Theodoros P. Vassilakopoulos1,*, Athanasios Liaskas1,*, Giuliana Rizzuto2, Maria K. Angelopoulou1, Maria N. Dimopoulou1, Alberto Mussetti2, Marina P. Siakantaris1, Ioannis Assimakopoulos1, Maria Arapaki1, Penelope Korkolopoulou3, Antonello Cabras4, George Rassidakis3, Maria Dimou5, Eleni Variami6, Panagiotis Panagiotidis5, Paolo Corradini2, Kostas Konstantopoulos1, Gerassimos A. Pangalis7, Simonetta Viviani2
1Department of Haematology and Bone Morrow Transplantation, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece,2Department of Hematology, Istituto Nazionale dei Tumori, Milan, Italy,3Department of Pathology, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece,4Department of Diagnostic Pathology and Laboratory Medicine, Istituto Nazionale dei Tumori, Milan, Italy,51st Propaedeutic Department of Internal Medicine,61st Department of Internal Medicine, National and Kapodistrian University of Athens, Laikon General Hospital,7Department of Haematology, Athens Medical Center, Psychikon Branch, Athens, Greece
*TPV and AL had equal contribution to this work.
Background: Traditionally, HL is considered cured after a 5-year disease-free period. However, our initial report and the recent large GHSG study have demonstrated that VLRs, occurring ≥5 years after initial treatment initiation, are a rather uncommon but non-negligible event. Due to the rarity of these events very few data exist describing the outcome of VLRs after CT ± RT, while there is no study focusing on potential prognostic factors.
Aim: To evaluate the treatment strategies adopted for patients with VLRs in 2 referral Centers in Greece and Northern Italy as well as their outcome and prognostic factors for Freedom From Second Progression (FF2P) and overall survival after failure (O2S).
Patients/Methods: Patients with HL, who experienced VLRs after CT ± RT were identified retrospectively from the databases of the participating centers. Statistical endpoints were the estimation of FF2P and O2S.
Results: 87 patients with VLRs after CT ± RT were identified. Relapse occurred >15 years after the initial diagnosis in 21% of the patients, 64% of the patients were males and 16% were ≥65 years old. Reinduction with the same regimen was given in 28% of the cases, 5 patients (6%) received salvage RT only and 22% proceeded to high-dose therapy and autologous stem cell transplantation (HDT/ASCT). The 5- and 10-year FF2P was 56% and 51%, while the 10-year O2S was 56%. Among 32 deaths, only 19 were due to HL; 13 deaths were purely attributed to 2nd malignancies (n = 9) and unrelated causes (n = 4). Reinduction or HDT/ASCT did not significantly affect FF2P and O2S; 4/5 patients selected for salvage RT only had long-term remissions. A clear numerical difference was observed regarding 5-year FF2P for patients < 65 years old who received HDT/ASCT (88% vs 55%), but this was just 59% vs 55% at 10 years and did not reach statistical significance (p = 0.42). In multivariate analysis only anemia at relapse was independent predictor of FF2P; both anemia and age ≥65 years at relapse independently predicted for worse O2S. However, B-symptoms at relapse and relapse after >15 years were borderline in univariate analysis and deserve further consideration.
Conclusion: The prognosis of VLRs after CT ± RT for HL does not appear very favorable; however, a considerable proportion of patients succumb to 2nd malignancies and unrelated diseases. Treatment approaches are heterogenous and HDT/ASCT is underused. Advanced age and anemia at relapse were the most important prognostic factors in this series.