Haploidentical Transplants for Nonmalignant Diseases in Children

  • Christian Seitz
  • Patrick Schlegel
  • Rupert Handgretinger
Part of the Advances and Controversies in Hematopoietic Transplantation and Cell Therapy book series (ACHTCT)


Allogeneic hematopoietic cell transplantation (allo-HCT) offers a curative treatment strategy to a variety of nonmalignant hematological and immunological disorders as well as inborn errors of metabolism. Successful allo-HCT is able to restore functional hematopoiesis and immune function and can substitute disabled enzymatic activity. Nevertheless, allo-HCT can also be associated with serious risks for transplantation-related morbidities or even mortalities like graft-versus-host disease (GvHD) or life-threatening infectious complications. Especially in nonmalignant disorders (NMD), risks and benefits have to be carefully balanced on an individual patient basis. Up to now, human leukocyte antigen (HLA)-matched siblings are the preferred source of hematopoietic graft. Only about one third of patients have HLA-matched sibling donor (MSD) and the number further decreases in patients with inherited disorders as siblings might be carriers or affected as well. HLA-matched unrelated donors (MUD) have become an important alternative. Chances of finding a HLA-MUD are particularly dismal for individuals belonging to certain ethnic groups, with often less than 10% compared to approximately 75% in the Caucasian population. Therefore, alternative donor sources have to been taken into account, especially when the clinical condition of the patients does not allow a further delay of the allo-HCT. This chapter focuses on HLA-haploidentical hematopoietic cell transplant (haplo-HCT) in NMD. It will highlight recent developments in graft manipulation utilizing safe application of haplo-HCT grafts and discuss important advantages which might lift haplo-HCT to a standard therapy in NMDs in the near future.


Haploidentical transplant GvHD Nonmalignant disorders NK-cells T-cell depletion Bone marrow failure syndromes Fanconi anemia SCID Inborn errors Metabolism Immunodeficiency Thalassemia 


  1. 1.
    Beatty PG, Clift RA, Mickelson EM, Nisperos BB, Flournoy N, Martin PJ, et al. Marrow transplantation from related donors other than HLA-identical siblings. N Engl J Med. 1985;313(13):765–71.CrossRefGoogle Scholar
  2. 2.
    Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings. J Clin Oncol. 1997;15(5):1767–77.CrossRefGoogle Scholar
  3. 3.
    Ottinger H, Grosse-Wilde M, Schmitz A, Grosse-Wilde H. Immunogenetic marrow donor search for 1012 patients: a retrospective analysis of strategies, outcome and costs. Bone Marrow Transplant. 1994;14(Suppl 4):S34–8.PubMedGoogle Scholar
  4. 4.
    Switzer GE, Bruce JG, Myaskovsky L, DiMartini A, Shellmer D, Confer DL, et al. Race and ethnicity in decisions about unrelated hematopoietic stem cell donation. Blood. 2013;121(8):1469–76.CrossRefGoogle Scholar
  5. 5.
    Gragert L, Eapen M, Williams E, Freeman J, Spellman S, Baitty R, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371(4):339–48.CrossRefGoogle Scholar
  6. 6.
    Hansen JA, Clift RA, Mickelson EM, Nisperos B, Thomas ED. Marrow transplantation from donors other than HLA identical siblings. Hum Immunol. 1981;2(1):31–40.CrossRefGoogle Scholar
  7. 7.
    Powles RL, Morgenstern GR, Kay HE, McElwain TJ, Clink HM, Dady PJ, et al. Mismatched family donors for bone-marrow transplantation as treatment for acute leukaemia. Lancet. 1983;1(8325):612–5.CrossRefGoogle Scholar
  8. 8.
    Anasetti C, Amos D, Beatty PG, Appelbaum FR, Bensinger W, Buckner CD, et al. Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma. N Engl J Med. 1989;320(4):197–204.CrossRefGoogle Scholar
  9. 9.
