title: Unrelated donor and HLA-identical sibling haematopoietic stem cell transplantation cure chronic granulomatous disease with good long-term outcome and growth.
abstract: Chronic granulomatous disease (CGD) causes recurrent infection and inflammatory disease. Despite antimicrobial prophylaxis, patients experience frequent hospitalisations and 50% mortality by 30 years. Haematopoietic stem cell transplantation (HSCT) can cure CGD with resolution of infection and colitis. This study reports the survival and long-term outcome in 20 conditioned patients treated between 1998 and 2007, using 10 matched sibling (MSD) and 10 unrelated donors (URD). Age at HSCT, graft-versus-host disease (GvHD), growth, and outcome were analysed. Fourteen had > or = 1 invasive infection, 10 had colitis and seven had growth failure before HSCT. Median age at transplantation was 75 months (range 15 months-21 years). Eighteen (90%) were alive 4-117 months (median 61) after HSCT with normal neutrophil function. Two died from disseminated fungal infection. Two experienced significant chronic GvHD, with continuing sequelae in 1. Colitis resolved within 8 weeks of HSCT. Mean weight and height for age Z scores on recovery from HSCT rose significantly (P < 0.001). HSCT with MSD or URD gave excellent engraftment and survival, remission of colitis and catch-up growth, with low incidence of significant GvHD. Transplant-associated complications were restricted to those with pre-existing infection or inflammation, supporting the argument for early HSCT for more CGD patients with a well matched donor.
authors.affiliation: Department of Paediatric Immunology, Newcastle upon Tyne Hospitals Foundation Trust, Newcastle upon Tyne, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Soncini
authors.forename: Mary A
authors.initials: MA
authors.lastname: Slatter
authors.forename: Laura B K R
authors.initials: LB
authors.lastname: Jones
authors.forename: Stephen
authors.initials: S
authors.lastname: Hughes
authors.forename: Stephen
authors.initials: S
authors.lastname: Hodges
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Flood
authors.forename: Dawn
authors.initials: D
authors.lastname: Barge
authors.forename: Gavin P
authors.initials: GP
authors.lastname: Spickett
authors.forename: Graham H
authors.initials: GH
authors.lastname: Jackson
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Collin
authors.forename: Mario
authors.initials: M
authors.lastname: Abinun
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Cant
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000150:complications; D006105:Granulomatous Disease, Chronic / Q000276:immunology / Q000503:physiopathology / Q000628:therapy*; D006128:Growth; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D016016:Proportional Hazards Models; D035781:Siblings; D015996:Survival Rate; D014019:Tissue Donors; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult