The Influence of ATG on the Outcomes of Patients With AML at the Time of Unrelated Donor Transplantation
Abstract
Objectives: Anti-thymos globulin (ATG) can potentially eliminate alloreactive donor T-cells and reduce the graft-versus-host disease (GVHD). As a
result of this, increased disease relapse and reduced overall survival can be observed in ATG recipients. In addition, the presence of pre- allogeneic
hematopoietic stem cell transplantation (allo-HSCT) measurable residual disease has been associated with an increased risk of acute myeloid
leukemia (AML) relapse in multiple studies. Herein, we aimed to investigate the impact of ATG on the outcomes of patients with AML stratified by
flow cytometric minimal residual disease (MRD) status who underwent allo-HSCT from unrelated donor.
Materials and Methods: This was a retrospective single-center analysis using the data set of our institutional database. Eligibility criteria for this
analysis included 83 adult patients with AML who underwent allo‐HSCT from either an HLA 10/10 matched (n=34) or 9/10 mismatched (n=41) UD,
between October 2012 and June 2019.
Results: A total of 83 consecutive patients with AML who underwent allo-HSCT from a UD were evaluated. There were 44 MRD- and 18 MRD+
patients and 21 patients who were transplanted in the setting of active disease were also included in this analysis. We investigated the influence
of ATG on transplant outcomes separately in MRD-, MRD+ and active disease cohorts. As expected, lowest incidence of relapse was observed in
MRD- groups [MRD-; 29.5% (13/44) vs MRD+; 44.4% (8/18); p=0.17]. MRD status at the time of allo-HSCT impacted the progression free survival
significantly: MRD- (not reached) or MRD+ [median 17.3 (95% confidence interval (CI), 6.3-28.3)] or active disease [median 11 months (%95 CI,
3,9-18,1)] (p=0.02). In multivariate cox regression analyses; we could demonstrate the negative effect of detection of MRD [Hazard ratio (HR): 1.8;
%95 GA: 0.7-4.8; p=0.02] and active disease (HR: 3.6; %95 GA: 1.4-8.7; p=0.006) on PFS.
Conclusion: Based on this single-center study, the use of ATG was associated with a lower incidence of chronic GVHD. Most importantly, ATG could
increase the risk of disease relapse or mortality in patients with pre-transplant MRD+ and active diseases. However, further prospective, randomized
studies on a large number of patients are warranted to clarify these findings.
Keywords
Acute Myeloid Leukemia, Allogeneic Hematopoietic Stem Cell Transplantation, Measurable Residual Disease, ATG
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