The trajectory of prognostication and risk stratification for patients with myelodysplastic syndromes

MYELODYSPLASTIC SYNDROMES IN THE AGE OF GENOMIC MEDICINE| December 28, 2023 The trajectory of prognostication and risk stratification for patients with myelodysplastic syndromes Amy E. DeZern, Amy E. DeZern 1Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD https://orcid.org/0000-0001-5225-4609 Search for other works by this author on: This Site PubMed Google Scholar Peter L. Greenberg Peter L. Greenberg 2Hematology Division, Department of Medicine, Stanford University School of Medicine, Stanford, CA https://orcid.org/0000-0002-7615-9443 Search for other works by this author on: This Site PubMed Google Scholar Blood (2023) 142 (26): 2258–2267. https://doi.org/10.1182/blood.2023020081 Article history Submitted: June 1, 2023 Accepted: August 4, 2023 First Edition: August 10, 2023 Connected Content A related article has been published: Diagnosis and classification of myelodysplastic syndromes A related article has been published: Clinical decision-making and treatment of myelodysplastic syndromes A related article has been published: Causes and consequences of clonal hematopoiesis View more A related article has been published: Introduction to a review series on myelodysplastic syndromes in the age of genomic medicine View less Share Icon Share Facebook Twitter LinkedIn Email Tools Icon Tools Request Permissions Cite Icon Cite Search Site Citation Amy E. DeZern, Peter L. Greenberg; The trajectory of prognostication and risk stratification for patients with myelodysplastic syndromes. Blood 2023; 142 (26): 2258–2267. doi: https://doi.org/10.1182/blood.2023020081 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBlood Search AbstractRisk stratification and prognostication are crucial for the appropriate management of patients with myelodysplastic syndromes (MDSs) or myelodysplastic neoplasms, for whom the expected survival can vary from a few months to >10 years. For the past 5 decades, patients with MDS have been classified into higher-risk vs lower-risk disease phenotypes using sequentially developed clinical prognostic scoring systems. Factors such as morphologic dysplasia, clinical hematologic parameters, cytogenetics, and, more recently, mutational information have been captured in prognostic scoring systems that refine risk stratification and guide therapeutic management in patients with MDS. This review describes the progressive evolution and improvement of these systems which has led to the current Molecular International Prognostic Scoring System. Subjects: Myeloid Neoplasia, Review Articles, Review Series References 1.Cazzola M. Myelodysplastic syndromes. N Engl J Med. 2020;383(14):1358-1374.Google ScholarCrossrefSearch ADS 2.Malcovati L, Ambaglio I, Elena C. The genomic landscape of myeloid neoplasms with myelodysplasia and its clinical implications. Curr Opin Oncol. 2015;27(6):551-559.Google ScholarCrossrefSearch ADS PubMed 3.Block M, Jacobson LO, Bethard WF. Preleukemic acute human leukemia. J Am Med Assoc. 1953;152(11):1018-1028.Google ScholarCrossrefSearch ADS 4.Meacham GC, Weisberger AS. Early atypical manifestations of leukemia. Ann Intern Med. 1954;41(4):780-797.Google ScholarPubMed 5.Fisher WB, Armentrout SA, Weisman R, Graham RC. "Preleukemia." A myelodysplastic syndrome often terminating in acute leukemia. Arch Intern Med. 1973;132(2):226-232.Google ScholarCrossrefSearch ADS PubMed 6.Blair TR, Bayrd ED, Pease GI. Atypical leukemia. JAMA. 1966;198(1):139-142.Google ScholarCrossrefSearch ADS PubMed 7.Saarni MI, Linman JW. Preleukemia. The hematologic syndrome preceding acute leukemia. Am J Med. 1973;55(1):38-48.Google ScholarCrossrefSearch ADS PubMed 8.Linman JW, Bagby GC. The preleukemic syndrome (hemopoietic dysplasia). Cancer. 