The Influence of ATG on the Outcomes of Patients With AML at the Time of Unrelated Donor Transplantation
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Research Article
P: 337-342
December 2021

The Influence of ATG on the Outcomes of Patients With AML at the Time of Unrelated Donor Transplantation

J Ankara Univ Fac Med 2021;74(3):337-342
1. Ankara Üniversitesi Tıp Fakültesi, Hematoloji Anabilim Dalı, Ankara, Türkiye
No information available.
No information available
Received Date: 08.05.2021
Accepted Date: 28.05.2021
Publish Date: 17.09.2021
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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

References

1
Goerner M, Gooley T, Flowers ME, et al. Morbidity and mortality of chronic GVHD after hematopoietic stem cell transplantation from HLA-identical siblings for patients with aplastic or refractory anemias. Biol Blood Marrow Transplant. 2002;8:47-56.
2
Khera N, Zeliadt SB, Lee SJ. Economics of hematopoietic cell transplantation. Blood. 2012;120:1545-1551.
3
Gagelmann N, Ayuk F, Wolschke C, et al. Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in Allogeneic Stem Cell Transplantation: Systematic Literature Review and Network Meta-Analysis. Biol Blood Marrow Transplant. 2017;23:2184-2191.
4
Walker I, Panzarella T, Couban S, et al. Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol. 2016;17:164-173.
5
Soiffer RJ, Kim HT, McGuirk J, et al. Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation. J Clin Oncol. 2017;35:4003-4011.
6
Finke J, Bethge WA, Schmoor C, et al. Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009;10:855-864.
7
Oostenbrink LVE, Jol-van der Zijde CM, Kielsen K, et al. Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation. Front Immunol. 2019;10:315.
8
Devillier R, Labopin M, Chevallier P, et al. Impact of antithymocyte globulin doses in reduced intensity conditioning before allogeneic transplantation from matched sibling donor for patients with acute myeloid leukemia: a report from the acute leukemia working party of European group of Bone Marrow Transplantation. Bone Marrow Transplant. 2018;53:431-437.
9
Kröger N, Solano C, Wolschke C, et al. Antilymphocyte Globulin for Prevention of Chronic Graft-versus-Host Disease. N Engl J Med. 2016;374:43-53.
10
Finke J, Schmoor C, Bethge WA, et al. Long-term outcomes after standard graft-versus-host disease prophylaxis with or without anti-human-T-lymphocyte immunoglobulin in haemopoietic cell transplantation from matched unrelated donors: final results of a randomised controlled trial. Lancet Haematol. 2017;4:e293-e301.
11
Rubio MT, D’Aveni-Piney M, Labopin M, et al. Impact of in vivo T cell depletion in HLA-identical allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission conditioned with a fludarabine iv-busulfan myeloablative regimen: a report from the EBMT Acute Leukemia Working Party. J Hematol Oncol. 2017;10:31.
12
Mohty M, Labopin M, Balère ML, et al. Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire. Leukemia. 2010;24:1867-1874.
13
Canaani J, Labopin M, Huang XJ, et al. Minimal residual disease status predicts outcome of acute myeloid leukaemia patients undergoing T-cell replete haploidentical transplantation. An analysis from the Acute Leukaemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT). Br J Haematol. 2018;183:411-420.
14
Gilleece MH, Labopin M, Yakoub-Agha I, et al. Measurable residual disease, conditioning regimen intensity, and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: A registry analysis of 2292 patients by the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation. Am J Hematol. 2018;93:1142-1152.
15
Shah MV, Jorgensen JL, Saliba RM, et al. Early Post-Transplant Minimal Residual Disease Assessment Improves Risk Stratification in Acute Myeloid Leukemia. Biol Blood Marrow Transplant. 2018;24:1514-1520.
16
Liu J, Ma R, Liu YR, et al. The significance of peri-transplantation minimal residual disease assessed by multiparameter flow cytometry on outcomes for adult AML patients receiving haploidentical allografts. Bone Marrow Transplant. 2019;54:567-577.
17
Schuurhuis GJ, Heuser M, Freeman S, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018;131:1275-1291.
18
Oran B, Jorgensen JL, Marin D, et al. Pre-transplantation minimal residual disease with cytogenetic and molecular diagnostic features improves risk stratification in acute myeloid leukemia. Haematologica. 2017;102:110-117.
19
Anthias C, Dignan FL, Morilla R, et al. Pre-transplant MRD predicts outcome following reduced-intensity and myeloablative allogeneic hemopoietic SCT in AML. Bone Marrow Transplant. 2014;49:679-683.
20
Walter RB, Gyurkocza B, Storer BE, et al. Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia. 2015;29:137-144.
21
Buckley SA, Wood BL, Othus M, et al. Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis. Haematologica. 2017;102:865-873.
22
Ustun C, Courville EL, DeFor T, et al. Myeloablative, but not Reduced-Intensity, Conditioning Overcomes the Negative Effect of Flow-Cytometric Evidence of Leukemia in Acute Myeloid Leukemia. Biol Blood Marrow Transplant. 2016;22:669-675.
23
Walter RB, Gyurkocza B, Storer BE, et al. Comparison of minimal residual disease as outcome predictor for AML patients in first complete remission undergoing myeloablative or nonmyeloablative allogeneic hematopoietic cell transplantation. Leukemia. 2015;29:137-144.
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