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Everyone has a donor: contribution of the Chinese experience to global practice of haploidentical hematopoietic stem cell transplantation

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Abstract

Human leukocyte antigen (HLA)-matched donors for hematopoietic stem cell transplantation (HSCT) have long been scarce in China. Haploidentical (haplo) donors are available for the vast majority of patients, but toxicity has limited this approach. Three new approaches for haplo-HSCT originated from Italy, China, and USA in 1990 and have been developed to world-renowned system up to now. The Chinese approach have been greatly improved by implementing new individualized conditioning regimens, donor selection based on non-HLA systems, risk-directed strategies for graft-versus-host disease and relapse, and infection management. Haplo-HSCT has exhibited similar efficacy to HLA-matched HSCT and has gradually become the predominant donor source and the first alternative donor choice for allo-HSCT in China. Registry-based analyses and multicenter studies adhering to international standards facilitated the transformation of the unique Chinese experience into an inspiration for the refinement of global practice. This review will focus on how the new era in which “everyone has a donor” will become a reality in China.

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References

  1. Lv M, Huang XJ. Allogeneic hematopoietic stem cell transplantation in China: where we are and where to go. J Hematol Oncol 2012; 5(1): 10

    Article  PubMed  PubMed Central  Google Scholar 

  2. Xu LP, Wu DP, Han MZ, Huang H, Liu QF, Liu DH, Sun ZM, Xia LH, Chen J, Wang HX, Wang C, Li CF, Lai YR, Wang JM, Zhou DB, Chen H, Song YP, Liu T, Liu KY, Huang XJ. A review of hematopoietic cell transplantation in China: data and trends during 2008–2016. Bone Marrow Transplant 2017; 52(11):1512–1518

    Article  CAS  PubMed  Google Scholar 

  3. Reisner Y, Hagin D, Martelli MF. Haploidentical hematopoietic transplantation: current status and future perspectives. Blood 2011; 118(23): 6006–6017

    Article  CAS  PubMed  Google Scholar 

  4. Velardi A. Haplo-BMT: which approach? Blood 2013; 121(5): 719–720

    Article  CAS  PubMed  Google Scholar 

  5. Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, Bradley BA, Casper JT, Flomenberg N, Gajewski JL, Gluckman E, Henslee-Downey PJ, Hows JM, Jacobsen N, Kolb HJ, Lowenberg B, Masaoka T, Rowlings PA, Sondel PM, van Bekkum DW, van Rood JJ, Vowels MR, Zhang MJ, Horowitz MM. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol 1997; 15(5): 1767–1777

    Article  CAS  PubMed  Google Scholar 

  6. Fuchs EJ. Haploidentical transplantation for hematologic malignancies: where do we stand? Hematology Am Soc Hematol Educ Program 2012; 2012: 230–236

    PubMed  Google Scholar 

  7. Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLAhaploidentical blood or marrow transplantation. Nat Rev Clin Oncol 2016; 13(1): 10–24

    Article  CAS  PubMed  Google Scholar 

  8. Apperley J, Niederwieser D, Huang XJ, Nagler A, Fuchs E, Szer J, Kodera Y. Haploidentical hematopoietic stem cell transplantation: a global overview comparing Asia, the European Union, and the United States. Biol Blood Marrow Transplant 2016; 22(1): 23–26

    Article  PubMed  Google Scholar 

  9. Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni C, Iacucci R, Zei T, Martelli MP, Gambelunghe C, et al. Successful engraftment of T-cell-depleted haploidentical “three-loci” incompatible transplants in leukemia patients by addition of recombinant human granulocyte colony-stimulating factor-mobilized peripheral blood progenitor cells to bone marrow inoculum. Blood 1994; 84 (11): 3948–3955

    CAS  PubMed  Google Scholar 

  10. Aversa F, Tabilio A, Velardi A, Cunningham I, Terenzi A, Falzetti F, Ruggeri L, Barbabietola G, Aristei C, Latini P, Reisner Y, Martelli MF, Felicini R, Falcinelli F, Carotti A, Perruccio K, Ballanti S, Santucci A, Gambelunghe C. Treatment of high-risk acute leukemia with T-cell-depleted stem cells from related donors with one fully mismatched HLA haplotype. N Engl J Med 1998; 339(17): 1186–1193

    Article  CAS  PubMed  Google Scholar 

  11. Aversa F, Terenzi A, Tabilio A, Falzetti F, Carotti A, Ballanti S, Felicini R, Falcinelli F, Velardi A, Ruggeri L, Aloisi T, Saab JP, Santucci A, Perruccio K, Martelli MP, Mecucci C, Reisner Y, Martelli MF. Full haplotype-mismatched hematopoietic stem-cell transplantation: a phase II study in patients with acute leukemia at high risk of relapse. J Clin Oncol 2005; 23(15): 3447–3454

    Article  PubMed  Google Scholar 

  12. Huang XJ, Chen YH, Xu LP, Zhang YC, Liu DH, Guo NL, Lu DP. Combined transplantation of G-CSF primed allogeneic bone marrow cells and peripheral blood stem cells in treatment of severe aplastic anemia. Chin Med J (Engl) 2004; 117(4): 604–607