1978;42(suppl 2):854-864.Google ScholarPubMed 9.Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol. 1982;51(2):189-199.Google ScholarCrossrefSearch ADS PubMed 10.Greenberg PL, Nichols WC, Schrier SL. Granulopoiesis in acute myeloid leukemia and preleukemia. N Engl J Med. 1971;284(22):1225-1232.Google ScholarCrossrefSearch ADS 11.Senn JS, Pinkerton PH. Defective in vitro colony formation by human bone marrow preceding overt leukaemia. Br J Haematol. 1972;23(3):277-281.Google ScholarCrossrefSearch ADS PubMed 12.Greenberg PL, Mara B. The preleukemic syndrome: correlation of in vitro parameters of granulopoiesis with clinical features. Am J Med. 1979;66(6):951-958.Google ScholarCrossrefSearch ADS PubMed 13.Sanz GF, Sanz MA, Vallespi T, et al. Two regression models and a scoring system for predicting survival and planning treatment in myelodysplastic syndromes: a multivariate analysis of prognostic factors in 370 patients. Blood. 1989;74(1):395-408.Google ScholarCrossrefSearch ADS PubMed 14.Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D. Myelodysplastic syndromes: a scoring system with prognostic significance. Br J Haematol. 1985;59(3):425-433.Google ScholarCrossrefSearch ADS PubMed 15.Aul C, Gattermann N, Heyll A, Germing U, Derigs G, Schneider W. Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. Leukemia. 1992;6(1):52-59.Google ScholarPubMed 16.Morel P, Hebbar M, Lai JL, et al. Cytogenetic analysis has strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases. Leukemia. 1993;7(9):1315-1323.Google ScholarPubMed 17.Toyama K, Ohyashiki K, Yoshida Y, et al. Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan. Leukemia. 1993;7(4):499-508.Google ScholarPubMed 18.Oscier DG. Myelodysplastic syndromes. Baillieres Clin Haematol. 1987;1(2):389-426.Google ScholarCrossrefSearch ADS PubMed 19.Tricot G, Boogaerts MA, De Wolf-Peeters C, Van den Berghe H, Verwilghen RL. The myelodysplastic syndromes: different evolution patterns based on sequential morphological and cytogenetic investigations. Br J Haematol. 1985;59(4):659-670.Google ScholarCrossrefSearch ADS PubMed 20.Jacobs RH, Cornbleet MA, Vardiman JW, Larson RA, Le Beau MM, Rowley JD. Prognostic implications of morphology and karyotype in primary myelodysplastic syndromes. Blood. 1986;67(6):1765-1772.Google ScholarCrossrefSearch ADS PubMed 21.Yunis JJ, Lobell M, Arnesen MA, et al. Refined chromosome study helps define prognostic subgroups in most patients with primary myelodysplastic syndrome and acute myelogenous leukaemia. Br J Haematol. 1988;68(2):189-194.Google ScholarCrossrefSearch ADS PubMed 22.Pierre RV, Catovsky D, Mufti GJ, et al. Clinical-cytogenetic correlations in myelodysplasia (preleukemia). Cancer Genet Cytogenet. 1989;40(2):149-161.Google ScholarCrossrefSearch ADS PubMed 23.Greenberg P, Cox C, LeBeau MM, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079-2088.Google ScholarCrossrefSearch ADS PubMed 24.Malcovati L, Porta MG, Pascutto C, et al. 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.Google ScholarCrossrefSearch ADS 25.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. 2007;25(23):3503-3510.Google ScholarCrossrefSearch ADS 26.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. 2008;113(6):1351-1361.Google ScholarCrossrefSearch ADS PubMed 27.Della Porta MG, Malcovati L, Strupp C, et al. Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica. 2011;96(3):441-449.Google ScholarCrossrefSearch ADS PubMed 28.Vardiman JW, Thiele J, Arber DA, et al. 