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Combination of haploidentical haematopoietic stem cell transplantation with an unrelated cord-blood unit in patients with severe aplastic anemia: a report of 146 cases

Bone Marrow Transplantation volume 55, pages 2017–2025 (2020)Cite this article

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Abstract

We analyzed the outcomes of 146 severe aplastic anemia (SAA) patients who received a combination of haploidentical haematopoietic stem cell transplantation (haplo-HSCT) and an unrelated cord-blood (UCB) unit between September 2011 and December 2017. One hundred and seventeen patients underwent transplantation as first-line therapy. Seven patients experienced early mortality, and among the evaluable 139 patients, one patient experienced primary graft failure (GF), while the other 138 patients achieved successful haploidentical donor engraftment; additionally, three patients experienced secondary GF. Six patients demonstrated delayed platelet recovery, and three patients demonstrated platelet GF. The median time for myeloid and platelet engraftment was 11 (range: 9–28) days and 15 (range: 9–330) days, respectively. With a median follow-up of 40 (range: 18–93) months, the cumulative incidences were 31.43% and 10.00% for grades II–IV and grades III–IV acute graft-versus-host disease (GVHD), respectively. The cumulative incidences of chronic GVHD (cGVHD) and moderate–severe cGVHD were 36.23% and 11.71%, respectively. There was no patient relapse. The probabilities of 4-year overall survival and GVHD-free, failure-free survival were 81.4 ± 3.3% and 69.2 ± 3.9%, respectively. These encouraging preliminary results indicated that haplo-HSCT combined with the infusion of UCB is a feasible choice for SAA patients without matched donors.

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Fig. 1: The cumulative incidences of GVHD.
Fig. 2: The TRM rate during follow-up.
Fig. 3: Patient overall survival (OS) and GVHD-free, failure-free survival (GFFS), as assessed using Kaplan–Meier analysis.

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References

  1. Young NS. Acquired aplastic anemia. Ann Intern Med. 2002;136:534–46.

    Article  Google Scholar 

  2. Bacigalupo A. How I treat acquired aplastic anemia. Blood. 2017;129:1428–36.

    Article  CAS  Google Scholar 

  3. Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, et al. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol. 2016;172:187–207.

    Article  Google Scholar 

  4. Wu Y, Cao Y, Li X, Xu L, Wang Z, Liu P, et al. Cotransplantation of haploidentical hematopoietic and umbilical cord mesenchymal stem cells for severe aplastic anemia: Successful engraftment andmild GVHD. Stem Cell Res. 2014;12:132–8.

    Article  CAS  Google Scholar 

  5. Young NS. Aplastic anemia. N Engl J Med. 2018;379:1643–56.

    Article  CAS  Google Scholar 

  6. Scheinberg P, Nunez O, Weinstein B, Scheinberg P, Biancotto A, Wu CO, et al. Horse versus rabbit antithymocyte globulin in acquired aplastic anemia. N Engl J Med. 2011;365:430–8.

    Article  CAS  Google Scholar 

  7. Xu LP, Liu KY, Liu DH, Han W, Chen H, Chen YH, et al. A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia. Bone Marrow Transpl. 2012;47:1507–12.

    Article  CAS  Google Scholar 

  8. Im HJ, Koh KN, Choi ES, Jang S, Kwon SW, Park CJ, et al. Excellent outcome of haploidentical hematopoietic stem cell transplantation in children and adolescents with acquired severe aplastic anemia. Biol Blood Marrow Transpl. 2013;19:754–9.

    Article  Google Scholar 

  9. Keever CA, Small TN, Flomenberg N, Heller G, Pekle K, Black P, et al. Immune reconstitution following bone marrow transplantation: comparison of recipients of T-cell depleted marrow with recipients of conventional marrow grafts. Blood. 1989;73:1340–50.

    Article  CAS  Google Scholar 

  10. Handgretinger R, Klingebiel T, Lang P, Niethammer D. Megadose transplantation of highly purified haploidentical stem cells: current results and future prospects. Pediatr Ttransplant. 2003;7:51–55.

