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Haploidentical Transplantation pp 55–79Cite as

Haploidentical Transplantation Using Unmanipulated G-CSF-Primed Blood and Marrow as Allografts: Clinical Data and Challenges

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Abstract

Haploidentical hematopoietic cell transplantation (haplo-HCT) is available for nearly all patients, with no search or acquisition costs to the patient. However, successful use of haplo-HCT has been hampered by T-cell alloreactivity, due to differences in human leukocyte antigen (HLA) loci on an unshared chromosome 6. Novel approaches to overcome these barriers require expensive laboratory facilities and well-trained staff with high expertise in cell manipulation and are not widely applicable to most transplant centers. Over the last 10 years, based on immune tolerance induced by granulocyte colony-stimulating factor (G-CSF) and antithymocyte globulin (ATG), the Peking University groups established a protocol for unmanipulated haplo-HCT using myeloablative conditioning (MAC) regimen using G-CSF-primed bone marrow (G-BM) and peripheral blood (G-PB) hematopoietic CD34+ cell grafts. A series of studies demonstrated that unmanipulated G-CSF-stimulated haploidentical grafts can lead to rapid immune recovery, desirable health-related quality of life (QoL), and a survival rate comparable to that following HLA-matched sibling donor hematopoietic cell transplant (MSD-HCT) or HLA-matched unrelated donor hematopoietic cell transplant (MUD-HCT). This chapter begins with an overview of immunoregulatory effects of G-CSF on graft composition, followed by a presentation of clinical results after unmanipulated haplo-HCT with ATG preparative regimen using G-BM and/or G-PB as allografts. Thereafter, strategies on improvement of the abovementioned transplant modalities are discussed.

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References

  1. Yan CH, Liu DH, Liu KY, 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;119:3256–62.

    Article  CAS  PubMed  Google Scholar 

  2. Chang YJ, Huang XJ. Donor lymphocyte infusions for relapse after allogeneic transplantation: when, if and for whom? Blood Rev. 2013;27:55–62.

    Article  CAS  PubMed  Google Scholar 

  3. Wang Y, Liu DH, Liu KY, 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  PubMed  Google Scholar 

  4. Wang Y, Chang YJ, Xu LP, et al. Who is the best donor for a related HLA haplotype-mismatched transplant? Blood. 2014;124:843–50.

    Article  CAS  PubMed  Google Scholar 

  5. Mo XD, Xu LP, Zhang XH, et al. Haploidentical hematopoietic stem cell transplantation in adults with Philadelphia-negative acute lymphoblastic leukemia: no difference in the high- and low-risk groups. Int J Cancer. 2015;136:1697–707.

    Article  CAS  PubMed  Google Scholar 

  6. Wang Y, Liu QF, Xu LP, et al. Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood. 2015;125:3956–62.

    Article  CAS  PubMed  Google Scholar 

  7. Chang YJ, Huang XJ. Haploidentical stem cell transplantation: anti-thymocyte globulin-based experience. Semin Hematol. 2016;53:82–9.

    Article  CAS  PubMed  Google Scholar 

  8. Aversa F, Terenzi A, Tabilio A, et al. 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;23:3447–54.

    Article  PubMed  Google Scholar 

  9. Federmann B, Bornhauser M, Meisner C, et al. Haploidentical allogeneic hematopoietic cell transplantation in adults using CD3/CD19 depletion and reduced intensity conditioning: a phase II study. Haematologica. 2012;97:1523–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Luznik L, O'Donnell PV, Fuchs EJ. Post-transplantation cyclophosphamide for tolerance induction in HLA-haploidentical bone marrow transplantation. Semin Oncol. 2012;39:683–93.

    Article  CAS  PubMed  Google Scholar 

  11. Chang YJ, Huang XJ. Improving the clinical outcome of unmanipulated haploidentical blood and marrow transplantation. Bone Marrow Transplant. 2015;50(Suppl 2):S21–3.

    Article  PubMed  Google Scholar 

  12. Mancusi A, Ruggeri L, Urbani E, et al. Haploidentical hematopoietic transplantation from KIR ligand-mismatched donors with activating KIRs reduces nonrelapse mortality. Blood. 2015;125:3173–82.