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.Google ScholarCrossrefSearch ADS PubMed 29.Della Porta MG, Tuechler H, Malcovati L, et al. 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.Google ScholarCrossrefSearch ADS PubMed 30.Fenaux P, Rose C. Impact of iron overload in myelodysplastic syndromes. Blood Rev. 2009;23(suppl 1):S15-19.Google ScholarPubMed 31.Garcia-Manero G, Shan J, Faderl S, et al. A prognostic score for patients with lower risk myelodysplastic syndrome. Leukemia. 2008;22(3):538-543.Google ScholarCrossrefSearch ADS PubMed 32.Itzykson R, Thepot S, Quesnel B, et al. Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine. Blood. 2011;117(2):403-411.Google ScholarCrossrefSearch ADS PubMed 33.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. 2009;10(3):223-232.Google ScholarCrossrefSearch ADS PubMed 34.Wimazal F, Sperr WR, Kundi M, et al. Prognostic value of lactate dehydrogenase activity in myelodysplastic syndromes. Leuk Res. 2001;25(4):287-294.Google ScholarCrossrefSearch ADS PubMed 35.Germing U, Hildebrandt B, Pfeilstocker M, et al. 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.Google ScholarCrossrefSearch ADS PubMed 36.Sanz G, Nomdedeu B, Such E, et al. Independent impact of iron overload and transfusion dependency on survival and leukemic evolution in patients with myelodysplastic syndrome. Blood. 2008;112(11):640.Google ScholarCrossrefSearch ADS 37.Gatto S, Ball G, Onida F, Kantarjian HM, Estey EH, Beran M. Contribution of beta-2 microglobulin levels to the prognostic stratification of survival in patients with myelodysplastic syndrome (MDS). Blood. 2003;102(5):1622-1625.Google ScholarCrossrefSearch ADS PubMed 38.Neumann F, Gattermann N, Barthelmes HU, Haas R, Germing U. Levels of beta 2 microglobulin have a prognostic relevance for patients with myelodysplastic syndrome with regard to survival and the risk of transformation into acute myelogenous leukemia. Leuk Res. 2009;33(2):232-236.Google ScholarCrossrefSearch ADS PubMed 39.Verburgh E, Achten R, Maes B, et al. Additional prognostic value of bone marrow histology in patients subclassified according to the International Prognostic Scoring System for myelodysplastic syndromes. J Clin Oncol. 2003;21(2):273-282.Google ScholarCrossrefSearch ADS 40.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. 2009;27(5):754-762.Google ScholarCrossrefSearch ADS 41.Buesche G, Teoman H, Wilczak W, et al. Marrow fibrosis predicts early fatal marrow failure in patients with myelodysplastic syndromes. Leukemia. 2008;22(2):313-322.Google ScholarCrossrefSearch ADS PubMed 42.Wang R, Gross CP, Halene S, Ma X. Comorbidities and survival in a large cohort of patients with newly diagnosed myelodysplastic syndromes. Leuk Res. 2009;33(12):1594-1598.Google ScholarCrossrefSearch ADS PubMed 43.Naqvi K, Garcia-Manero G, Sardesai S, et al. Association of comorbidities with overall survival in myelodysplastic syndrome: development of a prognostic model. J Clin Oncol. 2011;29(16):2240-2246.Google ScholarCrossrefSearch ADS 44.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. 2012;30(8):820-829.Google ScholarCrossrefSearch ADS 45.Greenberg PL, Tuechler H, Schanz J, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120(12):2454-2465.Google ScholarCrossrefSearch ADS PubMed 46.Pfeilstocker M, Tuchler H, Schonmetzler A, Nosslinger T, Pittermann E. 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.Google ScholarCrossrefSearch ADS PubMed 47.Voso MT, Fenu S, Latagliata R, et al. 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.Google ScholarCrossrefSearch ADS 48.Neukirchen J, Lauseker M, Blum S, et al. 