Treatment of chronic granulomatous disease with nonmyeloablative conditioning and a T-cell-depleted hematopoietic allograft.

Journal Article (Clinical Trial;Journal Article)

BACKGROUND: The treatment of chronic granulomatous disease with conventional allogeneic hematopoietic stem-cell transplantation carries a high risk of serious complications and death. We investigated the feasibility of stem-cell transplantation without ablation of the recipient's bone marrow. METHODS: Ten patients, five children and five adults, with chronic granulomatous disease underwent peripheral-blood stem-cell transplantation from an HLA-identical sibling. We used a nonmyeloablative conditioning regimen consisting of cyclophosphamide, fludarabine, and antithymocyte globulin. The allograft was depleted of T cells to reduce the risk of severe graft-versus-host disease. Donor lymphocytes were administered at intervals of 30 days or more after the transplantation to facilitate engraftment. RESULTS: After a median follow-up of 17 months (range, 8 to 26), the proportion of donor neutrophils in the circulation in 8 of the 10 patients was 33 to 100 percent, a level that can be expected to provide normal host defense; in 6 the proportion was 100 percent. In two patients, graft rejection occurred. Acute graft-versus-host disease (grade II, III, or IV) developed in three of the four adult patients with engraftment, one of whom subsequently had chronic graft-versus-host disease. None of the five children had grade II, III, or IV acute graft-versus-host disease. During the follow-up period, four serious infections occurred among the patients who had engraftment. Three of the 10 recipients died. Preexisting granulomatous lesions resolved in the patients in whom transplantation was successful. CONCLUSIONS: Nonmyeloablative conditioning followed by a T-cell-depleted hematopoietic stem-cell allograft is a feasible option for patients with chronic granulomatous disease, recurrent life-threatening infections, and an HLA-identical family donor.

Full Text

Duke Authors

Cited Authors

  • Horwitz, ME; Barrett, AJ; Brown, MR; Carter, CS; Childs, R; Gallin, JI; Holland, SM; Linton, GF; Miller, JA; Leitman, SF; Read, EJ; Malech, HL

Published Date

  • March 22, 2001

Published In

Volume / Issue

  • 344 / 12

Start / End Page

  • 881 - 888

PubMed ID

  • 11259721

International Standard Serial Number (ISSN)

  • 0028-4793

Digital Object Identifier (DOI)

  • 10.1056/NEJM200103223441203


  • eng

Conference Location

  • United States