University of Wisconsin Hematology

Myelodysplastic syndromes

General; biology & pathophysiology

  1. Hasserjian et al. Diagnosis and classification of myelodysplastic syndromes. Blood 2023;142:2247
  2. DeZern and Greenberg. The trajectory of prognostication and risk stratification for patients with myelodysplastic syndromes. Blood 2023;142:2258
  3. Cazzola M. Myelodysplastic syndromes. NEJM 2020;383:1358
  4. Estey et al. Distinguishing AML from MDS: a fixed blast percentage may no longer be optimal. Blood 2022;139:323 (Suggests that blast counts from 10-30% might be classified as either MDS or AML)
  5. Goldberg et al. Incidence and Clinical Complications of Myelodysplastic Syndromes Among United States Medicare BeneficiariesJ Clin Oncol 2010;28:2847
  6. Kwok et al. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. Blood 2015;126:2355(Over 30% of patients with unexplained cytopenias but not overt MDS have an MDS-associated somatic mutation)
  7. Cargo et al. Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression. Blood 2015;126:2362(MDS-associated mutations common in patients with idiopathic cytopenias)
  8. Steensma D. How I use molecular genetic tests to evaluate patients who have or may have myelodysplastic syndromes. Blood 2018;132:1663
  9. Ogawa S. Genetics of MDS. Blood 2019;133:1049
  10. Bernard et al. Molecular taxonomy of myelodysplastic syndromes and its clinical implications. Blood 2024;144:1617
  11. Steensma et al. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes. Blood 2015;126:9
  12. Joshi et al. How do messenger RNA splicing alterations drive myelodysplasia? Blood 2017;129:2465
  13. Tanaka and Bejar. MDS overlap disorders and diagnostic boundaries. Blood 2019;133:1086
  14. Pronk and Raaijamakers. The mesencymal niche in MDS. Blood 2019;133:1031
  15. Sallman and List. The central role of inflammatory signaling in the pathogenesis of myelodysplastic syndromes. Blood 2019;133:1039
  16. Kennedy and Shimamura. Genetic predisposition to MDS: clinical features and clonal evolution. Blood 2018;133:1071
  17. Greenbert et al. Revised international prognositic scoring system for myelodysplastic syndromes. Blood 2012;120:2454
  18. Schanz 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 2012;30:820
  19. Valcárcel et al. Complex, Not Monosomal, Karyotype Is the Cytogenetic Marker of Poorest Prognosis in Patients With Primary Myelodysplastic Syndrome. J Clin Oncol 2013;31:916
  20. Kuendgen et al. Myelodysplastic Syndromes in Patients Younger Than Age 50. J Clin Oncol 2006;24:5358
  21. Menssen and Walter. Genetics of progression from MDS to secondary leukemia. Blood 2020;136:50
  22. Pfeilstöcker et al. Time-dependent changes in mortality and transformation risk in MDS. Blood 2016;128:902(Risk of death and leukemic transformation decreases over time in high-risk MDS, not in low-risk disease)
  23. Szpurka et al. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T), another myeloproliferative condition characterized by JAK2 V617F mutation. Blood 2006;108:2173  (6/9 pts with RARS + thrombocytosis had JAK-2 mutation; this mutation was rare in other forms of MDS)
  24. Huls et al. Efficacy of single-agent lenalidomide in patients with JAK2 (V617F) mutated refractory anemia with ring sideroblasts and thrombocytosis. Blood 2010;116:180
  25. Malcovati et al. Molecular and clinical features of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Blood 2009;114:3538
  26. Steensma et al.  Acquired a-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies.  Blood 2005;105:443
  27. Cazzola et al. Natural history of idiopathic refractory sideroblastic anemia. Blood 1988;71:305
  28. West et al. Cytogenetic abnormalities in the myelodysplastic syndromes and occupational or environmental exposure. Blood 2000;95:2093
  29. Bejar et al. Clinical effect of point mutations in myelodysplastic syndromes. NEJM 2011;364:2496
  30. Papaemmanuil et al. Somatic SF3B1 Mutation in Myelodysplasia with Ring Sideroblasts. NEJM 2011;365:1384
  31. Malcovati et al. Clinical significance of SF3B1 mutations in myelodysplastic syndromes and myelodysplastic/myeloproliferative neoplasms. Blood 2011;118:6239(Mutation associated with better prognosis, presence of ringed sideroblasts)
  32. Malcovati et al. SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS. Blood 2020;136:157
  33. Visconte et al. SF3B1 haploinsufficiency leads to formation of ring sideroblasts in myelodysplastic syndromes. Blood 2012;120:3173
  34. Cazzola et al. Biologic and clinical significance of somatic mutations of SF3B1 in myeloid and lymphoid neoplasms. Blood 2013;121:260
  35. Malcovati et al. SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts. Blood 2015;126:233
  36. Wu et al. The clinical implication of SRSF2 mutation in patients with myelodysplastic syndrome and its stability during disease evolution. Blood 2012;120:3106
  37. Inaba et al. The enigma of monosomy 7. Blood 2018;131:2891
  38. Issa J. The myelodysplastic syndrome as a prototypical epigenetic disease. Blood 2013;121:3811
  39. Gupta et al. Myelodysplastic syndrome with isolated deletion of chromosome 20q: an indolent disease with minimal morphological dysplasia and frequent thrombocytopenic presentation. Br J Haematol 2007; 139:265(can mimic ITP)
  40. Della Porta et al. Clinical Relevance of Bone Marrow Fibrosis and CD34-Positive Cell Clusters in Primary Myelodysplastic Syndromes. J Clin Oncol 2009;27:754
  41. Wang et al. Atypical chronic myeloid leukemia is clinically distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms. Blood 2014;123:2645
  42. Barreyro et al. Chronic immune response dysregulation in MDS pathogenesis. Blood 2018;132:1553
  43. Rodruigez-Sevilla and Colla. T-cell dysfunctions in myelodysplastic syndromes. Blood 2024;143:1329
  44. Wagner et al. Increased Ripk1-mediated bone marrow necroptosis leads to myelodysplasia and bone marrow failure in mice. Blood 2019;133:107(Necrosis of defective progenitor cells generates cytokines that suppress normal hematopoiesis)
  45. Bernard et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat Med 2020;26:1549(Biallelic TP53 mutations associated with worse outcomes; cases with monoallelic mutations not different from non-mutated cases)
  46. Sallman et al. TP53 mutations in myelodysplastic syndromes and secondary AML confer an immunosuppressive phenotype. Blood 2020;136:2812
  47. Ganan-Gomez et al. Stem cell architecture drives myelodysplastic syndrome progression and predicts response to venetoclax-based therapy. Nat Med 2022;28:557
  48. Delaleu et al. Clinical, pathological, and molecular features of myelodysplasia cutis. Blood 2022;139:1251

