Myelodysplastic syndrome

Decision analysis of allogeneic hematopoietic stem cell transplantation for patients with myelodysplastic syndrome stratified according to the revised International Prognostic Scoring System

Article metrics

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-SCT) represents the only curative treatment for patients with myelodysplastic syndrome (MDS), but involves non-negligible morbidity and mortality. Crucial questions in clinical decision-making include the definition of optimal timing of the procedure and the benefit of cytoreduction before transplant in high-risk patients. We carried out a decision analysis on 1728 MDS who received supportive care, transplantation or hypomethylating agents (HMAs). Risk assessment was based on the revised International Prognostic Scoring System (IPSS-R). We used a continuous-time multistate Markov model to describe the natural history of disease and evaluate the effect of different treatment policies on survival. Life expectancy increased when transplantation was delayed from the initial stages to intermediate IPSS-R risk (gain-of-life expectancy 5.3, 4.7 and 2.8 years for patients aged 55, 60 and 65 years, respectively), and then decreased for higher risks. Modeling decision analysis on IPSS-R versus original IPSS changed transplantation policy in 29% of patients, resulting in a 2-year gain in life expectancy. In advanced stages, HMAs given before transplant is associated with a 2-year gain-of-life expectancy, especially in older patients. These results provide a preliminary evidence to maximize the effectiveness of allo-SCT in MDS.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4

References

  1. 1

    Ades L, Itzykson R, Fenaux P . Myelodysplastic syndromes. Lancet 2014; 383: 2239–2252.

  2. 2

    Cazzola M, Della Porta MG, Malcovati L . The genetic basis of myelodysplasia and its clinical relevance. Blood 2013; 122: 4021–4034.

  3. 3

    Cazzola M, Della Porta MG, Travaglino E, Malcovati L . Classification and prognostic evaluation of myelodysplastic syndromes. Semin Oncol 2011; 38: 627–631.

  4. 4

    Malcovati L, Hellstrom-Lindberg E, Bowen D, Adès L, Cermak J et al. Diagnosis and treatment of primary myelodysplastic syndromes in adults: recommendations from the European LeukemiaNet. Blood 2013; 122: 2943–2964.

  5. 5

    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: 2079–2088.

  6. 6

    Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F et al. Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndromes. Blood 2012; 120: 2454–2465.

  7. 7

    Della Porta MG, Tuechler H, Malcovati L, Schanz J, Sanz G 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: 1502–1513.

  8. 8

    Della Porta MG, Alessandrino EP, Bacigalupo A, van Lint MT, Malcovati L, Pascutto C et al. Predictive factors for the outcome of allogeneic transplantation in patients with MDS stratified according to the revised IPSS-R. Blood 2014; 123: 2333–2342.

  9. 9

    Deeg HJ, Shulman HM, Anderson JE, Bryant EM, Gooley TA, Slattery JT et al. Allogeneic and syngeneic marrow transplantation for myelodysplastic syndrome in patients 55 to 66 years of age. Blood 2000; 95: 1188–1194.

  10. 10

    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.

  11. 11

    Alessandrino EP, Della Porta MG, Bacigalupo A, Van Lint MT, Falda M, Onida F et al. 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: 895–902.

  12. 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.

  13. 13

    Kroger N . Allogeneic stem cell transplantation for elderly patients with myelodysplastic syndrome. Blood 2012; 119: 5632–5639.

  14. 14

    Malcovati L, Della Porta MG, Pascutto C, Invernizzi R, Boni M, Travaglino E 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: 7594–7603.

  15. 15

    Cutler CS, Lee SJ, Greenberg P, Deeg HJ, Pérez 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.

  16. 16

    Nakai K, Kanda Y, Fukuhara S, Sakamaki H, Okamoto S, Kodera Y et al. Value of chemotherapy before allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor for myelodysplastic syndrome. Leukemia 2005; 19: 396–401.

  17. 17

    de Witte T, Hermans J, Vossen J, Bacigalupo A, Meloni G, Jacobsen N et al. Haematopoietic stem cell transplantation for patients with myelo-dysplastic syndromes and secondary acute myeloid leukaemias: a report on behalf of the Chronic Leukaemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Br J Haematol 2000; 10: 620–630.

