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Vol 13, No 3-4 (2022)
Review paper
Published online: 2023-02-16

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Therapeutic options in high-risk myelodysplastic syndrome

Marcela Maksymowicz1, Sara Moqbil1, Piotr Machowiec1, Monika Podhorecka2
DOI: 10.5603/HCP.a2022.0017
Hematology in Clinical Practice 2022;13(3-4):97-111.

Abstract

Myelodysplastic syndromes (MDS) constitute a heterogeneous group of diseases characterised by ineffective haematopoiesis, dysplasia and cytopenias. The treatment for high-risk MDS (HR-MDS) depends on individual factors such as the stage of the disease, age, comorbidities, and infections.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning has allowed more HR-MDS patients to be transplant-eligible, regardless of age. Hypomethylating agents, including azacitidine and decitabine, remain the standard of care for HR-MDS patients who are not qualified for curative allo-HSCT. Combination therapy of azacitidine with some new drugs resulted in higher response rates than azacitidine in monotherapy. Other targeted therapies are under investigation. They include HMA with different antibodies targeting immune checkpoints — programmed cell death (ligand) 1, cytotoxic T lymphocyte antigen 4, T-cell immunoglobulin mucin-3 or cluster of differentiation 47. Larger studies are necessary to confirm their efficacy in the treatment of HR-MDS.

Keywords: myelodysplastic syndromesMDShypomethylating agentcombination therapyimmune checkpoint inhibitiontargeted therapies

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References

  1. Goldberg SL, Chen Er, Corral M, et al. Incidence and clinical complications of myelodysplastic syndromes among United States Medicare beneficiaries. J Clin Oncol. 2010; 28(17): 2847–2852.
    CrossRefPubMed
  2. Saygin C, Carraway HE. Current and emerging strategies for management of myelodysplastic syndromes. Blood Rev. 2021; 48: 100791.
    CrossRefPubMed
  3. Bazinet A, Bravo GM. New approaches to myelodysplastic syndrome treatment. Curr Treat Options Oncol. 2022; 23(5): 668–687.
    CrossRefPubMed
  4. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20): 2391–2405.
    CrossRefPubMed
  5. Haferlach T, Nagata Y, Grossmann V, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014; 28(2): 241–247.
    CrossRefPubMed
  6. Haase D, Stevenson KE, Neuberg D, et al. International Working Group for MDS Molecular Prognostic Committee. TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. Leukemia. 2019; 33(7): 1747–1758.
    CrossRefPubMed
  7. Jain AG, Elmariah H. BMT for myelodysplastic syndrome: when and where and how. Front Oncol. 2021; 11: 771614.
    CrossRefPubMed
  8. Papaemmanuil E, Gerstung M, Malcovati L, et al. Chronic Myeloid Disorders Working Group of the International Cancer Genome Consortium. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013; 122(22): 3616–27; quiz 3699.
    CrossRefPubMed
  9. Nielsen AB, Hansen JW, Ørskov AD, et al. Inflammatory cytokine profiles do not differ between patients with idiopathic cytopenias of undetermined significance and myelodysplastic syndromes. Hemasphere. 2022; 6(5): e0713.
    CrossRefPubMed
  10. Jiang H, Fu R, Wang H, et al. CD47 is expressed abnormally on hematopoietic cells in myelodysplastic syndrome. Leuk Res. 2013; 37(8): 907–910.
    CrossRefPubMed
  11. Haroun F, Solola SA, Nassereddine S, et al. PD-1 signaling and inhibition in AML and MDS. Ann Hematol. 2017; 96(9): 1441–1448.
    CrossRefPubMed
  12. Yang H, Bueso-Ramos C, DiNardo C, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia. 2014; 28(6): 1280–1288.
    CrossRefPubMed
  13. Garcia-Manero G, Sasaki K, Montalban-Bravo G, et al. A phase II study of nivolumab or ipilimumab with or without azacitidine for patients with myelodysplastic syndrome (MDS). Blood. 2018; 132(Suppl 1): 465–465.
    CrossRef
  14. Kikushige Y, Shima T, Takayanagi Si, et al. TIM-3 is a promising target to selectively kill acute myeloid leukemia stem cells. Cell Stem Cell. 2010; 7(6): 708–717.
    CrossRefPubMed
  15. Sharma P, Pollyea DA. Shutting down acute myeloid leukemia and myelodysplastic syndrome with BCL-2 family protein inhibition. Curr Hematol Malig Rep. 2018; 13(4): 256–264.