    Reisner Y, Kapoor N, Kirkpatrick D, Pollack MS, Cunningham-Rundles S, Dupont B, et al. Transplantation for severe combined immunodeficiency with HLA-A,B,D,DR incompatible parental marrow cells fractionated by soybean agglutinin and sheep red blood cells. Blood. 1983;61(2):341–8.PubMedGoogle Scholar
  10. 10.
    Buckley RH, Schiff SE, Schiff RI, Markert L, Williams LW, Roberts JL, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 1999;340(7):508–16.CrossRefGoogle Scholar
  11. 11.
    Aversa F, Tabilio A, Terenzi A, Velardi A, Falzetti F, Giannoni 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):3948–55.PubMedGoogle Scholar
  12. 12.
    Reisner Y, Gur H, Reich-Zeliger S, Martelli MF, Bachar-Lustig E. Hematopoietic stem cell transplantation across major genetic barriers: tolerance induction by megadose CD34 cells and other veto cells. Ann N Y Acad Sci. 2003;996:72–9.CrossRefGoogle Scholar
  13. 13.
    Handgretinger R, Lang P, Schumm M, Taylor G, Neu S, Koscielnak E, et al. Isolation and transplantation of autologous peripheral CD34+ progenitor cells highly purified by magnetic-activated cell sorting. Bone Marrow Transplant. 1998;21(10):987–93.CrossRefGoogle Scholar
  14. 14.
    Handgretinger R. New approaches to graft engineering for haploidentical bone marrow transplantation. Semin Oncol. 2012;39(6):664–73.CrossRefGoogle Scholar
  15. 15.
    Bleakley M, Heimfeld S, Jones LA, Turtle C, Krause D, Riddell SR, et al. Engineering human peripheral blood stem cell grafts that are depleted of naive T cells and retain functional pathogen-specific memory T cells. Biol Blood Marrow Transplant. 2014;20(5):705–16.CrossRefGoogle Scholar
  16. 16.
    Lang P, Schumm M, Taylor G, Klingebiel T, Neu S, Geiselhart A, et al. Clinical scale isolation of highly purified peripheral CD34+progenitors for autologous and allogeneic transplantation in children. Bone Marrow Transplant. 1999;24(6):583–9.CrossRefGoogle Scholar
  17. 17.
    Handgretinger R, Klingebiel T, Lang P, Schumm M, Neu S, Geiselhart A, et al. Megadose transplantation of purified peripheral blood CD34(+) progenitor cells from HLA-mismatched parental donors in children. Bone Marrow Transplant. 2001;27(8):777–83.CrossRefGoogle Scholar
  18. 18.
    Lang P, Greil J, Bader P, Handgretinger R, Klingebiel T, Schumm M, et al. Long-term outcome after haploidentical stem cell transplantation in children. Blood Cells Mol Dis. 2004;33(3):281–7.CrossRefGoogle Scholar
  19. 19.
    Bonneville M, O’Brien RL, Born WK. Gammadelta T cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol. 2010;10(7):467–78.CrossRefGoogle Scholar
  20. 20.
    Ziegler H, Welker C, Sterk M, Haarer J, Rammensee HG, Handgretinger R, et al. Human peripheral CD4(+) Vdelta1(+) gammadeltaT cells can develop into alphabetaT cells. Front Immunol. 2014;5:645.CrossRefGoogle Scholar
  21. 21.
    Ruggeri L, Capanni M, Urbani E, Perruccio K, Shlomchik WD, Tosti A, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295(5562):2097–100.CrossRefGoogle Scholar
  22. 22.
    Handgretinger R, Chen X, Pfeiffer M, Mueller I, Feuchtinger T, Hale GA, et al. Feasibility and outcome of reduced-intensity conditioning in haploidentical transplantation. Ann N Y Acad Sci. 2007;1106:279–89.CrossRefGoogle Scholar
  23. 23.
    Bader P, Soerensen J, Jarisch A, Ponstingl E, Krenn T, Faber J, et al. Rapid immune recovery and low TRM in haploidentical stem cell transplantation in children and adolescence using CD3/CD19-depleted stem cells. Best Pract Res Clin Haematol. 2011;24(3):331–7.CrossRefGoogle Scholar
  24. 24.
