No Lymphocytes in an Infant

  • Beatriz Morillo-Gutierrez
  • Mary SlatterEmail author


  • Hematopoietic stem cell transplantation (HSCT) is a curative and lifesaving treatment for many primary immunodeficiency disorders, with the best overall survival for severe combined immunodeficiency (>90%)

  • Advanced techniques for graft manipulation allow for the use of donor sources other than matched siblings, with very good outcomes

  • Current regimens with reduced intensity/toxicity conditioning allow better engraftment with lower toxicity

  • Long-term side effects of transplantation such as growth failure and infertility need to be monitored in follow up of children undergoing HSCT


Hematopoietic stem cell transplantation Severe combined immunodeficiency 


  1. 1.
    Fischer A. Severe combined immunodeficiencies (SCID). Clin Exp Immunol. 2000;122:143–9.CrossRefGoogle Scholar
  2. 2.
    Burg M, Gennery A. Educational paper. Eur J Pediatr. 2011;170:561–71.CrossRefGoogle Scholar
  3. 3.
    Pai S-Y, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC, Kapoor N, Hanson IC, Filipovich AH, Jyonouchi S, Sullivan KE, Small TN, Burroughs L, Skoda-Smith S, Haight AE, Grizzle A, Pulsipher MA, Chan KW, Fuleihan RL, Haddad E, Loechelt B, Aquino VM, Gillio A, Davis J, Knutsen A, Smith AR, Moore TB, Schroeder ML, Goldman FD, Connelly JA, Porteus MH, Xiang Q, Shearer WT, Fleisher TA, Kohn DB, Puck JM, Notarangelo LD, Cowan MJ, O’Reilly RJ. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371:434–46.CrossRefGoogle Scholar
  4. 4.
    Brown L, Xu-Bayford J, Allwood Z, Slatter M, Cant A, Davies EG, Veys P, Gennery AR, Gaspar HB. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117:3243–6.CrossRefGoogle Scholar
  5. 5.
    Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P, Amrolia PJ, Gaspar HB, Davies EG, Friedrich W, Hoenig M, Notarangelo LD, Mazzolari E, Porta F, Bredius RG, Lankester AC, Wulffraat NM, Seger R, Gungor T, Fasth A, Sedlacek P, Neven B, Blanche S, Fischer A, Cavazzana-Calvo M, Landais P. 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.e1-11.CrossRefGoogle Scholar
  6. 6.
    Slatter MA, Engelhardt KR, Burroughs LM, Arkwright PD, Nademi Z, Skoda-Smith S, Hagin D, Kennedy A, Barge D, Flood T, Abinun M, Wynn RF, Gennery AR, Cant AJ, Sansom D, Hambleton S, Torgerson TR. Hematopoietic stem cell transplantation for CTLA4 deficiency. J Allergy Clin Immunol. 2016;138(2):615–9.e1.CrossRefGoogle Scholar
  7. 7.
    Leiding JW, Okada S, Hagin D, Abinun M, Shcherbina A, Balashov DN, Kim VHD, Ovadia A, Guthery SL, Pulsipher M, Lilic D, Devlin LA, Christie S, Depner M, Fuchs S, van Royen-Kerkhof A, Lindemans C, Petrovic A, Sullivan KE, Bunin N, Kilic SS, Arpaci F, Calle-Martin O, Martinez-Martinez L, Aldave JC, Kobayashi M, Ohkawa T, Imai K, Iguchi A, Roifman CM, Gennery AR, Slatter M, Ochs HD, Morio T, Torgerson TR. Hematopoietic stem cell transplantation in patients with gain-of-function signal transducer and activator of transcription 1 mutations. J Allergy Clin Immunol. 2018;141(2):704–17.e5.CrossRefGoogle Scholar
  8. 8.
    Picard C, Bobby Gaspar H, Al-Herz W, Bousfiha A, Casanova JL, Chatila T, Crow YJ, Cunningham-Rundles C, Etzioni A, Franco JL, Holland SM, Klein C, Morio T, Ochs HD, Oksenhendler E, Puck J, Tang MLK, Tangye SG, Torgerson TR, Sullivan KE. International Union of Immunological Societies: 2017 primary immunodeficiency diseases committee report on inborn errors of immunity. J Clin Immunol. 2018;38(1):96–128.CrossRefGoogle Scholar
  9. 9.
    Slatter M, Gennery A. Advances in hematopoietic stem cell transplantation for primary immunodeficiency. Expert Rev Clin Immunol. 2013;9:991–9.CrossRefGoogle Scholar
