Stem Cell Transplantation for Primary Immunodeficiency

  • Juliana Silva
  • Claire Booth
  • Paul VeysEmail author


Primary immunodeficiency diseases (PID) are a group of heterogeneous inherited disorders affecting the development and function of the innate and acquired immune system. The disorders are characterized by increased susceptibility to recurrent and severe infections, autoimmunity and in some cases malignancies. Allogeneic haematopoietic stem cell transplant (HSCT), and in some cases gene therapy, is the only curative approach for many of these disorders. With the expanding field of molecular genetics, new immune disorders are being identified, but the role of HSCT or other therapy in these disorders remains to be determined. This chapter will review the current indications for HSCT in PID and will examine the specific challenges associated with HSCT in (1) severe combined immunodeficiency (SCID) where the landscape is changing due the introduction of newborn screening; (2) other combined immune deficiencies, some of which have only very recently been described; and (3) phagocytic and haemophagocytic cell disorders. The role of alternative therapies including gene therapy and thymic transplantation will also be discussed.


Primary immunodeficiencies Haematopoietic stem cell transplant SCID Newborn screening Thymic transplant 



Adenosine deaminase


Activated PI3Kδ syndrome


Anti-thymocyte globulin


Chronic granulomatous disease


Cytotoxic T lymphocytes


Donor lymphocyte infusion


Dedicator of cytokinesis 8


Epstein-Barr virus


Familial haemophagocytic lymphohistiocytosis


Graft versus host disease


Human leukocyte antigen


Haemophagocytic lymphohistiocytosis


Haematopoietic stem cell transplant


Inducible human caspase 9


Leukocyte adhesion deficiency type 1


Myeloablative conditioning

MHC class II

Major histocompatibility complex class II


Minimal intensity conditioning


Mismatched family donor


Matched related donor


Matched sibling donor


Mammalian target of rapamycin


Matched unrelated donor


Newborn screening


NK+ T cells


Overall survival


Peripheral blood stem cells


Polyethylene glycol-conjugated adenosine deaminase


Phosphatidylinositol-3 kinase


Primary immunodeficiency diseases


Reduced intensity conditioning


Stem cell transplant for immunodeficiencies in Europe


Severe combined immunodeficiency


T-cell receptor


T-cell receptor excision circles


Transplant-related mortality


Umbilical cord blood stem cell transplantation


Wiskott-Aldrich syndrome


X-linked inhibitor of apoptosis


X-linked lymphoproliferative disease


  1. 1.
    Schultz RK, Baker KS, Boelens JJ, Bollard CM, Egeler RM, Cowan M, et al. Challenges and opportunities for international cooperative studies in pediatric hematopoeitic cell transplantation: priorities of the Westhafen Intercontinental Group. Biol Blood Marrow Transplant. 2013;19(9):1279–87.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Conley ME, Cunningham-Rundles C, et al. Primary immunodeficiency diseases: an update on the classification from the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2014;5:162.PubMedPubMedCentralGoogle Scholar
  3. 3.
    Hassan A, Lee P, Maggina P, Xu JH, Moreira D, Slatter M, et al. Host natural killer immunity is a key indicator of permissiveness for donor cell engraftment in patients with severe combined immunodeficiency. J Allergy Clin Immunol. 2014;133(6):1660–6.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010;126(3):602–10. e1–11CrossRefPubMedGoogle Scholar
  5. 5.
    Fernandes JF, Rocha V, Labopin M, Neven B, Moshous D, Gennery AR, et al. Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood? Blood. 2012;119(12):2949–55.CrossRefPubMedGoogle Scholar
  6. 6.
    Veys P, Danby R, Vora A, Slatter M, Wynn R, Lawson S, et al. UK experience of unrelated cord blood transplantation in paediatric patients. Br J Haematol. 2016;172(3):482–6.CrossRefPubMedGoogle Scholar
  7. 7.
    Dvorak CC, Hassan A, Slatter MA, Honig M, Lankester AC, Buckley RH, et al. Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency. J Allergy Clin Immunol. 2014;134(4):935–43. e15CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gaspar HB, Qasim W, Davies EG, Rao K, Amrolia PJ, Veys P. How I treat severe combined immunodeficiency. Blood. 2013;122(23):3749–58.CrossRefPubMedGoogle Scholar