    Article  Google Scholar 

  11. Ji SQ, Chen HR, Wang HX, Yan HM, Zhu L, Liu J, et al. G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high risk leukemia. Bone Marrow Transpl. 2002;30:861–6.

    Article  Google Scholar 

  12. Lu DP, Dong L, Wu T, Huang XJ, Zhang MJ, Han W, et al. Conditioning including antithymocyte globulin followed by unmanipulated HLA-mismatched/haploidentical blood and marrow transplantation can achieve comparable outcomes with HLA-identical sibling transplantation. Blood. 2006;107:3065–73.

    Article  CAS  Google Scholar 

  13. Wang HX, Yan HM, Duan LN, Wang ZD, Zhu L, Xue M, et al. Haploidentical hematopoietic stem cell transplantation in children hematologic malignancies with G-CSF mobilized marrow grafts without T cell depletion: a single center report of 45 cases. Pediatr Hematol Oncol. 2009;26:119–28.

    Article  CAS  Google Scholar 

  14. 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;119:978–85.

    Article  Google Scholar 

  15. 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;125:3956–62.

    Article  CAS  Google Scholar 

  16. Xu LP, Wang SQ, Wu DP, Wang JM, Gao SJ, Jiang M, et al. Haplo-identical transplantation for acquired severe aplastic anaemia in a multicentre prospective study. Br J Haematol. 2016;175:265–74.

    Article  Google Scholar 

  17. Xu LP, Jin S, Wang SQ, Xia LH, Bai H, Gao SJ, et al. Upfront haploidentical transplant for acquired severe aplastic anemia: registrybased comparison with matched related transplant. J Hematol Oncol. 2017;10:25.

    Article  Google Scholar 

  18. Xu L, Chen H, Chen J, Han M, Huang H, Lai Y, et al. The consensus on indications, conditioning regimen, and donor selection of allogeneic hematopoietic cell transplantation for hematological diseases in China—recommendations from the Chinese Society of Hematology. J Hematol Oncol. 2018;11:33.

    Article  Google Scholar 

  19. Chen J, Wang RX, Chen F, Sun AN, Qiu HY, Jin ZM, et al. Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study. Bone Marrow Transpl. 2014;49:206–11.

    Article  CAS  Google Scholar 

  20. Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transpl. 1995;15:825–8.

    CAS  Google Scholar 

  21. Filiovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. diagnosis and staging working group report. Biol Blood Marrow Transpl. 2005;11:945–56.

    Article  Google Scholar 

  22. Zhang Y, Guo Z, Liu XD, He XP, Yang K, Chen P, et al. Comparison of haploidentical hematopoietic stem cell transplantation and immunosuppressive therapy for the treatment of acquired severe aplaStic Anemia in Pediatric patients. Am J Ther. 2017;24:e196–201.

    Article  Google Scholar 

  23. Xu ZL, Zhou M, Jia JS, Mo WJ, Zhang XH, Zhang YP, et al. Immunosuppressive therapy versus haploidentical transplantation in adults with acquired severe aplastic anemia. Bone Marrow Transplant. 2019. https://doi.org/10.1038/s41409-018-0410-3.

  24. Lacerda JF, Martins C, Carmo JA, Lourenco F, Juncal C, Ismail S, et al. Haploidentical stem cell transplantation with purified CD34+ cells after a chemotherapy-alone conditioning regimen in heavily transfused severe aplastic anemia. Biol Blood Marrow Transplant. 2005;11:399–400.

    Article  CAS  Google Scholar 

  25. Woodard P, Cunningham JM, Benaim E, Chen X, Hale G, Horwitz E, et al. Effectiv donor lymphohematopoietic reconstitution after haplo-identical CD34+/− selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia. Bone Marrow Transplant. 2004;33:411–8.

    Article  CAS  Google Scholar 

  26. Liu Z, Zhang Y, Xiao H, Yao Z, Zhang H, Liu Q, et al. Cotransplantation of bone marrow-derived mesenchymal stem cells in haploidentical hematopoietic stem cell transplantation in patients with severe aplastic anemia: an interim summary for a multicenter phase II trial results. Bone Marrow Transplant. 2017;52:704–10.

