Autologous Stem Cell (AUTO) vs Non-Myeloablative Allogeneic Transplantation (NMT) after High-Dose Rituximab (HD-R) -Containing Conditioning Regimens for Relapsed Chemosensitve Follicular Lymphoma (FL).
Authors: Khouri Issa F. , Saliba Rima M. , Hosing Chitra M. , Acholonu Sandra A. , Fayad Luis E. , Korbling Martin J. , Saenz Celina , Pro Barbara , Samuels Barry I. , de Lima Marcos J. , Giralt Sergio A. , Younes Anas , McLaughlin Peter W. , Champlin Richard E. 
Published: April 2020

Abstract
We evaluated the safety and efficacy of NMT vs. AUTO as a treatment modality for patients (pts) with relapsed chemosensitive FL. Pts were considered for AUTO if they did not have a matched sibling donor. Pts were eligible for NMT if they had a donor, especially if pts were &gt; 1st relapse or failed a prior AUTO. Between March 1999 and April 2005, 68 consecutive pts were treated. 47 received a NMT after conditioning with fludarabine, cyclophosphamide, HD-R (Blood89:3595, 2001). Twenty-one other pts received AUTO after either Cy/TBI/HD-R (N=8) or BEAM/HD-R (N= 13) (JCO23:2240,2005). The HD-R regimen consisted of 2 injections pre-transplant in NMT or during cell mobilization for AUTO, at 375 mg/m2 and 1000 mg/m2, respectively. Pts then received two additional doses of 1000 mg/m2 at days +1 and +8 post-transplant. Median age of pts (53 yrs), time from diagnosis to transplant (3yrs), % pts in PR (57%) at study entry were equal in both groups. There was no statistically significant difference in gender distribution, histology subtypes of FL grades, history of marrow involvement, beta-2 microglobulin (b2-m), IPI and LDH levels between the two groups. There were however more pts in the NMT group who had &gt; 1 relapse (38% vs 19%, P = 0.09), or had &gt; 3 lines of therapy (28% vs none). Eight pts (17%) in the NMT group had failed a prior AUTO. Sixty-six pts (97%) had peripheral blood (PB) transplant, two other pts with NMT received marrow from an unrelated donor. With a median follow-up time of 34 months, overall survival rates at 3-year were 88% and 84% for the NMT and AUTO groups, respectively (P=0.8). DFS and risk of progression were comparable between the two groups (85% vs 84%, and 3% vs 5%, respectively). DFS for the 8 pts who received NMT after failing a prior AUTO was 87% at 4-year. Causes of death varied between the AUTO group [Secondary leukemia (2), viral encephalitis (1)] and the NMT group [acute GVHD (2), chronic GVHD (2), unknown (1)]. We compared the outcome of AUTO in this study [AUTO Study Group), to a historical group [AUTO Control Group] of pts who received an AUTO under an immediately preceding protocol (years of therapy: 1994-1998). Pts in the AUTO Control Group were younger [Median age was 47 vs. 53 yrs, respectively, P = 0.007)], received Cy/VP-16/TBI without HD-R as conditioning regimen, and mostly (84% of pts) received in-vitro purged marrow as the source of graft (P &lt; 0.001). Other disease characteristics were not statistically different between them. Results at 3-years demonstrated a higher risk of progression in the AUTO Control Group compared to the AUTO Study Group (26% vs. 5%, respectively, P = 0.09), an inferior DFS (58% vs. 84%, respectively, P = 0.04), and a tendency for a shorter survival (74% vs 84%, respectively, P = 0.2). These data suggest that NMT has a spectrum of safety that becoming comparable to AUTO. HD-R appears to improve the outcome after AUTO. Longer follow-up is needed to assess remission duration in the 2 study groups. A prospective controlled trial of AUTO vs. NMT using HD-R in each arm is warranted to assess the optimal strategy for treatment of relapsed FL.