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Clinical Reviews in Allergy & Immunology

30-04-2024 | Stem Cell Transplantation | Review

Survival After Hematopoietic Stem Cell Transplantation in Severe Combined Immunodeficiency (SCID): A Worldwide Review of the Prognostic Variables

Authors: Gabriela Assunção Goebel, Cíntia Silva de Assis, Luciana Araújo Oliveira Cunha, Fernanda Gontijo Minafra, Jorge Andrade Pinto

Published in: Clinical Reviews in Allergy & Immunology

Abstract

This study aims to perform an extensive review of the literature that evaluates various factors that affect the survival rates of patients with severe combined immunodeficiency (SCID) after hematopoietic stem cell transplantation (HSCT) in developed and developing countries. An extensive search of the literature was made in four different databases (PubMed, Embase, Scopus, and Web of Science). The search was carried out in December 2022 and updated in July 2023, and the terms such as “hematopoietic stem cell transplantation,” “bone marrow transplant,” “mortality,” “opportunistic infections,” and “survival” associated with “severe combined immunodeficiency” were sought based on the MeSH terms. The language of the articles was “English,” and only articles published from 2000 onwards were selected. Twenty-three articles fulfilled the inclusion criteria for review and data extraction. The data collected corroborates that early HSCT, but above all, HSCT in patients without active infections, is related to better overall survival. The universal implementation of newborn screening for SCID will be a fundamental pillar for enabling most transplants to be carried out in this “ideal scenario” at an early age and free from infection. HSCT with an HLA-identical sibling donor is also associated with better survival rates, but this is the least common scenario. For this reason, transplantation with matched unrelated donors (MUD) and mismatched related donors (mMRD/Haploidentical) appear as alternatives. The results obtained with MUD are improving and show survival rates similar to those of MSD, as well as they do not require manipulation of the graft with expensive technologies. However, they still have high rates of complications after HSCT. Transplants with mMRD/Haplo are performed just in a few large centers because of the high costs of the technology to perform CD3/CD19 depletion and TCRαβ/CD19 depletion or CD34 + selection techniques in vitro. The new possibility of in vivo T cell depletion using post-transplant cyclophosphamide could also be a viable alternative for performing mMRD transplants in centers that do not have this technology, especially in developing countries.

Tangye SG, Al-Herz W, Bousfiha A, Cunningham-Rundles C, Franco JL, Holland SM et al (2022) Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol 42(7):1473–1507. https://doi.org/10.1007/s10875-022-01289-3. Epub: 20220624; PubMed PMID: 35748970; PubMed Central PMCID: PMC9244088CrossRefPubMedPubMedCentral

Dvorak CC, Haddad E, Heimall J, Dunn E, Buckley RH, Kohn DB et al (2023) The diagnosis of severe combined immunodeficiency (SCID): The Primary Immune Deficiency Treatment Consortium (PIDTC) 2022 definitions. J Allergy Clin Immunol 151(2):539–46. https://doi.org/10.1016/j.jaci.2022.10.022. Epub: 20221128; PubMed PMID: 36456361; PubMed Central PMCID: PMC9905311CrossRefPubMed

Dvorak CC, Cowan MJ, Logan BR, Notarangelo LD, Griffith LM, Puck JM et al (2013) The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. J Clin Immunol 33(7):1156–1164. https://doi.org/10.1007/s10875-013-9917-yCrossRefPubMedPubMedCentral

Gatti RA, Meuwissen HJ, Allen HD, Hong R, Good RA (1968) Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet 2(7583):1366–1369. https://doi.org/10.1016/s0140-6736(68)92673-1. PubMed PMID: 4177932CrossRefPubMed

Gaspar HB, Aiuti A, Porta F, Candotti F, Hershfield MS, Notarangelo LD (2009) How I treat ADA deficiency. Blood 114(17):3524–3532. https://doi.org/10.1182/blood-2009-06-189209. Epub: 20090728; PubMed PMID: 19638621; PubMed Central PMCID: PMC2766674CrossRefPubMedPubMedCentral

