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Myelodysplasias

HLA-matched allogeneic stem cell transplantation improves outcome of higher risk myelodysplastic syndrome A prospective study on behalf of SFGM-TC and GFM

Abstract

Allogeneic hematopoietic stem cell transplantation (HSCT) is considered the only a curative treatment in patients with higher risk myelodysplastic syndrome (MDS), although demethylating agents (DMA) have been reported to improve survival. The advantage of HSCT over other treatment comes from retrospective studies and the aim of the current study was to prospectively test this hypothesis, analyzing in particular patients from the pre-transplant period to avoid the selection bias of performing transplantation. This study was conducted to compare overall survival in MDS patients candidates to transplantation according to donor availability. The majority of patients (76%) received a treatment with DMA after registration, 69% had a human leukocyte antigen (HLA)-identical donor, 70% of whom were transplanted. Baseline patient and disease characteristics were similar according to donor availability. Four-year overall survival was significantly better in patients with an HLA matched donor (37%) compared to patients without donor (15%). There was also evidence that this overall survival advantage was because of transplantation. Mortality risk was decreased after transplantation but it became significant only after the second year post transplant, because of early transplant-related mortality. Our results appear to justify, in higher risk MDS, a transplantation approach in all potential candidates who have an HLA identical donor.

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References

  1. Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G et al. Scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997; 89: 2079–2088.

    CAS  PubMed  Google Scholar 

  2. 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: 2454–2465.

    Article  CAS  Google Scholar 

  3. 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: 579–585.

    Article  CAS  Google Scholar 

  4. 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: 2662–2670.

    Article  Google Scholar 

  5. Platzbecker U, Schetelig J, Finke J, Trenschel R, Scott BL, Kobbe G et al. Allogeneic hematopoietic cell transplantation in patients age 60-70 years with de novo high-risk myelodysplastic syndrome or secondary acute myelogenous leukemia: comparison with patients lacking donors who received azacitidine. Biol Blood Marrow Transplant 2012; 18: 1415–1421.

    Article  Google Scholar 

  6. 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.

    Article  CAS  Google Scholar 

  7. Sierra J, Perez WS, Rozman C, Carreras E, Klein JP, Rizzo GD et al. Bone marrow transplantation from HLA-identical siblings as treatment for myelodysplasia. Blood 2002; 100: 1997–2004.

    CAS  PubMed  Google Scholar 

  8. 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: 4370–4378.

    Article  CAS  Google Scholar 

  9. de Lima M, Anagnostopoulos A, Munsell M, Shahjahan M, Ueno N, Ippoliti C et al. Nonablative versus reduced-intensity conditioning regimens in the treatment of acute myeloid leukemia and high-risk myelodysplastic syndrome: dose is relevant for long-term disease control after allogeneic hematopoietic stem cell transplantation. Blood 2004; 104: 865–872.

    Article  CAS  Google Scholar 

  10. Scott BL, Sandmaier BM, Storer B, Maris MB, Sorror ML, Maloney DG et al. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia 2006; 20: 128–135.

    Article  CAS  Google Scholar 

  11. 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: 836–846.

    Article  CAS  Google Scholar 

  12. Lim Z, Brand R, Martino R, van Biezen A, Finke J, Bacigalupo A et al. Allogeneic hematopoietic stem-cell transplantation for patients 50 years or older with myelodysplastic syndromes or secondary acute myeloid leukemia. J Clin Oncol 2010; 28: 405–411.

    Article  Google Scholar 

  13. Saber W, Le Rademacher J, Sekeres M, Logan B, Lewis M, Mendizabal A et al. Multicenter biologic assignment trial comparing reduced-intensity allogeneic hematopoietic cell transplant to hypomethylating therapy or best supportive care in patients aged 50 to 75 with intermediate-2 and high-risk myelodysplastic syndrome: blood and marrow transplant clinical trials network #1102 study rationale, design, and methods. Biol Blood Marrow Transplant 2014; 20: 1566–1572.

    Article  Google Scholar 

  14. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A 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: 937–951.