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.Google ScholarCrossrefSearch ADS PubMed 49.de Swart L, Smith A, Johnston TW, et al. Validation of the revised international prognostic scoring system (IPSS-R) in patients with lower-risk myelodysplastic syndromes: a report from the prospective European LeukaemiaNet MDS (EUMDS) registry. Br J Haematol. 2015;170(3):372-383.Google ScholarCrossrefSearch ADS PubMed 50.Ok CY, Hasserjian RP, Fox PS, et al. Application of the international prognostic scoring system-revised in therapy-related myelodysplastic syndromes and oligoblastic acute myeloid leukemia. Leukemia. 2014;28(1):185-189.Google ScholarCrossrefSearch ADS PubMed 51.Kuendgen A, Nomdedeu M, Tuechler H, et al. Therapy-related myelodysplastic syndromes deserve specific diagnostic sub-classification and risk-stratification – an approach to classification of patients with t-MDS. Leukemia. 2021;35(3):835-849.Google ScholarCrossrefSearch ADS PubMed 52.Patel SS, Sekeres MA, Nazha A. Prognostic models in predicting outcomes in myelodysplastic syndromes after hypomethylating agent failure. Leuk Lymphoma. 2017 11;58(11):2532-2539.Google ScholarCrossrefSearch ADS PubMed 53.Sakatoku K, Takeoka Y, Miura A, et al. Combination of frailty status and comorbidity score improves the stratification of survival in patients with myelodysplastic syndrome owing to good predictive capability for infection-related mortality. Clin Lymphoma Myeloma Leuk. 2019;19(12):799-805.Google ScholarCrossrefSearch ADS PubMed 54.Starkman R, Alibhai S, Wells RA, et al. An MDS-specific frailty index based on cumulative deficits adds independent prognostic information to clinical prognostic scoring. Leukemia. 2020;34(5):1394-1406.Google ScholarCrossrefSearch ADS PubMed 55.Stauder R, Yu G, Koinig KA, et al. Health-related quality of life in lower-risk MDS patients compared with age- and sex-matched reference populations: a European LeukemiaNet study. Leukemia. 2018;32(6):1380-1392.Google ScholarCrossrefSearch ADS PubMed 56.Stauder R, Nosslinger T, Pfeilstocker M, et al. Impact of age and comorbidity in myelodysplastic syndromes. J Natl Compr Canc Netw. 2008;6(9):927-934.Google ScholarCrossrefSearch ADS 57.Wouters H, Conrads-Frank A, Koinig KA, et al. The anemia-independent impact of myelodysplastic syndromes on health-related quality of life. Ann Hematol. 2021;100(12):2921-2932.Google ScholarCrossrefSearch ADS PubMed 58.Abel GA, Efficace F, Buckstein RJ, et al. Prospective international validation of the Quality of Life in Myelodysplasia Scale (QUALMS). Haematologica. 2016;101(6):781-788.Google ScholarCrossrefSearch ADS PubMed 59.Abel GA, Hebert D, Lee C, et al. Health-related quality of life and vulnerability among people with myelodysplastic syndromes: a US National Study. Blood Adv. 2023;7(14):3506-3515.Google ScholarCrossrefSearch ADS PubMed 60.Bejar R, Stevenson K, Abdel-Wahab O, et al. Clinical effect of point mutations in myelodysplastic syndromes. N Engl J Med. 2011;364(26):2496-2506.Google ScholarCrossrefSearch ADS 61.Papaemmanuil E, Gerstung M, Malcovati L, et al. Clinical and biological implications of driver mutations in myelodysplastic syndromes [quiz]. Blood. 2013;122(22):3616-3627.Google ScholarCrossrefSearch ADS PubMed 62.Haferlach T, Nagata Y, Grossmann V, et al. Landscape of genetic lesions in 944 patients with myelodysplastic syndromes. Leukemia. 2014;28(2):241-247.Google ScholarCrossrefSearch ADS PubMed 63.Nazha A, Al-Issa K, Hamilton BK, et al. Adding molecular data to prognostic models can improve predictive power in treated patients with myelodysplastic syndromes. Leukemia. 2017;31(12):2848-2850.Google ScholarCrossrefSearch ADS PubMed 64.Bersanelli M, Travaglino E, Meggendorfer M, et al. Classification and personalized prognostic assessment on the basis of clinical and genomic features in myelodysplastic syndromes. J Clin Oncol. 