ADJUSTED-DOSE CONTINUOUS-INFUSION CYCLOSPORINE-A TO PREVENT GRAFT-VERSUS-HOST DISEASE FOLLOWING ALLOGENEIC BONE-MARROW TRANSPLANTATION

Graft-versus-host disease (GVHD) remains a major obstacle to allogenei c bone marrow transplantation. We administered cyclosporin A (CsA) by continuous intravenous infusion for prophylaxis against GVHD and adjus ted the dose to maintain a constant whole blood level. Forty-five pati ents, ranging in age from 16 to 56, mean 39.5 years, undergoing alloge neic transplantation for various hematological malignancies received C sA as a continuous intravenous infusion. CsA was started on day -1 and continued until day +22 when oral CsA was initiated. The whole blood level of CsA was determined and the dose adjusted to maintain a fixed level. Methotrexate 15 mg/m(2) i.v. was given on day +1, followed by 1 0 mg/m(2) on days +3 and +6. CsA administered as a continuous infusion was well tolerated. All patients required multiple adjustments of the infused dose of CsA to maintain the targeted whole blood level. The m ean rise in creatinine was 0.89 mg/dl. There was an association betwee n the Concomitant administration of amphotericin B and CsA and the dev elopment of nephrotoxicity. Hypertension developed in 30/45 patients, and all responded to oral nifedipine. Tremors were noted in 16/45 pati ents. None of the patients developed serious neurological side effects . Greater than grade-I acute GVHD developed in only 13% of the patient s. We conclude that administering CsA as an adjusted dose by continuou s intravenous infusion is well tolerated and effective in preventing a cute GVHD in patients undergoing allogeneic bone marrow transplantatio n.