Stem cell transplantation for the treatment of immunodeficiency in children: current status and hopes for the future

References

• Braun CJ, Boztug K, Paruzynski A, et al. Gene therapy for Wiskott–Aldrich syndrome–long-term efficacy and genotoxicity. Sci Transl Med. 2014;6:227ra233.
   Web of Science ®Google Scholar
• Schultz RK, Baker KS, Boelens JJ, 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;19:1279–1287.
   PubMed Web of Science ®Google Scholar
• Gennery AR, Slatter MA, Grandin L, 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;126:602–610 e601–611.
   PubMed Web of Science ®Google Scholar
• Fernandes JF, Rocha V, Labopin M, et al. Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood? Blood. 2012;119:2949–2955.
   PubMed Web of Science ®Google Scholar
• Veys P, Danby R, Vora A, et al. UK experience of unrelated cord blood transplantation in paediatric patients. Br J Haematol 2016;172:482–486.
   Google Scholar
• Pai S-Y, Logan BR, Griffith LM, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371:434–446.
   PubMed Web of Science ®Google Scholar
• Cowan MJ, Gennery AR. Radiation-sensitive severe combined immunodeficiency: the arguments for and against conditioning before hematopoietic cell transplantation-what to do? J Allergy Clin Immunol. 2015;136:1178–1185.
   PubMed Web of Science ®Google Scholar
• Hassan A, Lee P, Maggina P, 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;133:1660–1666.
   PubMed Web of Science ®Google Scholar
• Dvorak CC, Hassan A, Slatter MA, 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;134:935–943.e15.
   PubMed Web of Science ®Google Scholar
• Brown L, Xu-Bayford J, Allwood Z, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117:3243–3246.
   PubMed Web of Science ®Google Scholar
• Baker MW, Grossman WJ, Laessig RH, et al. Development of a routine newborn screening protocol for severe combined immunodeficiency. J Allergy Clin Immunol. 2009;124:522–527.
   PubMed Web of Science ®Google Scholar
• Verbsky JW, Baker MW, Grossman WJ, et al. Newborn screening for severe combined immunodeficiency; the Wisconsin experience (2008–2011). J Clin Immunol. 2012;32:82–88.
   PubMed Web of Science ®Google Scholar
• Van Der Spek J, Groenwold RH, Van Der Burg M, et al. TREC based newborn screening for severe combined immunodeficiency disease: a systematic review. J Clin Immunol. 2015;35:416–430.
   PubMed Web of Science ®Google Scholar
• Kobrynski L. Newborn screening for severe combined immune deficiency (technical and political aspects). Curr Opin Allergy Clin Immunol. 2015;15:539–546.
   PubMed Web of Science ®Google Scholar
• Gaspar HB, Hammarström L, Mahlaoui N, et al. The case for mandatory newborn screening for severe combined immunodeficiency (SCID). J Clin Immunol. 2014;34:393–397.
   PubMed Web of Science ®Google Scholar
• Clement MC, Mahlaoui N, Mignot C, 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;135:1589–1593.
   PubMed Web of Science ®Google Scholar
• De Felipe B, Olbrich P, Lucenas JM, et al. Prospective neonatal screening for severe T- and B-lymphocyte deficiencies in Seville. Pediatr Allergy Immunol. 2016;27:70–77.
   PubMed Web of Science ®Google Scholar
• de Pagter AP, Bredius RG, Kuijpers TW, et al. Dutch working party for I: overview of 15-year severe combined immunodeficiency in the Netherlands: towards newborn blood spot screening. Eur J Pediatr. 2015;174:1183–1188.
   PubMed Web of Science ®Google Scholar
• Kwan A, Abraham RS, Currier R, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. Jama. 2014;312:729–738.