    Google Scholar 

  13. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Wang JZ, Gao ZY, Zhang YC, Jiang Q, Shi HX, Lu DP. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant 2006; 38(4): 291–297

    Article  PubMed  Google Scholar 

  14. Luznik L, Engstrom LW, Iannone R, Fuchs EJ. Posttransplantation cyclophosphamide facilitates engraftment of major histocompatibility complex-identical allogeneic marrow in mice conditioned with low-dose total body irradiation. Biol Blood Marrow Transplant 2002; 8(3): 131–138

    Article  CAS  PubMed  Google Scholar 

  15. Luznik L, O’Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, Gooley TA, Piantadosi S, Kaup M, Ambinder RF, Huff CA, Matsui W, Bolaños-Meade J, Borrello I, Powell JD, Harrington E, Warnock S, Flowers M, Brodsky RA, Sandmaier BM, Storb RF, Jones RJ, Fuchs EJ. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant 2008; 14(6): 641–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Jun HX, Jun CY, Yu ZX. In vivo induction of T-cell hyporesponsiveness and alteration of immunological cells of bone marrow grafts using granulocyte colony-stimulating factor. Haematologica 2004; 89(12): 1517–1524

    CAS  PubMed  Google Scholar 

  17. Jun HX, Jun CY, Yu ZX. A direct comparison of immunological characteristics of granulocyte colony-stimulating factor (G-CSF)- primed bone marrow grafts and G-CSF-mobilized peripheral blood grafts. Haematologica 2005; 90(5): 715–716

    PubMed  Google Scholar 

  18. Chang YJ, Huang XJ. Haploidentical SCT: the mechanisms underlying the crossing of HLA barriers. Bone Marrow Transplant 2014; 49(7): 873–879

    Article  CAS  PubMed  Google Scholar 

  19. Hu Y, He GL, Zhao XY, Zhao XS, Wang Y, Xu LP, Zhang XH, Yu XZ, Liu KY, Chang YJ, Huang XJ. Regulatory B cells promote graft-versus-host disease prevention and maintain graft-versusleukemia activity following allogeneic bone marrow transplantation. OncoImmunology 2017; 6(3): e1284721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhao XS, Wang XH, Zhao XY, Chang YJ, Xu LP, Zhang XH, Huang XJ. Non-traditional CD4+CD25–CD69+ regulatory T cells are correlated to leukemia relapse after allogeneic hematopoietic stem cell transplantation. J Transl Med 2014; 12(1): 187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lu SY, Huang XJ, Liu KY, Liu DH, Xu LP. High frequency of CD4+CD25–CD69+ T cells is correlated with a low risk of acute graft-versus-host disease in allotransplants. Clin Transplant 2012; 26(2): E158–E167

    Article  PubMed  Google Scholar 

  22. Lu SY, Liu KY, Liu DH, Xu LP, Huang XJ. High frequencies of CD62L+ naive regulatory T cells in allografts are associated with a low risk of acute graft-versus-host disease following unmanipulated allogeneic haematopoietic stem cell transplantation. Clin Exp Immunol 2011; 165(2): 264–277

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lv M, Zhao XS, Hu Y, Chang YJ, Zhao XY, Kong Y, Zhang XH, Xu LP, Liu KY, Huang XJ. Monocytic and promyelocytic myeloid-derived suppressor cells may contribute to G-CSFinduced immune tolerance in haplo-identical allogeneic hematopoietic stem cell transplantation. Am J Hematol 2015; 90(1): E9–E16

    Article  CAS  PubMed  Google Scholar 

  24. Zhao XY, Wang YT, Mo XD, Zhao XS, Wang YZ, Chang YJ, Huang XJ. Higher frequency of regulatory T cells in granulocyte colony-stimulating factor (G-CSF)-primed bone marrow grafts compared with G-CSF-primed peripheral blood grafts. J Transl Med 2015; 13(1): 145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhao XY, Xu LL, Lu SY, Huang XJ. IL-17-producing T cells contribute to acute graft-versus-host disease in patients undergoing unmanipulated blood and marrow transplantation. Eur J Immunol 2011; 41(2): 514–526

    Article  CAS  PubMed  Google Scholar 

  26. Huang XJ, Han W, Xu LP, Chen YH, Liu DH, Lu J, Chen H, Zhang YC, Jiang Q, Liu KY, Lu DP. A novel approach to human leukocyte antigen-mismatched transplantation in patients with malignant hematological disease. Chin Med J (Engl) 2004; 117 (12): 1778–1785

    PubMed  Google Scholar 

  27. Huang X, Chen Y, Han W, Chen Y, Hong H, Lu D. Human leukocyte antigen mismatched hemopietic stem cell transplants for the treatment of leukemia. J Peking Univ (Health Sci) (Beijing Da Xue Xue Bao (Yi Xue Ban)) 2003; 35(2): 115–118 (in Chinese)

