Thymus transplantation after allogeneic bone marrow graft to prevent chronic graft-versus-host disease in humans
Seventeen patients, aged 24 to 43 years and receiving HLA-identical sibling marrow transplants for treatment of acute nonlymphoblastic leukemia (ANL) or aplastic anemia (AA), were given additional transplants of thymic tissue from unrelated donors in an attempt to prevent the development of chronic graft-versus-host disease (GVHD). They were conditioned for grafting with cyclophosphamide alone (AA) or cyclophosphamide and total body irradiation, and received methotrexate after marrow transplant. Thymus tissue was given either as cultured fragments without matching recipient and thymic donor for HLA or as cultured monolayers of thymic epithelial cells that shared an HLA-A and an HLA-B antigen with the recipient. Eight age-matched marrow graft recipients transplanted from HLA-identical siblings for ANL during the same time period, but for whom thymus tissue was not available, served as controls. Thymus transplantation had no adverse effect on marrow engraftment, and there was no infection or hemorrhage at the site of the implant. Short-term complications such as veno-occlusive disease of the liver and acute GVHD were similar in recipients and nonrecipients of thymic tissue as was the incidence of interstitial pneumonia and varicella-zoster infections. Eight patients in the thymic transplant group and four patients in the control died before 3 months. Of the evaluable patients, two of five receiving cultured thymic fragments, four of four receiving thymic epithelial monolayer cells, and three of four in the control group developed chronic GVHD. Thus, thymic transplantation as performed in this study did not prevent chronic GVHD. Modifications of the technique have been devised and those currently in use are described.
Atkinson, K; Storb, R; Ochs, HD; Goehle, S; Sullivan, KM; Witherspoon, RP; Lum, LG; Tsoi, MS; Sanders, JE; Parr, M; Stewart, P; Thomas, ED
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