    Dufort G, Pisano S, Incoronato A, Castiglioni M, Carracedo M, Pages C, et al. Feasibility and outcome of haploidentical SCT in pediatric high-risk hematologic malignancies and Fanconi anemia in Uruguay. Bone Marrow Transplant. 2012;47(5):663–8.CrossRefGoogle Scholar
  25. 25.
    Sodani P, Isgro A, Gaziev J, Polchi P, Paciaroni K, Marziali M, et al. Purified T-depleted, CD34+ peripheral blood and bone marrow cell transplantation from haploidentical mother to child with thalassemia. Blood. 2010;115(6):1296–302.CrossRefGoogle Scholar
  26. 26.
    Lang P, Feuchtinger T, Teltschik HM, Schwinger W, Schlegel P, Pfeiffer M, et al. Improved immune recovery after transplantation of TCRalphabeta/CD19-depleted allografts from haploidentical donors in pediatric patients. Bone Marrow Transplant. 2015;50(Suppl 2):S6–10.CrossRefGoogle Scholar
  27. 27.
    Balashov D, Shcherbina A, Maschan M, Trakhtman P, Skvortsova Y, Shelikhova L, et al. Single-center experience of unrelated and haploidentical stem cell transplantation with TCRalphabeta and CD19 depletion in children with primary immunodeficiency syndromes. Biol Blood Marrow Transplant. 2015;21(11):1955–62.CrossRefGoogle Scholar
  28. 28.
    Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R, et al. HLA-haploidentical stem cell transplantation after removal of alphabeta+ T and B cells in children with nonmalignant disorders. Blood. 2014;124(5):822–6.CrossRefGoogle Scholar
  29. 29.
    Huang XJ, Chang YJ, Zhao XY. Maintaining hyporesponsiveness and polarization potential of T cells after in vitro mixture of G-CSF mobilized peripheral blood grafts and G-CSF primed bone marrow grafts in different proportions. Transpl Immunol. 2007;17(3):193–7.CrossRefGoogle Scholar
  30. 30.
    DP L, 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(8):3065–73.CrossRefGoogle Scholar
  31. 31.
    Wang Y, Liu QF, LP X, Liu KY, Zhang XH, Ma X, et al. Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood. 2015;125(25):3956–62.CrossRefGoogle Scholar
  32. 32.
    Eto M, Mayumi H, Tomita Y, Yoshikai Y, Nishimura Y, Nomoto K. Sequential mechanisms of cyclophosphamide-induced skin allograft tolerance including the intrathymic clonal deletion followed by late breakdown of the clonal deletion. J Immunol. 1990;145(5):1303–10.PubMedGoogle Scholar
  33. 33.
    Ross D, Jones M, Komanduri K, Levy RB. Antigen and lymphopenia-driven donor T cells are differentially diminished by post-transplantation administration of cyclophosphamide after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2013;19(10):1430–8.CrossRefGoogle Scholar
  34. 34.
    Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641–50.CrossRefGoogle Scholar
  35. 35.
    Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, et al. Transplantation outcomes for severe combined immunodeficiency, 2000-2009. N Engl J Med. 2014;371(5):434–46.CrossRefGoogle Scholar
  36. 36.
    Gaspar HB, Qasim W, Davies EG, Rao K, Amrolia PJ, Veys P. How I treat severe combined immunodeficiency. Blood. 2013;122(23):3749–58.CrossRefGoogle Scholar
  37. 37.
    Ouederni M, Mellouli F, Khaled MB, Kaabi H, Picard C, Bejaoui M. Successful haploidentical stem cell transplantation with post-transplant cyclophosphamide in a severe combined immune deficiency patient: a first report. J Clin Immunol. 2016;36(5):437–40.CrossRefGoogle Scholar
  38. 38.
    Caillat-Zucman S, Le Deist F, Haddad E, Gannage M, Dal Cortivo L, Jabado N, et al. Impact of HLA matching on outcome of hematopoietic stem cell transplantation in children with inherited diseases: a single-center comparative analysis of genoidentical, haploidentical or unrelated donors. Bone Marrow Transplant. 2004;33(11):1089–95.CrossRefGoogle Scholar
  39. 39.