    Google Scholar 

  28. Liu D, Huang X, Liu K, Xu L, Chen H, Han W, Chen Y, Zhang X, Jiang Q. Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for treatment of hematological malignancies in children. Biol Blood Marrow Transplant 2008; 14 (4): 469–477

    Article  CAS  PubMed  Google Scholar 

  29. Huang XJ, Xu LP, Liu KY, Liu DH, Chen H, Han W, Chen YH, Wang JZ, Chen Y, Zhang XH, Shi HX, Lu DP. HLA-mismatched/haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for chronic myeloid leukemia: improved outcomes in patients in accelerated phase and blast crisis phase. Ann Med 2008; 40(6): 444–455

    Article  CAS  Google Scholar 

  30. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Zhang XH, Lu DP. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant 2009; 15(2): 257–265

    Article  CAS  PubMed  Google Scholar 

  31. Wang Y, Liu DH, Liu KY, Xu LP, Zhang XH, Han W, Chen H, Chen YH, Wang FR, Wang JZ, Sun YQ, Huang XJ. 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(5): 978–985

    Article  PubMed  Google Scholar 

  32. Chen H, Ji S, Wang H. A clinical study of haploidentical transplantation using granulocyte colony-stimulating factor stimulating donor bone marrow. Chin J Intern Med (Zhonghua Nei Ke Za Zhi) 2001; 40(11): 760–763 (in Chinese)

    CAS  Google Scholar 

  33. Ji SQ, Chen HR, Wang HX, Yan HM, Zhu L, Liu J, Xue M, Xun CQ. G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia. Bone Marrow Transplant 2002; 30(12): 861–866

    Article  PubMed  Google Scholar 

  34. Chang YJ, Wang Y, Mo XD, Zhang XH, Xu LP, Yan CH, Chen H, Chen YH, Chen Y, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Optimal dose of rabbit thymoglobulin in conditioning regimens for unmanipulated, haploidentical, hematopoietic stem cell transplantation: long-term outcomes of a prospective randomized trial. Cancer 2017; 123(15): 2881–2892

    Article  CAS  PubMed  Google Scholar 

  35. Wang Y, Fu HX, Liu DH, Xu LP, Zhang XH, Chang YJ, Chen YH, Wang FR, Sun YQ, Tang FF, Liu KY, Huang XJ. Influence of two different doses of antithymocyte globulin in patients with standardrisk disease following haploidentical transplantation: a randomized trial. Bone Marrow Transplant 2014; 49(3): 426–433

    Article  CAS  PubMed  Google Scholar 

  36. Luo Y, Xiao H, Lai X, Shi J, Tan Y, He J, Xie W, Zheng W, Zhu Y, Ye X, Yu X, Cai Z, Lin M, Huang H. T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin compared with matched sibling HSCT and unrelated HSCT. Blood 2014; 124(17): 2735–2743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Fu H, Xu L, Liu D, Liu K, Zhang X, Chen H, Chen Y, Han W, Wang Y, Wang J, Wang F, Huang X. Total body irradiation and cyclophosphamide plus antithymocyte globulin regimen is well tolerated and promotes stable engraftment as a preparative regimen before T cell-replete haploidentical transplantation for acute leukemia. Biol Blood Marrow Transplant 2014; 20(8): 1176–1182

    Article  CAS  PubMed  Google Scholar 

  38. Liu QF, Fan ZP, Zhang Y, Jiang ZJ, Wang CY, Xu D, Sun J, Xiao Y, Tan H. Sequential intensified conditioning and tapering of prophylactic immunosuppressants for graft-versus-host disease in allogeneic hematopoietic stem cell transplantation for refractory leukemia. Biol Blood Marrow Transplant 2009; 15(11): 1376–1385

    Article  CAS  PubMed  Google Scholar 

  39. Liu QF, Fan ZP, Wu MQ, Sun J, Wu XL, Xu D, Jiang QL, Zhang Y, Huang F, Wei YQ, Zhao J, Yu GP, Meng FY. Allo-HSCT for acute leukemia of ambiguous lineage in adults: the comparison between standard conditioning and intensified conditioning regimens. Ann Hematol 2013; 92(5): 679–687

    Article  CAS  PubMed  Google Scholar 

  40. Xuan L, Fan Z, Zhang Y, Zhou H, Huang F, Dai M, Nie D, Lin D, Xu N, Guo X, Jiang Q, Sun J, Xiao Y, Liu Q. Sequential intensified conditioning followed by prophylactic DLI could reduce relapse of refractory acute leukemia after allo-HSCT. Oncotarget 2016; 7 (22): 32579–32591

    Article  PubMed  PubMed Central  Google Scholar 

  41. Zhang R, Shi W, Wang HF, You Y, Zhong ZD, Li WM, Zhang C, Lu X, Wang YD, Zheng P, Fang J, Hong M, Wu QL, Xia LH. Idarubicin-intensified haploidentical HSCT with GvHD prophylaxis of ATG and basiliximab provides comparable results to sibling donors in high-risk acute leukemia. Bone Marrow Transplant 2017; 52(9): 1253–1260

