Impact of Conditioning Regimen Intensity On the Outcomes of Allogeneic Hematopoietic Cell Transplantation for Refractory Grade-III Follicular (FL-III) and Diffuse Large B-Cell Lymphomas (DLBCL): A Cibmtr Analysis

Patients with chemorefractory aggressive B-cell non-Hodgkin lymphomas (aB-NHL) have a poor prognosis. The role of allogeneic hematopoietic cell transplantation (allo-HCT) and the optimal intensity of conditioning regimen employed for this high-risk group are poorly defined.

We report here the outcomes of allo-HCT in patients with chemorefractory aB-NHL according to the intensity of transplant conditioning regimens, using the CIBMTR database. The study population included all patients with chemorefractory DLBCL and FL-III receiving an allo-HCT reported to the CIBMTR between 1998 and 2010. Patients with evidence of chemosensitive disease (i.e. patients in CR or PR) at the time of allo-HCT were excluded. Primary outcomes were non-relapse mortality (NRM), progression/relapse (P/R), progression-free survival (PFS), and overall survival (OS). The outcomes of patients undergoing myeloablative conditioning (MA) were compared with those of patients receiving reduced intensity/non-myeloablative conditioning (RIC/NST). Conditioning regimen intensity was defined according to CIBMTR guidelines (Bacigalupo A. BBMT).

A total of 307 patients received MA, and 226 underwent RIC/NST. Median follow up of survivors for MA and RIC/NST groups was 35mos and 30mos, respectively. Completeness of follow up at 3 years was 80%. The baseline characteristics of both groups are described in Table 1. No significant differences at baseline were observed between the MA and RIC/NST groups in terms of disease stage at diagnosis, B-symptoms, lines of prior therapy, bone marrow or extranodal involvement, disease bulk, central nervous system involvement, prior rituximab use, and donor type. Significantly more patients in the RIC/NST group had a prior autologous-HCT (38% vs. 15%; p<0.001) and received a peripheral blood allograft (88% vs. 79%; p=0.008). Cumulative incidence of grade II-IV acute GVHD at day +100 was 29% and 31% in MA and RIC/NST groups (p=0.68), respectively. Cumulative incidence of chronic GVHD at 1 year post transplantation in similar order was 33% and 38%, respectively (p=0.27). On univariate analysis, at 3 years, MA allo-HCT was associated with a higher NRM compared to RIC/NST (53% vs. 42%; p=0.03), similar PFS (19% vs. 23%; p=0.40), and lower OS (19% vs. 28%; p=0.02), respectively. On multivariate analysis, FL-III histology was associated with lower NRM (relative risk [RR]=0.52; 95% CI 0.35–0.79, p=0.002), reduced risk of R/P (RR=0.42; 95% CI 0.25–0.73, p=0.002) and superior PFS (RR=0.51; 95% CI 0.37–0.7; p<0.001) and OS (RR=0.53; 95% CI 0.39–0.72; p<0.001), while MA conditioning was associated with reduced risk of R/P (RR=0.66; 95% CI 0.47–0.92; p=0.015), but similar OS, NRM, and PFS. Multivariate analysis constructed by excluding patients undergoing a prior autologous-HCT showed similar results. On subgroup analysis, the 3 year PFS of FL-III patients (N=80) in our study for MA and RIC/NST cohorts was 41% and 40% respectively.

Despite a refractory disease state, a small subset (∼25%) of DLBCL and FL-III NHL patients can attain durable remissions after allo-HCT. Conditioning regimen intensity was not associated with NRM, PFS and OS despite a higher risk of relapse/progression with RIC/NST allo-HCT.

No relevant conflicts of interest to declare.