LOW INCIDENCE OF ACUTE GRAFT-VERSUS-HOST DISEASE AND RECURRENT LEUKEMIA IN PATIENTS UNDERGOING ALLOGENEIC HEMATOPOIETIC STEM-CELL TRANSPLANTATION FROM SIBLING DONORS WITH METHOTREXATE AND DOSE-MONITORED CYCLOSPORINE-A PROPHYLAXIS

One of the major aims of allogeneic haemopoietic stem cell transplanta tion has been the effective suppression of graft-versus-host disease ( GVHD) without loss of a graft-versus-leukaemia effect. For GVHD suppre ssion, one of the most frequently used regimens has been the combinati on of cyclosporin (CsA) and a short course of methotrexate (MTX) altho ugh the optimal usage of these agents remains unclear, Here, we report the results of 55 patients with standard risk leukaemia who have unde rgone allogeneic transplantation using either bone marrow (n = 48) or G-CSF mobilised peripheral blood stem cells (n = 7) using CsA and MTX for GVHD prophylaxis where the dosage of CsA was regularly adjusted to maintain a trough whole blood level of 95-205 ng/ml for the first 50 days post-transplant. To achieve this level of CsA in the immediate po st-transplant period, over 40% of patients required dose adjustments o f CsA as a result of sub-therapeutic levels an day +1 post-transplant. The achievement of CsA levels within the therapeutic range was expedi ted following the introduction of a sliding scale for dose adjustment. With this regimen me have observed a low incidence of acute GVHD with only 11% of patients developing greater than or equal to grade II dis ease. With a median follow-up of 66 months (range 8-132) the probabili ty of relapse is only 6.6%, The disease-free survival probability for all patients was 72% at 5 years, These results demonstrate that effect ive GVHD prevention with CsA and MTX can be achieved without a high ri sk of recurrent leukaemia provided that rapid attainment of therapeuti c CsA levels is achieved and maintenance within a low therapeutic rang e may help to maximise this effect.