    Article  CAS  PubMed  Google Scholar 

  42. Chen Y, Wang Y, Xu LP, Liu KY, Chen H, Chen YH, Zhang XH, Wang FR, Han W, Wang JZ, Yan CH, Zhang YY, Sun YQ, Huang XJ. Haploidentical stem cell transplantation in patients aged 50 yr and older with leukemia: similar outcomes compared to younger adults. Clin Transplant 2015; 29(6): 523–530

    Article  PubMed  Google Scholar 

  43. Sun YQ, Xu LP, Zhang XH, Liu DH, Chen H, Wang Y, Yan CH, Wang JZ, Wang FR, Zhang YY, Liu KY, Huang XJ. A retrospective comparison of BU-fludarabine and BU-CY regimens in elderly patients or in patients with comorbidities who received unmanipulated haploidentical hematopoietic SCT. Bone Marrow Transplant 2015; 50(4): 601–603

    Article  CAS  PubMed  Google Scholar 

  44. Guo M, Hu KX, Yu CL, Sun QY, Qiao JH, Wang DH, Liu GX, Sun WJ, Wei L, Sun XD, Huang YJ, Qiao JX, Dong Z, Ai HS. Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. Blood 2011; 117(3): 936–941

    Article  CAS  PubMed  Google Scholar 

  45. Zhao X, Gao F, Zhang X, Wang Y, Xu L, Liu K, Zhao X, Chang Y, Wei H, Chen H, Chen Y, Jiang Z, Huang X. Improved clinical outcomes of rhG-CSF-mobilized blood and marrow haploidentical transplantation compared to propensity score-matched rhG-CSFprimed peripheral blood stem cell haploidentical transplantation: a multicenter study. Sci China Life Sci 2016; 59(11): 1139–1148

    Article  CAS  PubMed  Google Scholar 

  46. Lee KH, Lee JH, Lee JH, Kim DY, Seol M, Lee YS, Kang YA, Jeon M, Hwang HJ, Jung AR, Kim SH, Yun SC, Shin HJ. 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(9): 2609–2617

    Article  CAS  PubMed  Google Scholar 

  47. Di Bartolomeo P, Santarone S, De Angelis G, Picardi A, Cudillo L, Cerretti R, Adorno G, Angelini S, Andreani M, De Felice L, Rapanotti MC, Sarmati L, Bavaro P, Papalinetti G, Di Nicola M, Papola F, Montanari M, Nagler A, Arcese W. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood 2013; 121(5): 849–857

    Article  CAS  PubMed  Google Scholar 

  48. Chen J, Wang RX, Chen F, Sun AN, Qiu HY, Jin ZM, Tang XW, Han Y, Fu ZZ, He GS, Miao M, Ma X, Wu DP. Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study. Bone Marrow Transplant 2014; 49(2): 206–211

    Article  CAS  PubMed  Google Scholar 

  49. Gao L, Wen Q, Chen X, Liu Y, Zhang C, Gao L, Kong P, Zhang Y, Li Y, Liu J, Wang Q, Su Y, Wang C, Wang S, Zeng Y, Sun A, Du X, Zeng D, Liu H, Peng X, Zhang X. Effects of priming with recombinant human granulocyte colony-stimulating factor on conditioning regimen for high-risk acute myeloid leukemia patients undergoing human leukocyte antigen-haploidentical hematopoietic stem cell transplantation: a multicenter randomized controlled study in southwest China. Biol Blood Marrow Transplant 2014; 20(12): 1932–1939

    Article  CAS  PubMed  Google Scholar 

  50. Ikegame K, Yoshida T, Yoshihara S, Daimon T, Shimizu H, Maeda Y, Ueda Y, Kaida K, Ishii S, Taniguchi K, Okada M, Tamaki H, Okumura H, Kaya H, Kurokawa T, Kodera Y, Taniguchi S, Kanda Y, Ogawa H. Unmanipulated haploidentical reduced-intensity stem cell transplantation using fludarabine, busulfan, low-dose antithymocyte globulin, and steroids for patients in non-complete remission or at high risk of relapse: a prospective multicenter phase I/II study in Japan. Biol Blood Marrow Transplant 2015; 21(8): 1495–1505

    Article  CAS  PubMed  Google Scholar 

  51. Yahng SA, Kim JH, Jeon YW, Yoon JH, Shin SH, Lee SE, Cho BS, Eom KS, Kim YJ, Lee S, Min CK, Cho SG, Kim DW, Lee JW, Min WS, Park CW, Kim HJ. A well-tolerated regimen of 800 cGy TBI-fludarabine-busulfan-ATG for reliable engraftment after unmanipulated haploidentical peripheral blood stem cell transplantation in adult patients with acute myeloid leukemia. Biol Blood Marrow Transplant 2015; 21(1): 119–129