   PubMed Web of Science ®Google Scholar
• Chiesa R, Veys P. Reduced-intensity conditioning for allogeneic stem cell transplant in primary immune deficiencies. Expert Rev Clin Immunol. 2012;8:255–266. Quiz 267
   PubMed Web of Science ®Google Scholar
• Satwani P, Cooper N, Rao K, et al. Reduced intensity conditioning and allogeneic stem cell transplantation in childhood malignant and nonmalignant diseases. Bone Marrow Transplant. 2008;41:173–182.
   PubMed Web of Science ®Google Scholar
• Winkelstein JA, Marino MC, Johnston RB Jr., et al. Chronic granulomatous disease. Report on a national registry of 368 patients. Medicine (Baltimore). 2000;79:155–169.
   PubMed Web of Science ®Google Scholar
• Seger RA:. Advances in the diagnosis and treatment of chronic granulomatous disease. Curr Opin Hematol. 2011;18:36–41.
   PubMed Web of Science ®Google Scholar
• Horwitz ME, Barrett AJ, Brown MR, et al. Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft. N Engl J Med. 2001;344:881–888.
   PubMed Web of Science ®Google Scholar
• Gungor T, Teira P, Slatter M, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383:436–448.
   PubMed Web of Science ®Google Scholar
• Ochs HD, Filipovich AH, Veys P, et al. Wiskott–Aldrich syndrome: diagnosis, clinical and laboratory manifestations, and treatment. Biol Blood Marrow Transplant. 2009;15:84–90.
   PubMed Web of Science ®Google Scholar
• Bosticardo M, Marangoni F, Aiuti A, et al. Recent advances in understanding the pathophysiology of Wiskott–Aldrich syndrome. Blood. 2009;113:6288–6295.
   PubMed Web of Science ®Google Scholar
• Worth AJ, Thrasher AJ. Current and emerging treatment options for Wiskott–Aldrich syndrome. Expert Rev Clin Immunol. 2015;11:1015–1032.
   PubMed Web of Science ®Google Scholar
• Moratto D, Giliani S, Bonfim C, 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;118:1675–1684.
   PubMed Web of Science ®Google Scholar
• Slatter MA, Rao K, Amrolia P, et al. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood. 2011;117:4367–4375.
   PubMed Web of Science ®Google Scholar
• Marsh RA, Vaughn G, Kim M-O, et al. Reduced-intensity conditioning significantly improves survival of patients with hemophagocytic lymphohistiocytosis undergoing allogeneic hematopoietic cell transplantation. Blood. 2010;116:5824–5831.
   PubMed Web of Science ®Google Scholar
• Marsh RA, Rao K, Satwani P, et al. Allogeneic hematopoietic cell transplantation for XIAP deficiency: an international survey reveals poor outcomes. Blood. 2013;121:877–883.
   PubMed Web of Science ®Google Scholar
• Chinen J, Notarangelo LD, Shearer WT. Advances in basic and clinical immunology in 2014. J Allergy Clin Immunol. 2015;135:1132–1141.
   PubMed Web of Science ®Google Scholar
• Aydin SE, Kilic SS, Aytekin C, et al. DOCK8 deficiency: clinical and immunological phenotype and treatment options - a review of 136 patients. J Clin Immunol. 2015;35:189–198.
   PubMed Web of Science ®Google Scholar
• Locatelli F, Vinti L, Palumbo G, et al. Strategies to optimize the outcome of children given T-cell depleted HLA-haploidentical hematopoietic stem cell transplantation. Best Pract Res Clin Haematol. 2011;24:339–349.
   PubMed Web of Science ®Google Scholar
• Amrolia PJ, Muccioli-Casadei G, Huls H, et al. Adoptive immunotherapy with allodepleted donor T-cells improves immune reconstitution after haploidentical stem cell transplantation. Blood. 2006;108:1797–1808.
   PubMed Web of Science ®Google Scholar
• Chaleff S, Otto M, Barfield RC, et al. A large-scale method for the selective depletion of alphabeta T lymphocytes from PBSC for allogeneic transplantation. Cytotherapy. 2007;9:746–754.
