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Stem cell transplantation

Haploidentical transplant for myelodysplastic syndrome: registry-based comparison with identical sibling transplant

Leukemia volume 30, pages 2055–2063 (2016)Cite this article

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Abstract

Encouraging results from a small sample of patients with myelodysplastic syndrome (MDS) undergoing haploidentical donor (HID) hematopoietic stem cell transplantation (HSCT) must be extended. Furthermore, an algorithm derived from a comparison of the outcomes of HID and identical-sibling donor (ISD) HSCT must be established. Therefore, the outcomes of 454 MDS patients who underwent HSCT from HIDs (n=226) or ISDs (n=228) between 2003 and 2013 that were reported to the Chinese Bone Marrow Transplantation Registry were analyzed. Among the 3/6 HID (n=136), 4–5/6 HID (n=90) and ISD patient groups, the 4-year adjusted cumulative incidences of non-relapse mortality were 34, 29 and 16%, respectively (overall P=0.004), and of relapse were 6, 7 and 10%, respectively (overall P=0.36). The 4-year adjusted probabilities of overall survival were 58, 63 and 73%, respectively (overall P=0.07), and of relapse-free-survival were 58, 63 and 71%, respectively (overall P=0.14); pairwise comparison showed that the difference was only statistically significant in the 3/6 HID vs ISD pair. The data suggest that ISDs remain the best donor source for MDS patients while HIDs (perhaps 4–5/6 HID in particular) could be a valid alternative when an ISD is not available; human leukocyte antigen disparity had no effect on survival among the HID patients.

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References

  1. de Witte T, Pikkemaat F, Hermans J, van Biezen A, Mackinnan S, Cornelissen J et al. Genotypically nonidentical related donors for transplantation of patients with myelodysplastic syndromes: comparison with unrelated donor transplantation and autologous stem cell transplantation. Leukemia 2001; 15: 1878–1884.

    Article  CAS  PubMed  Google Scholar 

  2. Castro-Malaspina H, Harris RE, Gajewski J, Ramsay N, Collins R, Dharan B et al. Unrelated donor marrow transplantation for myelodysplastic syndromes: outcome analysis in 510 transplants facilitated by the National Marrow Donor Program. Blood 2002; 99: 1943–1951.

    Article  CAS  PubMed  Google Scholar 

  3. Sierra J, Pérez 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.

    CAS  PubMed  Google Scholar 

  4. 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; 110: 620–630.

    Article  CAS  PubMed  Google Scholar 

  5. Chang YJ, Huang XJ . Haploidentical hematopoietic stem cell transplantation with unmanipulated granulocyte colony stimulating factor mobilized marrow and blood grafts. Curr Opin Hematol 2012; 19: 454–461.

    Article  CAS  PubMed  Google Scholar 

  6. Chang YJ, Huang XJ . Haploidentical bone marrow transplantation without T-cell depletion. Semin Oncol 2012; 39: 653–663.

    Article  PubMed  Google Scholar 

  7. Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W et al. Long-term follow-up of haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of leukemia: nine years of experience at a single center. Cancer 2013; 119: 978–985.

    Article  PubMed  Google Scholar 

  8. Chen Y, Liu K, Xu L, Chen H, Liu D, Zhang X et al. Haplo-identical/mismatched hematopoietic stem cell transplantation without in vitro T-cell depletion for myelodysplastic syndrome. Bone Marrow Transplant 2010; 45: 1333–1339.

    Article  CAS  PubMed  Google Scholar 

  9. Lee KH, Lee JH, Lee JH, Kim DY, Seol M, Lee YS et al. Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome. Blood 2011; 118: 2609–2617.

    Article  CAS  PubMed  Google Scholar 

  10. Shin SH, Kim JH, Jeon YW, Yoon JH, Yahng SA, Lee SE et al. Feasible outcomes of T cell-replete haploidentical stem cell transplantation with reduced-intensity conditioning in patients with myelodysplastic syndrome. Biol Blood Marrow Transplant 2015; 21: 342–349.

    Article  CAS  PubMed  Google Scholar 

  11. Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W et al. Conditioning including antithymocyte globulin followed by unmanipulated HLAmismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood 2006; 107: 3065–3073.

    Article  CAS  PubMed  Google Scholar 

  12. Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X et al. Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood 2015; 125: 3956–3962.

    Article  CAS  PubMed  Google Scholar 

  13. Klingebiel T, Cornish J, Labopin M, Locatelli F, Darbyshire P, Handgretinger R et al. Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group. Blood 2010; 115: 3437–3446.