Treatment

  1. Hellström-Lindberg and Kröger. Clinical decision-making and treatment of myelodysplastic syndromes. Blood 2023;142:2268
  2. Platzbecker U. Treatment of MDS. Blood 2019;133:1096
  3. Fenaux and Adès. How we treat lower-risk myelodysplastic syndromes. Blood 2013;121:4280
  4. Mina and Kimrokji. How I treat higher-risk MDS. Blood 2025;145:2002
  5. Garcia et al. Efficacy and safety of venetoclax plus azacitidine for patients with treatment-naive high-risk myelodysplastic syndromes. Blood 2025;145:1126
  6. Santini V. How I treat MDS after hypomethylating agent failure. Blood 2019;133:521
  7. Odenike O. How I treat the blast phase of Philadelphia chromosome–negative myeloproliferative neoplasms. Blood 2018;132:2339
  8. Gotlib et al. How I treat atypical chronic myeloid leukemia. Blood 2017;129:838
  9. Adès and Fenaux. Immunomodulating drugs in myelodysplastic syndromes. Hematology 2011:556
  10. Casadevall et al. Health, economic, and quality-of-life effects of erythropoietin and granulocyte colony-stimulating factor for the treatment of myelodysplastic syndromes: a randomized, controlled trial.  Blood 2004;104:321 (Treatment was expensive, and did not improve quality of life)
  11. Jädersten et al. Long-term outcome of treatment of anemia in MDS with erythropoietin and G-CSF. Blood 2005;106:803
  12. Mannone et al. High-dose darbepoetin alpha in the treatment of anaemia of lower risk myelodysplastic syndrome results of a phase II study. Br J Haematol 2006;133:513
  13. Park et al. Predictive factors of response and survival in myelodysplastic syndrome treated with erythropoietin and G-CSF: the GFM experience. Blood 2008;111:574
  14. Greenberg 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 the Eastern Cooperative Oncology Group (E1996). Blood 2009;114:2393
  15. Jädersten et al. Erythropoietin and Granulocyte-Colony Stimulating Factor Treatment Associated With Improved Survival in Myelodysplastic Syndrome. J Clin Oncol 2008;26:3607
  16. Park et al. Efficacy and safety of darbepoetin alpha in patients with myelodysplastic syndromes: a systematic review and meta-analysis. Br J Haem 2016;174:730
  17. Park et al. Outcome of Lower-Risk Patients With Myelodysplastic Syndromes Without 5q Deletion After Failure of Erythropoiesis-Stimulating Agents. J Clin Oncol 2017;35:1591(None of the commonly used second-line agents improved OS. ESA failure associated with higher risk of progression to AML)
  18. Oliva et al. Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial. Lancet Haematol 2017;4:e127(47% of treated patients had platelet response vs 3% of controls, with fewer bleeding events; more non-heme adverse events in treated group)
  19. Silverman 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
  20. Lyons et al. Hematologic Response to Three Alternative Dosing Schedules of Azacitidine in Patients With Myelodysplastic Syndromes. J Clin Oncol 2009;27:1850(Approximately 50% response rate regardless of dosing regimen used)
  21. Itzykson et al. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood 2011;117:403
  22. Garcia-Manero et al. Phase III, Randomized, Placebo-Controlled Trial of CC-486 (Oral Azacitidine) in Patients With Lower-Risk Myelodysplastic Syndromes. J Clin Oncol 2021;39:1426 (Oral Aza reduced transfusion requirements but caused more early deaths from infection)
  23. Dickinson et al. Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia. Blood 2018;132:2629(Adding eltrombopag associated with worse outcomes)
  24. Kantarjian 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
  25. Lübbert 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;29:1987(No significant improvement in OS, some improvement in quality of life in decitabine-treated pts)
  26. Garcia-Manero et al. Randomized Open-Label Phase II Study of Decitabine in Patients With Low- or Intermediate-Risk Myelodysplastic Syndromes. J Clin Oncol 2013;31:2548
