Clinical Effects of Two Different Antithymocyte Globulins as Part of the Conditioning for Unrelated Stem Cell Transplantation.
Authors: Baurmann Herrad , Hoppe Gregor , Davis Karin , Judith Dirk , Schleuning Michael , Schwerdtfeger Rainer 
Published: October 2019

Abstract
Introduction: Antithymocyte globulin (ATG) is increasingly incorporated into conditioning in unrelated stem cell transplantation (UD-HCT) in an attempt to modulate alloreactivity. Several brands of ATG with different antibody spectrum and potencies are available. Little is known about their optimal use, their clinical action and their potentially different effects in this setting. We reported on the immune reconstitution of 108 patients (pts) after UD-HCT between 1998 and 2003 at our center, after conditioning with either rabbit ATG Genzyme (Thymoglobulin®, ATG-G) or ATG Fresenius (ATG-F) (BMT2004, 33, S3). We here analyze the clinical results of these pts.
Patients: 66 pts (cohort 1) received ATG-G, the following 42 pts (cohort 2) ATG-F. Median (md) age of the cohort (co) was 40 y, underlying diseases were AML 40%, MPS 24%, ALL 14%, MDS 7%, lymphoma 15%. There were no significant differences (sigdif)between groups regarding age, Karnofsky index, underlying disease, disease or risk status, CMV risk status and HLA match. 69 % of donor/recipient pairs were 8/8 matched, 31 % had at least one class I Ag MM or one class II allel MM. There was a trend towards more female donors for male recipients (15 vs 7%) in co1 whereas co2 had more pAML (36 vs 17%), more use of reduced conditioning (47 vs 26%), PBSC (60 vs 42%) and MMF instead of MTX (26 vs 5%). Three quarters of ATG-G pts received the product from day (d)-5 to -2, the later ones from d-4 to -1, whereas ATG-F was given from d-3 to -1. The vast majority of co1 had a daily ATG-G dose of 2.5 mg/kg BW compared to 15–20 mg/kg BW ATG-F in co2.
Results: At a md follow up of 938 d (1051 for co1 and 908 for co2) there was no sigdif in engraftment, chimerism, disease status or overall survival (OS). Probability of OS for co1 is 63% and 69 % for co2. ATG-G pts were more likely to be readmitted after discharge (73 vs 57%), time to readmission was significantly shorter. Infection (46 vs 29 %) and CMV reactivation (23 vs 14%) were the most frequent reasons for hospitalization with a md number of infectious episodes of 3 for ATG-G and 2 for ATG-F pts from d30 to 365. Infections were categorized as equally severe in both groups. 64% of ATG-G pts developed aGvHD °II–IV compared to 43% of ATG-F pts - however aGvHD responded well to treatment (complete resolution in 63 vs 57%). 76% of co1 and 67% of co2 pts developed cGvHD with a maximum severity of extended cGvHD in 46 vs 26%. ATG-F pts had more skin (57 vs 44%) and gut cGvHD (21 vs 9%) whereas liver (33 vs 14%), lung manifestations (12 vs 5%) and wasting (14 vs 5%) were more frequent after ATG-G. cGvHD in co1 was more often judged to be severe (11 vs 5%), treated by more than one modality in 85 vs 55%, lasted longer (md of 296 vs 69 d) and was more often the primary cause of death (9 vs 2%).
Conclusion: Retrospective comparisons of sequential cohorts are subject to biases and have to be interpreted with great caution. Better donor selection, new immunosuppressive and anti-infectious drugs and less toxic conditioning regimens may work in favour of co2. Both treatment regimens gave good results in matched and mismatched UD-HCT without sigdif in OS and disease free survival. However differences in the occurrence and type of cGvHD seem to emerge which need further evaluation. Our results suggest that at least at the given schedule the probably lower equivalence dose of ATG-F was able to prevent at least as much severe cGvHD as ATG-G. A prospective randomized trial with ATG given from d-3 to -1 is warranted.