Is myeloablative dose intensity necessary in allogeneic hematopoietic cell transplantation for lymphomas?

Abstract

The advent of novel immunotherapy and tyrosine kinase inhibitors has ushered a new era in the treatment of Hodgkin and non-Hodgkin lymphomas. Allogeneic hematopoietic cell transplantation remains, however, a vital component in the management and potential cure of lymphomas, especially in the relapsed setting. Considering the biological and clinical heterogeneity of various subtypes of lymphomas, the optimal intensity of conditioning regimens remains controversial. Reduced intensity conditioning regimens have broadened applicability of the procedure to older and frail patients. Observational studies suggest that although reduced intensity allografting is associated with higher risk of relapse, overall survival is comparable and in some cases even better, than observed with myeloablative regimens. Here, we review the available published data pertaining to allogeneic hematopoietic cell transplantation using reduced intensity or myeloablative conditioning for various lymphoma histologies. Owing to the lack of randomized prospective trials, recommendations are mainly based on registry and single-institution studies. Special emphasis must be given to implementing strategies to prevent relapse when using reduced intensity regimens. Identifying particular patients who may benefit from myeloablative regimens in lymphomas remains to be better defined.

Efficacy of Allogeneic Hematopoietic Cell Transplantation in Cutaneous T Cell Lymphoma: Results of a Systematic Review and Meta-Analysis

“…RIC and NMA conditioning regimens were most commonly prescribed, recognizing the increased toxicity resulting from allo-HCT myeloablative conditioning regimens without a clearly established benefit of higher ablation [30]. Moreover, RIC and NMA conditioning regimens were prescribed despite the relatively young age of patients in most studies (median age, 46.5 to 51.5 years) ( Table 1).…”

Identification of an Optimal Population for Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Mature T and NK Cell Neoplasms

“…Conditioning regimen MAC/RIC 5 (33.3%)/5 (33.3%) 5 (33.3%)/0 (0%) 2 (13.3%)/2 (13.3%) 4 (26.7%)/0 (0%) 1 (6.7%)/3 (20.0%) 1 (6.7%)/0 (0%) 2 (13.3%)/0 (0%) 1 st line Chemotherapy CHOP/Non-CHOP 8 (53.3%)/2 (13.3%) 3 (20.0%)/2 (13.3%) 3 (20.0%)/1 (6.7%) 2 (13.3%)/2 (13.3%) 3 (20.0%)/1 (6.7%) 1 (6.7%)/0 (0%) 2 (13.3%)/0 (0%) 22 (19)(20)(21)(22)(23)(24)/33 Onset of aGVHD/ 2 (13.3%)/1 (6.7%) 1 (6.7%)/1 (6.7%) 0 (0%)/0 (0%) 1 (6.7%)/1 (6.7%) 2 (13.3%)/1 (6.7%) 0 (0%)/0 (0%) 0 (0%)/0 (0%) (18), and our data supports their findings. Another focus of interest was the intensity of conditioning regimen.…”

“…Conditioning regimen for lymphomas has traditionally been MAC in nature, but this entails higher risk of TRM and GVHD (16). In recent years, alloSCT with RIC has gained popularity based on acceptable RFS and OS, but the major pitfall is the higher relapse rates (4, [19][20][21]. In our cohort, there were no differences in survival and GVHD incidence according to conditioning intensity, but RIC showed lower 1-year TRM rates (RIC, 10.5% vs. MAC, 26.1%).…”

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products

“…16,17 In patients who ultimately receive an allogeneic HCT (allo-HCT), the 5-year OS ranges from 18–37%, based on two registry studies from the Center for International Blood and Marrow Transplant Research (CIBMTR). 18–20 This limited efficacy of allo-HCT is in large part due to the high nonrelapse mortality (NRM), which may exceed 40%, mainly when using myeloablative conditioning (MAC) regimens. 18,21,22…”