Severe microangiopathy has been reported as a rare complication of cyclosporine A (CsA) prophylaxis in allogeneic bone marrow transplantation (BMT). We found morphological and biochemical changes indicative of generalized endothelial damage in 49 of 66 allogeneic marrow graft recipients receiving cyclosporine, but none in 11 patients treated with methotrexate for prophylaxis of graft-v-host disease (GVHD). Changes occurred after engraftment of bone marrow and consisted of intravascular hemolysis with red cell fragmentation and de novo thrombocytopenia. They were preceded by a decrease in activated partial thromboplastin time and fibrinogen indicating activation of coagulation. Endothelial damage as the central lesion of microangiopathy was confirmed by a simultaneous increase of factor VIII related antigen. Severe microangiopathy was observed in ten patients and was fatal in seven. Risk factor analysis revealed a highly significant association of microangiopathy with severity of acute GVHD (aGVHD) (P less than .001) and use of CsA prophylaxis (P less than .001). Our data suggest endothelial damage as a result of cellular activation and subsequent release of cytokines in the course of a aGVHD, which is not inhibited by CsA prophylaxis.

We analysed the effect of chemotherapy dose reductions on survival in 35 patients with Hodgkin’s disease stage IIIB or IV treated at our institution by three double courses of C-MOPP/ABVD chemotherapy followed by either one further course or by involved-field radiotherapy. Patients receiving reduced doses of alkylating agents had markedly slower responses and worse survival than those not requiring dose reductions. This experience with a very limited number of cases suggests that dose intensity may be an important prognostic factor in advanced Hodgkin’s lymphoma, although dose reductions might have been necessary in patients with an intrinsically poor prognosis. Prospective randomized trials comparing standard chemotherapy with intensified protocols supported by hematopoietic growth factors are needed and are being conducted to determine the role of total chemotherapy dose and delivery time in the cure of Hodgkin’s disease.