Reconstitution in Severe Combined Immunodeficiency by Transplantation of Marrow from an Unrelated Donor

A patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution. The first four transplants achieved restricted engraftment with evidence of rudimentary immunologic function. A fifth transplant, given after low-dose cyclophosphamide, produced reconstitution of cell-mediated immunity. Marrow aplasia developed after recontamination with a non-pathogenic microflora. Transplantation of marrow previously stored in liquid nitrogen was ineffective. A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution. Seventeen months after transplantation, full functional engraftment persists. Graft-versus-host disease has been chronic and moderately severe, but limited to the skin and oral mucosa. Transplantation of marrow from unrelated histocompatible donors may provide a useful treatment for patients with severe combined immunodeficiency or aplastic anemia who lack a matched sibling or related donor. (N Engl J Med 297:1311–1318, 1977) A MAJOR obstacle to the general application of bone-marrow transplantation is that the majority of the patients afflicted with the lethal disorders for which this approach is indicated will lack a histocompatible sibling donor.¹² The probability that any one sibling will be HLA genotypically identical to the patient is only one in four. If, however, histocompatible unrelated persons could be used as marrow-transplant donors, this therapeutic approach would be available to a larger number of patients. We here report the successful immunologic and hematologic reconstitution of a child with severe combined immunodeficiency and secondary marrow aplasia by transplantation of marrow.