    Article  CAS  Google Scholar 

  15. Robins JM, Hernan MA, Brumback B . Marginal structural models and causal inference in epidemiology. Epidemiology 2000; 11: 550–560.

    Article  CAS  Google Scholar 

  16. Hernan MA, Brumback B, Robins JM . Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 2000; 11: 561–570.

    Article  CAS  Google Scholar 

  17. Cole SR, Hernan MA . Constructing inverse probability weights for marginal structural models. Am J Epidemiol 2008; 168: 656–664.

    Article  Google Scholar 

  18. Robins JM, Finkelstein DM . Correcting for noncompliance and dependent censoring in an AIDS Clinical Trial with inverse probability of censoring weighted (IPCW) log-rank tests. Biometrics 2000; 56: 779–788.

    Article  CAS  Google Scholar 

  19. Cole SR, Hernan MA . Adjusted survival curves with inverse probability weights. Comput Methods Programs Biomed 2004; 75: 45–49.

    Article  Google Scholar 

  20. Grambsch P, Therneau T . Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994, 515–556.

    Article  Google Scholar 

  21. Kalbfleich J, Prentice R . The Statistical Analysis of Failure Time Data. New York, 1980.

    Google Scholar 

  22. Prentice R, Kalbfleisch J, Peterson A, Flournoy N, Farewell V, Breslow N . The analysis of failure times in the presence of competing risks. Biometrics 1978; 34: 541.

    Article  CAS  Google Scholar 

  23. van der Wal W, Geskus R . ipw: an R package for inverse probability weighting. J Stat Softw 2011; 43: 1.

    Google Scholar 

  24. Cheson BD, Greenberg PL, Bennett JM, Lowenberg B, Wijermans PW, Nimer SD et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood 2006; 108: 419–425.

    Article  CAS  Google Scholar 

  25. Patriarca F, Einsele H, Spina F, Bruno B, Isola M, Nozzoli C et al. Allogeneic stem cell transplantation in multiple myeloma relapsed after autograft: a multicenter retrospective study based on donor availability. Biol Blood Marrow Transplant 2012; 18: 617–626.

    Article  CAS  Google Scholar 

  26. Sarina B, Castagna L, Farina L, Patriarca F, Benedetti F, Carella AM et al. Allogeneic transplantation improves the overall and progression-free survival of Hodgkin lymphoma patients relapsing after autologous transplantation: a retrospective study based on the time of HLA typing and donor availability. Blood 2010; 115: 3671–3677.

    Article  CAS  Google Scholar 

  27. Damaj G, Duhamel A, Robin M, Beguin Y, Michallet M, Mohty M et al. Impact of azacitidine before allogeneic stem-cell transplantation for myelodysplastic syndromes: a study by the Societe Francaise de Greffe de Moelle et de Therapie-Cellulaire and the Groupe-Francophone des Myelodysplasies. J Clin Oncol 2012; 30: 4533–4540.

    Article  CAS  Google Scholar 

  28. Alessandrino EP, Della Porta MG, Pascutto C, Bacigalupo A, Rambaldi A . Should cytoreductive treatment be performed before transplantation in patients with high-risk myelodysplastic syndrome? J Clin Oncol 2013; 31: 2761–2762.

    Article  Google Scholar 

  29. de Witte T, Hagemeijer A, Suciu S, Belhabri A, Delforge M, Kobbe G et al. Value of allogeneic versus autologous stem cell transplantation and chemotherapy in patients with myelodysplastic syndromes and secondary acute myeloid leukemia. Final results of a prospective randomized European Intergroup Trial. Haematologica 2010; 95: 1754–1761.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank members of GFM and SFGM-TC for their participation and support. We thank Alix O’Meara for the English review. We thank Pierre Fabre for their contribution to this study.

Author Contributions

MR, GS, HD, ER, LA and PF designed research, RP and MR analyzed the data; all co-authors performed the research and recruited patients, MR, GS, LA, PF and RP wrote the paper and all authors gave their comments.

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Correspondence to M Robin.

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Robin, M., Porcher, R., Adès, L. 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 29, 1496–1501 (2015). https://doi.org/10.1038/leu.2015.37

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