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.