2021;39(11):1223-1233.Google ScholarCrossrefSearch ADS 65.Nazha A, Komrokji R, Meggendorfer M, et al. Personalized prediction model to risk stratify patients with myelodysplastic syndromes. J Clin Oncol. 2021;39(33):3737-3746.Google ScholarCrossrefSearch ADS 66.Radakovich N, Sallman DA, Buckstein R, et al. A machine learning model of response to hypomethylating agents in myelodysplastic syndromes. iScience. 2022;25(10):104931.Google ScholarCrossrefSearch ADS PubMed 67.GenoMed4All consortium. A sex-informed approach to improve the personalised decision making process in myelodysplastic syndromes: a multicentre, observational cohort study. Lancet Haematol. 2023;10(2):e117-e128.CrossrefSearch ADS PubMed 68.Bernard E, Tuechler H, Greenberg PL, et al. Molecular international prognostic scoring system for myelodysplastic syndromes. NEJM Evid. 2022;1(7). Evidoa2200008.Google Scholar 69.Baer C, Huber S, Hutter S, et al. Risk prediction in MDS: independent validation of the IPSS-M-ready for routine?. Leukemia. 2023;37(4):938-941.Google ScholarCrossrefSearch ADS PubMed 70.Sauta E, Robin M, Bersanelli M, et al. Real-world validation of molecular international prognostic scoring system for myelodysplastic syndromes. J Clin Oncol. 2023;41(15):2827-2842.Google ScholarCrossrefSearch ADS 71.Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia. 2022;36(7):1703-1719.Google ScholarCrossrefSearch ADS PubMed 72.Arber DA, Orazi A, Hasserjian RP, et al. International consensus classification of myeloid neoplasms and acute leukemia: integrating morphological, clinical, and genomic data. Blood. 2022;140(11):1200-1228.Google ScholarCrossrefSearch ADS PubMed 73.Zhang Y, Wu J, Xu Z, et al. Impact of the International Consensus Classification of myelodysplastic syndromes. Br J Haematol. 2023;201(3):443-448.Google ScholarCrossrefSearch ADS PubMed 74.Paterlini M. There shall be order. The legacy of Linnaeus in the age of molecular biology. EMBO Rep. 2007;8(9):814-816.Google ScholarCrossrefSearch ADS PubMed 75.Bernard E, Hasserjian R, Greenberg PL, et al. Genomic classification of myelodysplastic syndromes. Leuk Res. 2023:128S.Google Scholar 76.Gerstung M, Pellagatti A, Malcovati L, et al. Combining gene mutation with gene expression data improves outcome prediction in myelodysplastic syndromes. Nat Commun. 2015;6:5901.Google ScholarCrossrefSearch ADS PubMed 77.Shiozawa Y, Malcovati L, Galli A, et al. Gene expression and risk of leukemic transformation in myelodysplasia. Blood. 2017;130(24):2642-2653.Google ScholarCrossrefSearch ADS PubMed 78.Im H, Rao V, Sridhar K, et al. Distinct transcriptomic and exomic abnormalities within myelodysplastic syndrome marrow cells. Leuk Lymphoma. 2018;59(12):2952-2962.Google ScholarCrossrefSearch ADS PubMed 79.Kwok B, Hall JM, Witte JS, et al. MDS-associated somatic mutations and clonal hematopoiesis are common in idiopathic cytopenias of undetermined significance. Blood. 2015;126(21):2355-2361.Google ScholarCrossrefSearch ADS PubMed 80.Galli A, Todisco G, Catamo E, et al. Relationship between clone metrics and clinical outcome in clonal cytopenia. Blood. 2021;138(11):965-976.Google ScholarCrossrefSearch ADS PubMed 81.Malcovati L, Galli A, Travaglino E, et al. Clinical significance of somatic mutation in unexplained blood cytopenia. Blood. 2017;129(25):3371-3378.Google ScholarCrossrefSearch ADS PubMed 82.Weeks LD, Niroula A, Neuberg D, et al. Prediction of risk for myeloid malignancy in clonal hematopoiesis. NEJM Evid. 2023;2(5).Google Scholar © 2023 by The American Society of Hematology2023 You do not currently have access to this content. Sign in via your Institution