    CrossRefPubMed
  16. Garcia-Manero G, Chien KS, Montalban-Bravo G. Myelodysplastic syndromes: 2021 update on diagnosis, risk stratification and management. Am J Hematol. 2020; 95(11): 1399–1420.
    CrossRefPubMed
  17. Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012; 120(12): 2454–2465.
    CrossRefPubMed
  18. Hong M, He G. The 2016 Revision to the World Health Organization Classification of Myelodysplastic Syndromes. J Transl Int Med. 2017; 5(3): 139–143.
    CrossRefPubMed
  19. Bernard E, Tuechler H, Greenberg P, et al. Molecular International Prognostic Scoring System for Myelodysplastic Syndromes. NEJM Evid. 2022; 1(7).
    CrossRef
  20. Zeng X, Zhang Yu, Zhao Ke, et al. Somatic mutations predict prognosis in myelodysplastic syndrome patients with normal karyotypes. Signal Transduct Target Ther. 2021; 6(1): 274.
    CrossRefPubMed
  21. Garcia-Manero G, Daver N, Xu J, et al. Magrolimab + azacitidine versus azacitidine + placebo in untreated higher risk (HR) myelodysplastic syndrome (MDS): The phase 3, randomized, ENHANCE study. J Clin Oncol. 2021; 39(15_suppl): TPS7055–TPS7055.
    CrossRef
  22. Greenberg P, Cox C, LeBeau M, et al. International Scoring System for Evaluating Prognosis in Myelodysplastic Syndromes. Blood. 1997; 89(6): 2079–2088.
    CrossRef
  23. Diamantopoulos PT, Viniou NA. Factors affecting response to 5-azacytidine and prognosis of myelodysplastic syndrome. Is long-term survival a realistic goal? Leuk Res. 2021; 103: 106543.
    CrossRefPubMed
  24. Palacios-Berraquero ML, Alfonso-Piérola A. Current therapy of the patients with MDS: walking towards personalized therapy. J Clin Med. 2021; 10(10).
    CrossRefPubMed
  25. Joeckel TE, Lübbert M. Clinical results with the DNA hypomethylating agent 5-aza-2'-deoxycytidine (decitabine) in patients with myelodysplastic syndromes: an update. Semin Hematol. 2012; 49(4): 330–341.
    CrossRefPubMed
  26. Boultwood J, Wainscoat JS. Gene silencing by DNA methylation in haematological malignancies. Br J Haematol. 2007; 138(1): 3–11.
    CrossRefPubMed
  27. Stomper J, Rotondo JC, Greve G, et al. Hypomethylating agents (HMA) for the treatment of acute myeloid leukemia and myelodysplastic syndromes: mechanisms of resistance and novel HMA-based therapies. Leukemia. 2021; 35(7): 1873–1889.
    CrossRefPubMed
  28. Lee P, Yim R, Yung Y, et al. Molecular targeted therapy and immunotherapy for myelodysplastic syndrome. Int J Mol Sci. 2021; 22(19).
    CrossRefPubMed
  29. 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(3): 223–232.
    CrossRefPubMed
  30. Garcia JS, Swords RT, Roboz GJ, et al. A systematic review of higher-risk myelodysplastic syndromes clinical trials to determine the benchmark of azacitidine and explore alternative endpoints for overall survival. Leuk Res. 2021; 104: 106555.
    CrossRefPubMed
  31. Liu L, Jia M, Sun L, et al. Meta-analysis of the benefit of hypomethylating agents before allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes. Clin Exp Med. 2021; 21(4): 537–543.
    CrossRefPubMed
  32. Mądry K, Lis K, Tukiendorf A, et al. Low serum albumin level deteriorates prognosis in azacitidine-treated myelodysplastic syndromes patients - results of the PALG study 'PolAZA'. Hematology. 2021; 26(1): 556–564.
    CrossRefPubMed
  33. Oran B, de Lima M, Garcia-Manero G, et al. A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients. Blood Adv. 2020; 4(21): 5580–5588.
    CrossRefPubMed
  34. Kantarjian H, Issa JPJ, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006; 106(8): 1794–1803.
    CrossRefPubMed
  35. Ma J, Ge Z. Comparison between decitabine and azacitidine for patients with acute myeloid leukemia and higher-risk myelodysplastic syndrome: a systematic review and network meta-analysis. Front Pharmacol. 2021; 12: 701690.