  10. 10.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Chiesa R, Gilmour K, Qasim W, Adams S, Worth AJ, Zhan H, et al. Omission of in vivo T-cell depletion promotes rapid expansion of naive CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant. Br J Haematol. 2012;156(5):656–66.CrossRefPubMedGoogle Scholar
  12. 12.
    Locatelli F, Bauquet A, Palumbo G, Moretta F, Bertaina A. Negative depletion of alpha/beta+ T cells and of CD19+ B lymphocytes: a novel frontier to optimize the effect of innate immunity in HLA-mismatched hematopoietic stem cell transplantation. Immunol Lett. 2013;155(1–2):21–3.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Grosso D, Carabasi M, Filicko-O'Hara J, Kasner M, Wagner JL, Colombe B, et al. A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing. Blood. 2011;118(17):4732–9.CrossRefPubMedGoogle Scholar
  16. 16.
    McCurdy SR, Kanakry JA, Showel MM, Tsai HL, Bolanos-Meade J, Rosner GL, et al. Risk-stratified outcomes of nonmyeloablative HLA-haploidentical BMT with high-dose posttransplantation cyclophosphamide. Blood. 2015;125(19):3024–31.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Robinson TM, O'Donnell PV, Fuchs EJ, Luznik L. Haploidentical bone marrow and stem cell transplantation: experience with post-transplantation cyclophosphamide. Semin Hematol. 2016;53(2):90–7.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    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;36:437–40.CrossRefPubMedGoogle Scholar
  19. 19.
    Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117(11):3243–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Kobrynski L. Newborn screening for severe combined immune deficiency (technical and political aspects). Curr Opin Allergy Clin Immunol. 2015;15(6):539–46.CrossRefPubMedGoogle Scholar
  21. 21.
    Gaspar HB, Hammarstrom L, Mahlaoui N, Borte M, Borte S. The case for mandatory newborn screening for severe combined immunodeficiency (SCID). J Clin Immunol. 2014;34(4):393–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Clement MC, Mahlaoui N, Mignot C, Le Bihan C, Rabetrano H, Hoang L, et al. Systematic neonatal screening for severe combined immunodeficiency and severe T-cell lymphopenia: analysis of cost-effectiveness based on French real field data. J Allergy Clin Immunol. 2015;135(6):1589–93.CrossRefPubMedGoogle Scholar
  23. 23.
    de Felipe B, Olbrich P, Lucenas JM, Delgado-Pecellin C, Pavon-Delgado A, Marquez J, et al. Prospective neonatal screening for severe T- and B-lymphocyte deficiencies in Seville. Pediatr Allergy Immunol. 2016;27(1):70–7.CrossRefPubMedGoogle Scholar
  24. 24.
    de Pagter AP, Bredius RG, Kuijpers TW, Tramper J, van der Burg M, van Montfrans J, et al. Overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening. Eur J Pediatr. 2015;174(9):1183–8.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, Abbott JK, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014;312(7):729–38.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    van der Spek J, Groenwold RH, van der Burg M, van Montfrans JM. TREC based newborn screening for severe combined immunodeficiency disease: a systematic review. J Clin Immunol. 2015;35(4):416–30.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2005;115(2):391–8.CrossRefPubMedGoogle Scholar
  28. 28.
    Rao K, Amrolia PJ, Jones A, Cale CM, Naik P, King D, et al. Improved survival after unrelated donor bone marrow transplantation in children with primary immunodeficiency using a reduced-intensity conditioning regimen. Blood. 2005;105(2):879–85.CrossRefPubMedGoogle Scholar
  29. 29.
    Chiesa R, Veys P. Reduced-intensity conditioning for allogeneic stem cell transplant in primary immune deficiencies. Expert Rev Clin Immunol. 2012;8(3):255–66. quiz 67CrossRefPubMedGoogle Scholar
  30. 30.
    Satwani P, Cooper N, Rao K, Veys P, Amrolia P. Reduced intensity conditioning and allogeneic stem cell transplantation in childhood malignant and nonmalignant diseases. Bone Marrow Transplant. 2007;41(2):173–82.CrossRefPubMedGoogle Scholar
  31. 31.
    DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint Basile G. CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature. 1993;361(6412):541–3.CrossRefPubMedGoogle Scholar
