High Dose Therapy and Autologous Stem Cell Transplantation in Marginal Zone Lymphoma : An EBMT-FIL-Gimeto Retrospective Study
Authors: Avivi Irit , Arcaini Luca , Ferretti Virginia , Boumendil Ariane , Finel Herve , Pascutto Cristiana , Milone Giuseppe , Zaja Francesco , Liliana Devizzi , Musso Maurizio , Didier Blaise , Salles Gilles , Wattad Mohammed , Nicolas-Virelizier Emmanuelle , Gramatzki Martin , Bourhis Jean-Henri , Caillot Denis , Haenel Shannon , Haenel Anette , Held Gerhard , Thieblemont Catherine , Jindra Pavel , Pohlreich David , Guilhot François , Bornhaeuser Martin , Ljungman Per T. , Scheid Christof , Ifrah Norbert , Berthou Christian , Dreger Peter , Montoto Silvia , Conconi Annarita 
Published: November 2019

Abstract
Introduction:The role of autologous stem cell transplantation (ASCT) in patients with marginal zone lymphomas (MZL) is not fully elucidated. The aim of the present study was to determine the outcome of patients undergoing ASCT for relapsed/refractory MZL, and define prognostic factors affecting that outcome.
Methods: Eligible for this study were patients with nodal, extra-nodal (MALT) or splenic MZL , aged ≥18 ears, who underwent a first ASCT between July 1994 and February 2013, and reported to the European Society for Blood and Marrow Transplantation (EBMT) registry, and/or the Fondazione Italiana Linfomi (FIL) and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) networks.
Patients with a history of MZL transformation were excluded. Review of written diagnostic reports was mandatory for inclusion. Log rank tests were used to assess the impact of baseline characteristics on overall survival (OS) and event-free survival (EFS). In multivariate analysis, the effect of prognostic factors was evaluated using Cox regression models. Cumulative incidence of relapse (IR) and cumulative incidence of non-relapse mortality (NRM) were estimated with a competing-risk approach. Risk factors for IR and NRM were estimated by Pepe & Mori test or by Fine & Gray model.
Results: The study included 199 patients, 111 patients (56%) with MALT lymphoma, 55 patients with nodal MZL (28%) and 33 patients (16%) with splenic MZL.. Median age at transplantation was 56 years (range, 25-71 years). Median time from diagnosis to ASCT was 2 years (0.1-28.0). Median number of prior therapies was 1 , (range 1-8) , including rituximab in 74%. 96% were transplanted with chemosensitive disease; 70 (37%) in CR1/PR1 ,113(59%) in CR/PR >1 and 7 in SD (4%) Median calendar year of ASCT was 2006, with 17,1% of transplants being performed before 2001. Total body irradiation-based high-dose regimen was used in 16 patients (8%), whilst 92% of the patients received high-dose chemotherapy only. Median follow-up was 4.1 years (0.1-19.1). Five-year cumulative incidence of relapse/progression (IR) and non-relapse mortality (NRM) were 38% (95%CI 30-45%) and 9 %( 95%CI 6-14%) respectively. Five-year event-free survival (EFS) and overall survival (OS) were 53% (95%CI 45-61%) and 73% (95%CI 65-79%), respectively.
Multivariate analysis revealed age >65 years to be associated with shorter EFS and a shorter OS (HR=8.6, 95%CI 2.8-26.2, p<0.001 and HR=5.2,95%CI 1.9-14, p=0.001 respectively).
Additionally, MZL predicted a shorter OS than MALT (HR=3.2, 95%CI 1.2-8.7, p=0.023). Notably, rituximab had no statistically significant effect on transplant outcome.Risk of secondary malignancies approached 6.8%.
Conclusions: ASCT is a feasible and effective procedure when offered to MZL patients younger than 65 years, even in those previously exposed to rituximab.

Disclosures
Zaja: MedImmune: Research Funding.