Myelodysplastic syndromes: moving towards personalized management
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Arber DA, Orazi A, Hasserjian R. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20):2391-2405.
Vardiman JW, Thiele J, Arber DA. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009; 114(5):937-951.
Jaiswal S, Ebert BL. Clonal hematopoiesis in human aging and disease. Science. 2019; 366(6465):eaan4673.
Baliakas P, Tesi B, Wartiovaara-Kautto U. Nordic guidelines for germline predisposition to myeloid neoplasms in adults: recommendations for genetic diagnosis, clinical management and follow-up. HemaSphere. 2019; 3(6):e321.
Bennett JM, Catovsky D, Daniel M. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982; 51(2):189-199.
Malcovati L, Karimi M, Papaemmanuil E. SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts. Blood. 2015; 126(2):233-241.
Greenberg P, Anderson J, De Witte T. Problematic WHO reclassification of myelodysplastic syndromes. Members of the International MDS Study Group. J Clin Oncol. 2000; 18(19):3447-3452.
Hasserjian RP, Campigotto F, Klepeis V. De novo acute myeloid leukemia with 20– 29% blasts is less aggressive than acute myeloid leukemia with ≥30% blasts in older adults: a Bone Marrow Pathology Group study. Am J Hematol. 2014; 89(11):E193-E199.
Greenberg PL, Stone RM, Al-Kali A. Myelodysplastic syndromes, version 2.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2017; 15(1):60-87.
Bains A, Luthra R, Medeiros LJ. FLT3 and NPM1 mutations in myelodysplastic syndromes: frequency and potential value for predicting progression to acute myeloid leukemia. Am J Clin Pathol. 2011; 135(1):62-69.
Neukirchen J, Schoonen WM, Strupp C. Incidence and prevalence of myelodysplastic syndromes: data from the Dusseldorf MDS-registry. Leuk Res. 2011; 35(12):1591-1596.
Greenberg PL, Tuechler H, Schanz J. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012; 120(12):2454-2465.
Bonadies N, Feller A, Rovo A. Trends of classification, incidence, mortality, and survival of MDS patients in Switzerland between 2001 and 2012. Cancer Epidemiol. 2017; 46:85-92.
Moreno Berggren D, Folkvaljon Y, Engvall M. Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population‐ based setting: a report from the Swedish MDS register. Br J Haematol. 2018; 181(5):614-627.
Ryden J, Edgren G, Karimi M. Male sex and the pattern of recurrent myeloid mutations are strong independent predictors of blood transfusion intensity in patients with myelodysplastic syndromes. Leukemia. 2019; 33(2):522-527.
Mekinian A, Grignano E, Braun T. Systemic inflammatory and autoimmune manifestations associated with myelodysplastic syndromes and chronic myelomonocytic leukaemia: a French multicentre retrospective study. Rheumatology. 2016; 55(2):291-300.
Wolach O, Stone R.. Autoimmunity and Inflammation in myelodysplastic syndromes. Acta Haematol. 2016; 136(2):108-117.
Troy JD, de Castro CM, Pupa MR. Patient-reported distress in myelodysplastic syndromes and its association with clinical outcomes: a retrospective cohort study. J Natl Compr Canc Netw. 2018; 16(3):267-273.
Stauder R, Yu G, Koinig KA. Healthrelated quality of life in lower-risk MDS patients compared with age- and sexmatched reference populations: a European LeukemiaNet study. Leukemia. 2018; 32(6):1380-1392.
Efficace F, Cottone F, Abel G. Patientreported outcomes enhance the survival prediction of traditional disease risk classifications: an international study in patients with myelodysplastic syndromes. Cancer. 2018; 124(6):1251-1259.
Kroger N. Induction, Bridging, or straight ahead: the ongoing dilemma of allografting in advanced myelodysplastic syndrome. Biol Blood Marrow Transplant. 2019; 25(8):e247-e249.
Haase D, Germing U, Schanz J. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007; 110(13):4385-4395.
Bejar R, Stevenson K, Abdel-Wahab O. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011; 364(26):2496-2506.
Papaemmanuil E, Gerstung M, Malcovati L. Clinical and biological implications of driver mutations in myelodysplastic syndromes. Blood. 2013; 122(22):3616-3627.
Haferlach T, Nagata Y, Grossmann V. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014; 28(2):241-247.
Jaiswal S, Fontanillas P, Flannick J. Agerelated clonal hematopoiesis associated with adverse outcomes. N Engl J Med. 2014; 371(26):2488-2498.
Genovese G, Kahler AK, Handsaker RE. Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence. N Engl J Med. 2014; 371(26):2477-2487.
Figueroa ME, Abdel-Wahab O, Lu C. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell. 2010; 18(6):553-567.