  32. 32.
    Korthauer U, Graf D, Mages HW, Briere F, Padayachee M, Malcolm S, et al. Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM. Nature. 1993;361(6412):539–41.CrossRefPubMedGoogle Scholar
  33. 33.
    Cunningham CK, Bonville CA, Ochs HD, Seyama K, John PA, Rotbart HA, et al. Enteroviral meningoencephalitis as a complication of X-linked hyper IgM syndrome. J Pediatr. 1999;134(5):584–8.CrossRefPubMedGoogle Scholar
  34. 34.
    Gennery AR, Khawaja K, Veys P, Bredius RG, Notarangelo LD, Mazzolari E, et al. Treatment of CD40 ligand deficiency by hematopoietic stem cell transplantation: a survey of the European experience, 1993–2002. Blood. 2004;103(3):1152–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Deau MC, Heurtier L, Frange P, Suarez F, Bole-Feysot C, Nitschke P, et al. A human immunodeficiency caused by mutations in the PIK3R1 gene. J Clin Invest. 2014;124(9):3923–8.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Angulo I, Vadas O, Garcon F, Banham-Hall E, Plagnol V, Leahy TR, et al. Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. Science. 2013;342(6160):866–71.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lucas CL, Kuehn HS, Zhao F, Niemela JE, Deenick EK, Palendira U, et al. Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. Nat Immunol. 2014;15(1):88–97.CrossRefPubMedGoogle Scholar
  38. 38.
    Nademi Z, Slatter MA, Dvorak CC, Neven B, Fischer A, Suarez F, et al. Hematopoietic stem cell transplant in patients with activated PI3K delta syndrome. J Allergy Clin Immunol. 2017;139(3):1046–9.CrossRefPubMedGoogle Scholar
  39. 39.
    Small TN, Qasim W, Friedrich W, Chiesa R, Bleesing JJ, Scurlock A, et al. Alternative donor SCT for the treatment of MHC class II deficiency. Bone Marrow Transplant. 2013;48(2):226–32.CrossRefPubMedGoogle Scholar
  40. 40.
    Ouederni M, Vincent QB, Frange P, Touzot F, Scerra S, Bejaoui M, et al. Major histocompatibility complex class II expression deficiency caused by a RFXANK founder mutation: a survey of 35 patients. Blood. 2011;118(19):5108–18.CrossRefPubMedGoogle Scholar
  41. 41.
    Saleem MA, Arkwright PD, Davies EG, Cant AJ, Veys PA. Clinical course of patients with major histocompatibility complex class II deficiency. Arch Dis Child. 2000;83(4):356–9.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    J Allergy Clin Immunol. 2018 Jan 31. pii: S0091-6749(18)30083-6. doi: [Epub ahead of print]CrossRefPubMedGoogle Scholar
  43. 43.
    Aydin SE, Kilic SS, Aytekin C, Kumar A, Porras O, Kainulainen L, et al. DOCK8 deficiency: clinical and immunological phenotype and treatment options – a review of 136 patients. J Clin Immunol. 2015;35(2):189–98.CrossRefPubMedGoogle Scholar
  44. 44.
    Al-Herz W, Chu JI, van der Spek J, Raghupathy R, Massaad MJ, Keles S, et al. Hematopoietic stem cell transplantation outcomes for 11 patients with dedicator of cytokinesis 8 deficiency. J Allergy Clin Immunol. 2016;138:852–9.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Aydin S, Freeman AF, Su H, Hickstein D, Pai S-Y, Geha R, et al. HSCT for DOCK8 deficiency – an international study on 74 patients. Biol Blood Marrow Transplant. 2016;22(3, Supplement):S103–S4.CrossRefGoogle Scholar
  46. 46.
    Jin Y, Mazza C, Christie JR, Giliani S, Fiorini M, Mella P, et al. Mutations of the Wiskott-Aldrich syndrome protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation. Blood. 2004;104(13):4010–9.CrossRefPubMedGoogle Scholar
  47. 47.
    Moratto D, Giliani S, Bonfim C, Mazzolari E, Fischer A, Ochs HD, et al. Long-term outcome and lineage-specific chimerism in 194 patients with Wiskott-Aldrich syndrome treated by hematopoietic cell transplantation in the period 1980–2009: an international collaborative study. Blood. 2011;118(6):1675–84.CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Ozsahin H, Cavazzana-Calvo M, Notarangelo LD, Schulz A, Thrasher AJ, Mazzolari E, et al. Long-term outcome following hematopoietic stem-cell transplantation in Wiskott-Aldrich syndrome: collaborative study of the European Society for Immunodeficiencies and European Group for blood and marrow transplantation. Blood. 2008;111(1):439–45.CrossRefPubMedGoogle Scholar
  49. 49.