    Article  CAS  PubMed  Google Scholar 

  13. Piemontese S, Ciceri F, Labopin M, et al. A survey on unmanipulated haploidentical hematopoietic stem cell transplantation in adults with acute leukemia. Leukemia. 2015;29:1069–75.

    Article  CAS  PubMed  Google Scholar 

  14. Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to HLA-haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2016;13:10–24.

    Article  CAS  PubMed  Google Scholar 

  15. Chang YJ, Huang XJ. Haploidentical SCT: the mechanisms underlying the crossing of HLA barriers. Bone Marrow Transplant. 2014;49:873–9.

    Article  CAS  PubMed  Google Scholar 

  16. Wang Y, Liu QF, Xu LP, et al. 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;22:3467–76.

    Article  CAS  PubMed  Google Scholar 

  17. Shimoni A. Haploidentical stem-cell transplant: the challenge of immune reconstitution. Leuk Lymphoma. 2013;54:2579–80.

    Article  PubMed  Google Scholar 

  18. Rutella S, Zavala F, Danese S, Kared H, Leone G. Granulocyte colony-stimulating factor: a novel mediator of T cell tolerance. J Immunol. 2005;175:7085–91.

    Article  CAS  PubMed  Google Scholar 

  19. 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;89:1517–24.

    CAS  PubMed  Google Scholar 

  20. Huang XJ, Liu DH, Liu KY, et al. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant. 2006;38:291–7.

    Article  PubMed  Google Scholar 

  21. Huang XJ, Liu DH, Liu KY, et al. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant. 2009;15:257–65.

    Article  CAS  PubMed  Google Scholar 

  22. Chang YJ, Zhao XY, Huang XJ. Immune reconstitution after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2014;20:440–9.

    Article  CAS  PubMed  Google Scholar 

  23. Chang YJ, Zhao XY, Huo MR, et al. Immune reconstitution following unmanipulated HLA-mismatched/haploidentical transplantation compared with HLA-identical sibling transplantation. J Clin Immunol. 2012;32:268–80.

    Article  CAS  PubMed  Google Scholar 

  24. Mo XD, Xu LP, Liu DH, et al. Patients receiving HLA-haploidentical/partially matched related allo-HSCT can achieve desirable health-related QoL that is comparable to that of patients receiving HLA-identical sibling allo-HSCT. Bone Marrow Transplant. 2012;47:1201–5.

    Article  PubMed  Google Scholar 

  25. Lu DP, Dong L, Wu T, 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  PubMed  Google Scholar 

  26. Xiao-Jun H, Lan-Ping X, Kai-Yan L, et al. Partially matched related donor transplantation can achieve outcomes comparable with unrelated donor transplantation for patients with hematologic malignancies. Clin Cancer Res. 2009;15:4777–83.

    Article  PubMed  Google Scholar 

  27. Shier LR, Schultz KR, Imren S, et al. Differential effects of granulocyte colony-stimulating factor on marrow- and blood-derived hematopoietic and immune cell populations in healthy human donors. Biol Blood Marrow Transplant. 2004;10:624–34.

    Article  CAS  PubMed  Google Scholar 

  28. Arpinati M, Green CL, Heimfeld S, Heuser JE, Anasetti C. Granulocyte-colony stimulating factor mobilizes T helper 2-inducing dendritic cells. Blood. 2000;95:2484–90.

    CAS  PubMed  Google Scholar 

  29. Franzke A, Piao W, Lauber J, et al. G-CSF as immune regulator in T cells expressing the G-CSF receptor: implications for transplantation and autoimmune diseases. Blood. 2003;102:734–9.

    Article  CAS  PubMed  Google Scholar 

  30. Rutella S, Bonanno G, Pierelli L, et al. Granulocyte colony-stimulating factor promotes the generation of regulatory DC through induction of IL-10 and IFN-alpha. Eur J Immunol. 2004;34:1291–302.