    Article  CAS  PubMed  Google Scholar 

  14. Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR et alThe French-American-British (FAB) Co-Operative Group. Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982; 51: 189–199.

    Article  CAS  PubMed  Google Scholar 

  15. Brunning RD, Bennett JM, Flandrin G, Matutes E, Head D, Vardiman JW et al Myeodyaplastic syndromes. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds). World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Haemopoietic and Lymphoid Tissues. LARC Press: Lyon, 2001, pp 61–73.

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  17. Kröger N1, Zabelina T, de Wreede L, Berger J, Alchalby H, van Biezen A et al. Allogeneic stem cell transplantation for older advanced MDS patients: improved survival with young unrelated donor in comparison with HLA-identical siblings. Leukemia 2013; 27: 604–609.

    Article  PubMed  Google Scholar 

  18. Greenberg PL, Tuechler H, Schanz J, Sanz G, Garcia-Manero G, Solé F et al. Revised international prognostic scoring system for myelodysplastic syndromes. Blood 2012; 120: 2454–2465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Fenaux P, Ades L . How we treat lower-risk myelodysplastic syndromes. Blood 2013; 121: 4280–4286.

    Article  CAS  PubMed  Google Scholar 

  20. Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Zhang XH et al. Granulocyte colony-stimulating factor-primed peripheral blood progenitor cells infusion in the prophylaxis of relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation for advanced-stage acute leukemia: a retrospective risk factors analysis. Bone Marrow Transplant 2012; 47: 1099–1104.

    Article  CAS  PubMed  Google Scholar 

  21. Zhang X, Zhang MJ . SAS macros for estimation of direct adjusted cumulative incidence curves under proportional subdistribution hazards models. Comput Methods Programs Biomed 2011; 101: 87–93.

    Article  PubMed  Google Scholar 

  22. Saber W, Cutler CS, Nakamura R, Zhang MJ, Atallah E, Rizzo JD et al. Impact of donor source on hematopoietic cell transplantation outcomes for patients with myelodysplastic syndromes (MDS). Blood 2013; 122: 1974–1982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Chang C, Storer BE, Scott BL, Bryant EM, Shulman HM, Flowers ME et al. Hematopoietic cell transplantation in patients with myelodysplastic syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar outcomes in patients with de novo disease and disease following prior therapy or antecedent hematologic disorders. Blood 2007; 110: 1379–1387.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Wang Y, Chang YJ, Xu LP, Liu KY, Liu DH, Zhang XH et al. Who is the best donor for a related HLA haplotype-mismatched transplant? Blood 2014; 124: 843–850.

    Article  CAS  PubMed  Google Scholar 

  25. Di Stasi A, Milton DR, Poon LM, Hamdi A, Rondon G, Chen J et al. Similar transplantation outcomes for acute myeloid leukemia and myelodysplastic syndrome patients with haploidentical versus 10/10 human leukocyte antigen-matched unrelated and related donors. Biol Blood Marrow Transplant 2014; 20: 1975–1981.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR et al. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med 2012; 367: 1487–1496.

    Article  CAS  PubMed  Google Scholar 

  27. de Witte T, Brand R, van Biezen A, Mufti G, Ruutu T, Finke J et al. Allogeneic stem cell transplantation for patients with refractory anaemia with matched related and unrelated donors: delay of the transplant is associated with inferior survival. Br J Haematol 2009; 146: 627–636.

    Article  CAS  PubMed  Google Scholar 

  28. Al Ali HK, Brand R, van Biezen A, Finke J, Boogaerts M, Fauser AA et al. A retrospective comparison of autologous and unrelated donor hematopoietic cell transplantation in myelodysplastic syndrome and secondary acute myeloid leukemia: a report on behalf of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation (EBMT). Leukemia 2007; 21: 1945–1951.

    Article  CAS  PubMed  Google Scholar 

  29. Wang Y, Liu DH, Xu LP, Liu KY, Chen H, Chen YH et al. Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high risk acute leukemia: a historical comparison. Biol Blood Marrow Transplant 2011; 17: 821–830.

    Article  PubMed  Google Scholar 

  30. Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H et al. Risk stratification directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood 2012; 119: 3256–3262.

    Article  CAS  PubMed  Google Scholar 

  31. Zhao XS, Chen Y, Zhao XY, Liu DH, Xu LP, Wang Y et al. Improved outcomes using G-CSF-mobilized blood and bone marrow grafts as the source of stem cells compared with G-PB after HLA-identical sibling transplantation in patients with acute leukemia. Clin Transplant 2013; 27: 844–851.