    Shin CR, Kim MO, Li D, Bleesing JJ, Harris R, Mehta P, et al. Outcomes following hematopoietic cell transplantation for Wiskott-Aldrich syndrome. Bone Marrow Transplant. 2012;47(11):1428–35.CrossRefPubMedGoogle Scholar
  50. 50.
    Slatter MA, Rao K, Amrolia P, Flood T, Abinun M, Hambleton S, et al. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood. 2011;117(16):4367–75.CrossRefPubMedGoogle Scholar
  51. 51.
    Worth AJ, Thrasher AJ. Current and emerging treatment options for Wiskott-Aldrich syndrome. Expert Rev Clin Immunol. 2015;11(9):1015–32.CrossRefPubMedGoogle Scholar
  52. 52.
    Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Diez IA, Dewey RA, et al. Stem-cell gene therapy for the Wiskott-Aldrich syndrome. N Engl J Med. 2010;363(20):1918–27.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    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.CrossRefPubMedGoogle Scholar
  54. 54.
    Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science. 2013;341(6148):1233151.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Hacein-Bey Abina S, Gaspar HB, Blondeau J, Caccavelli L, Charrier S, Buckland K, et al. Outcomes following gene therapy in patients with severe Wiskott-Aldrich syndrome. JAMA. 2015;313(15):1550–63.CrossRefPubMedGoogle Scholar
  56. 56.
    Seger RA, Gungor T, Belohradsky BH, Blanche S, Bordigoni P, Di Bartolomeo P, et al. Treatment of chronic granulomatous disease with myeloablative conditioning and an unmodified hemopoietic allograft: a survey of the European experience, 1985–2000. Blood. 2002;100(13):4344–50.CrossRefPubMedGoogle Scholar
  57. 57.
    Soncini E, Slatter MA, Jones LB, Hughes S, Hodges S, Flood TJ, et al. Unrelated donor and HLA-identical sibling haematopoietic stem cell transplantation cure chronic granulomatous disease with good long-term outcome and growth. Br J Haematol. 2009;145(1):73–83.CrossRefPubMedGoogle Scholar
  58. 58.
    Schuetz C, Hoenig M, Gatz S, Speth F, Benninghoff U, Schulz A, et al. Hematopoietic stem cell transplantation from matched unrelated donors in chronic granulomatous disease. Immunol Res. 2009;44(1–3):35–41.CrossRefPubMedGoogle Scholar
  59. 59.
    Tewari P, Martin PL, Mendizabal A, Parikh SH, Page KM, Driscoll TA, et al. Myeloablative transplantation using either cord blood or bone marrow leads to immune recovery, high long-term donor chimerism and excellent survival in chronic granulomatous disease. Biol Blood Marrow Transplant. 2012;18(9):1368–77.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Ahlin A, Fugelang J, de Boer M, Ringden O, Fasth A, Winiarski J. Chronic granulomatous disease-haematopoietic stem cell transplantation versus conventional treatment. Acta Paediatr. 2013;102(11):1087–94.PubMedGoogle Scholar
  61. 61.
    Cole T, Pearce MS, Cant AJ, Cale CM, Goldblatt D, Gennery AR. Clinical outcome in children with chronic granulomatous disease managed conservatively or with hematopoietic stem cell transplantation. J Allergy Clin Immunol. 2013;132(5):1150–5.CrossRefPubMedGoogle Scholar
  62. 62.
    Martinez CA, Shah S, Shearer WT, Rosenblatt HM, Paul ME, Chinen J, et al. Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease. J Allergy Clin Immunol. 2012;129(1):176–83.CrossRefPubMedGoogle Scholar
  63. 63.
    Gungor T, Teira P, Slatter M, Stussi G, Stepensky P, Moshous D, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet (London, England). 2014;383(9915):436–48.CrossRefGoogle Scholar
  64. 64.
    Uzel G, Orange JS, Poliak N, Marciano BE, Heller T, Holland SM. Complications of tumor necrosis factor-alpha blockade in chronic granulomatous disease-related colitis. Clin Infect Dis. 2010;51(12):1429–34.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Nikolajeva O, Mijovic A, Hess D, Tatam E, Amrolia P, Chiesa R, et al. Single-donor granulocyte transfusions for improving the outcome of high-risk pediatric patients with known bacterial and fungal infections undergoing stem cell transplantation: a 10-year single-center experience. Bone Marrow Transplant. 2015;50(6):846–9.CrossRefPubMedGoogle Scholar
  66. 66.
    Parta M, Hilligoss D, Kelly C, Kwatemaa N, Theobald N, Malech H, et al. Haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in a patient with chronic granulomatous disease and active infection: a first report. J Clin Immunol. 2015;35(7):675–80.CrossRefPubMedGoogle Scholar
  67. 67.