    Article  CAS  PubMed  Google Scholar 

  31. Rossetti M, Gregori S, Roncarolo MG. Granulocyte-colony stimulating factor drives the in vitro differentiation of human dendritic cells that induce anergy in naive T cells. Eur J Immunol. 2010;40:3097–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Chang YJ, Zhao XY, Huo MR, Huang XJ. Expression profiles of adhesion molecules on naive T cells in bone marrow grafts of healthy donors treated with granulocyte colony-stimulating factor. Transpl Immunol. 2009;21:228–33.

    Article  CAS  PubMed  Google Scholar 

  33. Zhao XY, Wang YT, Mo XD, et al. 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;13:145.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. D’Aveni M, Rossignol J, Coman T, et al. G-CSF mobilizes CD34+ regulatory monocytes that inhibit graft-versus-host disease. Sci Transl Med. 2015;7:281ra242.

    Article  CAS  Google Scholar 

  35. Chang Y-J, Zhao X-S, Lv M, et al. CD19+CD24highCD38high B cells exhibit higher ability in TGF-{beta} and IL-10 secretion and suppressing of CD4+ T cell proliferation but are quantitatively decreased in G-BM of healthy donors (P2146). J Immunol. 2013;190(69):11.

    Google Scholar 

  36. Mielcarek M, Graf L, Johnson G, Torok-Storb B. Production of interleukin-10 by granulocyte colony-stimulating factor-mobilized blood products: a mechanism for monocyte-mediated suppression of T-cell proliferation. Blood. 1998;92:215–22.

    CAS  PubMed  Google Scholar 

  37. Mielcarek M, Martin PJ, Torok-Storb B. Suppression of alloantigen-induced T-cell proliferation by CD14+ cells derived from granulocyte colony-stimulating factor-mobilized peripheral blood mononuclear cells. Blood. 1997;89:1629–34.

    CAS  PubMed  Google Scholar 

  38. Wang D, Yu Y, Haarberg K, et al. Dynamic change and impact of myeloid-derived suppressor cells in allogeneic bone marrow transplantation in mice. Biol Blood Marrow Transplant. 2013;19:692–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Luyckx A, Schouppe E, Rutgeerts O, et al. G-CSF stem cell mobilization in human donors induces polymorphonuclear and mononuclear myeloid-derived suppressor cells. Clin Immunol. 2012;143:83–7.

    Article  CAS  PubMed  Google Scholar 

  40. Thakar MS, Santos EB, Fricker S, Bridger G, Storb R, Sandmaier BM. Plerixafor-mobilized stem cells alone are capable of inducing early engraftment across the MHC-haploidentical canine barrier. Blood. 2010;115:916–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Gaugler B, Arbez J, Legouill S, et al. Characterization of peripheral blood stem cell grafts mobilized by granulocyte colony-stimulating factor and plerixafor compared with granulocyte colony-stimulating factor alone. Cytotherapy. 2013;15:861–8.

    Article  CAS  PubMed  Google Scholar 

  42. Zheng H, Matte-Martone C, Li H, et al. Effector memory CD4+ T cells mediate graft-versus-leukemia without inducing graft-versus-host disease. Blood. 2008;111:2476–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Di Ianni M, Falzetti F, Carotti A, et al. Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood. 2011;117:3921–8.

    Article  PubMed  CAS  Google Scholar 

  44. Zhang J, Barefoot BE, Mo W, et al. CD62L-memory T cells enhance T-cell regeneration after allogeneic stem cell transplantation by eliminating host resistance in mice. Blood. 2012;119:6344–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Kean LS, Sen S, Onabajo O, et al. Significant mobilization of both conventional and regulatory T cells with AMD3100. Blood. 2011;118:6580–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Huang XJ, Han W, Xu LP, et al. A novel approach to HLA-mismatched transplantation. Beijing Da Xue Xue Bao. 2004;36:229–33.

    PubMed  Google Scholar 

  47. Alyea EP. Graft-versus-host disease prevention: corticosteroids revisited. J Clin Oncol. 2016;34:1836–7.

    Article  CAS  PubMed  Google Scholar 

  48. Chang YJ, Luznik L, Fuchs EJ, Huang XJ. How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation? J Hematol Oncol. 2016;9:35.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Chang YJ, Xu LP, Wang Y, et al. Controlled, randomized, open-label trial of risk-stratified corticosteroid prevention of acute graft-versus-host disease after haploidentical transplantation. J Clin Oncol. 2016;34:1855–63.

