Lübbert M, Suciu S, Baila L 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. 29(15), 1987–1996 (2011).
  • Itzykson R, Thépot S, Quesnel B et al. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood 117(2), 403–411 (2011).
  • Zeidan A, Faltas B, Smith BD et al. Myelodysplastic syndromes: what do hospitalists need to know? J. Hosp. Med. 8(6), 351–357 (2013).
  • Oosterveld M, Muus P, Suciu S et al. Chemotherapy only compared to chemotherapy followed by transplantation in high risk myelodysplastic syndrome and secondary acute myeloid leukemia; two parallel studies adjusted for various prognostic factors. Leukemia 16(9), 1615–1621 (2002).
  • Kantarjian H, Beran M, Cortes J et al. Long-term follow-up results of the combination of topotecan and cytarabine and other intensive chemotherapy regimens in myelodysplastic syndrome. Cancer 106(5), 1099–1109 (2006).
  • Sierra J, Pérez WS, Rozman C et al. Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia. Blood 100(6), 1997–2004 (2002).
  • Cutler CS, Lee SJ, Greenberg P 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 104(2), 579–585 (2004).
  • Alessandrino EP, Della Porta MG, Bacigalupo A et al. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Blood 112(3), 895–902 (2008).
  • Onida F, Brand R, van Biezen A. Impact of cytogenetics on outcome of patients with MDS or secondary AML undergoing allogeneic HSCT from HLA-identical siblings: a retrospective analysis of the EBMT-CLWP [abstract]. Blood 108, Abstract 2653 (2006).
  • Ruter B, Wijermans P, Claus R, Kunzmann R, Lubbert M. Preferential cytogenetic response to continuous intravenous low-dose decitabine (DAC) administration in myelodysplastic syndrome with monosomy 7. Blood 110(3), 1080–1082, author reply 1083 (2007).
  • Lee SJ, Klein J, Haagenson M et al. High-resolution donor-recipient HLA matching contributes to the success of unrelated donor marrow transplantation. Blood 110(13), 4576–4583 (2007).
  • Gergis U, Wissa U. High-risk myelodysplastic syndromes: chemotherapy, transplantation, and beyond. Curr. Hematol. Malig. Rep. 5(1), 1–8 (2010).
  • Chang YJ, Zhao XY, Xu LP et al. Early lymphocyte recovery predicts superior overall survival after unmanipulated haploidentical blood and marrow transplantation for MDS and acute myeloid leukemia evolving from MDS. Leuk. Lymphoma. Doi:10.3109/10428194.2013.783912(2013) ( Epub ahead of print).
  • Gyurkocza B, Deeg HJ. Allogeneic hematopoietic cell transplantation for MDS: for whom, when and how? Blood Rev. 26(6), 247–254 (2012).
  • Platzbecker U. Allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndromes. Semin. Hematol. 49(4), 342–349 (2012).
  • Scott BL, Sandmaier BM, Storer B et al. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia 20(1), 128–135 (2006).
  • Gergis U, Markey K, Greene J. Voriconazole provides effective prophylaxis for invasive fungal infection in patients receiving glucocorticoid therapy for GVHD. Bone Marrow Transplant. 45(4), 662–667 (2009).
  • Zeidan A, Gore S, Komrokji R. Higher-risk myelodysplastic syndromes with del5q: is sequential azacitidine-lenalidomide combination the way to go? Expert Rev. Hematol. 6(3), 251–254 (2013).
  • Sekeres MA, List AF, Cuthbertson D et al. Phase I combination trial of lenalidomide and azacitidine in patients with higher-risk myelodysplastic syndromes. J. Clin. Oncol. 28(13), 2253–2258 (2010).
  • Sekeres MA, Gundacker H, Lancet J et al. A phase 2 study of lenalidomide monotherapy in patients with deletion 5q acute myeloid leukemia: Southwest oncology group study S0605. Blood 118(3), 523–528 (2011).
  • Greenberg PL, Attar E, Bennett JM et al. NCCN Clinical Practice Guidelines in Oncology: myelodysplastic syndromes. J. Natl Compr. Canc. Netw. 9, 30–56 (2011).

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