    Klein OR, Chen AR, Gamper C, Loeb D, Zambidis E, Llosa N, et al. Alternative-donor hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for nonmalignant disorders. Biol Blood Marrow Transplant. 2016;22(5):895–901.CrossRefGoogle Scholar
  40. 40.
    Feuchtinger T, Opherk K, Bethge WA, Topp MS, Schuster FR, Weissinger EM, et al. Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood. 2010;116(20):4360–7.CrossRefGoogle Scholar
  41. 41.
    Icheva V, Kayser S, Wolff D, Tuve S, Kyzirakos C, Bethge W, et al. Adoptive transfer of epstein-barr virus (EBV) nuclear antigen 1-specific t cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation. J Clin Oncol. 2013;31(1):39–48.CrossRefGoogle Scholar
  42. 42.
    Gerdemann U, Katari UL, Papadopoulou A, Keirnan JM, Craddock JA, Liu H, et al. Safety and clinical efficacy of rapidly-generated trivirus-directed T cells as treatment for adenovirus, EBV, and CMV infections after allogeneic hematopoietic stem cell transplant. Mol Ther. 2013;21(11):2113–21.CrossRefGoogle Scholar
  43. 43.
    Bollard CM, Heslop HE. T cells for viral infections after allogeneic hematopoietic stem cell transplant. Blood. 2016;127:3331–40.CrossRefGoogle Scholar
  44. 44.
    Touzot F, Neven B, Dal-Cortivo L, Gabrion A, Moshous D, Cros G, et al. CD45RA depletion in HLA-mismatched allogeneic hematopoietic stem cell transplantation for primary combined immunodeficiency: a preliminary study. J Allergy Clin Immunol. 2015;135(5):1303–9 e1-3.CrossRefGoogle Scholar
  45. 45.
    Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest. 2008;118(9):3143–50.CrossRefGoogle Scholar
  46. 46.
    Braun CJ, Boztug K, Paruzynski A, Witzel M, Schwarzer A, Rothe M, et al. Gene therapy for Wiskott-Aldrich syndrome—long-term efficacy and genotoxicity. Sci Transl Med. 2014;6(227):227ra33.CrossRefGoogle Scholar
  47. 47.
    Touzot F, Moshous D, Creidy R, Neven B, Frange P, Cros G, et al. Faster T-cell development following gene therapy compared with haploidentical HSCT in the treatment of SCID-X1. Blood. 2015;125(23):3563–9.CrossRefGoogle Scholar
  48. 48.
    Fischer A, Hacein-Bey Abina S, Touzot F, Cavazzana M. Gene therapy for primary immunodeficiencies. Clin Genet. 2015;88(6):507–15.CrossRefGoogle Scholar
  49. 49.
    Ginocchio VM, Brunetti-Pierri N. Progress toward improved therapies for inborn errors of metabolism. Hum Mol Genet. 2016;25(R1):R27–35.CrossRefGoogle Scholar
  50. 50.
    Parenti G, Andria G, Ballabio A. Lysosomal storage diseases: from pathophysiology to therapy. Annu Rev Med. 2015;66:471–86.CrossRefGoogle Scholar
  51. 51.
    Boelens JJ, Orchard PJ, Wynn RF. Transplantation in inborn errors of metabolism: current considerations and future perspectives. Br J Haematol. 2014;167(3):293–303.CrossRefGoogle Scholar
  52. 52.
    Krageloh-Mann I, Groeschel S, Kehrer C, Opherk K, Nagele T, Handgretinger R, et al. Juvenile metachromatic leukodystrophy 10 years post transplant compared with a non-transplanted cohort. Bone Marrow Transplant. 2013;48(3):369–75.CrossRefGoogle Scholar
  53. 53.
    Aldenhoven M, Jones SA, Bonney D, Borrill RE, Coussons M, Mercer J, et al. Hematopoietic cell transplantation for mucopolysaccharidosis patients is safe and effective: results after implementation of international guidelines. Biol Blood Marrow Transplant. 2015;21(6):1106–9.CrossRefGoogle Scholar
  54. 54.