    Article  CAS  PubMed  Google Scholar 

  50. Chang YJ, Zhao XY, Xu LP, et al. 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;8:84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Wang YT, Zhao XY, Zhao XS, et al. The impact of donor characteristics on the immune cell composition of mixture allografts of granulocyte-colony-stimulating factor-mobilized marrow harvests and peripheral blood harvests. Transfusion. 2015;55:2874–81.

    Article  CAS  PubMed  Google Scholar 

  52. Zhao XY, Chang YJ, Zhao XS, et al. Recipient expression of ligands for donor inhibitory KIRs enhances NK-cell function to control leukemic relapse after haploidentical transplantation. Eur J Immunol. 2015;45:2396–408.

    Article  CAS  PubMed  Google Scholar 

  53. Zhao XY, Chang YJ, Huang XJ. Conflicting impact of alloreactive NK cells on transplantation outcomes after haploidentical transplantation: do the reconstitution kinetics of natural killer cells create these differences? Biol Blood Marrow Transplant. 2011;17:1436–42.

    Article  PubMed  Google Scholar 

  54. Huang XJ, Liu DH, Liu KY, et al. Modified donor lymphocyte infusion after HLA-mismatched/haploidentical T cell-replete hematopoietic stem cell transplantation for prophylaxis of relapse of leukemia in patients with advanced leukemia. J Clin Immunol. 2008;28:276–83.

    Article  CAS  PubMed  Google Scholar 

  55. Huang XJ, Wang Y, Liu DH, et al. Modified donor lymphocyte infusion (DLI) for the prophylaxis of leukemia relapse after hematopoietic stem cell transplantation in patients with advanced leukemia--feasibility and safety study. J Clin Immunol. 2008;28:390–7.

    Article  CAS  PubMed  Google Scholar 

  56. 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;92:414–7.

    Article  PubMed  Google Scholar 

  57. Yan CH, Liu DH, Xu LP, et al. Modified donor lymphocyte infusion-associated acute graft-versus-host disease after haploidentical T-cell-replete hematopoietic stem cell transplantation: incidence and risk factors. Clin Transplant. 2012;26:868–76.

    Article  PubMed  Google Scholar 

  58. Zeidan AM, Forde PM, Symons H, et al. HLA-haploidentical donor lymphocyte infusions for patients with relapsed hematologic malignancies after related HLA-haploidentical bone marrow transplantation. Biol Blood Marrow Transplant. 2014;20:314–8.

    Article  CAS  PubMed  Google Scholar 

  59. Mo XD, Zhang XH, Xu LP, et al. Interferon-alpha: a potentially effective treatment for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21:1939–47.

    Article  CAS  PubMed  Google Scholar 

  60. Tang X, Song YH, Sun A, Zhu X, Ruan C, Wu D. Successful treatment of relapsed acute myeloid leukemia without chemotherapy. J Clin Oncol. 2016;34:e117–9.

    Article  PubMed  Google Scholar 

  61. Zhao XS, Jin S, Zhu HH, et al. Wilms’ tumor gene 1 expression: an independent acute leukemia prognostic indicator following allogeneic hematopoietic SCT. Bone Marrow Transplant. 2012;47:499–507.

    Article  CAS  PubMed  Google Scholar 

  62. Zhao XS, Liu YR, Zhu HH, et al. Monitoring MRD with flow cytometry: an effective method to predict relapse for ALL patients after allogeneic hematopoietic stem cell transplantation. Ann Hematol. 2012;91:183–92.

    Article  CAS  PubMed  Google Scholar 

  63. Ferrara JL, Levine JE, Reddy P, Holler E. Graft-versus-host disease. Lancet. 2009;373:1550–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Liu QF, Xu XJ, Chen YK, et al. Long-term outcomes of HLA-matched sibling compared with mismatched related and unrelated donor hematopoietic stem cell transplantation for chronic phase chronic myelogenous leukemia: a single institution experience in China. Ann Hematol. 2011;90:331–41.