Abdel-Wahab O, Gao J, Adli M. Deletion of Asxl1 results in myelodysplasia and severe developmental defects in vivo. J Exp Med. 2013; 210(12):2641-2659.
Feinberg AP, Irizarry RA. Evolution in health and medicine Sackler colloquium: stochastic epigenetic variation as a driving force of development, evolutionary adaptation, and disease. Proc Natl Acad Sci U S A. 2010; 107(Suppl 1):1757-1764.
Pellagatti A, Benner A, Mills KI. Identification of gene expression-based prognostic markers in the hematopoietic stem cells of patients with myelodysplastic syndromes. J Clin Oncol. 2013; 31(28):3557-3564.
Shiozawa Y, Malcovati L, Gallì A. Gene expression and risk of leukemic transformation in myelodysplasia. Blood. 2017; 130(24):2642-2653.
Im H, Rao V, Sridhar K. Distinct transcriptomic and exomic abnormalities within myelodysplastic syndrome marrow cells. Leuk Lymphoma. 2018; 59(12):2952-2962.
Chamuleau ME, Westers TM, van Dreunen L. Immune mediated autologous cytotoxicity against hematopoietic precursor cells in patients with myelodysplastic syndrome. Haematologica. 2009; 94(4):496-506.
Kordasti SY, Ingram W, Hayden J. CD4+CD25high Foxp3+ regulatory T cells in myelodysplastic syndrome (MDS). Blood. 2007; 110(3):847-850.
Kotsianidis I, Bouchliou I, Nakou E. Kinetics, function and bone marrow trafficking of CD4+CD25+FOXP3+ regulatory T cells in myelodysplastic syndromes (MDS). Leukemia. 2009; 23(3):510-518.
Roe C, Ali N, Epling-Burnette PK. T-cell large granular lymphocyte proliferation (LGL) in patients with myelodysplastic syndromes (MDS): not an Innocent bystander?. Clin Lymphoma Myeloma Leuk. 2016; 16:S89.
Durrani J, Awada H, Kishtagari A. Large granular lymphocytic leukemia coexists with myeloid clones and myelodysplastic syndrome. Leukemia. 2020; 34(3):957-962.
Yoshida Y, Oguma S, Ohno H. Cooccurrence of monoclonal gammopathy and myelodysplasia: a retrospective study of fourteen cases. Int J Hematol. 2014; 99(6):721-725.
Mailankody S, Pfeiffer RM, Kristinsson SY. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS). Blood. 2011; 118(15):4086-4092.
Blau O, Baldus CD, Hofmann WK. Mesenchymal stromal cells of myelodysplastic syndrome and acute myeloid leukemia patients have distinct genetic abnormalities compared with leukemic blasts. Blood. 2011; 118(20):5583-5592.
von der Heide EK, Neumann M, Vosberg S. Molecular alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients. Leukemia. 2017; 31(5):1069-1078.
Kim Y, Jekarl DW, Kim J. Genetic and epigenetic alterations of bone marrow stromal cells in myelodysplastic syndrome and acute myeloid leukemia patients. Stem Cell Res. 2015; 14(2):177-184.
Santamaria C, Muntion S, Roson B. Impaired expression of DICER, DROSHA, SBDS and some microRNAs in mesenchymal stromal cells from myelodysplastic syndrome patients. Haematologica. 2012; 97(8):1218-1224.
Lopez-Villar O, Garcia JL, Sanchez-Guijo FM. Both expanded and uncultured mesenchymal stem cells from MDS patients are genomically abnormal, showing a specific genetic profile for the 5q- syndrome. Leukemia. 2009; 23(4):664-672.
Zambetti NA, Ping Z, Chen S. Mesenchymal inflammation drives genotoxic stress in hematopoietic stem cells and predicts disease evolution in human preleukemia. Cell Stem Cell. 2016; 19(5):613-627.
Geyh S, Oz S, Cadeddu RP. Insufficient stromal support in MDS results from molecular and functional deficits of mesenchymal stromal cells. Leukemia. 2013; 27(9):1841-1851.
Geyh S, Rodriguez-Paredes M, Jager P. Functional inhibition of mesenchymal stromal cells in acute myeloid leukemia. Leukemia. 2016; 30(3):683-691.
Medyouf H, Mossner M, Jann JC. Myelodysplastic cells in patients reprogram mesenchymal stromal cells to establish a transplantable stem cell niche disease unit. Cell Stem Cell. 2014; 14(6):824-837.
Walkley CR, Olsen GH, Dworkin S. A microenvironment-induced myeloproliferative syndrome caused by retinoic acid receptor gamma deficiency. Cell. 2007; 129(6):1097-1110.
Dong L, Yu WM, Zheng H. Leukaemogenic effects of Ptpn11 activating mutations in the stem cell microenvironment. Nature. 2016; 539(7628):304-308.
