title: Non-myeloablative stem cell transplantation for congenital immunodeficiencies.
abstract: Allogeneic haematopoietic stem cell transplantation (HSCT) can be a highly successful treatment option for individuals with congenital immunodeficiency states. The strategy for HSCT is varied but in cases where there is preservation of residual T cell function, conditioning regimes have been used and have been based around a combination of busulphan and cyclophosphamide with or without serotherapy. In patients with coexisting organ damage this has resulted in significant morbidity and mortality. We have therefore used a low-intensity conditioning regime for transplantation in this group of immunodeficiency patients. Twenty-one patients with a variety of different immunodeficiencies were treated using the following conditioning regimes: (1) fludarabine/melphalan/ATG or Campath 1H (n=16), (2) fludarabine/cyclophosphamide/Campath 1H (n=1), (3) TBI/CyA/MMF (n=1), (4) fludarabine/melphalan/busulphan/ATG (n=3). In 13 cases matched (n=9) and 1 Ag mismatched (n=4) unrelated donors were used and in eight cases transplants from matched siblings (n=4), 1 Ag mismatched sibling (n=1), matched parent (n=1) and haploidentical parents (n=3) were performed. At a median follow-up of 13 months, 19 of 21 (90%) patients were still alive following the transplant procedure. Despite a T cell replete graft and the use of unrelated donor grafts in the majority of patients studied there was no evidence of significant organ disease. Immune reconstitution in terms of CD3+ and CD4+ T cell recovery and function was equivalent in comparison with a historical cohort. We believe that this low-intensity approach has significant implications for transplantation of individuals with immunodeficiency states with established organ disease.
authors.affiliation: Department of Immunology, Great Ormond Street Hospital NHS Trust, London, UK.
authors.forename: H B
authors.initials: HB
authors.lastname: Gaspar
authors.forename: P
authors.initials: P
authors.lastname: Amrolia
authors.forename: A
authors.initials: A
authors.lastname: Hassan
authors.forename: D
authors.initials: D
authors.lastname: Webb
authors.forename: A
authors.initials: A
authors.lastname: Jones
authors.forename: N
authors.initials: N
authors.lastname: Sturt
authors.forename: G
authors.initials: G
authors.lastname: Vergani
authors.forename: A
authors.initials: A
authors.lastname: Pagliuca
authors.forename: G
authors.initials: G
authors.lastname: Mufti
authors.forename: N
authors.initials: N
authors.lastname: Hadzic
authors.forename: G
authors.initials: G
authors.lastname: Davies
authors.forename: P
authors.initials: P
authors.lastname: Veys
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000628:therapy*; D007223:Infant; D008297:Male; D019172:Transplantation Conditioning / Q000379:methods; D016896:Treatment Outcome