Background: Despite the excellent long-term outcome of patients with Hodgkin Lymphoma (HL) some patients will eventually relapse, mainly within the initial 2 years from diagnosis. Typically the disease is considered cured after a 5-year continuous first complete remission. However, Very Late Relapses (VLRs), occurring≥5 years after treatment initiation, are non-negligible and possibly consist a patient subgroup with unique characteristics.
Aim: To describe the treatment strategies adopted for patients with VLRs as well as their outcome and search for relevant prognostic factors.
Methods: Patients with HL who experienced VLRs≥5 years after treatment initiation with chemotherapy±radiotherapy, were identified retrospectively from the databases of 6 referral centers. Statistical endpoints were the estimation of Freedom From Second Progression (FF2P), Overall Survival after Failure (O2S) and Disease Specific Survival after Failure (DS2S).
Results: Overall, 137 patients with VLRs were identified. The median age was 49 years (19-82), 69% were males and 19% were ≥65 years old at the time of relapse. In 21% of the patients ,relapse occurred >15 years after the initial diagnosis. Reinduction with the same regimen was given in 24% of the patients, and 25% proceeded or were treated with second-line regimen with the intention to proceed to high-dose therapy and autologous stem cell transplantation (HDT/ASCT). The 5- and 10-year FF2P were 57% and 52% respectively, the 10-year O2S was 57% and the 10-year DS2S was 75%. Among 50 deaths, only 28 were disease-related, whereas 22 were attributed to secondary malignancies or unrelated causes. Reinduction with the same regimen did not significantly affect FF2P and O2S. Despite the numerical difference in 5-year FF2P for patients <65 years old who received HDT/ASCT (75% vs 60%), there was no difference at 10 years. In multivariate analysis anemia, extranodal disease and age ≥65 were independent prognostic factors for FF2P, O2S and DS2S. Patients combining 2-3 adverse characteristics had significantly compromised outcome.
Conclusion: The outcome of VLRs does not appear favorable, however a considerable proportion of patients were ≥65 years old at the time of VLR when treatment options are limited and also, many patients succumb to disease-unrelated causes. Treatment approaches were heterogenous and HDT/ASCT was rather underused. In our study anemia,extranodal disease and age≥65 were the most relevant adverse prognostic factors.
Theodoros P. Vassilakopoulos, Athanasios Liaskas, Giuliana Rizzuto, Argyrios Symeonidis, Marzia Palma, Maria K. Angelopoulou, Chara Giatra, Flora Kondopidou, Maria Dimou, Alberto Musseti, Ioanna Xagoraris, Marina Siakantaris, Evgenia Verigou, Fotios Panitsas, John Asimakopoulos, Maria Arapaki, Chrysovalantou Chatzidimitriou, Marina Belia, Sotirios Sachanas, Penelope Korkolopoulou, Antonello Cabras, Eleni Variamis, Panayiotis Panayiotidis, Maria Bakiri, Themistoklis Karmiris, Georgios Z. Rassidakis, Paolo C