Article

SCID patients with ARTEMIS versus RAG deficiencies following HCT: increased risk of late toxicity in ARTEMIS deficient SCID.

Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Germany
Blood (Impact Factor: 10.43). 10/2013; 123(2). DOI: 10.1182/blood-2013-01-476432
Source: PubMed

ABSTRACT A subgroup of severe combined immunodeficiencies (SCID) is characterized by lack of T and B cells and is caused by defects in genes required for T- and B-cell receptor gene rearrangement. Several of these genes are also involved in non-homologous end-joining (NHEJ) of DNA double-strand break repair, the largest subgroup consisting of patients with T(-)B(-)NK(+)SCID due to DCLRE1C/ARTEMIS defects. We postulated that in patients with ARTEMIS deficiency early and late complications following hematopoietic cell transplantation (HCT) might be more prominent compared to patients with T(-)B(-)NK(+)SCID caused by RAG1/2 deficiencies. We analyzed 69 patients with ARTEMIS and 76 patients with RAG 1/2 deficiencies transplanted either from HLA identical donors without conditioning or from HLA non-identical donors without or with conditioning. There was no difference in survival or in the incidence or severity of acute graft-versus-host-disease (GvHD) regardless of exposure to alkylating agents. Secondary malignancies were not observed. Immune reconstitution was comparable in both groups, however ARTEMIS deficient patients had a significantly higher occurrence of infections in long-term follow-up. There is a highly significant association between poor growth in ARTEMIS deficiency and use of alkylating agents. Furthermore abnormalities in dental development and endocrine late-effects were associated with alkylation therapy in ARTEMIS deficiency.

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