title: Efficacy of total lymphoid irradiation for chronic allograft rejection following bilateral lung transplantation.
abstract: OBJECTIVE
  To assess the safety and efficacy of total lymphoid irradiation (TLI) in patients experiencing chronic rejection following bilateral lung transplantation (BLT).
  
  
  METHODS
  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. Serial pre- and post-RT pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements [use of methylprednisolone, murine anti-human mature T-cell monoclonal antibody (OKT3), polyclonal antithymocyte globulin (ATG), and tacrolimus] were monitored.
  
  
  RESULTS
  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 number of immunosuppression augmentations was 3 (range 0-5). Only 4 of 11 patients completed all 10 TLI treatment fractions. Reasons for discontinuation included progressive pulmonary decline (four patients), worsening pulmonary infection (two patients), and persistent thrombocytopenia (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. Six patients died. Two of these deaths were due to pulmonary infection from organisms isolated prior to the start of RT; the other four deaths were from progressive pulmonary decline. The four remaining patients had 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 FEV1 (40% decline vs. 1% improvement) and fewer median number of immunosuppressive augmentations (3.5 vs. 0). None of these patients has developed lymphoproliferative disease or has died. Features suggestive of a positive response to TLI included longer interval from transplant to RT, higher FEV1 at initiation of RT, and absence of preexisting pulmonary infection.
  
  
  CONCLUSIONS
  Total lymphoid irradiation for chronic allograft rejection refractory to conventional medical management following BLT was tolerable. A subset of patients experienced durable preservation of pulmonary function and decreased immunosuppressive requirements. Patients with rapidly progressive allograft rejection, low FEV1, or preexisting infection were least likely to benefit from irradiation. Early initiation of TLI for patients experiencing chronic allograft rejection following BLT may be warranted.
authors.affiliation: Division of Radiation Oncology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Diamond
authors.forename: J M
authors.initials: JM
authors.lastname: Michalski
authors.forename: J P
authors.initials: JP
authors.lastname: Lynch
authors.forename: E P
authors.initials: EP
authors.lastname: Trulock
mesh_terms: D000293:Adolescent; D000328:Adult; D001772:Blood Cell Count / Q000528:radiation effects; D001989:Bronchiolitis Obliterans / Q000097:blood / Q000503:physiopathology / Q000532:radiotherapy*; D002908:Chronic Disease; D005260:Female; D005541:Forced Expiratory Volume / Q000528:radiation effects; D006084:Graft Rejection / Q000097:blood / Q000503:physiopathology / Q000532:radiotherapy*; D006801:Humans; D016040:Lung Transplantation; D015182:Lymphatic Irradiation / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000097:blood / Q000503:physiopathology / Q000532:radiotherapy*