Fischer A, Hacein-Bey-Abina S, Cavazzana-Calvo M (2011) Gene therapy for primary adaptive immune deficiencies. J Allergy Clin Immunol 127(6):1356–1359. https://doi.org/10.1016/j.jaci.2011.04.030. PubMed PMID: 21624615CrossRefPubMed

Hacein-Bey-Abina S, Pai SY, Gaspar HB, Armant M, Berry CC, Blanche S et al (2014) A modified γ-retrovirus vector for X-linked severe combined immunodeficiency. N Engl J Med 371(15):1407–1417. https://doi.org/10.1056/NEJMoa1404588.PubMed PMID: 25295500; PubMed Central PMCID: PMC4274995CrossRefPubMedPubMedCentral

Kohn DB (2015) Gene therapy outpaces haplo for SCID-X1. Blood 125(23):3521–3522. https://doi.org/10.1182/blood-2015-04-641720. PubMed PMID: 26045591CrossRefPubMed

Lankester AC, Albert MH, Booth C, Gennery AR, Güngör T, Hönig M et al (2021) EBMT/ESID inborn errors working party guidelines for hematopoietic stem cell transplantation for inborn errors of immunity. Bone Marrow Transplant 56(9):2052–2062. https://doi.org/10.1038/s41409-021-01378-8. Epub: 20210705; PubMed PMID: 34226669; PubMed Central PMCID: PMC8410590CrossRefPubMedPubMedCentral

10.

Roifman CM, Grunebaum E, Dalal I, Notarangelo L (2007) Matched unrelated bone marrow transplant for severe combined immunodeficiency. Immunol Res 38(1–3):191–200. https://doi.org/10.1007/s12026-007-0042-y. PubMed PMID: 17917025CrossRefPubMed

11.

Dvorak CC, Hassan A, Slatter MA, Hönig M, Lankester AC, Buckley RH et al (2014) Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency. Journal of Allergy and Clinical Immunology 134(4):935–43.e15. https://doi.org/10.1016/j.jaci.2014.06.021CrossRefPubMed

12.

Heimall J, Logan BR, Cowan MJ, Notarangelo LD, Griffith LM, Puck JM et al (2017) Immune reconstitution and survival of 100 SCID patients post-hematopoietic cell transplant: A PIDTC natural history study. Blood 130(25):2718–2727. https://doi.org/10.1182/blood-2017-05-781849CrossRefPubMedPubMedCentral

13.

Haddad E, Logan BR, Griffith LM, Buckley RH, Parrott RE, Prockop SE et al (2018) SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery. Blood 132(17):1737–1749. https://doi.org/10.1182/blood-2018-03-840702CrossRefPubMedPubMedCentral

14.

Bayram O, Haskologlu S, Bayrakoğlu D, Bal SK, Islamoglu C, Cipe FE et al (2021) Single-center study of 72 patients with severe combined immunodeficiency: clinical and laboratory features and outcomes. J Clin Immunol 41(7):1563–1573. https://doi.org/10.1007/s10875-021-01062-yCrossRefPubMed

15.

Lankester AC, Neven B, Mahlaoui N, von Asmuth ECJ, Courteille V, Alligon M (2022) Hematopoietic cell transplantation in severe combined immunodeficiency: The SCETIDE 2006–2014 European cohort. J Allergy Clin Immunol 149(5):1744–1754.e8. https://doi.org/10.1016/j.jaci.2021.10.017. Epub: 20211027; PubMed PMID: 34718043CrossRefPubMed

16.

Thakar MS, Logan BR, Puck JM, Dunn EA, Buckley RH, Cowan MJ et al (2023) Measuring the effect of newborn screening on survival after haematopoietic cell transplantation for severe combined immunodeficiency: a 36-year longitudinal study from the Primary Immune Deficiency Treatment Consortium. Lancet 402(10396):129–140. https://doi.org/10.1016/S0140-6736(23)00731-6. Epub: 20230620; PubMed PMID: 37352885; PubMed Central PMCID: PMC10386791CrossRefPubMed

17.

Ikinciogullari A, Cagdas D, Dogu F, Tugrul T, Karasu G, Haskologlu S et al (2019) Clinical features and HSCT outcome for SCID in Turkey. J Clin Immunol. https://doi.org/10.1007/s10875-019-00610-xCrossRefPubMed

18.