    CrossRefPubMed
  36. Bewersdorf JP, Zeidan AM. Management of higher risk myelodysplastic syndromes after hypomethylating agents failure: are we about to exit the black hole? Expert Rev Hematol. 2020; 13(10): 1131–1142.
    CrossRefPubMed
  37. Montalban-Bravo G, Garcia-Manero G, Jabbour E. Therapeutic choices after hypomethylating agent resistance for myelodysplastic syndromes. Curr Opin Hematol. 2018; 25(2): 146–153.
    CrossRefPubMed
  38. Clavio M, Crisà E, Miglino M, et al. Overall survival of myelodysplastic syndrome patients after azacitidine discontinuation and applicability of the North American MDS Consortium scoring system in clinical practice. Cancer. 2021; 127(12): 2015–2024.
    CrossRefPubMed
  39. Guadecitabine (SGI-110) vs Treatment Choice in Adults With MDS or CMML Previously Treated With HMAs. https://www.clinicaltrials.gov/ct2/show/NCT02907359 (October 16, 2020).
  40. Issa JPJ, Roboz G, Rizzieri D, et al. Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study. Lancet Oncol. 2015; 16(9): 1099–1110.
    CrossRefPubMed
  41. Garcia-Manero G, Döhner H, Wei AH, et al. Oral azacitidine (CC-486) for the treatment of myeloid malignancies. Clin Lymphoma Myeloma Leuk. 2022; 22(4): 236–250.
    CrossRefPubMed
  42. Garcia-Manero G, Griffiths EA, Steensma DP, et al. Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study. Blood. 2020; 136(6): 674–683.
    CrossRefPubMed
  43. Savona MR, Odenike O, Amrein PC, et al. An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Lancet Haematol. 2019; 6(4): e194–e203.
    CrossRefPubMed
  44. Savona MR, McCloskey J, Griffiths E, et al. Clinical efficacy and safety of oral decitabine/cedazuridine in 133 patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). Blood. 2020; 136(Suppl 1): 37–38.
    CrossRef
  45. Komrokji R, Al Ali N, Padron E, et al. What is the optimal time to initiate hypomethylating agents (HMAs) in higher risk myelodysplastic syndromes (MDSs)? Leuk Lymphoma. 2021; 62(11): 2762–2767.
    CrossRefPubMed
  46. Schuck A, Goette MC, Neukirchen J, et al. A retrospective study evaluating the impact of infectious complications during azacitidine treatment. Ann Hematol. 2017; 96(7): 1097–1104.
    CrossRefPubMed
  47. Greenberg PL, Stone RM, Al-Kali A, et al. Myelodysplastic Syndromes, Version 2.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2017; 15(1): 60–87.
    CrossRefPubMed
  48. Kenealy M, Hertzberg M, Benson W, et al. Azacitidine with or without lenalidomide in higher risk myelodysplastic syndrome & low blast acute myeloid leukemia. Haematologica. 2019; 104(4): 700–709.
    CrossRefPubMed
  49. Adès L, Duployez N, Guerci-Bresler A, et al. A randomised phase II study of azacitidine (AZA) alone or with Lenalidomide (LEN), Valproic acid (VPA) or Idarubicin (IDA) in higher-Risk MDS or low blast AML: GFM's "pick a winner" trial, with the impact of somatic mutations. Br J Haematol. 2022; 198(3): 535–544.
    CrossRefPubMed
  50. Meng F, Li L, Lu F, et al. Overexpression of TIGIT in NK and T cells contributes to tumor immune escape in myelodysplastic syndromes. Front Oncol. 2020; 10: 1595.
    CrossRefPubMed
  51. Yang H, Bueso-Ramos C, DiNardo C, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia. 2014; 28(6): 1280–1288.
    CrossRefPubMed
  52. Yang X, Ma L, Zhang X, et al. Targeting PD-1/PD-L1 pathway in myelodysplastic syndromes and acute myeloid leukemia. Exp Hematol Oncol. 2022; 11(1): 11.
    CrossRefPubMed
  53. Chien KS, Kim K, Nogueras-Gonzalez GM, et al. Phase II study of azacitidine with pembrolizumab in patients with intermediate-1 or higher-risk myelodysplastic syndrome. Br J Haematol. 2021; 195(3): 378–387.
    CrossRefPubMed
  54. Zeidan A, Cavenagh J, Voso M, et al. Efficacy and safety of zzacitidine (AZA) in combination with the anti-PD-L1 durvalumab (durva) for the front-line treatment of older patients (pts) with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy (IC) and pts with higher-risk myelodysplastic syndromes (HR-MDS): results from a large, international, randomized phase 2 study. Blood. 2019; 134(Supplement_1): 829–829.
