Myeloablative or Reduced Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation for Mantle Cell Lymphoma? a Systematic Review and Meta-Analysis
Authors: Kharfan-Dabaja Mohamed A. , Reljic Tea , El-Asmar Jessica , Nishihori Taiga , Ayala Ernesto , Hamadani Mehdi , Kumar Ambuj 
Published: October 2019

Abstract
Background: Despite availability of novel agents to treat mantle cell lymphoma (MCL), the disease remains incurable with standard therapies. Allogeneic hematopoietic cell transplantation (allo-HCT) is generally offered in the setting of relapsed or refractory disease. Reduced intensity conditioning (RIC) allo-HCT has expanded availability of the procedure for patients deemed ineligible to receive a myeloablative (MAC) regimen in the past due to advanced age or associated comorbidities. We performed a systematic review and meta-analysis to assess the totality of evidence pertaining to efficacy of allo-HCT (RIC or MAC) in MCL.
Materials and methods: A comprehensive search of MEDLINE/PUBMED from inception until July 04, 2015 was undertaken. Data were collected on treatment benefits (event-free (EFS), progression-free (PFS) and overall survival (OS) and harms (non-relapse mortality (NRM) and graft-versus host disease (GVHD)).
Results: Fifty-nine manuscripts were identified of which 16 met inclusion criteria (710 patients). For RIC regimens, pooled analysis of 9 studies (n=507) showed an EFS/PFS rate of 47% (95%CI=32-61%) and an OS rate of 53% (95%CI=39-67%). NRM rate for RIC regimens from a pooled analysis of 9 studies (n=507) was 24% (95%CI=16-33%). Incidences of acute (grade 2-4) and chronic GVHD (all grades) following a RIC regimen were 31% (95%CI=20-45%, pooled from 6 studies (n=299)) and 42% (95%CI=30-54%, pooled from 7 studies (n=369)), respectively. For MAC regimens, pooled analysis of 4 studies (n=124) showed an EFS/PFS rate of 34% (95%CI=21-50%). The OS rate was 40% (95%CI=28-52%) from a pooled analysis of 5 studies (n=138). NRM rate for MAC regimens was 37% (95%CI=23-51%) based on a pooled analysis of 4 studies (n=119); only 1 study reported incidence of acute (grade 2-4) and chronic GVHD (all grades) of 36% (95%CI=23-50%) and 35% (95%CI=22-48%), respectively. When analysis was restricted to the late/salvage setting, we analyzed aforementioned outcomes regardless of regimen intensity (RIC+MAC) as well as specifically to RIC or MAC. When RIC and MAC regimens were combined, the pooled analysis of 12 studies (n=578) showed an EFS/PFS rate of 34% (95%=23-46%) and OS rate of 43% (95%CI=32-53%). The NRM rate was 30% (95%CI=20-41%, pooled analysis of 11 studies (n=563)). For RIC regimens in the late/salvage setting, the pooled analysis of 7 studies (n=436) showed an EFS/PFS rate of 40% (95%CI=26-56%) and OS rate of 48% (95%CI=33-62%). For MAC regimens in the late/salvage setting, the pooled analysis of 3 studies (n=105) showed an EFS/PFS rate of 35% (95%CI=17-55%) and OS rate of 38% (95%CI=22-56%). The observed heterogeneity was statistically significant among RIC studies for outcome of OS (p < 0.0001) but not for MAC (p= 0.1315).
Conclusion: These results demonstrate that allo-HCT is an effective strategy for treatment of MCL even in the late/salvage setting. On the basis of a relatively lower NRM and a slightly better EFS/PFS and OS, RIC regimens may be the preferred choice when an allo-HCT is being considered for MCL. However, a prospective comparative study in this setting is necessary to generate more conclusive evidence.

Disclosures
No relevant conflicts of interest to declare.