  27. Welch et al. TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes. NEJM 2016;375:2023(Presence of TP53 mutation predicted favorable response to treatment)
  28. Jabbour et al. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. Blood 2017;130:1514(Higher response rates with decitabine)
  29. Garcia-Manero et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood 2020;136:674
  30. Adès 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;113:3947(67% CR rate in patients with isolated 5q- defect)
  31. Raza 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
  32. Santini et al. Randomized Phase III Study of Lenalidomide Versus Placebo in RBC Transfusion-Dependent Patients With Lower-Risk Non-del(5q) Myelodysplastic Syndromes and Ineligible for or Refractory to Erythropoiesis-Stimulating Agents. J Clin Oncol 2016;34:2988(27% of patients became transfusion-independent for at least 2 mo with lenalidomide)
  33. Sekeres et al. Phase 2 study of the lenalidomide and azacitidine combination in patients with higher-risk myelodysplastic syndromes. Blood 2012;120:4945(44% CR, 28% PR)
  34. Komrokji et al. Combined treatment with lenalidomide and epoetin alfa in lower-risk patients with myelodysplastic syndrome. Blood 2012;120:3419
  35. List et al. Lenalidomide-Epoetin Alfa Versus Lenalidomide Monotherapy in Myelodysplastic Syndromes Refractory to Recombinant Erythropoietin. J Clin Oncol 2021;39:1001 (Lenalidomide restores sensitivity to EPO)
  36. Sekeres et al. Randomized Phase II Study of Azacitidine Alone or in Combination With Lenalidomide or With Vorinostat in Higher-Risk Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia: North American Intergroup Study SWOG S1117. J Clin Oncol 2017;35:2745(Adding lenalidomide appears beneficial in CMML)
  37. Leitch and Vickars. Supportive care and chelation therapy in MDS: are we saving lives or just lowering iron? Hematology 2009;664
  38. Shenoy et al. Impact of iron overload and potential benefit from iron chelation in low-risk myelodysplastic syndrome. Blood 2014;124:873
  39. Antypiuk et al. Genetic iron overload aggravates, and pharmacological iron restriction improves, MDS pathophysiology in a preclinical study. Blood 2025;145:155
  40. Olnes and Sloand. Targeting immune dysregulation in myelodysplastic syndromes. JAMA 2011;305:814 (Treatment of MDS with immunosuppressive drugs)
  41. Fenaux et al. Luspatercept for the treatment of anemia in myelodysplastic syndromes and primary myelofibrosis. Blood 2019;133:790
  42. Fenaux et al. Luspatercept in Patients with Lower-Risk Myelodysplastic Syndromes. NEJM 2020;382:140 (RARS patients benefit from treatment)
  43. Zeidan et al. Longer-term benefit of luspatercept in transfusion-dependent lower-risk myelodysplastic syndromes with ring sideroblasts. Blood 2022;140:2170
  44. Platzbecker et al. Long-Term Efficacy and Safety of Luspatercept for Anemia Treatment in Patients With Lower-Risk Myelodysplastic Syndromes: The Phase II PACE-MDS Study. J Clin Oncol 2022;40:3800
  45. Platzbecker et al. Efficacy and safety of luspatercept versus epoetin alfa in erythropoiesis-stimulating agent-naive, transfusion-dependent, lower-risk myelodysplastic syndromes (COMMANDS): interim analysis of a phase 3, open-label, randomised controlled trial. Lancet 2023;402:373 (59% on luspatercept became transfusion-independent vs 31% on EPO)
  46. Steensma et al. Imetelstat Achieves Meaningful and Durable Transfusion Independence in High Transfusion–Burden Patients With Lower-Risk Myelodysplastic Syndromes in a Phase II Study. J Clin Oncol 2021;39:48
  47. Platzbecker et al. Imetelstat in patients with lower-risk myelodysplastic syndromes who have relapsed or are refractory to erythropoiesis-stimulating agents (IMerge): a multinational, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2024;403:249