Kim YW, Koo BK, Jeong HW. Defective Notch activation in microenvironment leads to myeloproliferative disease. Blood. 2008; 112(12):4628-4638.
Takahashi K, Wang F, Kantarjian H. Preleukaemic clonal haemopoiesis and risk of therapy-related myeloid neoplasms: a case-control study. Lancet Oncol. 2017; 18(1):100-111.
Coombs CC, Zehir A, Devlin SM. Therapy-related clonal hematopoiesis in patients with non-hematologic cancers is common and associated with adverse clinical outcomes. Cell Stem Cell. 2017; 21(3):374-382.e4.
Wong TN, Ramsingh G, Young AL. Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia. Nature. 2015; 518(7540):552-555.
Krönke J, Fink EC, Hollenbach PW. Lenalidomide induces ubiquitination and degradation of CK1a in del (5q) MDS. Nature. 2015; 523(7559):183-188.
Basiorka AA, McGraw KL, De Ceuninck L. Lenalidomide stabilizes the erythropoietin receptor by inhibiting the E3 ubiquitin ligase RNF41. Cancer Res. 2016; 76(12):3531-3540.
Cazzola M, Invernizzi R, Bergamaschi G. Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia. Blood. 2003; 101(5):1996-2000.
Nikpour M, Scharenberg C, Liu A. The transporter ABCB7 is a mediator of the phenotype of acquired refractory anemia with ring sideroblasts. Leukemia. 2013; 27(4):889-896.
Papaemmanuil E, Cazzola M, Boultwood J. Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med. 2011; 365(15):1384-1395.
Yoshida K, Sanada M, Shiraishi Y. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011; 478(7367):64-69.
Shiozawa Y, Malcovati L, Galli A. Aberrant splicing and defective mRNA production induced by somatic spliceosome mutations in myelodysplasia. Nat Commun. 2018; 9(1):3649.
Obeng EA, Chappell RJ, Seiler M. Physiologic expression of Sf3b1(K700E) causes impaired erythropoiesis, aberrant splicing, and sensitivity to therapeutic spliceosome modulation. Cancer Cell. 2016; 30(3):404-417.
Mupo A, Seiler M, Sathiaseelan V. Hemopoietic-specific Sf3b1-K700E knock-in mice display the splicing defect seen in human MDS but develop anemia without ring sideroblasts. Leukemia. 2017; 31(3):720-727.
Mortera-Blanco T, Dimitriou M, Woll PS. SF3B1-initiating mutations in MDS-RSs target lymphomyeloid hematopoietic stem cells. Blood. 2017; 130(7):881-890.
Elvarsdottir EM, Mortera-Blanco T, Dimitriou M. A three-dimensional in vitro model of erythropoiesis recapitulates erythroid failure in myelodysplastic syndromes. Leukemia. 2020; 34(1):271-282.
Malcovati L, Stevenson K, Papaemmanuil E. SF3B1-mutant myelodysplastic syndrome as a distinct disease subtype - a proposal of the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM). Blood, in press. 2020.
Churpek JE. Familial myelodysplastic syndrome/ acute myeloid leukemia. Best Pract Res Clin Haematol. 2017; 30(4):287-289.
Godley LA, Shimamura A.. Genetic predisposition to hematologic malignancies: management and surveillance. Blood. 2017; 130(4):424-432.
Wlodarski MW, Collin M, Horwitz MS. GATA2 deficiency and related myeloid neoplasms. Semin Hematol. 2017; 54(2):81-86.
Tesi B, Davidsson J, Voss M. Gain-offunction SAMD9L mutations cause a syndrome of cytopenia, immunodeficiency, MDS, and neurological symptoms. Blood. 2017; 129(16):2266-2279.
Douglas SPM, Siipola P, Kovanen PE. ERCC6L2 defines a novel entity within inherited acute myeloid leukemia. Blood. 2019; 133(25):2724-2728.
Sebert M, Passet M, Raimbault A. Germline DDX41 mutations define a significant entity within adult MDS/AML patients. Blood. 2019; 134(17):1441-1444.
Greenberg P, Cox C, LeBeau MM. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997; 89(6):2079-2088.
Germing U, Hildebrandt B, Pfeilstöcker M. Refinement of the international prognostic scoring system (IPSS) by including LDH as an additional prognostic variable to improve risk assessment in patients with primary myelodysplastic syndromes (MDS). Leukemia. 2005; 19(12):2223-2231.
Sanz G, Nomdedeu B, Such E. Independent impact of iron overload and transfusion dependency on survival and leukemic evolution in patients with myelodysplastic syndrome. Blood. 2008; 112(11):640.
Della Porta MG, Malcovati L, Boveri E. Clinical relevance of bone marrow fibrosis and CD34-positive cell clusters in primary myelodysplastic syndromes. J Clin Oncol. 2009; 27(5):754-762.
