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Reduced intensity conditioning HLA identical sibling donor allogeneic stem cell transplantation for patients with follicular lymphoma: long-term follow-up from two prospective multicenter trials

¹ Clinical Hematology Hospital de la Santa Creu Sant Pau, (UAB) Barcelona, Spain
² Clinical Hematology, Hospital Gregorio Marañón, Madrid, Spain
³ Clinical Hematology, Hospital 12 de Octubre, Madrid, Spain
⁴ Clinical hematology, Hospital La Princesa, Madrid, Spain
⁵ Clinical Hematology, Fundación Jimenez-Díaz, Madrid, Spain;
⁶ Clinical Hematology, Hospital Son Dureta, Mallorca, Spain
⁷ Clinical Hematology, Hospital Clínico, Valencia, Spain
⁸ Clinical Hematology, Hospital Clínico de Salamanca, Salamanca, Spain

Correspondence: Jose Luis Piñana, MD, Division of Clinical Hematology, Hospital de la Santa Creu i Sant Pau, St Antoni Mª Claret 167, Barcelona 08021, Spain. E-mail: jpinana{at}hospitalmanises.es

ABSTRACT

Background: Allogeneic hematopoietic stem cell transplantation (alloSCT) is an effective treatment for poor risk lymphoma patients, at least in part due to the graft-versus-lymphoma effect. Over the past decade, reduced intensity conditioning (RIC) regimens have been shown to offer similar results than conventional high-dose conditioning regimens but with lower toxicity early post-transplant, especially in patients with chemosensitive disease at transplant.

Design and Methods: The aim of this study was to analyze the long-term outcome of patients with follicular lymphoma (FL) who received an HLA identical sibling alloSCT with a RIC regimen (Allo-RIC) within prospective trials. These prospective multicenter studies included 37 patients with FL who underwent Allo-RIC between 1998 and 2007 with a fludarabine plus melphalan-based Allo-RIC.

Results: The median age was 50 years (range 34–62) and the median follow-up was 52 months (range 0.6 to 113). Most patients (77%) had stage III–IV at diagnosis, and patients had received a median of three lines of therapy before Allo-RIC. At the time of transplant, 14 patients were in complete remission (CR), 16 in partial remission (PR) and 7 had refractory or progressive (PROG) disease after salvage chemotherapy. The 4-year overall survival for patients in CR, PR and with PROG disease were 71%, 48% and 29%, respectively (p=0.09), and the 4-year cumulative incidence of non-relapse mortality (NRM) was 26% (95% CI 11–61), 33% (95%CI 16–68) and 71% (95%CI 44–100), respectively, while the incidence of relapse for the whole group was only 8% (95% CI 2–23).

Conclusions: We conclude that this Allo-RIC strategy may be associated with significant NRM in heavily pre-treated patients with FL, but a remarkable low relapse rate and long-term survival is likely in patients without progressive and refractory disease at transplant.

Key words: follicular lymphoma, reduced intensity conditioning, HLA identical sibling donor, HSCT, Allo-RIC, GVHD.