MDS: Stem Cell Transplantation

CMML

  1. Solary and Itzykson. How I treat chronic myelomonocytic leukemia. Blood 2017;130:126
  2. Baumgartner et al. Comparing malignant monocytosis across the updated WHO and ICC classifications of 2022. Blood 2024;143:1139
  3. Such et al. Development and validation of a prognostic scoring system for patients with chronic myelomonocytic leukemia. Blood 2013;121:3005
  4. Itzykson et al. Prognostic Score Including Gene Mutations in Chronic Myelomonocytic Leukemia. J Clin Oncol 2013;31:2428
  5. Takahashi et al. Clinical characteristics and outcomes of therapy-related chronic myelomonocytic leukemia. Blood 2013;122:2807(Worse outcomes than de novo CMML)
  6. Pleyer et al. Outcomes of patients with chronic myelomonocytic leukaemia treated with non-curative therapies: a retrospective cohort study. Lancet Haematol 2021;8:e135(Hypomethylating agents preferred for higher-risk patients)
  7. Kantarjian 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
  8. Braun et al. Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial. Blood 2011;118:3824(38% overall response rate)
  9. Cargo et al. The use of targeted sequencing and flow cytometry to identify patients with a clinically significant monocytosis. Blood 2019;133:1325(Monocytosis with associated somatic mutation indistinguishable from CMML – with editorial)

5q- syndrome

  1. Mukherjee et al. Blood consult: treating del(5q) myelodysplastic syndromes. Blood 2012;119:342
  2. List et al.  Efficacy of Lenalidomide in Myelodysplastic Syndromes.  NEJM 2005;352:549
  3. List et al. Lenalidomide in the Myelodysplastic Syndrome with Chromosome 5q Deletion.  NEJM 2006;355:1456
  4. Fenaux 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 2011;118:3765(Lenalidomide reduced transfusion requirements and may have lowered risk of leukemic transformation)
  5. Tehranchi et al. Persistent Malignant Stem Cells in del(5q) Myelodysplasia in Remission. NEJM 2010;363:1025
  6. Fang et al. A calcium- and calpain-dependent pathway determines the response to lenalidomide in myelodysplastic syndromes. Nat Med 2016;22:727