    CrossRef
  55. Ravandi F, Assi R, Daver N, et al. Idarubicin, cytarabine, and nivolumab in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a single-arm, phase 2 study. Lancet Haematol. 2019; 6(9): e480–e488.
    CrossRefPubMed
  56. Assi R, Kantarjian H, Daver N, et al. Results of a phase 2, open-label study of idarubicin (I), cytarabine (A) and nivolumab (Nivo) in patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS). Blood. 2018; 132(Suppl 1): 905–905.
    CrossRef
  57. Oran B, Garcia-Manero G, Saliba RM, et al. Posttransplantation cyclophosphamide improves transplantation outcomes in patients with AML/MDS who are treated with checkpoint inhibitors. Cancer. 2020; 126(10): 2193–2205.
    CrossRefPubMed
  58. Sallman DA, Asch A, Malki MAl, et al. The first-in-class anti-CD47 antibody magrolimab (5F9) in combination withv azacitidine is effective in MDS and AML patients: ongoing phase 1b results. Blood. 2019; 134(Supplement_1): 569–569.
    CrossRef
  59. Brunner AM, Esteve J, Porkka K, et al. Efficacy and safety of sabatolimab (MBG453) in combination with hypomethylating agents (HMAs) in patients (pts) with very high/high-risk myelodysplastic syndrome (vHR/HR-MDS) and acute myeloid leukemia (AML): final analysis from a phase Ib study. Blood. 2021; 138(Supplement 1): 244–244.
    CrossRef
  60. Garcia JS. Prospects for venetoclax in myelodysplastic syndromes. Hematol Oncol Clin North Am. 2020; 34(2): 441–448.
    CrossRefPubMed
  61. Pagliuca S, Gurnari C, Visconte V. Molecular targeted therapy in myelodysplastic syndromes: new options for tailored treatments. Cancers (Basel). 2021; 13(4).
    CrossRefPubMed
  62. Gangat N, Tefferi A. Venetoclax-based chemotherapy in acute and chronic myeloid neoplasms: literature survey and practice points. Blood Cancer J. 2020; 10(11): 122.
    CrossRefPubMed
  63. Garcia JS, Wei A, Borate U, et al. Safety, efficacy, and patient-reported outcomes of venetoclax in combination with azacitidine for the treatment of patients with higher-risk myelodysplastic syndrome: a phase 1b study. Blood. 2020; 136(Suppl 1): 55–57.
    CrossRef
  64. Santini V, Park S, Hamel JF, et al. Life after hypomethylating agents in myelodysplastic syndrome: new strategies. Curr Opin Hematol. 2015; 22(2): 155–162.
    CrossRefPubMed
  65. Stemer G, Rowe JM, Ofran Y. Efficacy and safety profile of ivosidenib in the management of patients with acute myeloid leukemia (AML): an update on the emerging evidence. Blood Lymphat Cancer. 2021; 11: 41–54.
    CrossRefPubMed
  66. DiNardo CD, Watts J, Stein E, et al. Ivosidenib (AG-120) induced durable remissions and transfusion independence in patients with IDH1-mutant relapsed or refractory myelodysplastic syndrome: results from a phase 1 dose escalation and expansion study. Blood. 2018; 132(Suppl 1): 1812–1812.
    CrossRef
  67. Foran JM, DiNardo C, Watts J, et al. Ivosidenib (AG-120) in patients with IDH1-mutant relapsed/refractory myelodysplastic syndrome: updated enrollment of a phase 1 dose escalation and expansion study. Blood. 2019; 134(Suppl_1): 4254–4254.
    CrossRef
  68. DiNardo CD, Foran J, Watts J, et al. MDS-265: ivosidenib (IVO) in patients with IDH1-mutant relapsed/refractory myelodysplastic syndrome (R/R MDS): updated enrollment of a phase 1 dose escalation and expansion study. Clin. Lymphoma Myeloma Leuk. 2020; 20: S321.
    CrossRef
  69. Richard-Carpentier G, DeZern A, Takahashi K, et al. Preliminary results from the phase II study of the IDH2-inhibitor enasidenib in patients with high-risk IDH2-mutated myelodysplastic syndromes (MDS). Blood. 2019; 134(Suppl_1): 678–678.
    CrossRef
  70. Strati P, Kantarjian H, Ravandi F, et al. Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome. Am J Hematol. 2015; 90(4): 276–281.
