ISHL10 Abstract T026

Change in peripheral blood lymphocyte telomere length in relation to mortality and morbidity in Hodgkin Lymphoma patients

Background: Short telomeres in peripheral blood lymphocytes are associated to an increased cancer risk as well as age-related diseases. Our previous studies demonstrated the significant correlation between telomere dysfunction in peripheral blood lymphocytes of retrospective cohorts of Hodgkin lymphoma (HL) patients and the high risk of late complications, in particular secondary cancers and cardiovascular disease. In this study, we investigate telomere length in a prospective cohort of HL patients followed more than 12 years after diagnosis. Patients and methods Telomere length measurements were performed at several time points in a prospective cohort of 220 HL survivors patients (95.9% stage I and II). Patients were diagnosed between 1997 and 2005 with a median follow-up 11.2 years. All patients were treated with a combination of chemotherapy and radiation therapy. We evaluated the association between telomere length measured at diagnosis, after treatment and during follow-up. The dynamics of telomere change between those time points in relation to HL cancer specific and all-cause mortality and morbidity was assessed using Cox proportion hazards models. Cardiovascular evaluation has been described previously (Girinsky et al. 2014). Results: Fifty-seven patients developed cardiovascular disease, 19 a secondary cancer and 10 died. Telomere length at baseline and follow-up after treatment were associated with all-cause mortality (p=0.02 and p=0.008, respectively). A stable telomere length was associated with the absence of late complication. Changes in telomere length were associated to the occurrence of a late complication, either cardiovascular or secondary cancer (p<10-3). A high variation of telomere length and the presence of a sub population of cells with drastic telomere shortening was observed during follow-up preceding a secondary cancer (p<10-3). Telomere dysfunction was related to the presence of complex chromosomal exchanges. Conclusion: Telomere shortening was associated with an increased risk of the occurrence of secondary cancer and all-cause mortality. Changes in telomere length in circulating lymphocytes over time may represent valid biomarkers for the prognosis. Telomere dysfunction may play a significant role in the initiation of genomic instability during carcinogenesis. Further investigation to determine causes of telomere change is needed.