    Qasim W, Cavazzana-Calvo M, Davies EG, Davis J, Duval M, Eames G, et al. Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency. Pediatrics. 2009;123(3):836–40.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Hamidieh AA, Pourpak Z, Hosseinzadeh M, Fazlollahi MR, Alimoghaddam K, Movahedi M, et al. Reduced-intensity conditioning hematopoietic SCT for pediatric patients with LAD-1: clinical efficacy and importance of chimerism. Bone Marrow Transplant. 2012;47(5):646–50.CrossRefPubMedGoogle Scholar
  69. 69.
    Bauer TR Jr, Hickstein DD. Gene therapy for leukocyte adhesion deficiency. Curr Opin Mol Ther. 2000;2(4):383–8.PubMedGoogle Scholar
  70. 70.
    Hunter MJ, Tuschong LM, Fowler CJ, Bauer TR Jr, Burkholder TH, Hickstein DD. Gene therapy of canine leukocyte adhesion deficiency using lentiviral vectors with human CD11b and CD18 promoters driving canine CD18 expression. Mol Ther. 2011;19(1):113–21.CrossRefPubMedGoogle Scholar
  71. 71.
    Nelson EJ, Tuschong LM, Hunter MJ, Bauer TR Jr, Burkholder TH, Hickstein DD. Lentiviral vectors incorporating a human elongation factor 1alpha promoter for the treatment of canine leukocyte adhesion deficiency. Gene Ther. 2010;17(5):672–7.CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Leon-Rico D, Aldea M, Sanchez-Baltasar R, Mesa-Nunez C, Record J, Burns SO, et al. Lentiviral vector-mediated correction of a mouse model of leukocyte adhesion deficiency type I. Hum Gene Ther. 2016;27:668–78.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Bauer TR Jr, Allen JM, Hai M, Tuschong LM, Khan IF, Olson EM, et al. Successful treatment of canine leukocyte adhesion deficiency by foamy virus vectors. Nat Med. 2008;14(1):93–7.CrossRefPubMedGoogle Scholar
  74. 74.
    Hsu AP, McReynolds LJ, Holland SM. GATA2 deficiency. Curr Opin Allergy Clin Immunol. 2015;15(1):104–9.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Grossman J, Cuellar-Rodriguez J, Gea-Banacloche J, Zerbe C, Calvo K, Hughes T, et al. Nonmyeloablative allogeneic hematopoietic stem cell transplantation for GATA2 deficiency. Biol Blood Marrow Transplant. 2014;20(12):1940–8.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Henter JI, Horne A, Arico M, Egeler RM, Filipovich AH, Imashuku S, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–31.CrossRefPubMedGoogle Scholar
  77. 77.
    Chellapandian D, Das R, Zelley K, Wiener SJ, Zhao H, Teachey DT, et al. Treatment of Epstein Barr virus-induced haemophagocytic lymphohistiocytosis with rituximab-containing chemo-immunotherapeutic regimens. Br J Haematol. 2013;162(3):376–82.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Cooper N, Rao K, Gilmour K, Hadad L, Adams S, Cale C, et al. Stem cell transplantation with reduced-intensity conditioning for hemophagocytic lymphohistiocytosis. Blood. 2006;107(3):1233–6.CrossRefPubMedGoogle Scholar
  79. 79.
    Marsh RA, Vaughn G, Kim MO, Li D, Jodele S, Joshi S, et al. Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood. 2010;116(26):5824–31.CrossRefPubMedGoogle Scholar
  80. 80.
    Nishi M, Nishimura R, Suzuki N, Sawada A, Okamura T, Fujita N, et al. Reduced-intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis. Am J Hematol. 2012;87(6):637–9.CrossRefPubMedGoogle Scholar
  81. 81.
    Marsh RA, Rao K, Satwani P, Lehmberg K, Muller I, Li D, et al. Allogeneic hematopoietic cell transplantation for XIAP deficiency: an international survey reveals poor outcomes. Blood. 2013;121(6):877–83.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Worth AJ, Nikolajeva O, Chiesa R, Rao K, Veys P, Amrolia PJ. Successful stem cell transplant with antibody-based conditioning for XIAP deficiency with refractory hemophagocytic lymphohistiocytosis. Blood. 2013;121(24):4966–8.CrossRefPubMedGoogle Scholar
  83. 83.
    Janda A, Sedlacek P, Honig M, Friedrich W, Champagne M, Matsumoto T, et al. Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly. Blood. 2010;116(13):2229–36.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Markert ML, Devlin BH, McCarthy EA. Thymus transplantation. Clin Immunol. 2010;135(2):236–46.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Bone Marrow TransplantationGreat Ormond Street HospitalLondonUK
  2. 2.Department of Paediatric ImmunologyGreat Ormond Street HospitalLondonUK

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