    Article  PubMed  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

  33. Scott BL, Storer B, Loken M, Storb R, Appelbaum FR, Deeg HJ . Pretransplantation induction chemotherapy and posttransplantation relapse in patients with advanced myelodysplastic syndrome. Biol Blood Marrow Transplant 2005; 11: 65–73.

    Article  PubMed  Google Scholar 

  34. Yakoub-Agha I, de La Salmonière P, Ribaud P, Sutton L, Wattel E, Kuentz M et al. Allogeneic bone marrow transplantation for therapy-related myelodsyplastic syndrome and acute myeloid leukemia: a long-term study of 70 patients-report of the French Society of bone marrow transplantation. J Clin Oncol 2000; 18: 963–971.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Nakasone H, Remberger M, Tian L, Brodin P, Sahaf B, Wu F et al. Risks and benefits of sex-mismatched hematopoietic cell transplantation differ by conditioning strategies. Haematologica 2015; 100: 1477–1485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lee JH, Lee JH, Lim SN, Kim DY, Kim SH, Lee YS et al. Allogeneic hematopoietic cell transplantation for myelodysplastic syndrome: prognostic significance of pre-transplant IPSS score and comorbidity. Bone Marrow Transplant 2010; 45: 450–457.

    Article  PubMed  Google Scholar 

  38. Storb R1, Gyurkocza B, Storer BE, Sorror ML, Blume K, Niederwieser D et al. Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J Clin Oncol 2013; 31: 1530–1538.

    Article  CAS  PubMed  Google Scholar 

  39. Chen Y, Wang Y, Xu LP, Liu KY, Chen H, Chen YH et al. Haploidentical stem cell transplantation in patients aged 50 yr and older with leukemia: similar outcomes compared to younger adults. Clin Transplant 2015; 29: 523–530.

    Article  PubMed  Google Scholar 

  40. Mo XD, Xu LP, Liu DH, Zhang XH, Chen H, Chen YH et al. The hematopoietic cell transplantation-specific comorbidity index (HCT-CI) is an outcome predictor for partially matched related donor transplantation. Am J Hematol 2013; 88: 497–502.

    Article  PubMed  Google Scholar 

  41. Della Porta MG, Malcovati L, Strupp C, Ambaglio I, Kuendgen A, Zipperer E et al. Risk stratification based on both disease status and extra-hematologic comorbidities in patients with myelodysplastic syndrome. Haematologica 2011; 96: 441–449.

    Article  PubMed  Google Scholar 

  42. Sun Y, Xu L, Liu D, Zhang X, Han W, Wang Y et al. Incidence of invasive fungal disease after unmanipulated haploidentical stem cell transplantation was significantly higher than that after HLA-matched sibling transplantation. Clin Microbiol Infect 2013; 19: 1029–1034.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was partly supported by Collaborative Innovation Center of Hematology China, The Key Program of National Natural Science Foundation of China (Grant No. 81230013), National Natural Science Foundation of China (Grant No. 81400143) and Beijing Municipal Science & Technology Commission (No. Z121107002612035, Z141100000214011 and Z151100001615020).

Author contributions

X-JH designed the research; YW and X-JH analyzed the data and wrote the manuscript; and all authors provided patient data and gave final approval for the manuscript.

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, China

    Y Wang, L-P Xu & X-J Huang

  2. Air Force General Hospital, PLA, Beijing, China

    H-X Wang

  3. Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

    Y-R Lai

  4. Anhui Provincial Hospital, Hefei, Anhui, China

    Z-M Sun

  5. The first affiliated hospital of Soochow University, Suzhou, Jiangsu, China

    D-P Wu

  6. Department of Hematology, The First Affiliated Hospital of Xinjiang Medical University, Wulumuqi, Xinjiang, China

    M Jiang

  7. PLA General Hospital, Beijing, China

    D-H Liu

  8. The Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China

    K-L Xu

  9. Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

    Q-F Liu

  10. The first Affiliated Hospital of Chongqing Medical University, Chongqing, China

    L Liu

  11. Aero Center Space Hospital, Beijing, China

    J-B Wang

  12. The Affiliated Hospital of North China University Science and Technology, Tangshan, Hebei, China

    F Gao

  13. Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China

    J Ou-Yang

  14. The First Affiliated Hospital of Jilin University, Changchun, Jilin, China

    S-J Gao

  15. Peking-Tsinghua Center for Life Sciences, Beijing, China

    X-J Huang

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Wang, Y., Wang, HX., Lai, YR. et al. Haploidentical transplant for myelodysplastic syndrome: registry-based comparison with identical sibling transplant. Leukemia 30, 2055–2063 (2016). https://doi.org/10.1038/leu.2016.110

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