Risk for pulmonary late effects in childhood Hodgkin lymphoma survivors.

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112 Background: Survivors of Hodgkin lymphoma (HL) are at risk for pulmonary late effects, including pulmonary fibrosis (PF). Established risk factors such as younger age at diagnosis and specific therapeutic exposures explain a fraction of the risk for these outcomes. Notably, systemic inflammation and impaired telomere maintenance are associated with adverse pulmonary outcomes in adult populations, but have not been explored in cancer survivors. Our aim was to identify pulmonary diffusion defects in HL survivors, and evaluate the impact of short lymphocyte telomere length (LTL) and systemic inflammation on these outcomes. Methods: Blood samples, demographic and treatment data, and lung carbon monoxide diffusion capacity corrected for hemoglobin and alveolar volume (DLCO) were obtained from HL survivors ≥6 months off therapy and without history of relapse or transplant. LTL was measured by telomere flow FISH (Repeat Diagnostics), and age-based percentiles determined from population controls. Plasma elevations in pro-inflammatory cytokines (HCYTMAG panel, EMD Millipore) were detected on a Luminex platform. Associations between clinical features and most recent DLCO were determined by linear regression, adjusted for age, sex, radiation, and race/ethnicity. In a subset of subjects, cytokine levels and LTL were compared in survivors with DLCO above or below the mean using a Student t-test or Fisher’s Exact test, respectively. Results: Seventy-two HL survivors met inclusion criteria (mean age at diagnosis=14 years, range: 3-18 years). Mean off-therapy DLCO was 75% (range: 52-98%), below the lower limit of normal (76%) in healthy populations. DLCO was inversely associated with female sex (p = 0.002). Five of 24 survivors (21%) had LTL ≤10th percentile for age, but there was no difference in LTL relative to DLCO. Survivors with DLCO ≤75% had higher IL1α and IL1β levels (n = 30, p = 0.07). Conclusions: HL survivors had lower than expected DLCO, with females at highest risk for impaired pulmonary diffusion. Twice as many survivors as expected had LTL ≤10th percentile, and PF-related cytokine profiles were observed in survivors with lower DLCO, suggesting inflammation and telomere maintenance defects may contribute to late effects in HL survivors.