Theodoros P. Vassilakopoulos1,*, Maria K. Angelopoulou1, Euridiki Kravariti1, Maria N. Dimopoulou1, Marina P. Siakantaris2, Athanasios Liaskas1, Gabriela Gainaru1, Ioannis Assimakopoulos1, Maria Arapaki1, Panagiotis Diamantopoulos2, Ilianna Konstantinou1, Georgios Boutsikas1, Kyriaki Petevi1, Alexandros Kanellopoulos1, Theofanis Giannikos1, Chrisovalanti Chatzidimitriou1, Maria Efstathopoulou1, Maria Dimou3, Maria Moschogiannis4, Xanthi Giakoumis4, Ilias Pessach4, Sotirios Sachanas4, Theodoros Iliakis3, Dimitrios Maltezas3, Christina Kalpadakis1, Veroniki Komninaka1, Panagiotis Tsaftaridis1, Eleni Plata1, Marie Christine Kyrtsonis3, Panagiotis Panagiotidis3, Eleni Variami2, Nora Athina Viniou2, Kostas Konstantopoulos1, Gerassimos A. Pangalis4
1Department of Haematology and Bone Morrow Transplantation,21st Department of Internal Medicine,31st Propaedeutic Department of Internal Medicine, Laikon General Hospital, National and Kapodistrian University of Athens,4Department of Haematology, Athens Medical Center, Psychikon Branch, Athens, Greece
Background: Despite significant improvements in the outcome of HL, VLRs (≥5 years after initial CT ± RT) do occur. Data on VLRs after standard CT ± RT are very limited, including our initial report and the recent large observational GHSG study. However, the incidence and risk factors of developing VLRs in HL require further evaluation.
Aims: To examine the incidence and risk factors of developing VLRs in patients with HL, who remain in first complete remission (CR1) for ≥5 years from treatment initiation.
Methods: Retrospective study of 931 adult patients, diagnosed with HL and remained in CR1 for ≥5 years after treatment initiation (follow-up exceeding 35 years). Anthracycline-based chemotherapy was administered in 89% of patients [mainly A (E) BVD], whereas 11% received MOPP. Survival analysis was performed using competing-risk regression models.
Results: VLRs occurred in 52/931 patients (2/52 relapsed as composite lymphoma) and the most delayed relapse occurred after 35 years. The distribution and cumulative incidence (CI) of VLRs are presented in the table. CI rose linearly over time after 5 years and the annual incidence rate was roughly estimated at 0.40% per person-year. After treatment with ABVD CT ± RT, the CI of VLR at 20 and 30 years, was estimated at 7.2% and 9.7% respectively. In multivariate analysis, independent protective prognostic factors were nodular sclerosing (NS) histology [hazard ratio (HR) = 0.41, p = 0.007], anthracycline-based (ABVD-type) CT ± RT vs MOPP-type (HR = 0.49, p = 0.04) and CT+RT vs CT (HR = 0.43, p = 0.03). Among 830 patients treated with anthracycline-based CT, independent protective prognostic factor was the NS histology (HR = 0.33, p = 0.006); age ≤45 years was of borderline significance (HR = 0.57, p = 0.14).
Conclusion: This is the 2nd largest study aiming to determine the incidence of VLRs in HL, providing the longest follow-up. We confirm the linear pattern of VLR up to 20 years after ABVD-like CT ± RT, but we also highlight that VLRs can occur up to at least 35 years after initial treatment. VLRs were more common after MOPP than after ABVD. Patients with non-NS histology had an increased risk of VLRs with mixed cellularity being the most adverse. The final results with further follow-up and 56 VLRs will be presented at the Meeting.