Myers LA, Patel DD, Puck JM, Buckley RH (2002) Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood 99(3):872–878. https://doi.org/10.1182/blood.V99.3.872CrossRefPubMed

19.

Miyamoto S, Umeda K, Kurata M, Nishimura A, Yanagimachi M, Ishimura M et al (2021) Hematopoietic cell transplantation for severe combined immunodeficiency patients: a Japanese retrospective study. J Clin Immunol 41(8):1865–1877. https://doi.org/10.1007/s10875-021-01112-5CrossRefPubMedPubMedCentral

20.

Hassan A, Lee P, Maggina P, Xu JH, Moreira D, Slatter M (2014) Host natural killer immunity is a key indicator of permissiveness for donor cell engraftment in patients with severe combined immunodeficiency. J Allergy Clin Immunol 133(6):1660–1666. https://doi.org/10.1016/j.jaci.2014.02.042. Epub: 20140501; PubMed PMID: 24794685; PubMed Central PMCID: PMC4048544CrossRefPubMedPubMedCentral

21.

Railey MD, Lokhnygina Y, Buckley RH (2009) Long-term clinical outcome of patients with severe combined immunodeficiency who received related donor bone marrow transplants without pretransplant chemotherapy or post-transplant GVHD prophylaxis. J Pediatr 155(6):834-840.e1. https://doi.org/10.1016/j.jpeds.2009.07.049. Epub: 20091009; PubMed PMID: 19818451; PubMed Central PMCID: PMC2784223CrossRefPubMedPubMedCentral

22.

Antoine C, Müller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J et al (2003) Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968–99. Lancet 361(9357):553–560. https://doi.org/10.1016/s0140-6736(03)12513-5. PubMed PMID: 12598139CrossRefPubMed

23.

Fernandes JF, Rocha V, Labopin M, Neven B, Moshous D, Gennery AR (2012) Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood? Blood 119(12):2949–2955. https://doi.org/10.1182/blood-2011-06-363572. Epub: 20120203; PubMed PMID: 22308292CrossRefPubMed

24.

Buckley RH (2011) Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: long term outcomes. Immunol Res 49(1–3):25–43. https://doi.org/10.1007/s12026-010-8191-9.PubMedPMID:21116871;PubMedCentralPMCID:PMC3798033CrossRefPubMedPubMedCentral

25.

Pai SY, Logan BR, Griffith LM, Buckley RH, Parrott RE, Dvorak CC et al (2014) Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med 371(5):434–446. https://doi.org/10.1056/NEJMoa1401177.PubMedPMID:25075835;PubMedCentralPMCID:PMC4183064CrossRefPubMedPubMedCentral

26.

Mazzolari E, De Martiis D, Forino C, Lanfranchi A, Giliani S, Marzollo R et al (2009) Single-center analysis of long-term outcome after hematopoietic cell transplantation in children with congenital severe T cell immunodeficiency. Immunol Res 44(1–3):4–17. https://doi.org/10.1007/s12026-008-8022-4CrossRefPubMed

27.

Gennery AR, Slatter MA, Grandin L, Taupin P, Cant AJ, Veys P et al (2010) Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? Allergy Clin Immunol 126(3):602–610. https://doi.org/10.1016/j.jaci.2010.06.015. Epub: 20100731; PubMed PMID: 20673987CrossRef

28.

Yao CM, Han XH, Zhang YD, Zhang H, Jin YY, Cao RM et al (2013) Clinical characteristics and genetic profiles of 44 patients with severe combined immunodeficiency (SCID): Report from Shanghai, China (2004–2011). J Clin Immunol 33(3):526–539. https://doi.org/10.1007/s10875-012-9854-1CrossRefPubMed

29.

Vignesh P, Rawat A, Kumrah R, Singh A, Gummadi A, Sharma M et al (2021) Clinical, immunological, and molecular features of severe combined immune deficiency: a multi-institutional experience from India. Front immunol 11. https://doi.org/10.3389/fimmu.2020.619146. PubMed PMID: WOS:000620034200001

30.

