We conducted a prospective observational study of fit adults aged 60–75 with advanced MDS, enrolled hierarchically for adverse MDS risk (intermediate-2 or high-risk international prognostic score [IPSS], low or intermediate-1 IPSS with poor-risk cytogenetics, or therapy-related MDS) or standard risk with severe cytopenia. A total of 290 patients enrolled at two centers: 175 for adverse risk and 115 for standard risk with severe cytopenia. 113 underwent HCT after a median of 5 months; median follow-up for all was 39.5 months. In univariable analyses, the hazard ratio (HR) for death comparing HCT with no HCT was 0.84 (p = 0.30). The HR for death was 0.64 (p = 0.04) for HCT ≤ 5 months after enrollment and 1.20 (p = 0.39) for HCT > 5 months. In multivariable analyses controlling for age, gender, ECOG performance status, cytogenetic risk, and IPSS risk group, HR for death was 0.75 (p = 0.13) for HCT compared to no HCT, 0.57 (p = 0.01) for adverse MDS risk and 1.33 (p = 0.36) for standard risk with severe cytopenia. In this large, prospective cohort of fit older adults with advanced MDS, we found that survival was significantly improved if HCT was performed early or for adverse risk disease but not for standard risk disease with severe cytopenia.
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Malcovati L, Hellstrom-Lindberg E, Bowen D, Ades L, Cermak J, Del Canizo C, et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood. 2013;122:2943–64.
Steensma DP. Myelodysplastic syndromes: diagnosis and treatment. Mayo Clin Proc. 2015;90:969–83.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127:2391–405.
Montalban-Bravo G, Garcia-Manero G. Myelodysplastic syndromes: 2018 update on diagnosis, risk-stratification and management. Am J Hematol. 2018;93:129–47.
Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89:2079–88.
de Witte T, Bowen D, Robin M, Malcovati L, Niederwieser D, Yakoub-Agha I, et al. Allogeneic hematopoietic stem cell transplantation for MDS and CMML: recommendations from an international expert panel. Blood. 2017;129:1753–62.
Koreth J, Pidala J, Perez WS, Deeg HJ, Garcia-Manero G, Malcovati L, et al. Role of reduced-intensity conditioning allogeneic hematopoietic stem-cell transplantation in older patients with de novo myelodysplastic syndromes: an international collaborative decision analysis. J Clin Oncol. 2013;31:2662–70.
Kröger N, Sockel K, Wolschke C, Bethge W, Schlenk RF, Wolf D, et al. 5-azacytidine (5-Aza) induction followed by allogeneic stem cell transplantation versus continuous 5-Aza in elderly MDS patients (55–70 years). A prospective randomized study (VidazAllo study). The 45th Annual Meeting of the European Society for Blood and Marrow Transplantation: Van Bekkum Awards. Bone Marrow Transpl. 2019;54:7–9.
Robin M, Porcher R, Ades L, Raffoux E, Michallet M, Francois S, et al. HLA-matched allogeneic stem cell transplantation improves outcome of higher risk myelodysplastic syndrome. A prospective study on behalf of SFGM-TC and GFM. Leukemia. 2015;29:1496–501.
Kroger N, Iacobelli S, Franke GN, Platzbecker U, Uddin R, Hubel K, 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;35:2157–64.
El-Jawahri A, Kim HT, Steensma DP, Cronin AM, Stone RM, Watts CD, et al. Does quality of life impact the decision to pursue stem cell transplantation for elderly patients with advanced MDS? Bone Marrow Transpl. 2016;51:1121–6.
Haase D, Germing U, Schanz J, Pfeilstocker M, Nosslinger T, Hildebrandt B, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007;110:4385–95.
Malcovati L, Germing U, Kuendgen A, Della Porta MG, Pascutto C, Invernizzi R, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25:3503–10.
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55.
Lindsley RC, Saber W, Mar BG, Redd R, Wang T, Haagenson MD, et al. Prognostic mutations in myelodysplastic syndrome after stem-cell transplantation. N Engl J Med. 2017;376:536–47.
Kim HT, Gray R. Three-component cure rate model for nonproportional hazards alternative in the design of randomized clinical trials. Clin Trials. 2012;9:155–63.
Mantel NB, Byar DP. Evaluation of response-time data involving transient states: an illustration using heart-transplant data. J Am Stat Assoc. 1974;69:81–6.
Schultz LR, Peterson EL, Breslau N. Graphing survival curve estimates for time-dependent covariates. Int J Methods Psychiatr Res. 2002;11:68–74.
Simon R, Makuch RW. A non-parametric graphical representation of the relationship between survival and the occurrence of an event: application to responder versus non-responder bias. Stat Med. 1984;3:35–44.
van Houwelingen HC, Putter H. Dynamic predicting by landmarking as an alternative for multi-state modeling: an application to acute lymphoid leukemia data. Lifetime Data Anal. 2008;14:447–63.
Anderson JR, Cain KC, Gelber RD. Analysis of survival by tumor response. J Clin Oncol. 1983;1:710–9.
Murillo A, Cronin AM, Laubach JP, Hshieh TT, Tanasijevic AM, Richardson PG, et al. Performance of the International Myeloma Working Group myeloma frailty score among patients 75 and older. J Geri Oncol. 2018.
Guardiola P, Runde V, Bacigalupo A, Ruutu T, Locatelli F, Boogaerts MA, et al. Retrospective comparison of bone marrow and granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells for allogeneic stem cell transplantation using HLA identical sibling donors in myelodysplastic syndromes. Blood. 2002;99:4370–8.
Sierra J, Perez WS, Rozman C, Carreras E, Klein JP, Rizzo JD, et al. Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia. Blood. 2002;100:1997–2004.
Martino R, Henseler A, van Lint M, Schaap N, Finke J, Beelen D, et al. Long-term follow-up of a retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic transplantation from matched related donors in myelodysplastic syndromes. Bone Marrow Transpl. 2017;52:1107–12.
Martino R, Iacobelli S, Brand R, Jansen T, van Biezen A, Finke J, et al. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood. 2006;108:836–46.
Brand R, Putter H, van Biezen A, Niederwieser D, Martino R, Mufti G, et al. Comparison of allogeneic stem cell transplantation and non-transplant approaches in elderly patients with advanced myelodysplastic syndrome: optimal statistical approaches and a critical appraisal of clinical results using non-randomized data. PLoS One. 2013;8:e74368.
Abel GA, Koreth J. Optimal positioning of hematopoietic stem cell transplantation for older patients with myelodysplastic syndromes. Curr Opin Hematol. 2013;20:150–6.
Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Perez WS, Anasetti C, et al. A decision analysis of allogeneic bone marrow transplantation for the myelodysplastic syndromes: delayed transplantation for low-risk myelodysplasia is associated with improved outcome. Blood. 2004;104:579–85.
Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Sole F, et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood. 2012;120:2454–65.
This work was supported by a Leukemia and Lymphoma Society Research Scholar Grant (GAA), an American Cancer Society Clinical Scholar Award (GAA), an NCI P01 Award (1P01CA229092-01A1; RJS and HK), and an NCI/NIH T32 Grant (CA092203; AH). This work was presented in preliminary form at the American Society of Hematology 2018 Annual Meeting, Abstract #972.
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Abel, G.A., Kim, H.T., Hantel, A. et al. Fit older adults with advanced myelodysplastic syndromes: who is most likely to benefit from transplant?. Leukemia (2020). https://doi.org/10.1038/s41375-020-01092-2