Hematopoietic Stem-Cell Transplantation for the Treatment of Severe Combined Immunodeficiency
Rebecca H. Buckley, M.D., Sherrie E. Schiff, B.S., Richard I. Schiff, M.D., Ph.D., M. Louise Markert, M.D., Ph.D., Larry W. Williams, M.D., Joseph L. Roberts, M.D., Ph.D., Laurie A. Myers, M.D., and Frances E. Ward, Ph.D.
Background Since 1968 it has been known that bone marrow transplantationcan ameliorate severe combined immunodeficiency, but data onthe long-term efficacy of this treatment are limited. We prospectivelystudied immunologic function in 89 consecutive infants withsevere combined immunodeficiency who received hematopoieticstem-cell transplants at Duke University Medical Center betweenMay 1982 and September 1998.
Methods Serum immunoglobulin levels and lymphocyte phenotypesand function were assessed and genetic analyses performed accordingto standard methods. Bone marrow was depleted of T cells byagglutination with soybean lectin and by sheep-erythrocyte rosettingbefore transplantation.
Results Seventy-seven of the infants received T-cell–depleted,HLA-haploidentical parental marrow, and 12 received HLA-identicalmarrow from a related donor; 3 of the recipients of haploidenticalmarrow also received placental-blood transplants from unrelateddonors. Except for two patients who received placental blood,none of the recipients received chemotherapy before transplantationor prophylaxis against graft-versus-host disease. Of the 89infants, 72 (81 percent) were still alive 3 months to 16.5 yearsafter transplantation, including all of the 12 who receivedHLA-identical marrow, 60 of the 77 (78 percent) who were givenhaploidentical marrow, and 2 of the 3 (67 percent) who receivedboth haploidentical marrow and placental blood. T-cell functionbecame normal within two weeks after transplantation in thepatients who received unfractionated HLA-identical marrow butusually not until three to four months after transplantationin those who received T-cell–depleted marrow. At the timeof the most recent evaluation, all but 4 of the 72 survivorshad normal T-cell function, and all the T cells in their bloodwere of donor origin. B-cell function remained abnormal in manyof the recipients of haploidentical marrow. In 26 children (5recipients of HLA-identical marrow and 21 recipients of haploidenticalmarrow) between 2 percent and 100 percent of B cells were ofdonor origin. Forty-five of the 72 children were receiving intravenousimmune globulin.
Conclusions Transplantation of marrow from a related donor isa life-saving and life-sustaining treatment for patients withany type of severe combined immunodeficiency, even when thereis no HLA-identical donor.
Source Information
From the Departments of Pediatrics (R.H.B., S.E.S., R.I.S., M.L.M., L.W.W., J.L.R., L.A.M.) and Immunology (R.H.B., M.L.M., F.E.W.), Duke University Medical Center, Durham, N.C.
Address reprint requests to Dr. Buckley at Box 2898, Duke University Medical Center, Durham, NC 27710.
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