    Article  CAS  PubMed  Google Scholar 

  52. Peccatori J, Forcina A, Clerici D, Crocchiolo R, Vago L, Stanghellini MT, Noviello M, Messina C, Crotta A, Assanelli A, Marktel S, Olek S, Mastaglio S, Giglio F, Crucitti L, Lorusso A, Guggiari E, Lunghi F, Carrabba M, Tassara M, Battaglia M, Ferraro A, Carbone MR, Oliveira G, Roncarolo MG, Rossini S, Bernardi M, Corti C, Marcatti M, Patriarca F, Zecca M, Locatelli F, Bordignon C, Fleischhauer K, Bondanza A, Bonini C, Ciceri F. Sirolimus-based graft-versus-host disease prophylaxis promotes the in vivo expansion of regulatory T cells and permits peripheral blood stem cell transplantation from haploidentical donors. Leukemia 2015; 29(2): 396–405

    Article  CAS  PubMed  Google Scholar 

  53. Huang WR, Li HH, Gao CJ, Bo J, Li F, Dou LP, Wang LL, Jing Y, Wang L, Liu DH, Yu L. Haploidentical, unmanipulated G-CSFprimed peripheral blood stem cell transplantation for high-risk hematologic malignancies: an update. Bone Marrow Transplant 2016; 51(11): 1464–1469

    Article  CAS  PubMed  Google Scholar 

  54. Long H, Lu ZG, Song CY, Huang YX, Xu JH, Xu JX, Deng L, Tu SF, He YZ, Lin X, Guo KY, Wu BY. Long-term outcomes of HLA-haploidentical stem cell transplantation based on an FBCA conditioning regimen compared with those of HLA-identical sibling stem cell transplantation for haematologic malignancies. Bone Marrow Transplant 2016; 51(11): 1470–1475

    Article  CAS  PubMed  Google Scholar 

  55. Yang T, Lin Q, Ren J, Chen P, Yuan X, Luo X, Liu T, Zheng J, Zheng Z, Zheng X, Chen X, Zhang L, Zheng H, Chen Z, Hua X, Le S, Li J, Chen Z, Hu J. A 5-day cytoreductive chemotherapy followed by haplo-identical hsct (FA5-BUCY) as a tumor-ablative regimen improved the survival of patients with advanced hematological malignancies. Oncotarget 2016; 7(48): 78773–78786

    PubMed  PubMed Central  Google Scholar 

  56. Marsh JC, Ball SE, Cavenagh J, Darbyshire P, Dokal I, Gordon- Smith EC, Keidan J, Laurie A, Martin A, Mercieca J, Killick SB, Stewart R, Yin JA; British Committee for Standards in Haematology. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 2009; 147(1): 43–70

    Article  CAS  PubMed  Google Scholar 

  57. Scheinberg P, Young NS. How I treat acquired aplastic anemia. Blood 2012; 120(6): 1185–1196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Xu LP, Liu KY, Liu DH, Han W, Chen H, Chen YH, Zhang XH, Wang Y, Wang FR, Wang JZ, Huang XJ. A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia. Bone Marrow Transplant 2012; 47(12): 1507–1512

    Article  CAS  PubMed  Google Scholar 

  59. Xu LP, Wang SQ, Wu DP, Wang JM, Gao SJ, Jiang M, Wang CB, Zhang X, Liu QF, Xia LH, Wang X, Huang XJ. Haplo-identical transplantation for acquired severe aplastic anaemia in a multicentre prospective study. Br J Haematol 2016; 175(2): 265–274

    Article  PubMed  Google Scholar 

  60. Guo Z, Gao HY, Zhang TY, Liu XD, Yang K, Lou JX, He XP, Zhang Y, Chen P, Chen HR. Analysis of allogeneic hematopoietic stem cell transplantation with high-dose cyclophosphamideinduced immune tolerance for severe aplastic anemia. Int J Hematol 2016; 104(6): 720–728

    Article  CAS  PubMed  Google Scholar 

  61. Kojima S. Aplastic Anemia Treatment Guidelines of Asia-Pacific Hematology Consortium (APHCON). 2012. http://aphcon.org/aplastic-anemia-treatment-guidelines.html

    Google Scholar 

  62. Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology. Guidelines for the diagnosis and management of adult aplastic anaemia. Br J Haematol 2016; 172(2): 187–207

    Article  PubMed  Google Scholar 

  63. Wang M, Dong YJ, Qiu ZX, Wang MJ, Liu W, Wang LH, Li Y, Sun YH, Xu WL, Ou JP, Wang WS, Liang ZY, Wang Q, Cen XN, Ren HY. HLA Disparity is not crucial for the survival rate and severity of chronic health conditions in adult recipients following family donor hematopoietic stem cell transplantation. Int J Hematol 2015; 101(1): 75–82

    Article  PubMed  Google Scholar 

  64. Huo MR, Xu LP, Li D, Liu DH, Liu KY, Chen H, Han W, Chen YH, Wang Y, Wang JZ, Zhang XH, Zhao XY, Huang XJ. The effect of HLA disparity on clinical outcome after HLAhaploidentical blood and marrow transplantation. Clin Transplant 2012; 26(2): 284–291

