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-MP 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-MP 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.
D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006461:Hemolysis; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007770:L-Lactate Dehydrogenase; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008775:Methylprednisolone / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology / Q000503:physiopathology*; D010956:Plasmapheresis; D010976:Platelet Count; D012189:Retrospective Studies; D013577:Syndrome; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000139:chemically induced*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007770:L-Lactate Dehydrogenase; D008775:Methylprednisolone; D008727:Methotrexate