Aluri J, Desai M, Gupta M, Dalvi A, Terance A, Rosenzweig SD et al (2019) Clinical, immunological, and molecular findings in 57 patients with severe combined immunodeficiency (SCID) from India. Front immunol. https://doi.org/10.3389/fimmu.2019.00023

31.

Fazlollahi MR, Pourpak Z, Hamidieh AA, Movahedi M, Houshmand M, Badalzadeh M et al (2017) Clinical, laboratory, and molecular findings for 63 patients with severe combined immunodeficiency: a decade’s experience. J Investig Allergol Clin Immunol 27(5):299–304. https://doi.org/10.18176/jiaci.0147CrossRefPubMed

32.

Mazzucchelli JT, Bonfim C, Castro GG, Condino-Neto AA, Costa NM, Cunha L et al (2014) Severe combined immunodeficiency in Brazil: management, prognosis, and BCG-associated complications. J Investig Allergol Clin Immunol 24(3):184–191 PubMed PMID: 25011356PubMed

33.

Heimall J, Puck J, Buckley R, Fleisher TA, Gennery AR, Neven B, et al (2017) editors. Current knowledge and priorities for future research in late effects after hematopoietic stem cell transplantation (HCT) for severe combined immunodeficiency patients: a consensus statement from the Second Pediatric Blood and Marrow Transplant Consortium International Conference on Late Effects after Pediatric HCT. Biology of Blood and Marrow Transplantation.

34.

Pai SY, Cowan MJ (2014) Stem cell transplantation for primary immunodeficiency diseases: The North American experience. Curr Opin Allergy Clin Immunol 14(6):521–526. https://doi.org/10.1097/ACI.0000000000000115CrossRefPubMedPubMedCentral

35.

Bustamante Ogando JC, Partida Gaytán A, Aldave Becerra JC, Álvarez Cardona A, Bezrodnik L, Borzutzky A et al (2019) Latin American consensus on the supportive management of patients with severe combined immunodeficiency. Journal of Allergy and Clinical Immunology 144(4):897–905. https://doi.org/10.1016/j.jaci.2019.08.002CrossRefPubMed

36.

Cocchi N, Jacobsen EM, Hoenig M, Schulz A, Schuetz C (2022) BCG Disease in SCID: Three decades of experience in a pediatric transplant center. J Clin Immunol 42(1):195–198. https://doi.org/10.1007/s10875-021-01143-yCrossRefPubMed

37.

Marciano BE, Huang CY, Joshi G, Rezaei N, Carvalho BC, Allwood Z et al (2014) BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies. Journal of Allergy and Clinical Immunology 133(4):1134–1141. https://doi.org/10.1016/j.jaci.2014.02.028CrossRefPubMed

38.

Patel DD, Gooding ME, Parrott RE, Curtis KM, Haynes BF, Buckley RH (2000) Thymic function after hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med 342(18):1325–1332. https://doi.org/10.1056/nejm200005043421804. PubMed PMID: 10793165CrossRefPubMed

39.

Barzaghi F, Aiuti A (2023) Newborn screening for severe combined immunodeficiency: changing the landscape of post-transplantation survival. The Lancet 402(10396):84–85. https://doi.org/10.1016/S0140-6736(23)01057-7CrossRef

40.

Kwan A, Abraham RS, Currier R, Brower A, Andruszewski K, Abbott JK et al (2014) Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA 312(7):729–738. https://doi.org/10.1001/jama.2014.9132.PubMedPMID:25138334;PubMedCentralPMCID:PMC4492158CrossRefPubMedPubMedCentral

41.

Lev A, Somech R, Somekh I (2023) Newborn screening for severe combined immunodeficiency and inborn errors of immunity. Curr Opin Pediatr 35(6):692–702. https://doi.org/10.1097/mop.0000000000001291. Epub: 20230914; PubMed PMID: 37707504CrossRefPubMed

42.

Hamada S, Dubois V, Koenig A, Thaunat O (2021) Allograft recognition by recipient’s natural killer cells: Molecular mechanisms and role in transplant rejection. Hla 98(3):191–199. https://doi.org/10.1111/tan.14332. Epub: 20210615; PubMed PMID: 34050618CrossRefPubMed

43.

