Cyclosporine-Induced Nephrotoxicity and Dose Adjustments in Bone Marrow Transplantation.

Background and hypothesis: Cyclosporine is administered to all patients undergoing allogeneic bone marrow transplantation in Hamilton. It is given intravenously at first then orally after engraftment. The manufacturer’s recommendation is to use a dose ratio of 1:3, IV to oral; the Hamilton unit uses a ratio of 1:2, yet has observed frequent rises of cyclosporine to toxic levels. We wished to confirm that the dose conversion ratio of 1:2 is associated with significantly high cyclosporine levels and nephrotoxicity.

Methods and Results: Thirty-five consecutive patients undergoing allogeneic bone marrow transplantation at McMaster University Medical Centre were studied. We included patients who were diagnosed with a hematological cancer i.e. leukemia (76%), lymphoma (18%), or myelodysplastic syndrome (6%), and who underwent chemotherapy. The patients’ plasma cyclosporine levels were measured 4–5 days after its initiation and with every dose adjustment, and serum creatinine levels were measured daily. Forty four percent of the patients were males. In 53% of the patients 1:2 IV to oral conversion ratio caused elevation of plasma cyclosporine levels to the toxic range (p<0.001). The toxic cyclosporine levels were seen 5+/−2 days post IV to oral dose adjustment. Furthermore, 43% of these patients developed acute renal failure and significant elevation of their serum creatinine levels (p<0.001).

Conclusion: The traditional conversion rate of 1:2–3 for intravenous to oral cyclosporine is associated with rises in plasma cyclosporine to toxic levels and significant rises in serum creatinine level. We recommend that this conversion rate be lowered to 1:4/3 and further studied.