    Article  PubMed  Google Scholar 

  65. Xu LP, Liu KY, Liu DH, 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 Transplant. 2012;47:1507–12.

    Article  CAS  PubMed  Google Scholar 

  66. Chen J, Wang RX, Chen F, et al. Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study. Bone Marrow Transplant. 2013;49:206–11.

    Article  PubMed  Google Scholar 

  67. Gao L, Wen Q, Chen X, et al. 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;20:1932–9.

    Article  CAS  PubMed  Google Scholar 

  68. Luo Y, Xiao H, Lai X, et al. T-cell-replete haploidentical HSCT with low-dose anti-T-lymphocyte globulin compared with matched sibling HSCT and unrelated HSCT. Blood. 2014;124:2735–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Peccatori J, Forcina A, Clerici D, et al. 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;29:396–405.

    Article  CAS  PubMed  Google Scholar 

  70. Mohty M. Mechanisms of action of antithymocyte globulin: T-cell depletion and beyond. Leukemia. 2007;21:1387–94.

    Article  CAS  PubMed  Google Scholar 

  71. Wang Y, Fu HX, Liu DH, et al. Influence of two different doses of antithymocyte globulin in patients with standard-risk disease following haploidentical transplantation: a randomized trial. Bone Marrow Transplant. 2014;49:426–33.

    Article  CAS  PubMed  Google Scholar 

  72. Marchitto KS, Kindt TJ, Norgard MV. Monoclonal antibodies directed against major histocompatibility complex antigens bind to the surface of Treponema pallidum isolated from infected rabbits or humans. Cell Immunol. 1986;101:633–42.

    Article  CAS  PubMed  Google Scholar 

  73. Fu H, Xu L, Liu D, et al. 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;20:1176–82.

    Article  CAS  PubMed  Google Scholar 

  74. Gao L, Li Y, Zhang Y, et al. Long-term outcome of HLA-haploidentical hematopoietic SCT without in vitro T-cell depletion for adult severe aplastic anemia after modified conditioning and supportive therapy. Bone Marrow Transplant. 2014;49:519–24.

    Article  CAS  PubMed  Google Scholar 

  75. Li XH, Gao CJ, Da WM, et al. Reduced intensity conditioning, combined transplantation of haploidentical hematopoietic stem cells and mesenchymal stem cells in patients with severe aplastic anemia. PLoS One. 2014;9:e89666.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Wang Z, Zheng X, Yan H, Li D, Wang H. Good outcome of haploidentical hematopoietic SCT as a salvage therapy in children and adolescents with acquired severe aplastic anemia. Bone Marrow Transplant. 2014;49:1481–5.

    Article  CAS  PubMed  Google Scholar 

  77. Esteves I, Bonfim C, Pasquini R, et al. Haploidentical BMT and post-transplant Cy for severe aplastic anemia: a multicenter retrospective study. Bone Marrow Transplant. 2015;50:685–9.

    Article  CAS  PubMed  Google Scholar 

  78. Apperley J, Niederwieser D, Huang XJ, et al. reprint of: haploidentical hematopoietic stem cell transplantation: a global overview comparing Asia, the European Union, and the United States. Biol Blood Marrow Transplant. 2016;22:S15–8.

    Article  PubMed  Google Scholar 

  79. Wang Y, Liu DH, Liu KY, et al. Impact of pretransplantation risk factors on post transplantation outcome of patients with acute myeloid leukemia in remission after haploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19:283–90.

    Article  PubMed  Google Scholar 

  80. Wang YU, Liu Q, Xu LP, et al. Haploidentical versus matched-sibling transplant in adults with philadelphia-negative high-risk acute lymphoblastic leukemia: a biologically phase 3 randomized study. Clin Cancer Res. 2016;22:3467–76.

    Article  CAS  PubMed  Google Scholar 

  81. Wang Y, Wang HX, Lai YR, et al. Haploidentical transplant for myelodysplastic syndrome: registry-based comparison with identical-sibling transplant. Leukemia. 2016;30:2055–63.

    Article  CAS  PubMed  Google Scholar 

  82. Lee KH, Lee JH, Kim DY, 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;118:2609–17.

    Article  CAS  PubMed  Google Scholar 

  83. Yu S, Fan Q, Sun J, et al. Haploidentical transplantation without in vitro T-cell depletion results in outcomes equivalent to those of contemporaneous matched sibling and unrelated donor transplantation for acute leukemia. Medicine (Baltimore). 2016;95:e2973.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Di Bartolomeo P, Santarone S, De Angelis G, et al. Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies. Blood. 2013;121:849–57.

    Article  PubMed  CAS  Google Scholar 

  85. Chang YJ, Weng CL, Sun LX, Zhao YT. Allogeneic bone marrow transplantation compared to peripheral blood stem cell transplantation for the treatment of hematologic malignancies: a meta-analysis based on time-to-event data from randomized controlled trials. Ann Hematol. 2012;91:427–37.

    Article  PubMed  Google Scholar 

  86. Wang Y, Liu DH, Xu LP, et al. Superior graft-versus-leukemia effect associated with transplantation of haploidentical compared with HLA-identical sibling donor grafts for high-risk acute leukemia: an historic comparison. Biol Blood Marrow Transplant. 2011;17:821–30.

    Article  PubMed  Google Scholar 

  87. Xu LP, Liu KY, Liu DH, et al. The inferiority of G-PB to rhG-CSF-mobilized blood and marrow grafts as a stem cell source in patients with high-risk acute leukemia who underwent unmanipulated HLA-mismatched/haploidentical transplantation: a comparative analysis. Bone Marrow Transplant. 2010;45:985–92.

    Article  CAS  PubMed  Google Scholar 

  88. 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-CSF-primed peripheral blood stem cell haploidentical transplantation: a multicenter study. Sci China Life Sci. 2016;59(11):1139–48. Epub 2016 Aug 17

    Article  CAS  PubMed  Google Scholar 

  89. Wang HX, Yan HM, Wang ZD, Xue M, Liu J, Guo ZK. Haploidentical hematopoietic stem cell transplantation in hematologic malignancies with G-CSF mobilized bone marrow plus peripheral blood stem cells grafts without T cell depletion: a single center report of 29 cases. Leuk Lymphoma. 2012;53:654–9.

    Article  CAS  PubMed  Google Scholar 

  90. Ji SQ, Chen HR, Wang HX, et al. G-CSF-primed haploidentical marrow transplantation without ex vivo T cell depletion: an excellent alternative for high-risk leukemia. Bone Marrow Transplant. 2002;30:861–6.

    Article  PubMed  Google Scholar 

  91. Shin SH, Kim JH, Jeon YW, 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;21:342–9.

    Article  CAS  PubMed  Google Scholar 

  92. Huang W, Li H, Gao C, et al. Unmanipulated HLA-mismatched/haploidentical peripheral blood stem cell transplantation for high-risk hematologic malignancies. Transfusion. 2012;52:1354–62.

    Article  CAS  PubMed  Google Scholar 

  93. Sun YQ, He GL, Chang YJ, et al. The incidence, risk factors, and outcomes of primary poor graft function after unmanipulated haploidentical stem cell transplantation. Ann Hematol. 2015;94:1699–705.

    Article  CAS  PubMed  Google Scholar 

  94. Ciurea SO, de Lima M, Cano P, et al. High risk of graft failure in patients with anti-HLA antibodies undergoing haploidentical stem-cell transplantation. Transplantation. 2009;88:1019–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Yoshihara S, Maruya E, Taniguchi K, et al. Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT. Bone Marrow Transplant. 2012;47:508–15.

    Article  CAS  PubMed  Google Scholar 

  96. Yamamoto H, Uchida N, Matsuno N, et al. Anti-HLA antibodies other than against HLA-A, -B, -DRB1 adversely affect engraftment and nonrelapse mortality in HLA-mismatched single cord blood transplantation: possible implications of unrecognized donor-specific antibodies. Biol Blood Marrow Transplant. 2014;20:1634–40.

    Article  CAS  PubMed  Google Scholar 

  97. Locatelli F, Lucarelli B, Merli P. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation. Expert Opin Pharmacother. 2014;15:23–36.

    Article  CAS  PubMed  Google Scholar 

  98. Kong Y, Chang YJ, Wang YZ, et al. Association of an impaired bone marrow microenvironment with secondary poor graft function after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2013;19:1465–73.

