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

被引:203
作者
Horwitz, ME
Barrett, AJ
Brown, MR
Carter, CS
Childs, R
Gallin, JI
Gress, RE
Holland, SM
Linton, GF
Miller, JA
Leitman, SF
Read, EJ
Schermerhorn, J
Malech, HL
机构
[1] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA
[2] NHLBI, NIH, Bethesda, MD 20892 USA
[3] NIH, Dept Clin Pathol, Bethesda, MD 20892 USA
[4] NIH, Dept Transfus Med, Bethesda, MD 20892 USA
关键词
D O I
10.1056/NEJM200103223441203
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (N Engl J Med 2001;344:881-8.) Copyright (C) 2001 Massachusetts Medical Society.
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页码:881 / 888
页数:8
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