Sirolimus-induced thrombocytopenia and leukopenia in renal transplant recipients: Risk factors, incidence, progression, and management

Background. Our study assessed the factors that predispose renal transplant recipients to the occurrence of thrombocytopenia and leukopenia, as well. as the severity and the time- and concentration-dependence of these side-ef fects, after administration of sirolimus (SRL) in combination with a cyclos porine (CsA) and prednisone (Pred) regimen. Methods. The clinical courses of two cohorts of renal transplant recipients were compared over 1 year: 119 patients received SRL in addition to CsA an d Pred, and 65 demographically similar, concurrent patients received only C sA and Pred, Using an analysis of variance, pretransplant laboratory values and SRL trough concentrations (C-0) were correlated with the occurrence, s everity, and persistence of drug-induced thrombocytopenia (platelet count < 150 x 10(3) cell/mm(3)) and/or leukopenia (white blood cell count <5,000/m m(3)). Results. Neither the ethnic background nor the pretransplant cytomegaloviru s serological status was associated with the occurrence of hematological co mplications. Thrombocytopenia was usually observed during the first 4 weeks of treatment (P = 0.004). The occurrence, but not the severity or the pers istence, of both thrombocytopenia and leukopenia correlated significantly w ith SRL trough concentrations greater than or equal to 16 ng/ml (P = 0.001 and 0.0001, respectively). A significant correlation is evident between the occurrence of the two adverse effects (P = 0.001). In 89% of patients, the first episode of either type of cytopenia resolved spontaneously, Among th e remaining 11%, 7% responded to SRL dose reduction, and 4% to temporary su spension. No patient required permanent cessation of SRL therapy. Most pati ents experienced repeated, but self-limited, episodes of toxicity. Conclusion. Thrombocytopenia and leukopenia are not infrequent occurrences with SRL treatment, and they generally resolve spontaneously.