    Article  CAS  Google Scholar 

  27. Huang XJ. HLA-mismatched/haploidentical hematopoietic stem cell transplantation: a field in which Chinese doctors are making great contributions. Chin Med J. 2010;123:1235–40.

    CAS  PubMed  Google Scholar 

  28. Ciceri F, Lupo-Stanghellini MT, Korthof ET. Haploidentical transplantation in patients with acquired aplastic anemia. Bone Marrow Transplant. 2013;48:183–5.

    Article  CAS  Google Scholar 

  29. DeZern AE, Guinan EC. Aplastic anemia in adolescents and young adults. Acta Haematol. 2014;132:331–9.

    Article  CAS  Google Scholar 

  30. Hartung HD, Olson TS, Bessler M. Acquired aplastic anemia in children. Pediatr Clin North Am. 2013;60:1311–36.

    Article  Google Scholar 

  31. DeZern AE, Zahurak M, Symons H, Cooke K, Brodsky RA. Alternative donor transplantation with high-dose post-transplant cyclophosphamide for refractory severe aplastic anemia. Biol Blood Marrow Transpl. 2017;23:498–504.

    Article  CAS  Google Scholar 

  32. Wang Y, Chen F, Han Y, Fu ZZ, Tang XW, Miao M, et al. Partially matched related hematopoietic stem cell transplantation without ex vivo T cell depletion compared with matched unrelated transplantation in adult patients with hematologic malignancies. Bio Blood Marrow Transplant. 2009;15:1258–64.

    Article  CAS  Google Scholar 

  33. Zhu H, Luo RM, Luan Z, Lee V, Zhu YP, Luo CJ, et al. Unmanipulated haploidentical haematopoietic stem cell transplantation for children with severe aplastic anaemia. Br J Haematol. 2016;174:799–805.

    Article  CAS  Google Scholar 

  34. Barker JN, Scaradavou A, Stevens CE. Combined effect of tatal nucleated cell dose and HLA match on transplantation outcome in 1061 cord blood recipients with hematological malignancies. Blood. 2010;115:1843–9.

    Article  CAS  Google Scholar 

  35. Gutman JA, Turtle CJ, Manley TJ, Heimfeld S, Bernstein ID, Riddell SR, et al. Singleunit dominance after double-unit umbilical cord blood transplantation coincides with a specific CD8+ T-cell response against the nonengrafted unit. Blood. 2011;115:757–65.

    Article  Google Scholar 

Download references

Acknowledgements

This work was partially supported by grants from the National Natural Science Foundation of China (81730003); National Science and Technology Major Project (2017ZX09304021); National Key R&D Program of China (2017YFA0104502); Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD); Jiangsu Medical Outstanding Talents Project (JCRCA2016002); and Jiangsu Provincial Key Medical Center (YXZXA2016002).

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  1. These authors contributed equally: Limin Liu, Yanming Zhang, Wenjing Jiao

Authors and Affiliations

  1. National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China

    Limin Liu, Huifen Zhou, Qingyuan Wang, Huiying Qiu, Xiaowen Tang, Yue Han, Chengcheng Fu, Zhengming Jin, Suning Chen, Aining Sun, Miao Miao & Depei Wu

  2. Department of Hematology, The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’an, No 62, Huaihai Road (S.), Huai’an, China

    Yanming Zhang

  3. Department of Hematology, Xian Yang Central Hospital, Xianyang, Shanxi, China

    Wenjing Jiao

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Correspondence to Miao Miao or Depei Wu.

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Liu, L., Zhang, Y., Jiao, W. et al. Combination of haploidentical haematopoietic stem cell transplantation with an unrelated cord-blood unit in patients with severe aplastic anemia: a report of 146 cases. Bone Marrow Transplant 55, 2017–2025 (2020). https://doi.org/10.1038/s41409-020-0874-9

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