Unrelated donor and HLA‐identical sibling haematopoietic stem cell transplantation cure chronic granulomatous disease with good long‐term outcome and growth

Abstract

Summary 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 ≥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.

Gastrointestinal Abnormalities among Patients with Chronic Granulomatous Disease

“…Similar to our experience, several case series showed excellent survival of patients with CGD following HLA-matched allogeneic stem cells transplantations [16,19,21,22,[24][25][26]38]. Outcome was particularly favorable when transplantations were performed with an HLA-matched sibling donor and at an early age, although outcome of HLA-matched unrelated donor transplants is reported to be similar [21,27]. In contrast to a recent Swedish report [38], yet similar to the UK and Ireland CGD Registry [26], we did not find significant difference in mortality between patients that did or did not receive BMT, while morbidity was reduced following transplantation.…”

“…Importantly, we found that GI complications were significantly more common among patients who did not receive BMT than those who received BMT. Similar to our experience, several case series showed excellent survival of patients with CGD following HLA-matched allogeneic stem cells transplantations [16,19,21,22,[24][25][26]38]. Outcome was particularly favorable when transplantations were performed with an HLA-matched sibling donor and at an early age, although outcome of HLA-matched unrelated donor transplants is reported to be similar [21,27].…”

“…For CGD patients suffering also from inflammatory GI manifestations, conservative local and systemic immune modulating medications such as low or high doses of steroids, azathioprine [18] or monoclonal antibodies to TNFalpha have been used with varying degree of success [8]. Several studies have also shown resolution of the GI manifestations after BMT [15,16,[19][20][21][22][23][24][25][26][27]. However direct comparison of the outcome of the GI manifestations in CGD patients following the different treatment options are scarce.…”

Stem Cell Transplantation for Primary Immunodeficiency

“…Mean weight and height for age Z scores on recovery from HSCT rose significantly. Transplantassociated complications were restricted to those with pre-existing infection or inflammation, supporting the argument for early HSCT for all CGD patients with a well matched donor [25]. As transplantation techniques improve, and survival increases, earlier transplantation becomes a more attractive option for other primary immunodeficiencies requiring long term antimicrobials and immunosuppression to control symptoms.…”

Uma nova abordagem para o estudo dos defeitos genético-moleculares da doença granulomatosa crônica e análise de suas relações genótipo-fenótipo.

“…O sucesso dos transplantes de medula óssea é maior em crianças que em adultos. Relatórios recentes sobre independentes transplantes de medula óssea em Newcastle (Soncini et al, 2009) mostram uma taxa de sucesso global a longo prazo de 90%. Estes investigadores britânicos também mostraram uma reconstituição impressionante pré-transplante, sugerindo que muito da demora visto na DGC e retardo de crescimento é de fato devido a vários aspectos da disfunção hematopoiética, variando de colite a infecção crônica.…”