    Article  PubMed  Google Scholar 

  99. Chen H, K-y L, L-p X, et al. Haploidentical hematopoietic stem cell transplantation without in vitro T cell depletion for the treatment of philadelphia chromosome–positive acute lymphoblastic leukemia. Biol Blood Marrow Transplant. 2015;21:1110–6.

    Article  PubMed  Google Scholar 

  100. Mo XD, Zhao XY, Liu DH, et al. Umbilical cord blood transplantation and unmanipulated haploidentical hematopoietic SCT for pediatric hematologic malignances. Bone Marrow Transplant. 2014;49:1070–5.

    Article  CAS  PubMed  Google Scholar 

  101. Lin X, Lu ZG, Song CY, et al. Long-term outcome of HLA-haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion based on an FBCA conditioning regimen for hematologic malignancies. Bone Marrow Transplant. 2015;50:1092–7.

    Article  CAS  PubMed  Google Scholar 

  102. Chen J, Wang RX, Chen F, et al. Combination of a haploidentical SCT with an unrelated cord blood unit: a single-arm prospective study. Bone Marrow Transplant. 2014;49:206–11.

    Article  CAS  PubMed  Google Scholar 

  103. Tang BL, Zhu XY, Zheng CC, et al. Successful early unmanipulated haploidentical transplantation with reduced-intensity conditioning for primary graft failure after cord blood transplantation in hematologic malignancy patients. Bone Marrow Transplant. 2015;50:248–52.

    Article  CAS  PubMed  Google Scholar 

  104. Yahng SA, Kim JH, Jeon YW, et al. 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;21:119–29.

    Article  CAS  PubMed  Google Scholar 

  105. Yan CH, Jiang Q, Wang J, et al. Superior survival of unmanipulated haploidentical hematopoietic stem cell transplantation compared with chemotherapy alone used as post-remission therapy in adults with standard-risk acute lymphoblastic leukemia in first complete remission. Biol Blood Marrow Transplant. 2014;20:1314–21.

    Article  PubMed  Google Scholar 

  106. Sun YQ, Wang J, Jiang Q, et al. Haploidentical hematopoietic SCT may be superior to conventional consolidation/maintenance chemotherapy as post-remission therapy for high-risk adult ALL. Bone Marrow Transplant. 2015;50:20–5.

    Article  PubMed  Google Scholar 

  107. Chen XH, Zhang C, Zhang X, et al. Role of antithymocyte globulin and granulocyte-colony stimulating factor-mobilized bone marrow in allogeneic transplantation for patients with hematologic malignancies. Biol Blood Marrow Transplant. 2009;15:266–73.

    Article  CAS  PubMed  Google Scholar 

  108. Xu ZL, Huang XJ, Liu KY, et al. Haploidentical hematopoietic stem cell transplantation for paediatric high-risk T-cell acute lymphoblastic leukaemia. Pediatr Transplant. 2016;20:572–80.

    Article  PubMed  Google Scholar 

  109. Zhu HH, Zhang XH, Qin YZ, et al. MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial. Blood. 2013;121:4056–62.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

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

    Ying-Jun Chang, Meng Lv & Xiao-Jun Huang

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  1. Ying-Jun Chang
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  2. Meng Lv
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  3. Xiao-Jun Huang
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Correspondence to Xiao-Jun Huang .

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Editors and Affiliations

  1. Department of Stem Cell Transplantation, MD Anderson Cancer Center, Houston, Texas, USA

    Stefan O. Ciurea

  2. Department of General Pediatrics and Hematology/Oncology, University Children’s Hospital, Tübingen, Baden-Württemberg, Germany

    Rupert Handgretinger

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Chang, YJ., Lv, M., Huang, XJ. (2018). Haploidentical Transplantation Using Unmanipulated G-CSF-Primed Blood and Marrow as Allografts: Clinical Data and Challenges. In: Ciurea, S., Handgretinger, R. (eds) Haploidentical Transplantation. Advances and Controversies in Hematopoietic Transplantation and Cell Therapy. Springer, Cham. https://doi.org/10.1007/978-3-319-54310-9_5

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  • DOI: https://doi.org/10.1007/978-3-319-54310-9_5

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