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-effects, after administration of sirolimus (SRL) in combination with a cyclosporine (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 and Pred, and 65 demographically similar, concurrent patients received only CsA and Pred. Using an analysis of variance, pretransplant laboratory values and SRL trough concentrations (C0) were correlated with the occurrence, severity, and persistence of drug-induced thrombocytopenia (platelet count <150x10(3) cell/mm3) and/or leukopenia (white blood cell count <5,000/mm3).
Results: Neither the ethnic background nor the pretransplant cytomegalovirus serological status was associated with the occurrence of hematological complications. Thrombocytopenia was usually observed during the first 4 weeks of treatment (P=0.004). The occurrence, but not the severity or the persistence, of both thrombocytopenia and leukopenia correlated significantly with SRL trough concentrations > or =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 the remaining 11%, 7% responded to SRL dose reduction, and 4% to temporary suspension. No patient required permanent cessation of SRL therapy. Most patients experienced repeated, but self-limited, episodes of toxicity.
Conclusion: Thrombocytopenia and leukopenia are not infrequent occurrences with SRL treatment, and they generally resolve spontaneously.