Roifman CM (2010) Hematopoietic stem cell transplantation for profound T-cell deficiency (combined immunodeficiency). Immunol Allergy Clin North Am 30(2):209–219. https://doi.org/10.1016/j.iac.2010.03.001CrossRefPubMed

44.

Fernandes JF, Nichele S, Daudt LE, Tavares RB, Seber A, Kerbauy FR et al (2018) Transplantation of hematopoietic stem cells for primary immunodeficiencies in Brazil: challenges in treating rare diseases in developing countries. J Clin Immunol 38(8):917–926. https://doi.org/10.1007/s10875-018-0564-1CrossRefPubMed

45.

Slatter MA, Gennery AR (2022) Advances in the treatment of severe combined immunodeficiency. Clin Immunol 242:109084. Epub 20220805. https://doi.org/10.1016/j.clim.2022.109084. PubMed PMID: 35940359.

46.

Ouederni M, Mellouli F, Khaled MB, Kaabi H, Picard C, Bejaoui M (2016) Successful haploidentical stem cell transplantation with post-transplant cyclophosphamide in a severe combined immune deficiency patient: a first report. J Clin Immunol. 36. Netherland p. 437–40.

47.

Neven B, Diana JS, Castelle M, Magnani A, Rosain J, Touzot F et al (2019) Haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for primary immunodeficiencies and inherited disorders in children. Biol Blood Marrow Transplant 25(7):1963–1973. https://doi.org/10.1016/j.bbmt.2019.03.009. Epub: 20190312; PubMed PMID: 30876929CrossRef

48.

Kurzay M, Hauck F, Schmid I, Wiebking V, Eichinger A, Jung E et al (2019) T-cell replete haploidentical bone marrow transplantation and post-transplant cyclophosphamide for patients with inborn errors. Haematologica. 104. Italy . p. e478-e82

49.

Uppuluri R, Sivasankaran M, Patel S, Swaminathan VV, Ramanan KM, Ravichandran N et al (2019) Haploidentical stem cell transplantation with post-transplant cyclophosphamide for primary immune deficiency disorders in children: challenges and outcome from a tertiary care center in South India. J Clin Immunol 39(2):182–187. https://doi.org/10.1007/s10875-019-00600-z. Epub: 20190218; PubMed PMID: 30778805; PubMed Central PMCID: PMC7100782CrossRefPubMedPubMedCentral

50.

Buckley RH (2000) Advances in the understanding and treatment of human severe combined immunodeficiency. Immunol Res 22(2–3):237–251. https://doi.org/10.1385/ir:22:2-3:237. PubMed PMID: 11339359CrossRefPubMed

51.

Dvorak CC, Hung GY, Horn B, Dunn E, Oon CY, Cowan MJ (2008) Megadose CD34(+) cell grafts improve recovery of T cell engraftment but not B cell immunity in patients with severe combined immunodeficiency disease undergoing haplocompatible nonmyeloablative transplantation. Biol Blood Marrow Transplant 14(10):1125–1133. https://doi.org/10.1016/j.bbmt.2008.07.008. PubMed PMID: 18804042CrossRefPubMed

52.

Rastogi N, Katewa S, Thakkar D, Kohli S, Nivargi S, Yadav SP (2018) Reduced-toxicity alternate-donor stem cell transplantation with posttransplant cyclophosphamide for primary immunodeficiency disorders. Pediatr Blood Cancer 65(1). https://doi.org/10.1002/pbc.26783. Epub: 20170913; PubMed PMID: 28901730

Title: Survival After Hematopoietic Stem Cell Transplantation in Severe Combined Immunodeficiency (SCID): A Worldwide Review of the Prognostic Variables
Authors: Gabriela Assunção Goebel
Cíntia Silva de Assis
Luciana Araújo Oliveira Cunha
Fernanda Gontijo Minafra
Jorge Andrade Pinto
Publication date: 30-04-2024
Publisher: Springer US
Keywords: Stem Cell Transplantation
Stem Cell Transplantion
Stem Cell Transplantation
Immunodeficiency
Opportunistic Infection
Published in: Clinical Reviews in Allergy & Immunology
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI: https://doi.org/10.1007/s12016-024-08993-5

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