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Haploidentical Transplants for Nonmalignant Diseases in Children

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Haploidentical Transplantation

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Abstract

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.

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References

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  14. Handgretinger R. New approaches to graft engineering for haploidentical bone marrow transplantation. Semin Oncol. 2012;39(6):664–73.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  43. Bollard CM, Heslop HE. T cells for viral infections after allogeneic hematopoietic stem cell transplant. Blood. 2016;127:3331–40.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  48. Fischer A, Hacein-Bey Abina S, Touzot F, Cavazzana M. Gene therapy for primary immunodeficiencies. Clin Genet. 2015;88(6):507–15.

    Article  CAS  Google Scholar 

  49. Ginocchio VM, Brunetti-Pierri N. Progress toward improved therapies for inborn errors of metabolism. Hum Mol Genet. 2016;25(R1):R27–35.

    Article  CAS  Google Scholar 

  50. Parenti G, Andria G, Ballabio A. Lysosomal storage diseases: from pathophysiology to therapy. Annu Rev Med. 2015;66:471–86.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  61. Alter BP. Diagnosis, genetics, and management of inherited bone marrow failure syndromes. Hematology Am Soc Hematol Educ Program. 2007:29–39.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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 970

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  82. Canver MC, Orkin SH. Customizing the genome as therapy for the beta-hemoglobinopathies. Blood. 2016;127(21):2536–45.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Hematology/Oncology, Children’s University Hospital, Tübingen, Germany

    Christian Seitz, Patrick Schlegel & Rupert Handgretinger

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  1. Christian Seitz
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  2. Patrick Schlegel
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  3. Rupert Handgretinger
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Correspondence to Rupert Handgretinger .

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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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Seitz, C., Schlegel, P., Handgretinger, R. (2018). Haploidentical Transplants for Nonmalignant Diseases in Children. 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_12

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  • DOI: https://doi.org/10.1007/978-3-319-54310-9_12

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