    Aldenhoven M, Boelens JJ, de Koning TJ. The clinical outcome of Hurler syndrome after stem cell transplantation. Biol Blood Marrow Transplant. 2008;14(5):485–98.CrossRefGoogle Scholar
  55. 55.
    Boelens JJ, Aldenhoven M, Purtill D, Ruggeri A, Defor T, Wynn R, et al. Outcomes of transplantation using various hematopoietic cell sources in children with Hurler syndrome after myeloablative conditioning. Blood. 2013;121(19):3981–7.CrossRefGoogle Scholar
  56. 56.
    Schwinger W, Sovinz P, Benesch M, Lackner H, Seidel M, Strenger V, et al. Unrelated CD3/CD19-depleted peripheral stem cell transplantation for Hurler syndrome. Pediatr Hematol Oncol. 2014;31(8):723–30.CrossRefGoogle Scholar
  57. 57.
    Jester S, Larsson J, Eklund EA, Papadopoulou D, Mansson JE, Bekassy AN, et al. Haploidentical stem cell transplantation in two children with mucopolysaccharidosis VI: clinical and biochemical outcome. Orphanet J Rare Dis. 2013;8:134.CrossRefGoogle Scholar
  58. 58.
    Koc ON, Day J, Nieder M, Gerson SL, Lazarus HM, Krivit W. Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and Hurler syndrome (MPS-IH). Bone Marrow Transplant. 2002;30(4):215–22.CrossRefGoogle Scholar
  59. 59.
    Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, Kutschera I, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science. 2009;326(5954):818–23.CrossRefGoogle Scholar
  60. 60.
    Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, et al. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science. 2013;341(6148):1233158.CrossRefGoogle Scholar
  61. 61.
    Alter BP. Diagnosis, genetics, and management of inherited bone marrow failure syndromes. Hematology Am Soc Hematol Educ Program. 2007:29–39.CrossRefGoogle Scholar
  62. 62.
    Dalle JH, Peffault de Latour R. Allogeneic hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. Int J Hematol. 2016;103(4):373–9.CrossRefGoogle Scholar
  63. 63.
    Samarasinghe S, Steward C, Hiwarkar P, Saif MA, Hough R, Webb D, et al. Excellent outcome of matched unrelated donor transplantation in paediatric aplastic anaemia following failure with immunosuppressive therapy: a United Kingdom multicentre retrospective experience. Br J Haematol. 2012;157(3):339–46.CrossRefGoogle Scholar
  64. 64.
    Yoshida N, Kobayashi R, Yabe H, Kosaka Y, Yagasaki H, Watanabe K, et al. First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy. Haematologica. 2014;99(12):1784–91.CrossRefGoogle Scholar
  65. 65.
    Chu R, Brazauskas R, Kan F, Bashey A, Bredeson C, Camitta B, et al. Comparison of outcomes after transplantation of G-CSF-stimulated bone marrow grafts versus bone marrow or peripheral blood grafts from HLA-matched sibling donors for patients with severe aplastic anemia. Biol Blood Marrow Transplant. 2011;17(7):1018–24.CrossRefGoogle Scholar
  66. 66.
    Marsh JC, Pearce RM, Koh MB, Lim Z, Pagliuca A, Mufti GJ, et al. Retrospective study of alemtuzumab vs ATG-based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anemia: a study from the British Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2014;49(1):42–8.CrossRefGoogle Scholar
  67. 67.
    Peffault de Latour R, Purtill D, Ruggeri A, Sanz G, Michel G, Gandemer V, et al. Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anemia: a study by eurocord and the aplastic anemia working party of the European group for blood and marrow transplantation. Biol Blood Marrow Transplant. 2011;17(1):78–85.CrossRefGoogle Scholar
  68. 68.
    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(12):1481–5.CrossRefGoogle Scholar
  69. 69.
    Esteves I, Bonfim C, Pasquini R, Funke V, Pereira NF, Rocha V, et al. Haploidentical BMT and post-transplant Cy for severe aplastic anemia: a multicenter retrospective study. Bone Marrow Transplant. 2015;50(5):685–9.CrossRefGoogle Scholar
  70. 70.