    Article  PubMed  Google Scholar 

  65. Chang YJ, Zhao XY, Xu LP, Zhang XH, Wang Y, Han W, Chen H, Wang FR, Mo XD, Zhang YY, Huo MR, Zhao XS, y K, Liu KY, Huang XJ. Donor-specific anti-human leukocyte antigen antibodies were associated with primary graft failure after unmanipulated haploidentical blood and marrow transplantation: a prospective study with randomly assigned training and validation sets. J Hematol Oncol 2015; 8(1): 84

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Wang Y, Chang YJ, Xu LP, Liu KY, Liu DH, Zhang XH, Chen H, Han W, Chen YH, Wang FR, Wang JZ, Chen Y, Yan CH, Huo MR, Li D, Huang XJ. Who is the best donor for a related HLA haplotype-mismatched transplant? Blood 2014; 124(6): 843–850

    Article  CAS  PubMed  Google Scholar 

  67. Zhao XY, Chang YJ, Zhao XS, Xu LP, Zhang XH, Liu KY, Li D, Huang XJ. Recipient expression of ligands for donor inhibitory KIRs enhances NK-cell function to control leukemic relapse after haploidentical transplantation. Eur J Immunol 2015; 45(8): 2396–2408

    Article  CAS  PubMed  Google Scholar 

  68. Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, Fan ZP, Wu DP, Huang XJ. Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood 2015; 125(25): 3956–3962

    Article  CAS  PubMed  Google Scholar 

  69. Wang Y, Wang HX, Lai YR, Sun ZM, Wu DP, Jiang M, Liu DH, Xu KL, Liu QF, Liu L, Wang JB, Gao F, Ou-Yang J, Gao SJ, Xu LP, Huang XJ. Haploidentical transplant for myelodysplastic syndrome: registry-based comparison with identical sibling transplant. Leukemia 2016; 30(10): 2055–2063

    Article  CAS  PubMed  Google Scholar 

  70. Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, Wu MQ, Wu DP, Huang XJ. Haploidentical versus matched-sibling transplant in adults with Philadelphia-negative high-risk acute lymphoblastic leukemia: a biologically phase III randomized study. Clin Cancer Res 2016; 22(14): 3467–3476

    Article  CAS  PubMed  Google Scholar 

  71. Luo XH, Chang YJ, Xu LP, Liu DH, Liu KY, Huang XJ. The impact of graft composition on clinical outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic SCT. Bone Marrow Transplant 2009; 43(1): 29–36

    Article  CAS  PubMed  Google Scholar 

  72. Zhao XY, Chang YJ, Xu LP, Liu DH, Liu KY, Huang XJ. Association of natural killer cells in allografts with transplant outcomes in patients receiving G-CSF-mobilized PBSC grafts and G-CSF-primed BM grafts from HLA-haploidentical donors. Bone Marrow Transplant 2009; 44(11): 721–728

    Article  PubMed  Google Scholar 

  73. Chang YJ, Xu LP, Wang Y, Zhang XH, Chen H, Chen YH, Wang FR, Han W, Sun YQ, Yan CH, Tang FF, Mo XD, Liu KY, Huang XJ. Controlled, randomized, open-label trial of risk-stratified corticosteroid prevention of acute graft-versus-host disease after haploidentical transplantation. J Clin Oncol 2016; 34(16): 1855–1863

    Article  CAS  PubMed  Google Scholar 

  74. Ning H, Yang F, Jiang M, Hu L, Feng K, Zhang J, Yu Z, Li B, Xu C, Li Y, Wang J, Hu J, Lou X, Chen H. The correlation between cotransplantation of mesenchymal stem cells and higher recurrence rate in hematologic malignancy patients: outcome of a pilot clinical study. Leukemia 2008; 22(3): 593–599

    Article  CAS  PubMed  Google Scholar 

  75. Gao L, Zhang Y, Hu B, Liu J, Kong P, Lou S, Su Y, Yang T, Li H, Liu Y, Zhang C, Gao L, Zhu L, Wen Q, Wang P, Chen X, Zhong J, Zhang X. Phase II multicenter, randomized, double-blind controlled study of efficacy and safety of umbilical cord-derived mesenchymal stromal cells in the prophylaxis of chronic graftversus- host disease after HLA-haploidentical stem-cell transplantation. J Clin Oncol 2016; 34(24): 2843–2850

    Article  CAS  PubMed  Google Scholar 

  76. Yan CH, Xu LP, Wang FR, Chen H, Han W, Wang Y, Wang JZ, Liu KY, Huang XJ. Causes of mortality after haploidentical hematopoietic stem cell transplantation and the comparison with HLA-identical sibling hematopoietic stem cell transplantation. Bone Marrow Transplant 2016; 51(3): 391–397

    Article  CAS  PubMed  Google Scholar 

  77. Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W. Donor lymphocyte infusion for the treatment of leukemia relapse after HLA-mismatched/haploidentical T-cell-replete hematopoietic stem cell transplantation. Haematologica 2007; 92(3): 414–417

