The Role of Anti-Thymocyte Globulin (ATG) in Patients with AML Transplanted in CR1 from Sibling and Unrelated Donors with or without Measurable Residual Disease (MRD) at the Time of Allogeneic Stem Cell Transplantation:a Study on Behalf of the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT)

Abstract

Background Measurable residual disease (MRD) status pre- transplantation (alloSCT) predicts transplant outcome. Nonetheless, the impact of MRD persistence (MRD+) might be modulated by the use of anti thymocyte globulin (ATG) to prevent graft versus host disease (GVHD). Since GVHD is usually associated with the graft versus leukemia effect (GVL), there is a concern that ATG may increase relapse incidence (RI) in patients (pts) with a higher risk of relapse. We therefore investigated whether MRD status pre-alloSCT could impact the outcome in AML patients receiving alloSCT with ATG in CR1. Methods Study included adult AML pts undergoing alloSCT in CR1 during 2005-2016 period. First, we assessed the impact of MRD status, cytogenetics, FLT3-ITD and ATG in the whole population. Then, we studied the impact of ATG in relation to the MRD status at time of alloSCT. Results 1509 pts (1083 MRD negative (MRD-) and 426 MRD+) were included. In the MRD- group, 552 (48%) pts did not receive ATG (MRD− /no ATG) and 561 (52%) received ATG (MRD−/ATG), whereas within MRD+ cohort, 187 (44%) received no ATG (MRD+/no ATG) and 239 (58%) received ATG (MRD+/ATG). Median age was 51 (range 18-73) years, 51% were females. Acute GVHD grade III-IV and cGVHD were significantly lower in pts who received ATG in comparison to those who did not, translating into better GVHD-free, relapse-free survival (GRFS). Non-relapse mortality (NRM), RI, LFS and OS did not differ statistically. Focusing on the influence of MRD status, the overall RI was higher in MRD+ patients prior to alloSCT (38.7% vs. 22.8%, p Conclusions ATG reduces acute and cGVHD incidence and severity in AML pts undergoing alloSCT in CR1, resulting in improved GRFS. AML relapse risk remained unmodified by ATG use, even in the high risk subset of MRD+ patients' pre-alloSCT. Therefore, the use of ATG is not detrimental, and can allow for a significant clinical benefit in all CR1 AML patients who are candidate for alloSCT.