Naqvi K, Garcia-Manero G, Sardesai S. Association of comorbidities with overall survival in myelodysplastic syndrome: development of a prognostic model. J Clin Oncol. 2011; 29(16):2240-2246.
Stauder R, Nösslinger T, Pfeilstöcker M. Impact of age and comorbidity in myelodysplastic syndromes. J Natl Compr Cancer Netw. 2008; 6(9):927-934.
Schanz J, Tüchler H, Solé F. 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(8):820-829.
Della Porta M, Tuechler H, Malcovati L. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM). Leukemia. 2015; 29(7):1502-1513.
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Mishra A, Corrales‐Yepez M, Ali NA. Validation of the revised International Prognostic Scoring System in treated patients with myelodysplastic syndromes. Am J Hematol. 2013; 88(7):566-570.
Lamarque M, Raynaud S, Itzykson R. The revised IPSS is a powerful tool to evaluate the outcome of MDS patients treated with azacitidine: the GFM experience. Blood. 2012; 120(25):5084-5085.
Pfeilstöcker M, Tüchler H, Schönmetzler A. Time changes in predictive power of established and recently proposed clinical, cytogenetical and comorbidity scores for myelodysplastic syndromes. Leuk Res. 2012; 36(2):132-139.
Voso MT, Fenu S, Latagliata R. Revised International Prognostic Scoring System (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO Prognostic Scoring System: validation by the Gruppo Romano Mielodisplasie Italian Regional Database. J Clin Oncol. 2013; 31(21):2671-2677.
Neukirchen J, Lauseker M, Blum S. Validation of the revised international prognostic scoring system (IPSS-R) in patients with myelodysplastic syndrome: a multicenter study. Leuk Res. 2014; 38(1):57-64.
Bejar R, Papaemmanuil E, Haferlach T. Somatic mutations in MDS patients are associated with clinical features and predict prognosis independent of the IPSS-R: analysis of combined datasets from the International Working Group for Prognosis in MDS-Molecular Committee. Blood. 2015; 126(23):907.
Nazha A, Al-Issa K, Hamilton B. Adding molecular data to prognostic models can improve predictive power in treated patients with myelodysplastic syndromes. Leukemia. 2017; 31(12):2848-2850.
Tefferi A, Gangat N, Mudireddy M. Mayo alliance prognostic model for myelodysplastic syndromes: integration of genetic and clinical information. Mayo Clin Proc. 2018; 93(10):1363-1374.
Bernard E, Nannya Y, Yoshizato T. TP53 state dictates genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Blood. 2019; 134(Suppl_1):675.
Duetz C, Bachas C, Westers TM. Computational analysis of flow cytometry data in hematological malignancies: future clinical practice?. Curr Opin Oncol. 2020; 32(2):162-169.
Hansen JW, Pedersen DA, Larsen LA. Clonal hematopoiesis in elderly twins: concordance, discordance, and mortality. Blood. 2020; 135(4):261-268.
Malcovati L, Galli A, Travaglino E. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood. 2017; 129(25):3371-3378.
Luis TC, Wilkinson AC, Beerman I. Biological implications of clonal hematopoiesis. Exp Hematol. 2019; 77:1-5.
Breccia M, Federico V, Latagliata R. Evaluation of comorbidities at diagnosis predicts outcome in myelodysplastic syndrome patients. Leuk Res. 2011; 35(2):159-162.
Sorror ML, Sandmaier BM, Storer BE. Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol. 2007; 25(27):4246-4254.
de Swart L, Crouch S, Hoeks M. Impact of red blood cell transfusion dose density on progression-free survival in lower-risk myelodysplastic syndromes patients. Haematologica. 2020; 105(3):632-639.
Nilsson-Ehle H, Birgegard G, Samuelsson J. Quality of life, physical function and MRI T2* in elderly low-risk MDS patients treated to a haemoglobin level of >/=120 g/L with darbepoetin alfa +/- filgrastim or erythrocyte transfusions. Eur J Haematol. 2011; 87(3):244-252.
Stanworth SJ, Killick S, McQuilten ZK. Red cell transfusion in outpatients with myelodysplastic syndromes: a feasibility and exploratory randomised trial. Br J Haematol. 2020; 189(2):279-290.
Mittelman M, Platzbecker U, Afanasyev B. Eltrombopag for advanced myelodysplastic syndromes or acute myeloid leukaemia and severe thrombocytopenia (ASPIRE): a randomised, placebo-controlled, phase 2 trial. Lancet Haematol. 2018; 5(1):e34-e43.
Dickinson M, Cherif H, Fenaux P. Azacitidine with or without eltrombopag for first-line treatment of intermediate- or high-risk MDS with thrombocytopenia. Blood. 2018; 132(25):2629-2638.
Goldberg SL, Chen E, Corral M. Incidence and clinical complications of myelodysplastic syndromes among United States Medicare beneficiaries. J Clin Oncol. 2010; 28(17):2847-2852.
Malcovati L, Porta MGD, Pascutto C. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005; 23(30):7594-7603.
Schafer AI, Cheron RG, Dluhy R. Clinical consequences of acquired transfusional iron overload in adults. N Engl J Med. 1981; 304(6):319-324.
Hershko C, Link G, Cabantchik I.. Pathophysiology of iron overload. Ann N Y Acad Sci. 1998; 850:191-201.
Cabantchik ZI, Breuer W, Zanninelli G. LPI-labile plasma iron in iron overload. Best Pract Res Clin Haematol. 2005; 18(2):277-287.
Cortelezzi A, Cattaneo C, Cristiani S. Non-transferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis?. Hematol J. 2000; 1(3):153-158.
Greenberg PL, Rigsby CK, Stone RM. NCCN Task Force: transfusion and iron overload in patients with myelodysplastic syndromes. J Natl Compr Cancer Netw. 2009; 7(Suppl_9):S-1-S-16.
De Swart L, Smith A, Fenaux P. Transfusion-dependency is the most important prognostic factor for survival in 1000 newly diagnosed MDS patients with lowand intermediate-1 risk MDS in the European LeukemiaNet MDS registry. Blood. 2011; 118(21):2775.
Malcovati L, Della Porta MG, Strupp C. Impact of the degree of anemia on the outcome of patients with myelodysplastic syndrome and its integration into the WHO classification-based Prognostic Scoring System (WPSS). Haematologica. 2011; 96(10):1433-1440.
Lyons RM, Marek BJ, Paley C. Relation between chelation and clinical outcomes in lower-risk patients with myelodysplastic syndromes:registry analysis at 5 years. Leuk Res. 2017; 56:88-95.
Leitch HA, Parmar A, Wells RA. Overall survival in lower IPSS risk MDS by receipt of iron chelation therapy, adjusting for patient‐related factors and measuring from time of first red blood cell transfusion dependence: an MDS‐CAN analysis. Br J Haematol. 2017; 179(1):83-97.
Mainous AG, Tanner RJ, Hulihan MM. The impact of chelation therapy on survival in transfusional iron overload: a meta‐analysis of myelodysplastic syndrome. Br J Haematol. 2014; 167(5):720-723.
Zeidan AM, Giri S, DeVeaux M. Systematic review and meta-analysis of the effect of iron chelation therapy on overall survival and disease progression in patients with lower-risk myelodysplastic syndromes. Ann Hematol. 2019; 98(2):339-350.
Hoeks M, Yu G, Langemeijer S. Impact of treatment with iron chelation therapy in patients with lower-risk myelodysplastic syndromes participating in the European MDS registry. Haematologica. 2020; 105(3):640-651.
Angelucci E, Li J, Greenberg P. Iron chelation in transfusion-dependent low/intermediate-1-risk myelodysplastic syndromes patients: a randomized trial. Ann Intern Med. 2020; 172(8):513-522.
Leitch HA, Buckstein R, Zhu N. Iron overload in myelodysplastic syndromes: evidence based guidelines from the Canadian consortium on MDS. Leuk Res. 2018; 74:21-41.
Killick SB. Iron chelation therapy in low risk myelodysplastic syndrome. Br J Haematol. 2017; 177(3):375-387.
Meerpohl JJ, Antes G, Ruecker G. Deferasirox for managing iron overload in people with myelodysplastic syndrome. Cochrane Database Syst Rev. 2010; 11:CD007461.
Steensma DP, Gattermann N.. When is iron overload deleterious, and when and how should iron chelation therapy be administered in myelodysplastic syndromes?. Best Pract Res Clin Haematol. 2013; 26(4):431-444.
Fenaux P, Santini V, Spiriti MAA. A phase 3 randomized, placebo-controlled study assessing the efficacy and safety of epoetin-alpha in anemic patients with lowrisk MDS. Leukemia. 2018; 32(12):2648-2658.
Platzbecker U, Symeonidis A, Oliva EN. A phase 3 randomized placebo-controlled trial of darbepoetin alfa in patients with anemia and lower-risk myelodysplastic syndromes. Leukemia. 2017; 31(9):1944-1950.
Park S, Kelaidi C, Meunier M. The prognostic value of serum erythropoietin in patients with lower-risk myelodysplastic syndromes: a review of the literature and expert opinion. Ann Hematol. 2020; 99(1):7-19.
Balleari E, Filiberti RA, Salvetti C. Effects of different doses of erythropoietin in patients with myelodysplastic syndromes: a propensity score-matched analysis. Cancer Med. 2019; 8(18):7567-7576.
