Efficacy of High-Dose Therapy and Autologous Hematopoietic Cell Transplantation in Peripheral T-Cell Lymphomas As Front-Line Consolidation or in the Relapsed/Refractory Setting: A Meta-Analysis
Authors: El-Asmar Jessica , Reljic Tea , Ayala Ernesto , Nishihori Taiga , Hamadani Mehdi , Kumar Ambuj , Kharfan-Dabaja Mohamed A. 
Published: October 2019

Abstract
Background: No prospective randomized trials exist comparing high-dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT) against conventional therapy for management of peripheral T-cell lymphomas (PTCL) as upfront consolidation or in the relapsed/refractory (R/R) settings. Available data supporting this approach is limited to single-arm prospective or retrospective studies only. Accordingly, we performed a systematic review/meta-analysis of the published literature using PUBMED/MEDLINE from date of inception until March 4, 2015.
Patients and methods: Our search identified 1586 publications, but only 27 (n=1368) met our inclusion criteria. Data were collected on treatment benefits (progression-free (PFS) and overall survival (OS)) and harms (transplant-related mortality (TRM) and secondary malignancies).
Results: Specifically pertaining to HDT/auto-HCT as front-line consolidation data were available from 3 single-arm prospective (n=179) and 16 retrospective (n=599) studies. Moreover, for HDT/auto-HCT for R/R disease, 14 eligible retrospective (n=581) studies were identified. Pooled analysis of only prospective studies showed rates of PFS (2 studies, n=158) 33% (95%CI=14-56%), OS (3 studies, n=179) 54% (95%CI=32-75%), and TRM (2 studies, n=136) 2% (0.3-5%) for HDT/auto-HCT as front-line consolidation. When only retrospective studies were analyzed, pooled analysis showed rates of PFS (12 studies, n=518) 55% (95%CI=40-69%), OS (16 studies, n=599) 68% (95%CI=56-78%), TRM (7 studies, n=226) 6% (95%CI=2-11%), and incidence of secondary malignancies (4 studies, n=153) of 7% (95%CI=2-14%) with HDT/auto-HCT as front-line consolidation. Alternatively, pooled analysis of retrospective studies evaluating HDT/auto-HCT in the R/R setting showed rates of PFS (11 studies, n=511) 36% (95%CI=32-40%), OS (14 studies, n=581) 47% (95%CI=43-51%), TRM (5 studies, n=338) 10% (95%CI=5-17%), and incidence of secondary malignancies (1 study, n=29) of 3.4%. Additionally, we evaluated the efficacy of HDT/auto-HCT in various histologic subtypes both as front-line consolidation and in R/R disease. Only 1 prospective study using HDT/auto-HCT as front-line consolidation showed an apparently higher 5-year PFS and OS for ALK-negative anaplastic large cell lymphoma (ALK-neg-ALCL) (PFS=61%, OS=70%) compared to PTCL-NOS (PFS=38%, OS=47%) or angioimmunoblastic (AILT) (PFS=49%, OS=52%). Moreover, 2 retrospective studies using HDT/auto-HCT as front-line consolidation also showed higher rates of PFS and OS for ALCL (PFS=68%, OS=78%) compared to PTCL-NOS (PFS=64%, OS=75%) or AILT (PFS=48%, OS=63%). Finally, in the R/R setting, outcomes following HDT/auto-HCT from one retrospective study showed higher PFS for ALCL (67%) vs. PTCL-NOS (23%). The observed heterogeneity was statistically significant for PFS and OS among prospective (p=0.008 and p=0.0009) and retrospective (p<0.0001 and p<0.0001) studies evaluating HDT/auto-HCT as front-line consolidation but not for studies evaluating this strategy in the R/R setting (p=0.8 and p=0.7).
Conclusion: These results suggest that HDT/auto-HCT is a reasonable treatment option to offer as front-line consolidation with resulting OS ranging from 54% to 68% and a relatively low TRM ranging from 2% to 6%. In the R/R setting, HDT/auto-HCT is also a reasonable option yielding an OS of 47% but with slightly higher TRM of 10%. Among the various histologic subtypes, PFS and OS rates appear to be higher in ALCL but larger appropriately powered comparative prospective studies will be needed to confirm these findings. Patients should be made aware of the increased risk of secondary malignancies of up to 7% when considering HDT/auto-HCT.

Disclosures
No relevant conflicts of interest to declare.