   PubMed Web of Science ®Google Scholar
• Airoldi I, Bertaina A, Prigione I, et al. γδ T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-αβ+/CD19+ lymphocytes. Blood. 2015;125:2349–2358.
   PubMed Web of Science ®Google Scholar
• Daniele N, Scerpa MC, Caniglia M, et al. Transplantation in the onco-hematology field: focus on the manipulation of αβ and γδ T cells. Pathol Res Pract. 2012;208:67–73.
   PubMed Web of Science ®Google Scholar
• Locatelli F, Bauquet A, Palumbo G, et al. Negative depletion of α/β+ 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;155:21–23.
   PubMed Web of Science ®Google Scholar
• Bertaina A, Merli P, Rutella S, et al. HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders. Blood. 2014;124:822–826.
   PubMed Web of Science ®Google Scholar
• Chiesa R, Gilmour K, Qasim W, et al. Omission of in vivo T-cell depletion promotes rapid expansion of naïve CD4+ cord blood lymphocytes and restores adaptive immunity within 2 months after unrelated cord blood transplant. Br J Haematol. 2012;156:656–666.
   PubMed Web of Science ®Google Scholar
• Lindemans CA, Chiesa R, Amrolia PJ, et al. Impact of thymoglobulin prior to pediatric unrelated umbilical cord blood transplantation on immune reconstitution and clinical outcome. Blood. 2014;123:126–132.
   PubMed Web of Science ®Google Scholar
• Admiraal R, Van Kesteren C, Jol-Van Der Zijde CM, et al. Association between anti-thymocyte globulin exposure and CD4+ immune reconstitution in paediatric haemopoietic cell transplantation: a multicentre, retrospective pharmacodynamic cohort analysis. Lancet Haematol. 2015;2:e194–203.
   PubMed Web of Science ®Google Scholar
• Jagasia M, Arora M, Flowers ME, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012;119:296–307.
   PubMed Web of Science ®Google Scholar
• Arora M, Klein JP, Weisdorf DJ, et al. Chronic GVHD risk score: a Center for International Blood and Marrow Transplant Research analysis. Blood. 2011;117:6714–6720.
   PubMed Web of Science ®Google Scholar
• Ruutu T, Gratwohl A, De Witte T, et al. Prophylaxis and treatment of GVHD: EBMT-ELN working group recommendations for a standardized practice. Bone Marrow Transplant. 2014;49:168–173.
   PubMed Web of Science ®Google Scholar
• Ram R, Gafter-Gvili A, Yeshurun M, et al. Prophylaxis regimens for GVHD: systematic review and meta-analysis. Bone Marrow Transplant. 2009;43:643–653.
   PubMed Web of Science ®Google Scholar
• Luznik L, O’Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–650.
   PubMed Web of Science ®Google Scholar
• Kanakry CG, Tsai H-L, Bolanos-Meade J, et al. Single-agent GVHD prophylaxis with posttransplantation cyclophosphamide after myeloablative, HLA-matched BMT for AML, ALL, and MDS. Blood. 2014;124:3817–3827.
   PubMed Web of Science ®Google Scholar
• Zhou X, Di Stasi A, Tey S-K, et al. Long-term outcome after haploidentical stem cell transplant and infusion of T cells expressing the inducible caspase 9 safety transgene. Blood. 2014;123:3895–3905.
   PubMed Web of Science ®Google Scholar
• Leen AM, Myers GD, Sili U, et al. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med. 2006;12:1160–1166.
   PubMed Web of Science ®Google Scholar
• Peggs KS, Thomson K, Samuel E, et al. Directly selected cytomegalovirus-reactive donor T cells confer rapid and safe systemic reconstitution of virus-specific immunity following stem cell transplantation. Clin Infect Dis. 2011;52:49–57.
   PubMed Web of Science ®Google Scholar
• Gerdemann U, Keirnan JM, Katari UL, et al. Rapidly generated multivirus-specific cytotoxic T lymphocytes for the prophylaxis and treatment of viral infections. Mol Ther. 2012;20:1622–1632.
