Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency

Background Since 1968 it has been known that bone marrow transplantation ca n ameliorate severe combined immunodeficiency, bur data on the longterm eff icacy of this treatment are limited. We prospectively studied immunologic f unction in 89 consecutive infants with severe combined immunodeficiency who received hematopoietic stem-cell transplants at Duke University Medical Ce nter between May 1982 and September 1998. Methods Serum immunoglobulin levels and lymphocyte phenotypes and function were assessed and genetic analyses performed according to standard methods. Bone marrow was depleted of T cells by agglutination with soybean lectin a nd by sheep-erythrocyte resetting before transplantation. Results Seventy-seven of the infants received T-cell-depleted, HLA-haploide ntical parental marrow, and 12 received HLA-identical marrow from a related donor; 3 of the recipients of haploidentical marrow also received placenta l-blood transplants from unrelated donors. Except for two patients who rece ived placental blood, none of the recipients received chemotherapy before t ransplantation or prophylaxis against graft-versus-host: disease. Of the 89 infants, 72 (81 percent) were still alive 3 months to 16.5 years after tra nsplantation, including all of the 12 who received HLA-identical marrow, 60 of the 77 (78 percent) who were given haploidentical marrow, and 2 of the 3 (67 percent) who received both haploidentical marrow and placental blood. T-cell function became normal within two weeks after transplantation in th e patients who received unfractionated HLA-identical marrow but usually not until three to four months after transplantation in those who received T-c ell-depleted marrow. At the time of the most recent evaluation, all but 4 o f the 72 survivors had normal T-cell function, and all the T cells in their blood were of donor origin. B-cell function remained abnormal in many of t he recipients of haploidentical marrow. In 26 children (5 recipients of HLA -identical marrow and 21 recipients of haploidentical marrow) between 2 per cent and 100 percent of B cells were of donor origin. Forty-five of the 72 children were receiving intravenous immune globulin. Conclusions Transplantation of marrow from a related donor is a life-saving and life-sustaining treatment for patients with any type of severe combine d immunodeficiency, even when there is no HLA-identical donor. (N Engl J Me d 1999;340:508-16.) (C)1999. Massachusetts Medical Society.