Treatment of autosomal recessive lymphopenic agammaglobulinemia by transplantation of matched allogeneic bone marrow

Abstract

A five month old male infant with autosomal recessive lymphopenic agammaglobulinemia (Swiss type) was treated by transplantation with unfractionated bone marrow from a sibling donor. The donor and recipient were well matched by cytotoxic and one-way mixed lymphocyte stimulation assays but differed in major blood group antigens. Evidence for establishment of both cellular and humoral immunity was obtained within two weeks of the transplant. Mucocutaneous candidiasis cleared, the skin test for Candida albicans became positive and normal numbers of phytohemagglutinin responsive lymphocytes appeared in the circulation. Antibodies to host erythrocytes appeared, and circulating immunoglobulin M (IgM) levels rose. A clinically mild graft-versus-host reaction was accompanied by the appearance of large lymphoblasts, similar to transformed lymphocytes, in the peripheral blood. The patient died of Pneumocystis carinii pneumonia 21 days after transplantation. Large numbers of lymphocytes and plasma cells were found in peripheral lymphoid tissues, but there was no histologic evidence for thymic lymphopoiesis. Adoptive transfer of immunocompetent cells, rather than differentiation of uncommitted stem cells, probably accounted for the appearance of immune functions.