EFFICACY OF TOTAL LYMPHOID IRRADIATION FOR CHRONIC ALLOGRAFT-REJECTION FOLLOWING BILATERAL LUNG TRANSPLANTATION

Purpose: To assess the safety and efficacy of total lymphoid irradiati on (TLI) in patients experiencing chronic rejection following bilatera l lung transplantation (BLT). Patients and Materials: Eleven patients received TLI for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Radiation therapy (RT) was prescribed as 8 Gy delivered in 10 0.8-Gy fractions, 2 fractions/week, via mantle, paraaortic, and inverted-Y fields. Seria l pre- and post-RT pulmonary function values, complete blood counts, a nd immunosuppressive augmentation requirements [use of methylprednisol one, murine anti-human mature T-cell monoclonal antibody (OKT3), polyc lonal anti-thymocyte globulin (ATG), and tacrolimus] were monitored. R esults: In the 3 months preceding TLI, the average decrease in forced expiratory volume in 1 s (FEV1) was 34% (range 0-75%) and the median n umber of immunosuppression augmentations was 3 (range 0-5). Only 4 of II patients completed all 10 TLI treatment fractions. Reasons for disc ontinuation included progressive pulmonary decline (four patients), wo rsening pulmonary infection (two patients), and persistent thrombocyto penia (one patient). Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related-donor transplants; he is alive and well. Sis patients died. Two of these deaths were due to pulmonary infection fro m organisms isolated prior to the start of RT; the other four deaths w ere from progressive pulmonary decline. The four remaining patients ha d durable positive responses to TLI (mean follow-up of 47 weeks; range 24-72). Comparing the 3 months preceding RT to the 3 months following treatment, these four patients had improvements in average FEV, (40% decline vs. 1% improvement) and fewer median number of immunosuppressi ve augmentations (3.5 vs. 0). None of these patients has developed lym phoproliferative disease or has died. Features suggestive of a positiv e response to TLI included longer interval from transplant to RT, high er FEV, at initiation of RT, and absence of preexisting pulmonary infe ction. Conclusion: Total lymphoid irradiation for chronic allograft re jection refractory to conventional medical management following BLT wa s tolerable. A subset of patients experienced durable preservation of pulmonary function and decreased immunosuppressive requirements. Patie nts with rapidly progressive allograft rejection, low FEV1, or preexis ting infection were least likely to benefit from irradiation. Early in itiation of TLI for patients experiencing chronic allograft rejection following BLT may be warranted. (C) 1998 Elsevier Science Inc.