    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 Transplant. 2013;19(5):754–9.CrossRefGoogle Scholar
  71. 71.
    Fioredda F, Iacobelli S, van Biezen A, Gaspar B, Ancliff P, Donadieu J, et al. Stem cell transplantation in severe congenital neutropenia: an analysis from the European Society for Blood and Marrow Transplantation. Blood. 2015;126(16):1885–92. quiz 970CrossRefGoogle Scholar
  72. 72.
    Fagioli F, Quarello P, Zecca M, Lanino E, Corti P, Favre C, et al. Haematopoietic stem cell transplantation for Diamond Blackfan anaemia: a report from the Italian Association of Paediatric Haematology and Oncology Registry. Br J Haematol. 2014;165(5):673–81.CrossRefGoogle Scholar
  73. 73.
    Bizzetto R, Bonfim C, Rocha V, Socie G, Locatelli F, Chan K, et al. Outcomes after related and unrelated umbilical cord blood transplantation for hereditary bone marrow failure syndromes other than Fanconi anemia. Haematologica. 2011;96(1):134–41.CrossRefGoogle Scholar
  74. 74.
    Deeg HJ, Socie G, Schoch G, Henry-Amar M, Witherspoon RP, Devergie A, et al. Malignancies after marrow transplantation for aplastic anemia and fanconi anemia: a joint Seattle and Paris analysis of results in 700 patients. Blood. 1996;87(1):386–92.PubMedGoogle Scholar
  75. 75.
    Medeiros C, Zanis-Neto J, Pasquini R. Bone marrow transplantation for patients with Fanconi anemia: reduced doses of cyclophosphamide without irradiation as conditioning. Bone Marrow Transplant. 1999;24(8):849–52.CrossRefGoogle Scholar
  76. 76.
    Shimada A, Takahashi Y, Muramatsu H, Hama A, Ismael O, Narita A, et al. Excellent outcome of allogeneic bone marrow transplantation for Fanconi anemia using fludarabine-based reduced-intensity conditioning regimen. Int J Hematol. 2012;95(6):675–9.CrossRefGoogle Scholar
  77. 77.
    Chaudhury S, Auerbach AD, Kernan NA, Small TN, Prockop SE, Scaradavou A, et al. Fludarabine-based cytoreductive regimen and T-cell-depleted grafts from alternative donors for the treatment of high-risk patients with Fanconi anaemia. Br J Haematol. 2008;140(6):644–55.CrossRefGoogle Scholar
  78. 78.
    Zecca M, Strocchio L, Pagliara D, Comoli P, Bertaina A, Giorgiani G, et al. HLA-haploidentical T cell-depleted allogeneic hematopoietic stem cell transplantation in children with Fanconi anemia. Biol Blood Marrow Transplant. 2014;20(4):571–6.CrossRefGoogle Scholar
  79. 79.
    Thakar MS, Bonfim C, Sandmaier BM, O'Donnell P, Ribeiro L, Gooley T, et al. Cyclophosphamide-based in vivo T-cell depletion for HLA-haploidentical transplantation in Fanconi anemia. Pediatr Hematol Oncol. 2012;29(6):568–78.CrossRefGoogle Scholar
  80. 80.
    Giebel S, Locatelli F, Lamparelli T, Velardi A, Davies S, Frumento G, et al. Survival advantage with KIR ligand incompatibility in hematopoietic stem cell transplantation from unrelated donors. Blood. 2003;102(3):814–9.CrossRefGoogle Scholar
  81. 81.
    Oevermann L, Michaelis SU, Mezger M, Lang P, Toporski J, Bertaina A, et al. KIR B haplotype donors confer a reduced risk for relapse after haploidentical transplantation in children with ALL. Blood. 2014;124(17):2744–7.CrossRefGoogle Scholar
  82. 82.
    Canver MC, Orkin SH. Customizing the genome as therapy for the beta-hemoglobinopathies. Blood. 2016;127(21):2536–45.CrossRefGoogle Scholar
  83. 83.
    Sabloff M, Chandy M, Wang Z, Logan BR, Ghavamzadeh A, Li CK, et al. HLA-matched sibling bone marrow transplantation for beta-thalassemia major. Blood. 2011;117(5):1745–50.CrossRefGoogle Scholar
  84. 84.