    Article  PubMed  Google Scholar 

  78. Huang XJ, Liu DH, Liu KY, Xu LP, Chen YH, Wang Y, Han W, Chen H. Modified donor lymphocyte infusion after HLAmismatched/ haploidentical T cell-replete hematopoietic stem cell transplantation for prophylaxis of relapse of leukemia in patients with advanced leukemia. J Clin Immunol 2008; 28(3): 276–283

    Article  CAS  PubMed  Google Scholar 

  79. Mo XD, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, Chen YH, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Salvage chemotherapy followed by granulocyte colony-stimulating factorprimed donor leukocyte infusion with graft-vs.-host disease control for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation: prognostic factors and clinical outcomes. Eur J Haematol 2016; 96 (3): 297–308

    Article  CAS  PubMed  Google Scholar 

  80. Yan CH, Wang Y, Wang JZ, Chen YH, Chen Y, Wang FR, Sun YQ, Mo XD, Han W, Chen H, Zhang XH, Xu LP, Liu KY, Huang XJ. Minimal residual disease- and graft-vs.-host disease-guided multiple consolidation chemotherapy and donor lymphocyte infusion prevent second acute leukemia relapse after allotransplant. J Hematol Oncol 2016; 9(1): 87

    Article  PubMed  PubMed Central  Google Scholar 

  81. Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, Han W, Wang Y, Qin YZ, Huang XJ. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood 2012; 119(14): 3256–3262

    Article  CAS  PubMed  Google Scholar 

  82. Anguille S, Lion E, Willemen Y, Van Tendeloo VF, Berneman ZN, Smits EL. Interferon-α in acute myeloid leukemia: an old drug revisited. Leukemia 2011; 25(5): 739–748

    Article  CAS  PubMed  Google Scholar 

  83. Mo X, Zhao X, Xu L, Liu D, Zhang X, Chen H, Wang Y, Huang X. Interferon α: the salvage therapy for patients with unsatisfactory response to minimal residual disease-directed modified donor lymphocyte infusion. Chin Med J (Engl) 2014; 127(14): 2583–2587

    CAS  Google Scholar 

  84. Mo XD, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, Chen YH, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Interferon-α: a potentially effective treatment for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2015; 21(11): 1939–1947

    Article  CAS  PubMed  Google Scholar 

  85. Yan CH, Liu QF, Wu DP, Zhang X, Xu LP, Zhang XH, Wang Y, Huang H, Bai H, Huang F, Ma X, Huang XJ. Prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease and graft-versus-host disease-guided multiple DLIs could improve outcomes after allogeneic hematopoietic stem cell transplantation in patients with refractory/relapsed acute leukemia. Biol Blood Marrow Transplant 2017; 23(8): 1311–1319

    Article  PubMed  Google Scholar 

  86. Sun Y, Meng F, Han M, Zhang X, Yu L, Huang H, Wu D, Ren H, Wang C, Shen Z, Ji Y, Huang X. Epidemiology, management, and outcome of invasive fungal disease in patients undergoing hematopoietic stem cell transplantation in China: a multicenter prospective observational study. Biol Blood Marrow Transplant 2015; 21(6): 1117–1126

    Article  PubMed  Google Scholar 

  87. Jiang X, Xu L, Zhang Y, Huang F, Liu D, Sun J, Song C, Liang X, Fan Z, Zhou H, Dai M, Liu C, Jiang Q, Xu N, Xuan L, Wu M, Huang X, Liu Q. Rituximab-based treatments followed by adoptive cellular immunotherapy for biopsy-proven EBV-associated post-transplant lymphoproliferative disease in recipients of allogeneic hematopoietic stem cell transplantation. OncoImmunology 2016; 5(5): e1139274

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Xu LP, Jin S, Wang SQ, Xia LH, Bai H, Gao SJ, Liu QF, Wang JM, Wang X, Jiang M, Zhang X, Wu DP, Huang XJ. Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant. J Hematol Oncol 2017; 10(1): 25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Mo XD, Zhao XY, Liu DH, Chen YH, Xu LP, Zhang XH, Chen H, Han W, Wang Y, Wang FR, Wang JZ, Liu KY, Huang XJ. Umbilical cord blood transplantation and unmanipulated haploidentical hematopoietic SCT for pediatric hematologic malignances. Bone Marrow Transplant 2014; 49(8): 1070–1075

    Article  CAS  PubMed  Google Scholar 

  90. Ciurea SO, Bayraktar UD. “No donor”? Consider a haploidentical transplant. Blood Rev 2015; 29(2): 63–70

    Article  PubMed  Google Scholar 

  91. Rubio MT, Savani BN, Labopin M, Piemontese S, Polge E, Ciceri F, Bacigalupo A, Arcese W, Koc Y, Beelen D, Gülbas Z, Wu D, Santarone S, Tischer J, Afanasyev B, Schmid C, Giebel S, Mohty M, Nagler A. Impact of conditioning intensity in T-replete haploidentical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT. J Hematol Oncol 2016; 9(1): 25