  18. 18

    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.

  19. 19

    Fenaux P, Mufti GJ, Hellstrom-Lindberg E, Santini V, Finelli C, Giagounidis A 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: 223–232.

  20. 20

    Lübbert M, Suciu S, Baila L, Rüter BH, Platzbecker U, Giagounidis A 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: 1987–1996.

  21. 21

    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 Société Française de Greffe de Moelle et de Thérapie-Cellulaire and the Groupe-Francophone des Myélodysplasies. J Clin Oncol 2012; 30: 4533–4540.

  22. 22

    Kalbfleisch JD, Lawless JF, Vollmer WM . Estimation in Markov models from aggregate data. Biometrics 1983; 39: 907–919.

  23. 23

    Kay R . A Markov model for analysing cancer markers and disease states in survival studies. Biometrics 1986; 42: 855–865.

  24. 24

    Sung L, Buckstein R, Doyle JJ, Crump M, Detsky AS . Treatment options for patients with acute myeloid leukemia with a matched sibling donor: a decision analysis. Cancer 2003; 97: 592–600.

  25. 25

    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.

  26. 26

    Silverman LR, Demakos EP, Peterson BL, Kornblith AB, Holland JC, Odchimar-Reissig R et al. 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: 2429–2440.

  27. 27

    Alessandrino EP, Della Porta MG, Malcovati L, Jackson CH, Pascutto C, Bacigalupo A et al. Optimal timing of allogeneic hematopoietic stem cell transplantation in patients with myelodysplastic syndrome. Am J Hematol 2013; 88: 581–588.

  28. 28

    Chiodi S, Spinelli S, Ravera G, Petti AR, Van Lint MT, Lamparelli T et al. Quality of life in 244 recipients of allogeneic bone marrow transplantation. Br J Haematol 2000; 110: 614–619.

  29. 29

    Bush NE, Donaldson GW, Haberman MH, Dacanay R, Sullivan KM . Conditional and unconditional estimation of multidimensional quality of life after hematopoietic stem cell transplantation: a longitudinal follow-up of 415 patients. Biol Blood Marrow Transplant 2000; 6: 576–591.

  30. 30

    Jackson CH . Multi-state models for panel data: the msm package for R. J Stat Softw 2011; 38: 1–28.

  31. 31

    Della Porta MG, Malcovati L, Rigolin GM, Rosti V, Bonetti E, Travaglino E et al. Immunophenotypic, cytogenetic and functional characterization of circulating endothelial cells in myelodysplastic syndromes. Leukemia 2008; 22: 530–537.

  32. 32

    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.

  33. 33

    Robin M, Porcher R, Adès L, Raffoux E, Michallet M, François 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: 1496–1501.

  34. 34

    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.

Download references

Acknowledgements

The study was supported by AIRC (Associazione Italiana Per la Ricerca sul Cancro, IG_17554), Milan; Fondazione Veronesi, Milan, Fondazione Cariplo and Regione Lombardia, Milan (Grant ID 42916996); Beat Leukemia Foundation, Milan, Fondazione Banca del Monte di Lombardia, Pavia, Italy; Worldwide Cancer Research (Grant 15-1226), St Andrews – UK to MGDP; by UK Medical Research Council (Grant code U105260566) to CHJ; and by AIRC, Milan, Italy (Special Program Molecular Clinical Oncology 5x1000, project 1005) to MC.

Author contributions

MGDP, CHJ, MC and AR designed, performed and coordinated the research, collected, contributed, analyzed and interpreted the data, and wrote the manuscript; CHJ and CP performed the statistical analyses, produced the figures and edited the manuscript; EPA, MR, AB, MTvL, MB, BA, AB, SG, VS, LM, MU, CM, ET, MTV, PM, FO, API, RC, GG, AM, PP, LB, EA, EO, SS, VF, AS and FB collected and contributed data and critically reviewed the manuscript.

Author information

Correspondence to M G Della Porta.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Further reading