Postransplant lymphoproliferative disorder (PTLD) may not be associated with development of bronchiolitis obliterans

Abstract

Bronchiolitis obliterans and bronchiolitis obliterans syndrome (BOS) secondary to chronic rejection remains a major cause of mortality in lung transplant recipients. Identified risk factors for the development of BOS include the frequency and severity of acute rejections (AR) and CMV infection. Reduction of immunosuppression is a standard treatment of PTLD. We investigated whether PTLD and the relaxation of immunosuppression increases the risk of developing BOS. From a single institution between 1988 and 2003, 24/346 lung transplant recipients (7 %) were diagnosed with PTLD. The median age of recipients with PTLD was 35.5 years (12-55 years). There were 14 heart-lung, 5 single, and 5 double lung recipients. Median time to diagnosis of PTLD was 257 days (48-5221 days). Fifty-eight percent (14/24) were diagnosed with BOS within 180-1837 days (median 524 days). Fifty percent (12/24) are deceased. The median follow-up from time of PTLD diagnosis was 31 mo (1-117 mo) for those with and 9.5 mo (1-115 mo) for those without BOS. Twenty-one percent (3/14) developed BOS prior to the diagnosis of PTLD. Two additional subjects met ISHLT criteria of BOS 0-p prior to diagnosis of PTLD. AR was diagnosed in 11/14 (79%) with PTLD + BOS and 4/10 (40%) with PTLD alone. Median time to first episode of AR was 17 days with only 2 subjects having a first AR after PTLD was diagnosed. Episodes of AR in the PTLD + BOS group were 2.0 episodes /pt vs. 0.8/pt in the PTLD alone group. Grade A1, A2, and A3 AR was diagnosed in those with BOS at rates of 0.28, 0.93, 0.36 vs. 0.1, 0.3, 0.2 episodes/pt, respectively with PTLD alone. CMV infection preceding the development of BOS was detected in 6/14 (43%) of the those with PTLD + BOS and 3/10 (30%) with PTLD alone. All CMV infections preceded the diagnosis of PTLD. In this series, subjects with PTLD + BOS had higher frequency and higher grade of AR and more CMV infection than those who did not develop BOS. Although those without BOS had shorter follow-up time, the diagnosis of PTLD and subsequent reduction of immunosuppression does not necessarily lead to increased rates of BOS.