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

Heimall, Jennifer; Buckley, Rebecca H.; Puck, Jennifer M.; Fleisher, Thomas A.; Gennery, Andrew R.; Haddad, Élie; Neven, Bénédicte; Slatter, Mary; Skinner, Roderick; Baker, K. Scott; Dietz, Andrew C.; Duncan, Christine; Griffith, Linda M.; Notarangelo, Luigi D.; Pulsipher, Michael A.; Cowan, Morton J.

doi:10.1016/j.bbmt.2017.04.026

Cited by 48 publications

(24 citation statements)

References 49 publications

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“…These data emphasize the importance of sequential assessments of immune reconstitution following HCT for SCID. 24 Ongoing analyses may also ascertain whether these patients are differentially susceptible to late complications. These data raise the question of whether retransplantation, or other measures to enhance reconstitution, should be considered for patients with low CD4 1 cell counts at 6 or 12 months post-HCT.…”

Section: Discussionmentioning

confidence: 99%

SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery

Haddad

Logan

Griffith

et al. 2018

Blood

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148

162

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The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with ,, or defects and was significantly better compared with patients with or mutations. Patients with or mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD4 and CD4CD45RA cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD4 cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.

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Section: Discussionmentioning

confidence: 99%

SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery

Haddad

Logan

Griffith

et al. 2018

Blood

Self Cite

148

162

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“…Consensus recommendations for screening of late effects following HCT for SCID were recently published [70]. These guidelines suggest a timetable for basic testing of immune function and engraftment along with recommendations for use of immunoglobulin replacement, antibiotic prophylaxis and vaccine administration.…”

Section: Late Effectsmentioning

confidence: 99%

Long term outcomes of severe combined immunodeficiency: therapy implications

Heimall

Cowan

2017

Expert Review of Clinical Immunology

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Introduction Newborn screening has led to a better understanding of the prevalence of Severe Combined Immunodeficiency (SCID) overall and in terms of specific genotypes. Survival has improved following hematopoietic stem cell transplantation (HCT) with the best outcomes seen following use of a matched sibling donor. However, questions remain regarding the optimal alternative donor source, appropriate use of conditioning and the impact of these decisions on immune reconstitution and other late morbidities. Areas covered The currently available literature reporting late effects after HCT for SCID and use of alternative therapies including enzyme replacement, alternative donors and gene therapy are reviewed. A literature search was performed on Pubmed and ClinicalTrials.gov using key words ‘Severe Combined Immunodeficiency’, ‘SCID’, ‘hematopoietic stem cell transplant’, ‘conditioning’, ‘gene therapy’, ‘SCID newborn screening’, ‘TREC’ and ‘late effects’. Expert commentary Newborn screening has dramatically changed the clinical presentation of newborn SCID. While the majority of patients with SCID survive HCT, data regarding late effects in these patients is limited and additional studies focused on genotype specific late effects are needed. Prospective studies aimed at minimizing the use of alkylating agents and reducing late effects beyond survival are needed. Gene therapy is being developed and will likely become a more commonly used treatment that will require separate consideration of survival and late effects.

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“…NBS for SCID was initially developed to identify affected infants, preferably at an asymptomatic stage, facilitating medical intervention before life-threatening complications arise (1)(2)(3)(4)(5). The assay is based on the absence or low count of T-cell receptor (TCR) excision circles (TREC), a by-product of TCR V (D) J rearrangement in the thymus during early T-cell development, and is universally available in the United States.…”

Section: Introductionmentioning

confidence: 99%