    Dallas MH, Triplett B, Shook DR, Hartford C, Srinivasan A, Laver J, et al. Long-term outcome and evaluation of organ function in pediatric patients undergoing haploidentical and matched related hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2013;19(5):820–30.CrossRefGoogle Scholar
  85. 85.
    Bernardo ME, Piras E, Vacca A, Giorgiani G, Zecca M, Bertaina A, et al. Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan. Blood. 2012;120(2):473–6.CrossRefGoogle Scholar
  86. 86.
    Jaing TH, Chen SH, Tsai MH, Yang CP, Hung IJ, Tsay PK. Transplantation of unrelated donor umbilical cord blood for nonmalignant diseases: a single institution's experience with 45 patients. Biol Blood Marrow Transplant. 2010;16(1):102–7.CrossRefGoogle Scholar
  87. 87.
    Sodani P, Isgro A, Gaziev J, Paciaroni K, Marziali M, Simone MD, et al. T cell-depleted hla-haploidentical stem cell transplantation in thalassemia young patients. Pediatr Rep. 2011;3(Suppl 2):e13.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Anurathapan U, Hongeng S, Pakakasama S, Sirachainan N, Songdej D, Chuansumrit A, et al. Hematopoietic stem cell transplantation for homozygous beta-thalassemia and beta-thalassemia/hemoglobin E patients from haploidentical donors. Bone Marrow Transplant. 2016;51(6):813–8.CrossRefGoogle Scholar
  89. 89.
    Andreani M, Testi M, Lucarelli G. Mixed chimerism in haemoglobinopathies: from risk of graft rejection to immune tolerance. Tissue Antigens. 2014;83(3):137–46.CrossRefGoogle Scholar
  90. 90.
    Bolanos-Meade J, Fuchs EJ, Luznik L, Lanzkron SM, Gamper CJ, Jones RJ, et al. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood. 2012;120(22):4285–91.CrossRefGoogle Scholar
  91. 91.
    Bastien JP, Roy J, Roy DC. Selective T-cell depletion for haplotype-mismatched allogeneic stem cell transplantation. Semin Oncol. 2012;39(6):674–82.CrossRefGoogle Scholar
  92. 92.
    Martelli MF, Di Ianni M, Ruggeri L, Falzetti F, Carotti A, Terenzi A, et al. HLA-haploidentical transplantation with regulatory and conventional T-cell adoptive immunotherapy prevents acute leukemia relapse. Blood. 2014;124(4):638–44.CrossRefGoogle Scholar
  93. 93.
    Ciceri F, Bonini C, Stanghellini MT, Bondanza A, Traversari C, Salomoni M, et al. Infusion of suicide-gene-engineered donor lymphocytes after family haploidentical haemopoietic stem-cell transplantation for leukaemia (the TK007 trial): a non-randomised phase I-II study. Lancet Oncol. 2009;10(5):489–500.CrossRefGoogle Scholar
  94. 94.
    Zhou X, Di Stasi A, Tey SK, Krance RA, Martinez C, Leung KS, et al. Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene. Blood. 2014;123(25):3895–905.CrossRefGoogle Scholar
  95. 95.
    Muller I, Kordowich S, Holzwarth C, Isensee G, Lang P, Neunhoeffer F, et al. Application of multipotent mesenchymal stromal cells in pediatric patients following allogeneic stem cell transplantation. Blood Cells Mol Dis. 2008;40(1):25–32.CrossRefGoogle Scholar
  96. 96.
    Oyekunle A, Koehl U, Schieder H, Ayuk F, Renges H, Fehse N, et al. CD34(+)-selected stem cell boost for delayed or insufficient engraftment after allogeneic stem cell transplantation. Cytotherapy. 2006;8(4):375–80.CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Christian Seitz
    • 1
  • Patrick Schlegel
    • 1
  • Rupert Handgretinger
    • 1
  1. 1.Department of Hematology/OncologyChildren’s University HospitalTübingenGermany

Personalised recommendations