MICROANGIOPATHY FOLLOWING ALLOGENEIC MARROW TRANSPLANTATION - ASSOCIATION WITH CYCLOSPORINE AND METHYLPREDNISOLONE FOR GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS

A microangiopathic syndrome was observed in 3 of 14 (21%) patients receiving cyclosporine and methylprednisolone (CSA-MP) for graft-versus-host disease (GVHD) prophylaxis between January 1991 and June 1992 at our center, The syndrome consisted of neurological abnormalities, arterial hypertension, intravascular hemolysis with red cell fragmentation, and a drop in platelet counts after allogeneic bone marrow transplantation (BMT) for hematological malignancy, and it occurred around day 50 after BMT. Treatment with plasma exchanges against fresh-frozen plasma resulted in a decrease of serum lactate dehydrogenase and an improvement of neurological symptoms, We compared CSA-MP patients retrospectively with patients who had received cyclosporine and methotrexate (CSA-MTX) for GVHD prophylaxis (n=70) at our institution. All patients in both groups engrafted Day 100 survival (80% vs, 79%) and transplant-related mortality (16% vs. 14%) were identical in the two groups, CSA-MP patients had significantly more acute GVHD II-IV (57% vs. 17%, P<0.01). Arterial hypertension (P<0.01) and neurological symptoms (P<0.01) were significantly more frequent in the CSA-RIP group. The 11 asymptomatic CSA-MP patients had significantly higher lactate dehydrogenase levels (P<0.01) and lower platelet counts (P<0.01) at 40, 60, and 100 days after BMT, which suggests the presence of a subclinical form of microangiopathy. Significantly higher plasma levels of von Willebrand factor antigen in CSA-RIP patients on day 50 after BMT (P<0.05) and absence of large von Willebrand factor multimers on gel electrophoresis in 4 of 13 (31%) CSA-MP patients compared with 0 of 14 (0%) CSA-MTX patients (P<0.01) further suggest profound endothelial damage in patients receiving CSA-MP for GVHD prophylaxis.