   PubMed Web of Science ®Google Scholar
• Saglio F, Hanley PJ, Bollard CM. The time is now: moving toward virus-specific T cells after allogeneic hematopoietic stem cell transplantation as the standard of care. Cytotherapy. 2014;16:149–159.
   PubMed Web of Science ®Google Scholar
• Hanley PJ, Lam S, Shpall EJ, et al. Expanding cytotoxic T lymphocytes from umbilical cord blood that target cytomegalovirus, Epstein-Barr virus, and adenovirus. J Vis Exp. 2012;e3627.
   PubMed Web of Science ®Google Scholar
• Hanley PJ, Martinez C, Leung KM, et al. Improving immune reconstitution after cord blood transplantation using ex vivo expanded virus-specific T cells: a Phase I clinical study. ASH Annu Meet Abstr. 2012;21:224.
   Google Scholar
• Leen AM, Bollard CM, Mendizabal AM, et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013;121:5113–5123.
   PubMed Web of Science ®Google Scholar
• Howe SJ, Mansour MR, Schwarzwaelder K, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest. 2008;118:3143–3150.
   PubMed Web of Science ®Google Scholar
• Hacein-Bey-Abina S, Garrigue A, Wang GP, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest. 2008;118:3132–3142.
   PubMed Web of Science ®Google Scholar
• Kang EM, Choi U, Theobald N, et al. Retrovirus gene therapy for X-linked chronic granulomatous disease can achieve stable long-term correction of oxidase activity in peripheral blood neutrophils. Blood. 2010;115:783–791.
   PubMed Web of Science ®Google Scholar
• Ott MG, Schmidt M, Schwarzwaelder K, et al. Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1. Nat Med. 2006;12:401–409.
   PubMed Web of Science ®Google Scholar
• Stein S, Ott MG, Schultze-Strasser S, et al. Genomic instability and myelodysplasia with monosomy 7 consequent to EVI1 activation after gene therapy for chronic granulomatous disease. Nat Med. 2010;16:198–204.
   PubMed Web of Science ®Google Scholar
• Boztug K, Schmidt M, Schwarzer A, et al. Stem-cell gene therapy for the Wiskott–Aldrich syndrome. N Engl J Med. 2010;363:1918–1927.
   PubMed Web of Science ®Google Scholar
• Hacein-Bey-Abina S, Hauer J, Lim A, et al. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2010;363:355–364.
   PubMed Web of Science ®Google Scholar
• Gaspar HB, Cooray S, Gilmour KC, et al. Long-term persistence of a polyclonal T cell repertoire after gene therapy for X-linked severe combined immunodeficiency. Sci Transl Med. 2011;3:97ra79.
   PubMed Web of Science ®Google Scholar
• Touzot F, Moshous D, Creidy R, et al. Faster T-cell development following gene therapy compared with haploidentical HSCT in the treatment of SCID-X1. Blood. 2015;125:3563–3569.
   PubMed Web of Science ®Google Scholar
• Hacein-Bey-Abina S, Pai S-Y, Gaspar HB, et al. A modified γ-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med. 2014;371:1407–1417.
   PubMed Web of Science ®Google Scholar
• Booth C, Gaspar HB, Thrasher AJ. Gene therapy for primary immunodeficiency. Curr Opin Pediatr. 2011;23:659–666.
   PubMed Web of Science ®Google Scholar
• Aiuti A, Cattaneo F, Galimberti S, et al. Gene therapy for immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009;360:447–458.
   PubMed Web of Science ®Google Scholar
• Gaspar HB, Cooray S, Gilmour KC, et al. Hematopoietic stem cell gene therapy for adenosine deaminase-deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction. Sci Transl Med. 2011;3:97ra80.
   PubMed Web of Science ®Google Scholar
• Gaspar HBB,K, Carbonaro DA, Shaw K, et al. Immunological and metabolic correction after lentiviral vector gene therapy for ADA deficiency. Mol Therapy. 2015;23:S102–S103.
