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

J Allergy Clin Immunol. 2012 Jan;129(1):176-83. doi: 10.1016/j.jaci.2011.10.005. Epub 2011 Nov 12.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Activities of Daily Living
  • Adolescent
  • Child
  • Child, Preschool
  • Educational Status
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Granulomatous Disease, Chronic / immunology
  • Granulomatous Disease, Chronic / mortality
  • Granulomatous Disease, Chronic / therapy*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Hematopoietic Stem Cell Transplantation / mortality*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Quality of Life
  • Sibling Relations
  • Tissue Donors*
  • Transplantation, Homologous
  • Treatment Outcome
  • Unrelated Donors*