Microangiopathy in patients on cyclosporine prophylaxis who developed acute graft-versus-host disease after HLA-identical bone marrow transplantation

E. Holler, H. J. Kolb, E. Hiller, W. Mraz, W. Lehmacher, B. Gleixner, C. Seeber, U. Jehn, H. H. Gerhartz, G. Brehm, W. Wilmanns

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215 Scopus citations

Abstract

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 < .001) and use of CsA prophylaxis (P < .001). Our data suggest endothelial damage as a result of cellular activation and subsequent release of cytokines in the course of aGVHD, which is not inhibited by CsA prophylaxis.

Original languageEnglish
Pages (from-to)2018-2024
Number of pages7
JournalBlood
Volume73
Issue number7
DOIs
StatePublished - 1989
Externally publishedYes

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