    Article  PubMed  PubMed Central  Google Scholar 

  92. Santoro N, Ruggeri A, Labopin M, Bacigalupo A, Ciceri F, Gülbaş Z, Huang H, Afanasyev B, Arcese W, Wu D, Koc Y, Tischer J, Santarone S, Giebel S, Mohty M, Nagler A. Unmanipulated haploidentical stem cell transplantation in adults with acute lymphoblastic leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT. J Hematol Oncol 2017; 10(1): 113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Piemontese S, Ciceri F, Labopin M, Arcese W, Kyrcz-Krzemien S, Santarone S, Huang H, Beelen D, Gorin NC, Craddock C, Gulbas Z, Bacigalupo A, Mohty M, Nagler A; Acute Leukemia Working Party of the European Society for Blood and Marrow Transplanta-tion (EBMT). A comparison between allogeneic stem cell transplantation from unmanipulated haploidentical and unrelated donors in acute leukemia. J Hematol Oncol 2017; 10(1): 24

    Article  PubMed  PubMed Central  Google Scholar 

  94. Bashey A, Zhang MJ, McCurdy SR, St Martin A, Argall T, Anasetti C, Ciurea SO, Fasan O, Gaballa S, Hamadani M, Munshi P, Al Malki MM, Nakamura R, O’Donnell PV, Perales MA, Raj K, Romee R, Rowley S, Rocha V, Salit RB, Solh M, Soiffer RJ, Fuchs EJ, Eapen M. Mobilized peripheral blood stem cells versus unstimulated bone marrow as a graft source for T-cell-replete haploidentical donor transplantation using post-transplant cyclophosphamide. J Clin Oncol 2017; 35(26): 3002–3009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Mancusi A, Ruggeri L, Urbani E, Pierini A, Massei MS, Carotti A, Terenzi A, Falzetti F, Tosti A, Topini F, Bozza S, Romani L, Tognellini R, Stern M, Aversa F, Martelli MF, Velardi A. Haploidentical hematopoietic transplantation from KIR ligandmismatched donors with activating KIRs reduces nonrelapse mortality. Blood 2015; 125(20): 3173–3182

    Article  CAS  PubMed  Google Scholar 

  96. Handgretinger R. Haploidentical transplantation: the search for the best donor. Blood 2014; 124(6): 827–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Passweg JR, Baldomero H, Bader P, Bonini C, Duarte RF, Dufour C, Gennery A, Kröger N, Kuball J, Lanza F, Montoto S, Nagler A, Snowden JA, Styczynski J, Mohty M. Use of haploidentical stem cell transplantation continues to increase: the 2015 European Society for Blood and Marrow Transplant activity survey report. Bone Marrow Transplant 2017; 52(6): 811–817

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Champlin R. Now everyone has a donor for HSCT. Blood 2011; 118(2): 218

    Article  CAS  PubMed  Google Scholar 

  99. Wang Y, Wu DP, Liu QF, Xu LP, Liu KY, Zhang XH, Xu Y, Huang F, Huang XJ. Donor and recipient age, gender and ABO incompatibility regardless of donor source: validated criteria for donor selection for haematopoietic transplants. Leukemia 2018; 32 (2): 492–498

    Article  CAS  PubMed  Google Scholar 

  100. Piemontese S, Ciceri F, Labopin M, Bacigalupo A, Huang H, Santarone S, Gorin NC, Koc Y, Wu D, Beelen D, Tischer J, Ehninger G, Arcese W, Nagler A, Mohty M; Acute Leukemia Working Party (ALWP) of the European Group for Blood and Marrow Transplantation (EBMT). A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia. Leukemia 2015; 29(5): 1069–1075

    Article  CAS  PubMed  Google Scholar 

  101. Locatelli F, Merli P, Pagliara D, Li Pira G, Falco M, Pende D, Rondelli R, Lucarelli B, Brescia LP, Masetti R, Milano GM, Bertaina V, Algeri M, Pinto RM, Strocchio L, Meazza R, Grapulin L, Handgretinger R, Moretta A, Bertaina A, Moretta L. Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion. Blood 2017; 130(5): 677–685

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank the American Journal Experts (https://www.aje.com) for providing editorial assistance. This work was supported by the National Natural Science Foundation of China (Nos. 81400146, 81470342, and 81670168), the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 81621001), and the Key Program of the National Natural Science Foundation of China (Nos. 81530046 and 81230013).

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  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Beijing, 100044, China

    Meng Lv, Yingjun Chang & Xiaojun Huang

  2. Peking-Tsinghua Center for Life Sciences, Beijing, 100044, China

    Xiaojun Huang

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  1. Meng Lv
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  2. Yingjun Chang
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Correspondence to Xiaojun Huang.

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Lv, M., Chang, Y. & Huang, X. Everyone has a donor: contribution of the Chinese experience to global practice of haploidentical hematopoietic stem cell transplantation. Front. Med. 13, 45–56 (2019). https://doi.org/10.1007/s11684-017-0595-7

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