  10. 10.
    Booth C, Silva J, Veys P. Stem cell transplantation for the treatment of immunodeficiency in children: current status and hopes for the future. Expert Rev Clin Immunol. 2016;12:713–23.CrossRefGoogle Scholar
  11. 11.
    Dvorak C, Cowan M. Hematopoietic stem cell transplantation for primary immunodeficiency disease. Bone Marrow Transplant. 2008;41:119–26.CrossRefGoogle Scholar
  12. 12.
    Larghero J, Garcia J, Gluckman E. Sources and procurement of stem cells. Haematop Stem Cell Transplant EBMT Handbook. 2008.Google Scholar
  13. 13.
    Rivers L, Gaspar H. Severe combined immunodeficiency: recent developments and guidance on clinical management. Arch Dis Child. 2015;100:667–72.CrossRefGoogle Scholar
  14. 14.
    Ferrua F, Aiuti A. Twenty-five years of gene therapy for ADA-SCID: from bubble babies to an approved drug. Hum Gene Ther. 2017;28:972–81.CrossRefGoogle Scholar
  15. 15.
    Shah RM, Elfeky R, Nademi Z, Qasim W, Amrolia P, Chiesa R, Rao K, Lucchini G, Silva JMF, Worth A, Barge D, Ryan D, Conn J, Cant AJ, Skinner R, Abd Hamid IJ, Flood T, Abinun M, Hambleton S, Gennery AR, Veys P, Slatter M. T-cell receptor alphabeta(+) and CD19(+) cell-depleted haploidentical and mismatched hematopoietic stem cell transplantation in primary immune deficiency. J Allergy Clin Immunol. 2018;141(4):1417–26.e1.CrossRefGoogle Scholar
  16. 16.
    Balashov D, Shcherbina A, Maschan M, Trakhtman P, Skvortsova Y, Shelikhova L, Laberko A, Livshits A, Novichkova G, Maschan A. 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
  17. 17.
    Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R, Pende D, Falco M, Handgretinger R, Moretta F, Lucarelli B, Brescia LP, Li Pira G, Testi M, Cancrini C, Kabbara N, Carsetti R, Finocchi A, Moretta A, Moretta L, Locatelli F. 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
  18. 18.
    Slatter MA, Gennery AR. Approaches to the removal of T-lymphocytes to minimize graft-versus-host disease in patients with primary immunodeficiencies who do not have a matched sibling donor. Curr Opin Allergy Clin Immunol. 2017;17(6):414–20.CrossRefGoogle Scholar
  19. 19.
    Gratwohl A. Principles of conditioning. ESH-EBMT Handb Haematop Stem Cell Transplant ESH. 2008.Google Scholar
  20. 20.
    Chiesa R, Veys P. Reduced-intensity conditioning for allogeneic stem cell transplant in primary immune deficiencies. Expert Rev Clin Immunol. 2012;8:255–66.CrossRefGoogle Scholar
  21. 21.
    Carreras E. Early complications after HSCT. In EBMT Handb Hematop Stem Cell Transplant. 5th ed. 2008.Google Scholar
  22. 22.
    Heimall J, Buckley R, Puck J, Fleisher T, Gennery A, Haddad E, Neven B, Slatter M, Roderick S, Baker K, Dietz A, Duncan C, Griffith L, Notarangelo L, Pulsipher M, Cowan M. Recommendations for screening and management of late effects in patients with severe combined immunodeficiency after allogenic hematopoietic cell transplantation: a consensus statement from the second pediatric blood and marrow transplant consortium international conference on late effects after pediatric HCT. Biol Blood Marrow Transplant. 2017;23:1229–40.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2020

Authors and Affiliations

  1. 1.Translational Paediatrics and Infectious Diseases UnitSantiago de Compostela University HospitalSantiago de CompostelaSpain
  2. 2.Department of Paediatric ImmunologyGreat North Children’s Hospital, Royal Victoria InfirmaryNewcastle upon TyneUK
  3. 3.Institute of Cellular MedicineNewcastle UniversityNewcastle upon TyneUK

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