The tolerability and efficacy of total lymphoid irradiation (TLI) in the control of rapidly progressive bronchiolitis obliterans syndrome

Abstract

Low dose radiotherapy (8 Gy in 10 fractions) to the lymphoid structures can be used as an adjunct to standard immunosuppressive therapy in progressive Bronchiolitis Obliterans Syndrome (BOS). Data on tolerability and efficacy of TLI is however limited. In our centre, 37 (16M:21F) recipients have received TLI for progressive BOS between 1988 and 2001. Mean (sd) recipient age was 37.6(12.7) years when they underwent 13 single, 12 bilateral and 12 heart-lung transplants. Baseline FEV1 was mean (sd) 2.60 (0.8)litres. BOS was diagnosed median (range) 18 (4 - 81) months after transplant. BOS grades at the time of TLI were BOS 1(7), BOS 2 (14), and BOS 3 (16). The mean (sd) FEV1 pre-TLI was 1.32 (0.57) litres. Twenty seven (73%) recipients successfully completed ≥8 fractions. Ten did not complete planned treatment: 2 died very early during TLI due to respiratory failure; 8 were stopped early (range 3-7 fractions) due to minor marrow suppression or infectious complications. The mean (sd) nadir leukocyte count was 2.98 (1.34) x 109 and platelet nadir 114 (41) x 106. Seven (19%) required blood transfusion and only 2(5%) had serious infections as complications. Duration of TLI course was mean (sd) 62.8 (41.7) days. Mean (sd) rate of decline in FEV1 was 122.7 (21.6) mls/month before TLI and 25.1(7.7) mls/month after TLI, (difference in rate of decline 95% CI 48.2-146.7), p=0.0004 (students paired t-test). Total survival in the 37 treated recipients is median (range) 59 (6-146) months and the post TLI survival is 27 (0-93) months. TLI is a well tolerated treatment with only mild marrow suppression and a low incidence of serious infection. It results in a significant reduction in the rate of FEV1 decline in rapidly progressive BOS. TLI should form part of the immunosuppressive armoury in patients with aggressive BOS.