Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report

Hamid, Intan Juliana Abd; Slatter, Mary; McKendrick, Fiona; Pearce, Mark S.; Gennery, Andrew R.

doi:10.1182/blood-2016-11-748616

Cited by 55 publications

(55 citation statements)

References 23 publications

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“…15,17 Our study confirms that use of RIC and MAC regimens increased the independence from Ig replacement, likely by allowing the development of donor B-cell chimerism in patients with nonfunctional B cells. 15,[18][19][20] Consistent with previous reports, 1,21 we observed that use of RIC/MAC was also associated with improved T-cell reconstitution. This may reflect stem cell engraftment with durable feeding of the thymic niche by lymphoid progenitor cells, resulting in a better thymic output assessed by T-cell receptor excision circles (TRECs) 11,18 or by naive CD4 1 CD45RA 1 T cells.…”

Section: Discussionsupporting

confidence: 90%

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

Haddad

Logan

Griffith

et al. 2018

Blood

140

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: Discussionsupporting

confidence: 90%

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

Haddad

Logan

Griffith

et al. 2018

Blood

140

162

View full text Add to dashboard Cite

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“…However, despite excellent long-term survival after curative therapy, a persistent susceptibility to human papillomavirus (HPV) infections is well described that does not appear overall to relate to the conditions of transplantation or immune reconstitution (Gaspar et al, 2004a; Laffort et al, 2004). In several independent studies, up to 64% of treated children developed warts, with lesion onset 4 to 19 years after transplantation (Abd Hamid et al, 2017; Gaspar et al, 2004a; Kamili et al, 2014; Laffort et al, 2004). …”

Section: Introductionmentioning

confidence: 99%

Absence of γ-Chain in Keratinocytes Alters Chemokine Secretion, Resulting in Reduced Immune Cell Recruitment

Nowak

Linzner

Thrasher

et al. 2017

Journal of Investigative Dermatology

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Loss-of-function mutations in the common gamma (γc) chain cytokine receptor subunit give rise to severe combined immunodeficiency characterized by lack of T and natural killer cells and infant death from infection. Hematopoietic stem cell transplantation or gene therapy offer a cure, but despite successful replacement of lymphoid immune lineages, a long-term risk of severe cutaneous human papilloma virus infections persists, possibly related to persistent γc-deficiency in other cell types. Here we show that keratinocytes, the only cell type directly infected by human papilloma virus, express functional γc and its co-receptors. After stimulation with the γc-ligand IL-15, γc-deficient keratinocytes show significantly impaired secretion of specific chemokines including CXCL1, CXCL8, and CCL20, resulting in reduced chemotaxis of dendritic cells and CD4+ T cells. Furthermore, γc-deficient keratinocytes also exhibit defective induction of T-cell chemotaxis in a model of stable human papilloma virus-18 infection. These findings suggest that persistent γc-deficiency in keratinocytes alters immune cell recruitment to the skin, which may contribute to the development and persistence of warts in this condition and would require different treatment approaches.

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“…At least 20 genes have been associated with SCID [1]. Currently, curative treatments such as hematopoietic stem cell transplantation (HSCT) [2][3][4] and gene therapy [5][6][7] can improve a patient's outcome if the treatment can be initiated before severe infections occur. Previously, a significant number of children with SCID would die before a diagnosis was made [8] or before a curative treatment could be administered [2,9,10].…”

Section: Introductionmentioning

confidence: 99%

Newborn Screening for Severe Combined Immunodeficiency in Taiwan

Chien

Lee

et al. 2017

IJNS

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A study of newborn screening for severe combined immunodeficiency (SCID) by detecting the T-cell receptor excision circle (TRECs) copy number in dried blood spots (DBSs) collected from newborns 3 days of age began in 2010 in Taiwan, and SCID screening was subsequently implemented country-wide in 2012. A total of 920,398 newborns were screened during a period of 78 months. Of these, 175 newborns (0.02%) were requested to undergo an immune function survey, and 136 cases (1 in 6768 newborns) were ultimately diagnosed as having T cell lymphopenia. The screening detected seven cases of typical SCID, with an incidence of 1 in 131,485 newborns (95% confidence interval, 1/63,693~1/271,434). Hematopoietic stem cell transplantation was performed in six patients before overt infection occurred, and the survival rate was 100%. The screening also detected eight cases of SCID variants and 20 cases of 22q11.2 deletion syndrome. Other etiologies of T lymphopenia were identified, and those newborns were evaluated and managed according to their immunological status. Owing to the introduction of newborn screening by measuring the TREC copy number, early administration of treatments became possible for newborns with conditions that put them at risk of primary or secondary immunodeficiency.

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Long-term outcome of hematopoietic stem cell transplantation for IL2RG/JAK3 SCID: a cohort report

Abstract: Key Points Conditioning is associated with better thymopoiesis, donor B-lymphocyte chimerism, cessation of immunoglobulin therapy, and normal QoL.

Cited by 55 publications

References 23 publications

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

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

Absence of γ-Chain in Keratinocytes Alters Chemokine Secretion, Resulting in Reduced Immune Cell Recruitment

Newborn Screening for Severe Combined Immunodeficiency in Taiwan

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