METHOTREXATE CAN HALT THE PROGRESSION OF BRONCHIOLITIS OBLITERANS SYNDROME IN LUNG-TRANSPLANT RECIPIENTS

Background: Methotrexate has been used successfully to treat refractor y or recurrent rejection in heart transplant recipients. We therefore conducted an open pilot study to determine whether methotrexate is use ful in the treatment of chronic rejection after lung transplantation. Methods: Between December 1993 and January 1995 methotrexate was presc ribed to 10 patients with persistent or progressive bronchiolitis obli terans despite multiple attempts to control the chronic rejection with conventional treatment (pulse steroids or antilymphocyte products. or both). Data from the nine patients with a minimum of 6 months of foll ow-up were collected. Results: No patients have died. The spirometry d ata of the eight patients with declining values of forced expiratory v olume in 1 second are presented. Before initiation of methotrexate the rapy the median decline in forced expiratory volume in 1 second was 1. 4 +/- 0.8 L, or 43% +/- 17%, from the highest preinterventional forced expiratory volume in 1 second value during the preceding 12 months. A t 6 months the median decline in forced expiratory volume in 1 second from the time methotrexate therapy was started was 0.1 +/- 0.2 L, or 3 % +/- 11%. At 9 months (n = 6) the value was 0.2 +/- 0.2 L, or 6% +/- 12%. At 12 months (n = 5) the median decline was 0.4 +/- 0.3 L, or 9% +/- 16%. Ln two patients there has been no further decline in forced e xpiratory volume in 1 second since methotrexate therapy was started (o ne patient has had a slight but sustained improvement). Five patients have had a reduction in forced expiratory volume in 1 second of 10% or less at most recent follow-up, and only one patient has derived no ap parent benefit from methotrexate therapy. Toxicity has been minimal. C onclusions: Methotrexate is a potentially promising therapeutic altern ative in the therapy of bronchiolitis obliterans syndrome in lung tran splant recipients.