LENGTH OF CYCLOSPORINE THERAPY AFTER BONE -MARROW TRANSPLANT

After organ transplantation, life-long immunosuppression is mandatory to prevent rejection. This is not the case after allogeneic bone marro w transplantation (BMT). The mechanisms of tolerance are little unders tood and there is little data about the required duration of immunosup pression. In a retrospective study we analyzed the use of cyclosporine A (CyA) treatment in all BMT patients who where transplanted in Basel from 1979 to 1991. 243 patients with a median age of 26 (2-49) years received CyA to prevent graft-versus-host-disease (GVHD) and rejection . 206 patients had leukemia, 26 severe aplastic anemia and 10 a lympho proliferative disorder. All were treated according to a common CyA reg imen with initial parenteral administration followed by oral treatment for a year; after 1988 treatment duration was reduced to 6 months. Dr ug dosage was adjusted according to clinical symptoms, plasma levels a nd toxicity. At relapse of the original disease CBA was always withdra wn. Three months after BMT 96% were still on CyA. After 6 months 79%, after 1 year 61%, after 2 years 29%, after 3 years 18%, after 4 years 15%, after 5 years 8% and after 8 years 2% of patients were still taki ng CyA. All 20 patients who are still alive 10 years after BMT are off CBA. CyA was administered parenterally for a median of 31 (5-147) day s. Oral treatment started at day 25 (4-28). The oral dose was reduced 5 (1-20) times, increased once (1-75) and finally discontinued after a median time lapse of 1 year (14d-8y). The most prominent side effect was an elevation in serum creatinine from 75 (20-187) mu mol/l to 130 (46-600) mu mol/l three months after BMT After one year the creatinine values had improved to 97 (38-128) mu mol/l and after four years to 9 2 (43-145) mu mol/l. The increase in serum creatinine did not change d uring the whole observation period in spite of a reduction of the init ial CyA dose from 20 mg/kg to 5 mg/kg and therefore a reduction of the CyA plasma level at day 20 from 740 (60-3403) ng/ml to 411 (183-981) ng/ml. These data show that 2 years after BMT only 30% and after 5 yea rs only 8% of patients require immunosuppression with CyA. We therefor e believe an attempt to omit CyA after three months in patients withou t GVHD, and once yearly in those who require CyA for a longer period, is justified.