Long-Term Disease-Free Survival in Patients with Relapsed/Refractory Follicular Lymphoma After Autologous Stem Cell Trasplantation
Authors: Garcia Pablo A , Remaggi Guillermina , de Goycoechea Diego A , Yantorno Sebastian , Rivas Maria Marta , Basquiera Ana , Prates Maria Virginia , Molnar Soledad , Rizzi Maria L , Jarchum Gustavo , Milone Gustavo , Milone Jorge H , Kusminsky Gustavo Daniel , Pavlovsky Miguel Arturo , Rolon Juliana Martinez , Garcia Juan 
Published: October 2019

Abstract
Abstract 2031

Background:
The role of High-Dose Therapy (HDT) and Autologous Stem Cell Transplantation (ASCT) as salvage therapy in relapsed Follicular Lymphoma (FL) has been questioned since the introduction of Rituximab in the treatment of FL. Our objectives were to evaluate the long-term event-free survival (EFS) and overall survival (OS) rates of patients with relapsed or refractory FL who received HDT and ASCT as salvage therapy. Our secondary objective was to compare EFS of patients who received ASCT before and after 2002 (the year Rituximab become fully available for use in our country).

Patients and Methods:
We conducted a retrospective analysis of 123 consecutive patients with relapsed or refractory FL who had received HDT and ASCT as salvage therapy in five Argentinean transplant centers from 1992 to 2012.

Results:
One hundred twenty tree patients (median age: 48 years, range: 23–72) were transplanted, 71 (58%) male, 37/106 (35%) had FL Grade 1, 47/106 (44%) FL Grade 2 and 22/106 (21%) FL Grade 3; 75/102 (73%) of patients have a stage III-IV disease at the moment of diagnosis and 27/102 (26%) have a disease stage I-II. Before transplantation 78/121 (64%) patients were in Complete Response (CR), 42/121 (35%) were in Partial Response (PR) and one patient had a Progressive Disease. Fifty four patients (44%) were transplanted before 2002 (before Rituximab era in our country). The conditioning regimens used were CBV 94 (76%), BEAM/BEAC 27 (22%), others regimens two patients; only one patient received TBI containing conditioning regimen and was excluded for conditioning regimen PFS curve calculation. The median time from FL diagnosis to ASCT was 29 (range 1–300) months. The transplant related mortality (until day 90 after ASCT) was 5%. With a median follow-up of 52 (range 0–247)months, the median EFS was reached at 44 months and a plateau on the EFS curve was evident starting at 6 years after ASCT. The 10 years-projected EFS was 36% (Figure 1). The median OS was not reached during follow-up. Median EFS for patients who were transplanted before 2002 (before Rituximab era) and for those who were transplanted after 2002 was 41 months and 47 months respectively [HR 1.01; IC (0.61–1.65); p=0.97]. EFS rates difference was not statically significant between patients who previously transplantation have achieved a CR or a PR, median EFS 47 and 68 months respectively [HR 0,94; IC (0,56–1,58); p= 0,82]. There was no difference in EFS rates between patients who received CBV as conditioning regimen and patients who received BEAM/BEAC, median EFS 57.6 months and 16.3 months respectively [HR 0.67; IC (0,34–1.35); p=0.2]. The median EFS rate for patients with FL Grade 1, FL Grade 2 and FL grade 3 were 58, 44 and 16 months respectively, P for trend = 0.78.
Seven cases (5,7%) of secondary malignancies were detected, six cases (6/94; 6,4%) in patients who received CBV as conditioning regimen (urotelial carcinoma, pancreas carcinoma, lynfoprolipherative disorders, non-melanoma skin malignancies and prostate carcinoma) and one case (1/27; 3,7%) in patients who received BEAM (urotelial carcinoma), p=0,85; there were no reports of secondary myelodysplastic syndromes/acute myeloid leukemia.

Conclusion:
In this study, 50% of the patients analyzed were free from progression after 44 months of ASCT and approximately a 30% of patients achieve long term remission. According to this, patients with relapsed or refractory FL can achieve long-term EFS with HDT followed by ASCT.

Disclosures:
No relevant conflicts of interest to declare.