Garelius HK, Johnston WT, Smith AG. Erythropoiesis-stimulating agents significantly delay the onset of a regular transfusion need in nontransfused patients with lower-risk myelodysplastic syndrome. J Intern Med. 2017; 281(3):284-299.
Negrin RS, Stein R, Doherty K. Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy. Blood. 1996; 87(10):4076-4081.
Hellstrom-Lindberg E, Ahlgren T, Beguin Y. Treatment of anemia in myelodysplastic syndromes with granulocyte colonystimulating factor plus erythropoietin: results from a randomized phase II study and long-term follow-up of 71 patients. Blood. 1998; 92(1):68-75.
Jadersten M, Malcovati L, Dybedal I. Erythropoietin and granulocyte-colony stimulating factor treatment associated with improved survival in myelodysplastic syndrome. J Clin Oncol. 2008; 26(21):3607-3613.
List A, Dewald G, Bennett J. Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med. 2006; 355(14):1456-1465.
Raza A, Reeves JA, Feldman EJ. Phase 2 study of lenalidomide in transfusiondependent, low-risk, and intermediate-1– risk myelodysplastic syndromes with karyotypes other than deletion 5q. Blood. 2008; 111(1):86-93.
Toma A, Kosmider O, Chevret S. Lenalidomide with or without erythropoietin in transfusion-dependent erythropoiesis- stimulating agent-refractory lowerrisk MDS without 5q deletion. Leukemia. 2016; 30(4):897-905.
Mossner M, Jann J-C, Nowak D. Prevalence, clonal dynamics and clinical impact of TP53 mutations in patients with myelodysplastic syndrome with isolated deletion (5q) treated with lenalidomide: results from a prospective multicenter study of the german MDS study group (GMDS). Leukemia. 2016; 30(9):1956-1959.
Sloand EM, Wu CO, Greenberg P. Factors affecting response and survival in patients with myelodysplasia treated with immunosuppressive therapy. J Clin Oncol. 2008; 26(15):2505-2511.
Kadia TM, Borthakur G, Garcia-Manero G. Final results of the phase II study of rabbit anti-thymocyte globulin, ciclosporin, methylprednisone, and granulocyte colonystimulating factor in patients with aplastic anaemia and myelodysplastic syndrome. Br J Haematol. 2012; 157(3):312-320.
Passweg JR, Giagounidis AA, Simcock M. 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. 2011; 29(3):303-309.
Stahl M, DeVeaux M, de Witte T. The use of immunosuppressive therapy in MDS: clinical outcomes and their predictors in a large international patient cohort. Blood Adv. 2018; 2(14):1765-1772.
Stahl M, Bewersdorf JP, Giri S. Use of immunosuppressive therapy for management of myelodysplastic syndromes: a systematic review and meta-analysis. Haematologica. 2020; 105(1):102-111.
Silverman LR, Holland JF, Weinberg RS. Effects of treatment with 5-azacytidine on the in vivo and in vitro hematopoiesis in patients with myelodysplastic syndromes. Leukemia. 1993; 7(Suppl 1):21-29.
Silverman LR, Demakos EP, Peterson BL. Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the Cancer and Leukemia Group B. J Clin Oncol. 2002; 20(10):2429-2440.
Silverman LR, McKenzie DR, Peterson BL. 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(24):3895-3903.
Fenaux P, Mufti GJ, Hellstrom-Lindberg E. 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.
Komrokji R, Swern AS, Grinblatt D. Azacitidine in lower-risk myelodysplastic syndromes: a meta-analysis of data from prospective studies. Oncologist. 2018; 23(2):159-70.
Tobiasson M, Dybedahl I, Holm MS. Limited clinical efficacy of azacitidine in transfusion-dependent, growth factor-resistant, low- and Int-1-risk MDS: results from the Nordic NMDSG08A phase II trial. Blood Cancer J. 2014; 4:e189.
Garcia-Manero G, Jabbour E, Borthakur G. Randomized open-label phase II study of decitabine in patients with low- or intermediate- risk myelodysplastic syndromes. J Clin Oncol. 2013; 31(20):2548-2553.
Itzykson R, Thepot S, Quesnel B. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011; 117(2):403-411.
Hwang KL, Song MK, Shin HJ. Monosomal and complex karyotypes as prognostic parameters in patients with International Prognostic Scoring System higher risk myelodysplastic syndrome treated with azacitidine. Blood Res. 2014; 49(4):234-240.
Bejar R, Lord A, Stevenson K. TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients. Blood. 2014; 124(17):2705-2712.
Traina F, Visconte V, Elson P. Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms. Leukemia. 2014; 28(1):78-87.
Itzykson R, Kosmider O, Cluzeau T. Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias. Leukemia. 2011; 25(7):1147-1152.
Jin J, Hu C, Yu M. Prognostic value of isocitrate dehydrogenase mutations in myelodysplastic syndromes: a retrospective cohort study and meta-analysis. PLoS One. 2014; 9(6):e100206.
Steensma DP, Baer MR, Slack JL. 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(23):3842-3848.
Kantarjian HM, O'Brien S, Shan J. Update of the decitabine experience in higher risk myelodysplastic syndrome and analysis of prognostic factors associated with outcome. Cancer. 2007; 109(2):265-273.
Welch JS, Petti AA, Miller CA. TP53 and decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016; 375(21):2023-2036.
de Witte T, Suciu S, Peetermans M. Intensive chemotherapy for poor prognosis myelodysplasia (MDS) and secondary acute myeloid leukemia (sAML) following MDS of more than 6 months duration. A pilot study by the Leukemia Cooperative Group of the European Organisation for Research and Treatment in Cancer (EORTC-LCG). Leukemia. 1995; 9(11):1805-1811.
Ganser A, Heil G, Seipelt G. Intensive chemotherapy with idarubicin, ara-C, etoposide, and m-AMSA followed by immunotherapy with interleukin-2 for myelodysplastic syndromes and high-risk acute myeloid leukemia (AML). Ann Hematol. 2000; 79(1):30-35.
Kantarjian H, O'Brien S, Cortes J. 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(5):1090-1098.
Martino R, Iacobelli S, Brand R. Retrospective comparison of reduced-intensity conditioning and conventional highdose conditioning for allogeneic hematopoietic stem cell transplantation using HLAidentical sibling donors in myelodysplastic syndromes. Blood. 2006; 108(3):836-846.
Koenecke C, Gohring G, de Wreede LC. Impact of the revised International Prognostic Scoring System, cytogenetics and monosomal karyotype on outcome after allogeneic stem cell transplantation for myelodysplastic syndromes and secondary acute myeloid leukemia evolving from myelodysplastic syndromes: a retrospective multicenter study of the European Society of Blood and Marrow Transplantation. Haematologica. 2015; 100(3):400-408.
Deeg HJ, Scott BL, Fang M. Five-group cytogenetic risk classification, monosomal karyotype, and outcome after hematopoietic cell transplantation for MDS or acute leukemia evolving from MDS. Blood. 2012; 120(7):1398-1408.
Kroger N, Iacobelli S, Franke GN. 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.
Cutler CS, Lee SJ, Greenberg P. 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(2):579-585.
Della Porta MG, Alessandrino EP, Bacigalupo A. Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R. Blood. 2014; 123(15):2333-2342.
Alessandrino EP, Della Porta MG, Bacigalupo A. WHO classification and WPSS predict posttransplantation outcome in patients with myelodysplastic syndrome: a study from the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Blood. 2008; 112(3):895-902.
Della Porta MG, Galli A, Bacigalupo A. Clinical effects of driver somatic mutations on the outcomes of patients with myelodysplastic syndromes treated with allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2016; 34(30):3627-3637.
Bejar R, Stevenson KE, Caughey B. Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation. J Clin Oncol. 2014; 32(25):2691-2698.
Yoshizato T, Nannya Y, Atsuta Y. Genetic abnormalities in myelodysplasia and secondary acute myeloid leukemia: impact on outcome of stem cell transplantation. Blood. 2017; 129(17):2347-2358.
Lindsley RC, Saber W, Mar BG. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N Engl J Med. 2017; 376(6):536-547.
Yahng SA, Kim M, Kim TM. Better transplant outcome with pre-transplant marrow response after hypomethylating treatment in higher-risk MDS with excess blasts. Oncotarget. 2017; 8(7):12342-12354.
Damaj G, Mohty M, Robin M. Upfront allogeneic stem cell transplantation after reduced-intensity/nonmyeloablative conditioning for patients with myelodysplastic syndrome: a study by the Societe Francaise de Greffe de Moelle et de Therapie Cellulaire. Biol Blood Marrow Transplant. 2014; 20(9):1349-1355.
Oran B, Kongtim P, Popat U. Cytogenetics, donor type, and use of hypomethylating agents in myelodysplastic syndrome with allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2014; 20(10):1618-1625.
Schroeder T, Wegener N, Lauseker M. 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.
Damaj G, Duhamel A, Robin M. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe- Francophone des Myélodysplasies. J Clin Oncol. 2012; 30(36):4533-4540.
Beelen DW, Trenschel R, Stelljes M. Treosulfan or busulfan plus fludarabine as conditioning treatment before allogeneic haemopoietic stem cell transplantation for older patients with acute myeloid leukaemia or myelodysplastic syndrome (MCFludT. 14/L): a randomised, non-inferiority, phase 3 trial. Lancet Haematol. 2020; 7(1):e28-e39.
Casper J, Knauf W, Kiefer T. Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation. Blood. 2004; 103(2):725-731.
