Impact of TBI-Based Conditioning Regimen on Outcomes of Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplant: Systematic Review and Meta-Analysis
Authors: Dutta Mudit , Mhaskar Rahul , Elmariah Hany , Nishihori Taiga , Shah Bijal , Nieder Michael , Perez Lia , Faramand Rawan , Pidala Joseph , Bejanyan Nelli , Khimani Farhad 
Published: November 2019

Introduction:
Allogeneic hematopoietic cell transplant (allo-HCT) is a curative treatment option for patients with acute lymphoblastic leukemia (ALL). Both total body irradiation(TBI)-based and chemotherapy only (non-TBI) transplant conditioning regimens have been utilized. But the optimal conditioning regimen for all-HCT in ALL remains unclear. We performed a systematic review to assess the totality of evidence pertaining to the efficacy of TBI-based vs- non-TBI conditioning regimens.
Methods:
We searched PubMed and Embase databases for all studies comparing TBI-based vs. non-TBI conditioning regimens in patients who received allo-HCT for ALL. Two authors independently reviewed all references for inclusion and extracted data related to overall survival (OS), progression free survival (PFS), non-relapse mortality (NRM), relapse, acute- and chronic graft-versus-host disease (GVHD) whenever available. We restricted inclusion criteria to studies published only as peer-reviewed manuscripts which included ALL only patients (both T-ALL and B-ALL) who received a myeloablative conditioning; pediatric only studies were excluded. We also assessed outcomes in subgroups of patients 16 years of age and older which were majority of the included studies.
Results:
Seven studies were included in the final analysis that met our inclusion criteria. The quality assessment rating for each study was good based on its study type. The results for all patients in these observational studies revealed that TBI-based regimen was significantly favorable (all p<.05) to non-TBI conditioning regimen with regards to OS (HR=0.74, 95% CI [0.62, 0.88], 6 studies, 4300 patients), PFS (HR=0.72, 95% CI [0.61, 0.85], 6 studies, 4300 patients), and relapse (RR=0.73, 95% CI [0.61, 0.86], 5 studies, 4664 patients). The TBI-based regimen did not increase (all p>.05) the risks of NRM (RR=1.09, 95% CI [0.75, 1.58], 6 studies, 4251 patients), grade II-IV acute GVHD (RR=1.11, 95% CI [0.90, 1.36], 5 studies, 4725 patients) or grade III-IV acute GVHD (RR=1.20, 95% CI [0.89, 1.63], 2 studies, 3248 patients). However, TBI-based regimen increased the risk of chronic GVHD (RR=1.12, 95% CI [1.02, 1.23], 5 studies, 4219 patients). Subgroup comparison of patients 16 years of age and older (range 16-70) showed similar results as shown in Table 1a-d.
Conclusion:
This meta-analysis represents evidence supporting the use of TBI-based conditioning regimens for allo-HCT in patients with ALL as it offers significantly lower risk of relapse and better survival yet acceptable NRM as compared to non-TBI regimens.

Disclosures
Nishihori: Karyopharm: Research Funding; Novartis: Research Funding. Shah:Celgene/Juno: Honoraria; Kite/Gilead: Honoraria; Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Pharmacyclics: Honoraria; Adaptive Biotechnologies: Honoraria; Spectrum/Astrotech: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria. Bejanyan:Kiadis Pharma: Other: advisory board.