Abstract
This study aimed to evaluate the role of RIC allo-SCT for relapsed or refractory non-Hodgkin’s lymphoma (NHL). We report here our experience in 25 consecutive patients transplanted in a single center for high grade (n=17) or follicular NHL (FL; n=8). In the high grade NHL group, median age was 46 (range, 24–63) years, and all 17 patients received 2 or more previous chemotherapy regimens prior to RIC allo-SCT. In addition, 12 patients (71%) had failed autologous SCT and 6 patients (35%) had chemoresistant disease at time of allo-SCT. Among the 8 patients transplanted for a heavily pretreated follicular NHL (FL), median age was 52 (range, 34–59) years and median number of prior lines of therapy was 3 (range, 2–5), with 3 patients (38%) having chemoresistant diseases and 4 patients (50%) relapsing after autologous SCT.
Among the 17 patients with aggressive high grade NHL, we compared the outcome of T-cell and B-cell aggressive NHL. With a median follow-up of 15.4 (range, 3.4-65.2) months, the cumulative incidence of non-relapse mortality was 6%, (95%CI, 0.3%-31%) and the Kaplan-Meier estimate of progression-free survival (PFS) was significantly higher in the T-cell as compared to the B-cell group (P= 0.03; 100% vs. 40% at 3 years).
In the FL group, the cumulative incidence of non-relapse mortality was 25% (95%CI, 3%–65%). Six patients (75%) showed objective disease response with complete remission (CR) occurring concomitantly to graft-versus-host disease, including one CR after donor lymphocytes infusion. With a median follow-up of 19 (range, 7–85) months, 6 patients from the FL group are still alive of whom 5 in CR.
We conclude that a potent graft-vs.-lymphoma (GVL) may be achieved in FL patients, even those with chemoresistant disease or who have relapsed after autologous SCT. In the high grade NHL group, strategies aiming to enhance the GVL effect (Rituximab-based RIC and/or Rituximab maintenance therapy) in the B cell subtype are still needed. However, RIC allo-SCT is a feasible and promising strategy for aggressive NHL, with particularly low toxicity, and T-cell aggressive NHL benefiting most from a potent GVL effect, likely overcoming the poor prognosis usually associated with this phenotype.
Immunotherapy of non-Hodgkin’s lymphoma with a defined ratio of CD8+and CD4+CD19-specific chimeric antigen receptor–modified T cells