Ruutu T, Volin L, Beelen DW. Reducedtoxicity conditioning with treosulfan and fludarabine in allogeneic hematopoietic stem cell transplantation for myelodysplastic syndromes: final results of an international prospective phase II trial. Haematologica. 2011; 96(9):1344-1350.
Schroeder T, Rachlis E, Bug G. Treatment of acute myeloid leukemia or myelodysplastic syndrome relapse after allogeneic stem cell transplantation with azacitidine and donor lymphocyte infusions--a retrospective multicenter analysis from the German Cooperative Transplant Study Group. Biol Blood Marrow Transplant. 2015; 21(4):653-660.
DiNardo CD, Stein EM, de Botton S. Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML. N Engl J Med. 2018; 378(25):2386-2398.
Stein EM, Fathi AT, DiNardo CD. Enasidenib in patients with mutant IDH2 myelodysplastic syndromes: a phase 1 subgroup analysis of the multicentre, AG221-C- 001 trial. Lancet Haematol. 2020; 7(4):e309-e319.
Wei AH, Garcia JS, Borate U. A phase 1b study evaluating the safety and efficacy of venetoclax in combination with azacitidine in treatment-naïve patients with higher- risk myelodysplastic syndrome. Blood. 2019; 134(Suppl_1):568.
Zeidan AM, Pollyea DA, Garcia JS. A phase 1b study evaluating the safety and efficacy of venetoclax as monotherapy or in combination with azacitidine for the treatment of relapsed/refractory myelodysplastic syndrome. Bood. 2019; 134(Suppl_1):565.
Kulasekararaj AG, Smith AE, Mian SA. TP 53 mutations in myelodysplastic syndrome are strongly correlated with aberrations of chromosome 5, and correlate with adverse prognosis. Br J Haemat. 2013; 160(5):660-672.
Deneberg S, Cherif H, Lazarevic V. An open-label phase I dose-finding study of APR-246 in hematological malignancies. Blood Cancer J. 2016; 6(7):e447.
Sallman DA, DeZern AE, Garcia-Manero G. Phase 2 results of APR-246 and azacitidine (AZA) in patients with TP53 mutant myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia (AML). Blood. 2019; 134(Suppl_1):676.
Carvajal LA, Ben-Neriah D, Senecal A. Dual inhibition of Mdmx and Mdm2 using an alpha-helical P53 stapled peptide (ALRN- 6924) as a novel therapeutic strategy in acute myeloid leukemia. Blood. 2017; 130(Suppl_1):795.
Rudolph KL, Chang S, Lee H-W. Longevity, stress response, and cancer in aging telomerase-deficient mice. Cell. 1999; 96(5):701-712.
di Fagagna FdA, Reaper PM, Clay-Farrace L. A DNA damage checkpoint response in telomere-initiated senescence. Nature. 2003; 426(6963):194-198.
Tefferi A, Lasho TL, Begna KH. A pilot study of the telomerase inhibitor imetelstat for myelofibrosis. N Engl J Med. 2015; 373(10):908-919.
Platzbecker U, Steensma DP, Van Eygen K. Imerge: a study to evaluate imetelstat (GRN163L) in transfusion-dependent subjects with IPSS low or intermediate-1 risk myelodysplastic syndromes (MDS) that is relapsed/refractory to erythropoiesis-stimulating agent (ESA) treatment. Blood. 2019; 134(Suppl_1):4248.
Bataller A, Montalban-Bravo G, Soltysiak KA. The role of TGFβ in hematopoiesis and myeloid disorders. Leukemia. 2019; 33(5):1076-1089.
Zhou L, Nguyen AN, Sohal D. Inhibition of the TGF-β receptor I kinase promotes hematopoiesis in MDS. Blood. 2008; 112(8):3434-3443.
Suragani RN, Cadena SM, Cawley SM. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med. 2014; 20(4):408-414.
Fenaux P, Platzbecker U, Mufti GJ. Luspatercept in patients with lower-risk myelodysplastic syndromes. N Engl J Med. 2020; 382(2):140-151.
Kurtz SE, Eide CA, Kaempf A. Molecularly targeted drug combinations demonstrate selective effectiveness for myeloid-and lymphoid-derived hematologic malignancies. Proc Natl Acad Sci U S A. 2017; 114(36):E7554-E7563.
Swords RT, Azzam D, Al-Ali H. Exvivo sensitivity profiling to guide clinical decision making in acute myeloid leukemia: a pilot study. Leuk Res. 2018; 64:34-41.
Spinner MA, Aleshin A, Santaguida MA. A feasibility study of biologically focused therapy for myelodysplastic syndrome patients refractory to hypomethylating agents. Blood. 2019; 134(Suppl 1):4239.
Drusbosky LM, Cogle CR. Computational modeling and treatment identification in the myelodysplastic syndromes. Curr Hematol Malig Rep. 2017; 12(5):478-483.