Impact on Pulmonary Function of Pre-Transplant Radiotherapy in Hodgkin Lymphoma Patients Undergoing Autologous Stem Cell Transplant (ASCT).
Authors: Stotler Christy , Elson Paul , Bolwell Brian , Kalaycio Matt , Pohlman Brad , Sobecks Ronald , Dean Robert , Andresen Steven , Copelan Edward , Chan Josephine , Sweetenham John 
Published: October 2019

Abstract
For patients (pts) with Hodgkin lymphoma (HL) undergoing initial treatment with chemotherapy, often in conjunction with radiation therapy (RT), the rate of relapse ranges from 10 to 15 % in favorable prognosis stage I-II disease to 30 to 40 % in advanced disease. Patients with poor prognosis after first relapse, those with a second relapse, and pts with progressive disease are candidates for high dose chemotherapy followed by ASCT. A noted risk factor in HL patients following ASCT is development of pulmonary toxicity. The effect of prior conditioning regimens and RT on lung function has been implicated. Scant data is available regarding whether proximity of RT to time of transplant increases the risk for development of subsequent pulmonary toxicity. To address this question we retrospectively reviewed 172 sequential HL patients with pre-and post-transplant pulmonary function data who underwent ASCT at the Cleveland Clinic between 1985 and 2008 using a prospectively maintained, IRB approved, database. Bu/Cy/VP was the preparative regimen in 83% of pts (n=142), BCNU/Cy/VP in 13% of pts (n=22), and Melphalan in 4% of pts (n=7). The post-transplant change in pulmonary function (percent predicted DLCO and FEV1) in pts who received RT prior to ASCT was compared to those who did not receive RT. The timing of the RT was also examined. Statistical analysis was performed using the Wilcoxon rank sum test. 67 pts (39%) received pre-transplant RT at a median of 14.1 months prior to ASCT; 10 pts received RT ≤6 months prior to ASCT, 50 pts received RT >6 months before, and timing was unknown for seven pts. Overall, pts experienced a median 3.2% decline in DLCO (range 53.7% decline to 137.5% improvement) and a 2.9% decline in FEV1 (range 71.8% decline to 33.3% improvement) following transplant. The decline in DLCO and/or FEV1 was significant (>25%) in 16% of patients. The change in DLCO post-ASCT was not significantly different between pts who did or did not receive pre-transplant RT (median declines of 2.7% vs. 3.7%, respectively, p=1.0). There was, however, a significant difference with respect to FEV1. Pts who had prior RT experienced a median 6.4% decline in FEV1 following ASCT compared to a median 1.1% decline in pts who did not have prior RT (p=.03). The proportion of pts in whom the decline in FEV1 was significant however was similar in the two groups (7% vs. 6% respectively, p=1.0). Pts treated with pre-transplant RT within 6 months of ASCT tended to have greater declines in both DLCO and FEV1 following ASCT than patients not treated with RT (median declines: DLCO: 8.8% versus 0%; FEV1: 7.7% versus 4.8%, respectively); however the differences were not significant (p=.25 and .98, respectively).
Conclusions: Pts treated with RT prior to ASCT experience a greater decline in FEV1 post-transplant than RT-naïve patients. The decline, however, is not generally of clinical significance, and the proportion of pts with clinically significant impairment of pulmonary function is similar in the two groups.