PURPOSE OF THE STUDY.
To determine outcomes and survival in patients with chronic granulomatous disease (CGD) after hematopoietic stem cell transplantation (HSCT) in both HLA-matched related (MRD) and unrelated donor (MUD) transplants.
This is a single-center retrospective cohort study of 11 children with a diagnosis of CGD, a history of at least 1 invasive infection, and 70% meeting parameters indicative of high-risk disease. Nine children had X-linked CGD, 1 had autosomal recessive CGD, and 1 did not have an identifiable mutation. Nine of the 11 patients were boys, and mean age at transplantation was 3.8 years (range: 11 months to 13 years).
Of the 11 patients studied, 4 received HSCT from 6/6 HLA-MRDs (siblings); 7 received HSCT from 10/10 HLA-genoidentical MUDs. All patients underwent busulfan-based myeloablation (with addition of cyclophosphamide, cytarabine, or fludarabine) and graft-versus-host disease (GvHD) prophylaxis with cyclosporine A. Time to engraftment was defined as time from transplantation to time of neutrophil count >500 cells/μL for 3 consecutive days. B- and T-cell recovery was measured by flow cytometry, and lymphoproliferative responses were measured by response to mitogens and antigens. Chimerism was measured in each patient.
Nine patients achieved full donor chimerism, whereas 2 had stable mixed chimerism. A neutrophil count of >500 cells/μL was reached at a median of 18 days for the cohort. Time to engraftment was not significantly different between MRD and MUD recipients, as measured by recovery of neutrophils, platelets, CD3+ and CD4+ T cells, and T-cell proliferative responses. Oxidative burst was normal by day 100 in all patients. Grade I acute GvHD of the skin occurred in 4 of 11 patients, 3 of whom received MUD transplants. One patient had a relapse of Aspergillus-associated pneumonia initially acquired before engraftment. Patients were followed for a mean of 4 years (range: 1–8 years), and all are well with significant improvements in quality of life, including the ability to attend school with no special care requirements.
The study reveals 100% survival at mean follow-up time of 4 years, no severe or chronic GvHD, no graft failure, and only 1 incidence of recurrent infection before engraftment for MRD and MUD transplant recipients. The authors suggest that both MRD and MUD HSCT should be considered early in the course of CGD in children with severe invasive infection.
Where previously HSCT was recommended only in patients with HLA-MRDs, these results suggest that earlier HSCT with related or unrelated donor stem cells provides good outcomes and low complication rates, and this may lead to improved survival and quality of life in patients with CGD as well as less end-organ damage.
- Copyright © 2012 by the American Academy of Pediatrics