    CrossRefPubMed
  71. Xu F, He Qi, Li X, et al. Rigosertib as a selective anti-tumor agent can ameliorate multiple dysregulated signaling transduction pathways in high-grade myelodysplastic syndrome. Sci Rep. 2014; 4: 7310.
    CrossRefPubMed
  72. Garcia-Manero G, Fenaux P, Al-Kali A, et al. ONTIME study investigators. Rigosertib versus best supportive care for patients with high-risk myelodysplastic syndromes after failure of hypomethylating drugs (ONTIME): a randomised, controlled, phase 3 trial. Lancet Oncol. 2016; 17(4): 496–508.
    CrossRefPubMed
  73. Navada SC, Fruchtman SM, Odchimar-Reissig R, et al. A phase 1/2 study of rigosertib in patients with myelodysplastic syndromes (MDS) and MDS progressed to acute myeloid leukemia. Leuk Res. 2018; 64: 10–16.
    CrossRefPubMed
  74. Navada SC, Garcia-Manero G, Atallah E, et al. Phase II study of oral rigosertib combined with azacitidine (AZA) as first line therapy in patients (pts) with higher-risk myelodysplastic syndromes (HR-MDS). Blood. 2019; 134(Suppl_1): 566–566.
    CrossRef
  75. Furukawa H, Makino T, Yamasaki M, et al. PRIMA-1 induces p53-mediated apoptosis by upregulating Noxa in esophageal squamous cell carcinoma with TP53 missense mutation. Cancer Sci. 2018; 109(2): 412–421.
    CrossRefPubMed
  76. Sallman DA, DeZern AE, Garcia-Manero G, et al. Eprenetapopt (APR-246) and azacitidine in TP53-mutant myelodysplastic syndromes. J Clin Oncol. 2021; 39(14): 1584–1594.
    CrossRefPubMed
  77. Cluzeau T, Sebert M, Rahmé R, et al. Eprenetapopt plus azacitidine in TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a phase II study by the Groupe Francophone des Myélodysplasies (GFM). J Clin Oncol. 2021; 39(14): 1575–1583.
    CrossRefPubMed
  78. Sekeres MA, Watts J, Radinoff A, et al. Randomized phase 2 trial of pevonedistat plus azacitidine versus azacitidine for higher-risk MDS/CMML or low-blast AML. Leukemia. 2021; 35(7): 2119–2124.
    CrossRefPubMed
  79. Sekeres MA, Watts JM, Radinoff A, et al. 653 Efficacy and safety of pevonedistat plus azacitidine vs azacitidine alone in higher-risk myelodysplastic syndromes (MDS) from study P-2001 (NCT02610777). https://ash.confex.com/ash/2020/webprogram/Paper135840.html (October 18, 2021).
  80. Kröger N, Sockel K, Wolschke C, et al. Comparison between 5-azacytidine treatment and allogeneic stem-cell transplantation in elderly patients with advanced MDS according to donor availability (VidazaAllo Study). J Clin Oncol. 2021; 39(30): 3318–3327.
    CrossRefPubMed
  81. Heidenreich S, Ziagkos D, de Wreede LC, et al. Allogeneic stem cell transplantation for patients age ≥ 70 years with myelodysplastic syndrome: a retrospective study of the MDS Subcommittee of the Chronic Malignancies Working Party of the EBMT. Biol Blood Marrow Transplant. 2017; 23(1): 44–52.
    CrossRefPubMed
  82. Brierley CK, Steensma DP. Thrombopoiesis-stimulating agents and myelodysplastic syndromes. Br J Haematol. 2015; 169(3): 309–323.
    CrossRefPubMed
  83. Fenaux P, Platzbecker U, Ades L. How we manage adults with myelodysplastic syndrome. Br J Haematol. 2020; 189(6): 1016–1027.
    CrossRefPubMed
  84. Passweg JR, Baldomero H, Bader P, et al. Hematopoietic stem cell transplantation in Europe 2014: more than 40 000 transplants annually. Bone Marrow Transplant. 2016; 51(6): 786–792.
    CrossRefPubMed
  85. Schroeder T, Wegener N, Lauseker M, et al. Comparison between upfront transplantation and different pretransplant cytoreductive treatment approaches in patients with high-risk myelodysplastic syndrome and secondary acute myelogenous leukemia. Biol Blood Marrow Transplant. 2019; 25(8): 1550–1559.
