Comparison of and Immune Reconstitution and Graft Versus Host Disease in 30mg/Kg Anti-T-Lymphocyte Globuline with 60mg/Kg ATLG As Graft Versus Host Disease Prophylaxis in Matched Unrelated Donor Myeloablative Peripheral Blood Stem Cell Transplantation
Authors: Massoud Radwan , Klyuchnikov Evgeny , Gagelmann Nico , Zabelina Tatjana , Christine Wolschke , Ayuk Francis Ayuketang , Fritsche-Friedland Ulrike , Zander Axel R. , Kröger Nicolaus 
Published: November 2021

Abstract
Introduction:
Data on the influence of different ATLG doses on immune reconstitution (IR) and GvHD in MUD allo-SCT is limited. In this study, we compared the impact of ATLG doses (30mg/kg vs 60 mg/kg) on IR and transplant outcomes.
Methods:
In this retrospective study we included 289 patients who received MUD allografts (HLA 10/10) between 2005-2019 in the University Cance Center University of Hamburg. All patients received PBSC-allo-SCT with MAC for various hematological malignancies. Seventy-three patients received 30mg/kg ATLG, and 216 patients received 60mg/kg (on days -3.-2 and -1) prior to allo-SCT. Periphereal blood samples were collected on days +30, +100 and +180 and analyzed by flow cytometry for following lymphocyte populations: T-cells (total and activated), T-helper cells (total, naïve and memory), cytotoxic T-cells (total, naïve and memory), B-Lymphocytes (total, naïve and memory), NK-cells, NKT-cells, γδT-cells and regulatory T-cells.
Results:
Neutrophil and platelet engraftments were significantly delayed after the 60mg/kg compared to 30mg/kg group with medians of 11 days (range, 8-23) vs 12 days (8-27) (p=0.009) for neutrophil and 14 days (range, 9-53) vs 16 days (range, 8-237) for platelets, respectively (p=0.002). We observed a higher incidence of EBV reactivation within the first 100 days in the 60mg/kg group (41% vs 21% in the 30mg/kg group, p=0.049).
Higher cumulative incidence of Infections Day +100 was observed in the 60 mg/Kg group with an incidence of 75% vs that of 67% in the 30mg/Kg group respectively (p=0.002). At day +30 we observed a faster reconstitution of naïve-B cells (p&lt;0.0001) and γδ T cells (p=0.045) in the 30mg/kg group. No significant differences in IR were observed at day +100. At day +180 the use of 30mg/Kg was associated with a faster naïve helper T-cell (p=0.046), NK-cells (p=0.035), and naïve B-cell reconstitution (p=0.009).
The incidence of aGVHD grade II-IV was comparable between the groups: 63% and 59% in the 30mg/Kg and 60mg/Kg groups, respectively. We observed a higher incidence of grade IV aGvHD in the 30mg/kg group (8%) comparing with the rate of 0.5% in the 60mg/kg group (p=0.0002), this was confirmed in multivariate analysis: RR 0.65 (95%CI 0.005-0.363) p= 0.004.
After a median follow up of 21 months (range, 1-161) there were no significant differences in OS, PFS, NRM, RI and cGVHD between the groups.
Conclusion:
The choice of ATLG dose has significant impact on IR after MUD-allo-SCT. Higher doses are associated with reduced severe aGVHD, however at the cost of delaying engraftment and increasing infections.

Disclosures
Ayuk: Celgene/BMS: Honoraria; Gilead: Honoraria; Janssen: Honoraria; Mallinckrodt/Therakos: Honoraria, Research Funding; Miltenyi Biomedicine: Honoraria; Novartis: Honoraria; Takeda: Honoraria.