期刊
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
卷 11, 期 7, 页码 551-557出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2005.04.007
关键词
thrombotic microangiopathy; hematopoictic stem cell transplantation; sirolimus; calcineurin inhibitor
资金
- NHLBI NIH HHS [P01 HL070149-01A1] Funding Source: Medline
Thrombotic microangiopathy (TMA) may occur after allogeneic hematopoietic stem cell transplantation (HSCT) and is related in part to calcineurin inhibitor toxicity. We observed a higher-than-expected rate of TMA when calcineurin inhibitors were combined with sirolimus. To determine the incidence of and risk factors for TMA after HSCT, we performed a retrospective cohort analysis of myeloalblative allogeneic HSCT recipients between 1997 and 2003. TMA diagnosis required the simultaneous occurrence of (1) creatinine increase > 2 mg/dL or > 50% above baseline, (2) schistocytosis, (3) increased lactate dehydrogenase, and (4) no evidence of disseminated intravascular coagulopathy. A total of 111 sirolimus-exposed subjects were compared with 216 nonexposed subjects after HSCT. TMA occurred in 10.8% of the sirolimus group and 4.2% in the nonsirolimus group (odds ratio, 2.79; P =.03). Sirolimus exposure was associated with TMA earlier than in nonsirolimus patients (25 versus 58 days; P =.04). Only the use of sirolimus (exact odds ratio, 3.49; P =.02) and grade II to IV acute graft-versus-host disease (exact odds ratio, 6.60; P =.0002) were associated with TMA in regression analyses. Treatment of TMA varied among affected individuals. Renal recovery was complete in 92% of sirolimus-treated patients. Overall survival after TMA diagnosis was better for sirolimus subjects than for nonsirolimus subjects (58.3% versus 11.1%; P =.02). Sirolimus seems to potentiate the effects of calcineurin inhibitors on TMA after HSCT. TMA associated with sirolimus seems reversible and has a favorable prognosis when compared with TMA associated with calcineurin inhibitors alone. A careful monitoring strategy for TMA should be used with a sirolimus-containing graft-versus-host disease prophylaxis regimen. (c) 2005 American Society for Blood and Marrow Transplantation.
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