    CrossRefPubMed
  86. Kröger N, Iacobelli S, Franke GN, et al. Dose-reduced versus standard conditioning followed by allogeneic stem-cell transplantation for patients with myelodysplastic syndrome: a prospective randomized phase III study of the EBMT (RICMAC Trial). J Clin Oncol. 2017; 35(19): 2157–2164.
    CrossRefPubMed
  87. Wedge E, Sengeløv H, Hansen JW, et al. Improved outcomes after allogenic hematopoietic stem cell transplantation with fludarabine/treosulfan for patients with myelodysplastic syndromes. Biol Blood Marrow Transplant. 2020; 26(6): 1091–1098.
    CrossRefPubMed
  88. Gelder MV, Schetelig J, Volin L, et al. Monosomal karyotype predicts poor outcome for MDS/sAML patients with chromosome 7 abnormalities after allogeneic stem cell transplantation for MDS/sAML. A study of the MDS Subcommittee of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Blood. 2009; 114(22): 293–293.
    CrossRef
  89. Della Porta MG, Gallì A, Bacigalupo A, et al. Clinical effects of driver somatic mutations on the outcomes of patients with myelodysplastic sndromes treated with allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2016; 34(30): 3627–3637.
    CrossRefPubMed
  90. Bejar R, Stevenson KE, Caughey B, et al. Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation. J Clin Oncol. 2014; 32(25): 2691–2698.
    CrossRefPubMed
  91. Claiborne J, Bandyopathyay D, Roberts C, et al. Managing post allograft relapse of myeloid neoplasms: azacitidine and donor lymphocyte infusions as salvage therapy. Leuk Lymphoma. 2019; 60(11): 2733–2743.
    CrossRefPubMed
  92. Zeiser R, Beelen DW, Bethge W, et al. Biology-driven approaches to prevent and treat relapse of myeloid neoplasia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019; 25(4): e128–e140.
    CrossRefPubMed
  93. 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. 2011; 29(15): 1987–1996.
    CrossRefPubMed
  94. Garcia-Manero G, Roboz G, Walsh K, et al. Guadecitabine (SGI-110) in patients with intermediate or high-risk myelodysplastic syndromes: phase 2 results from a multicentre, open-label, randomised, phase 1/2 trial. Lancet Haematol. 2019; 6(6): e317–e327.
    CrossRefPubMed
  95. Rasmussen B, Göhring G, Bernard E, et al. Randomized phase II study of azacitidine ± lenalidomide in higher-risk myelodysplastic syndromes and acute myeloid leukemia with a karyotype including del(5q). Leukemia. 2022; 36(5): 1436–1439.
    CrossRefPubMed
  96. Zeidan AM, Borate U, Pollyea D, et al. Venetoclax and azacitidine in the treatment of patients with relapsed/refractory myelodysplastic syndrome. Blood. 2021; 138(Suppl 1): 537–537.
    CrossRef
  97. Bazinet A, Jabbour E, Kantarjian H, et al. A Phase I/II study of venetoclax in combination with 5-azacytidine in treatment-naïve and relapsed/refractory high-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic Leukemia (CMML). Blood. 2021; 138(Suppl 1): 535–535.
    CrossRef
  98. Peterlin P, Turlure P, Chevallier P, et al. CPX 351 as first line treatment in higher risk MDS. A phase II trial by the GFM. Blood. 2021; 138(Suppl 1): 243.
    CrossRef
  99. Montalban-Bravo G, Jabbour E, Estrov Z, et al. Updated results of a phase 1/2 study of lower dose CPX-351 for patients with Int-2 or high risk IPSS myelodysplastic syndromes and chronic myelomonocytic leukemia after failure to hypomethylating agents. Blood. 2021; 138(Suppl 1): 3674–3674.
    CrossRef
  100. Moyo TK, Watts J, Skikne B, et al. Preliminary results from a phase II study of the combination of pevonedistat and azacitidine in the treatment of MDS and MDS/MPN after failure of DNA methyltransferase inhibition. Blood. 2019; 134(Suppl_1): 4236–4236.
    CrossRef
  101. Cortes JE, Wang E, Watts J, et al. Olutasidenib (FT-2102) induces rapid remissions in patients with IDH1-mutant myelodysplastic syndrome: results of phase 1/2 single agent treatment and combination with azacitidine. Blood. 2019; 134(Suppl_1): 674–674.
    CrossRef
  102. Zeidan AM, Knaus HA, Robinson TM, et al. A multi-center phase I trial of ipilimumab in patients with myelodysplastic syndromes following hypomethylating agent failure. Clin Cancer Res. 2018; 24(15): 3519–3527.
    CrossRefPubMed

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