Excellent survival after sibling or unrelated donor stem cell transplantation for chronic granulomatous disease

Abstract

Background: Matched related donor (MRD) hematopoietic stem cell transplantation (HSCT) is a successful treatment for chronic granulomatous disease (CGD), but the safety and efficacy of HSCT from unrelated donors is less certain.

Objective: We evaluated the outcomes and overall survival in patients with CGD after HSCT.

Methods: We report the outcomes for 11 children undergoing HSCT from an MRD (n = 4) or an HLA-matched unrelated donor (MUD) (n = 7); 9 children were boys, and the median age was 3.8 years (range, 1-13 years). We treated both X-linked (n = 9) and autosomal recessive (n = 2) disease. Nine children had serious clinical infections before transplantation. The conditioning regimens contained busulfan, cyclophosphamide, cytarabine, or fludarabine according to the donor used. All patients received alemtuzumab (anti-CD52 antibody). Additional graft-versus-host disease (GvHD) prophylaxis included cyclosporine and methotrexate for MUD recipients and cyclosporine and prednisone for MRD recipients.

Results: Neutrophil recovery took a median of 16 days (range, 12-40 days) and 18 days (range, 13-24 days) for MRD and MUD recipients, respectively. Full donor neutrophil engraftment occurred in 9 patients, and 2 had stable mixed chimerism; all patients had sustained correction of neutrophil oxidative burst defect. Four patients had grade I skin acute GVHD responding to topical treatment. No patient had grade II to IV acute GvHD or chronic GvHD. All patients are alive between 1 and 8 years after HSCT.

Conclusion: For CGD, equivalent outcomes can be obtained with MRD or MUD stem cells, and HSCT should be considered an early treatment option.

Conflict of interest statement

Authors declare no conflict of interest. No honorarium, grant or other form of payment was given to authors to produce the manuscript.

Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Figures

Figure 1. Neutrophil engraftment.

Cumulative incidence of neutrophil engraftment(defined as a neutrophil count greater than 500/ul) occurred at a median time of 18 days (range, 13–24).

Figure 2. Platelet engraftment.

Cumulative incidence of platelet engraftment(defined as a platelet count greater than 20,000 per cubic millimeter) occurred at a median time of 16 days (range, 12–40).

Figure 3. Neutrophil oxidative burst by DHR.

Pre-HSCT mean stimulation indices (SI) averaged less than 2 prior to HSCT and corrected to and were sustained normal following HSCT for all patients.

Figure 4. Immuno reconstituion.

a. CD3 T cell and b. CD4 T cell absolute number recovery, and c. function measured by proliferative responses to mitogen(PHA 10 µg/mL) after HSCT.