Fatal Lymphoma after Transplantation of Cultured Thymus in Children with Combined Immunodeficiency Disease

A fatal, widespread, polyclonal, B-cell immunoblastic lymphoproliferative disorder developed in three children with combined immunodeficiency shortly after intra-abdominal transplantation of cultured thymus epithelium for immunoreconstitution. All three had surface immunoglobulin-bearing cells (15 to 20 per cent) in the peripheral blood before transplantation and polyclonally elevated immunoglobulins afterward. Abnormal immunoregulation was demonstrated by a lack of concanavalin A-induced suppressor-cell activity in mixed leukocyte culture in all three patients before transplantation and in two afterward. We suggest that the transplant acted as a promoter through immunostimulation or production of promoter factors, and that excessive polyclonal B-cell proliferation resulted because of inadequate immunoregulatory mechanisms. Although this complication occurred in only three of 30 patients with various forms of immunodeficiency treated with cultured thymus, these cases illustrate a potential problem in immunoreconstitution of combined immunodeficiency disorders. (N Engl J Med 301:565–568, 1979) THE treatment of choice for combined immunodeficiency disease is an HLA-matched bone-marrow transplant, preferably from a sibling or relative, but, unfortunately, appropriate donors cannot often be found. Attempts at reconstitution with transplantation of organs, such as fetal liver or fetal thymus, or humoral factors, such as thymosin or transfer factor, have usually not been successful.¹ Recently, transplantation of allogeneic cultured thymus epithelium was used to treat combined immunodeficiency disease in patients for whom matched, related bone-marrow donors were not available.^2,3 In three patients who received cultured thymus, widespread, polyclonal B-cell immunoblastic lymphoproliferation was discovered at autopsy. In all three, this.