Relapsed Follicular Lymphoma Treatment - with or without Hematopoietic Stem Cell Transplant?

BACKGROUND: The best treatment strategy in patients with relapsed Follicular Lymphoma (FL) remains controversial. The incorporation of rituximab (R) in the 1^st line chemotherapy (CT) regimen and in treatment relapse resulted in better progression-free survival (PFS) but the benefit in overall survival (OS) was observed in only one trial (Hiddemann W. et al, Blood 2006). Hematopoietic stem cell transplant (HSCT) is the only treatment potentially curative, although the ideal time for its implementation remains undefined.

AIM: Evaluation of the best treatment strategy and the impact of HSCT in PFS and OS in patients with relapsed FL.

METHODS: Retrospective study including 85 patients with relapsed FL followed at a cancer care center between 2000-2012. Selection criteria: treatment naïve patients with the diagnosis of FL; absence of histological transformation at diagnosis and/or during the 1^st line treatment. Survival analysis using the Kaplan-Meier method. Type of response defined according to NCCN criteria.

RESULTS: Median follow-up of 64 months [4-158]. Disease progression after the 1st line CT was documented in 85 patients (median age 51 years [28-78], 42.4% male). 64 of the 85 patients had an Ann Arbor stage III-IV, of which 85.9% with follicular pattern, 95.3% grade 1/2 and 43.8% FLIPI ≥ 3. All patients underwent one or more CT regimens containing R, except in one case. In this study, 27.1% (n = 23) patients with age ≤ 60 years were submitted to HSCT (52.2% allogeneic HSCT from a related donor versus 47.8% autologous HSCT), almost all with ≥ 2 prior lines of CT (95.6%, n = 22). 78.3% (n = 18) had a CR or PR> 75% at the time of HSCT, and one death related to graft versus host disease was registered. Patients undergoing HSCT had a better PFS than those not transplanted (p = 0.022). A significant improvement in OS was observed in the HSCT subgroup (p = 0.007), especially in those with stage III-IV (p = 0.006). The type of HSCT had no impact on PFS and OS (p> 0.05), perhaps due to the small number of patients and short follow-up. By univariate Cox regression analysis, the number of regimens of CT before HSCT and the histological grade were independent predictors of PFS (p <0.05). The age and the histological grade were independent predictors of OS (p <0.05).

CONCLUSION: In this study, HSCT improved PFS and also OS in patients with relapsed FL, especially in patients receiving less than 3 CT regimen, highlighting the importance of completing the HSCT earlier, during the disease’s chemosensitive phase. Our data suggest the curative potential of HSCT in these patients, due to the GVL effect in allogeneic HSCT and/or intensive high-dose CT in autologous HSCT. More studies are needed to validate these observations.