   Web of Science ®Google Scholar
• Gaspar HB, Qasim W, Davies EG, et al. How I treat severe combined immunodeficiency. Blood. 2013;122:3749–3758.
   PubMed Web of Science ®Google Scholar
• Aiuti A, Biasco L, Scaramuzza S, et al. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott–Aldrich syndrome. Science. 2013;341:1233151.
   PubMed Web of Science ®Google Scholar
• Van Til NP, Sarwari R, Visser TP, et al. Recombination-activating gene 1 (Rag1)-deficient mice with severe combined immunodeficiency treated with lentiviral gene therapy demonstrate autoimmune Omenn-like syndrome. J Allergy Clin Immunol. 2014;133:1116–1123.
   PubMed Web of Science ®Google Scholar
• Van Til NP, De Boer H, Mashamba N, et al. Correction of murine Rag2 severe combined immunodeficiency by lentiviral gene therapy using a codon-optimized RAG2 therapeutic transgene. Mol Ther. 2012;20:1968–1980.
   PubMed Web of Science ®Google Scholar
• Benjelloun F, Garrigue A, Demerens-de Chappedelaine C, et al. Stable and functional lymphoid reconstitution in artemis-deficient mice following lentiviral artemis gene transfer into hematopoietic stem cells. Mol Ther. 2008;16:1490–1499.
   PubMed Web of Science ®Google Scholar
• Passerini L, Rossi Mel E, Sartirana C, et al. CD4+ T cells from IPEX patients convert into functional and stable regulatory T cells by FOXP3 gene transfer. Sci Transl Med. 2013;5:215ra174.
   PubMed Web of Science ®Google Scholar
• Rivat C, Booth C, Alonso-Ferrero M, et al. SAP gene transfer restores cellular and humoral immune function in a murine model of X-linked lymphoproliferative disease. Blood. 2013;121:1073–1076.
   PubMed Web of Science ®Google Scholar
• Carmo M, Risma KA, Arumugam P, et al. Perforin gene transfer into hematopoietic stem cells improves immune dysregulation in murine models of perforin deficiency. Mol Ther. 2015;23:737–745.
   PubMed Web of Science ®Google Scholar
• Ott De Bruin LM, Volpi S, Musunuru K. Novel genome-editing tools to model and correct primary immunodeficiencies. Front Immunol. 2015;6:250.
   PubMed Web of Science ®Google Scholar
• Genovese P, Schiroli G, Escobar G, et al. Targeted genome editing in human repopulating haematopoietic stem cells. Nature. 2014;510:235–240.
   PubMed Web of Science ®Google Scholar
• Ryan AK, Goodship JA, Wilson DI, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet. 1997;34:798–804.
   PubMed Web of Science ®Google Scholar
• Janda A, Sedlacek P, Honig M, et al. Multicenter survey on the outcome of transplantation of hematopoietic cells in patients with the complete form of DiGeorge anomaly. Blood. 2010;116:2229–2236.
   PubMed Web of Science ®Google Scholar
• Ip W, Zhan H, Gilmour KC, et al. 22q11.2 deletion syndrome with life-threatening adenovirus infection. J Pediatr. 2013;163:908–910.
   PubMed Web of Science ®Google Scholar
• Davies EG. Immunodeficiency in DiGeorge syndrome and options for treating cases with complete athymia. Front Immunol. 2013;4:322.
   PubMed Web of Science ®Google Scholar
• Markert ML, Devlin BH, McCarthy EA. Thymus transplantation. Clin Immunol. 2010;135:236–246.
   PubMed Web of Science ®Google Scholar
• Markert ML, Marques JG, Neven B, et al. First use of thymus transplantation therapy for FOXN1 deficiency (nude/SCID): a report of 2 cases. Blood. 2011;117:688–696.
   PubMed Web of Science ®Google Scholar