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. 2022 Aug 5:13:921293.
doi: 10.3389/fimmu.2022.921293. eCollection 2022.

Modified combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) as compared with standard ATG protocol in haploidentical peripheral blood stem cell transplantation for acute leukemia

Maryam Barkhordar  1 , Amir Kasaeian  1   2   3 , Ghasem Janbabai  1 , Hossein Kamranzadeh Fumani  1 , Sahar Tavakoli  1 , Amir Abbas Rashidi  1 , Seied Asadollah Mousavi  1 , Ardeshir Ghavamzadeh  1   4 , Mohammad Vaezi  1
Affiliations

Modified combination of anti-thymocyte globulin (ATG) and post-transplant cyclophosphamide (PTCy) as compared with standard ATG protocol in haploidentical peripheral blood stem cell transplantation for acute leukemia

Maryam Barkhordar et al. Front Immunol. .

Abstract

In haploidentical peripheral blood stem cell transplantation (haplo-PBSCT), the combination of anti-thymocyte globulin and post-transplant cyclophosphamide (ATG/PTCy) has a synergistic impact in preventing graft-versus-host disease (GvHD). However, little is known about the long-term consequences of the new combination approach. Our goal is to evaluate the efficacy of ATG/PTCy versus a standard ATG regimen by focusing at long-term outcomes in a more homogeneous group of patients. We retrospectively included 118 adult patients up to 60 years with acute leukemia who underwent haplo-PBSCT at our single institution, following the same myeloablative conditioning regimen. From 2010 to 2020, 78 patients received a modified combination of ATG (2.5 mg/kg/day, on days -3, -2, and -1) and PTCy (40 mg/kg/day on days +3 and +4) compared to 40 patients who had a standard ATG-based regimen (2.5 mg/kg/day from days -4 to -1) from 2008 to 2015. The median follow-up time for all patients was 5.36 years, respectively. The cumulative incidence (CI) of neutrophil and platelet engraftment, as well as CMV reactivation, did not differ statistically between the two groups. The CI of the acute GvHD of grades II-IV and III-IV and extensive chronic GvHD were considerably lower in the ATG/PTCy (34.6%, 8.97%, and 13.63%) than in the ATG cohort (57.5%, 30%, and 38.23%) as validated by multivariable modeling. Additionally, compared to the ATG arm, the ATG/PTCy was a hazard factor associated with a higher risk of relapse (HR = 2.23, p = 0.039). The probability of 5-year overall survival, disease-free survival, and GvHD-free relapse-free survival in the ATG/PTCy group (53.34%, 49.77%, and 36.04%) was comparable with the ATG group (47.5%, 42.5%, and 22.5%), respectively. Our finding suggested that a modified ATG/PTCy combination resulted in a lower risk of acute and chronic GvHD and a higher risk of relapse than the standard ATG-based protocol but had no effect on long-term outcomes. However, certain adjustments in the immunosuppression protocol are warranted to improve the outcome.

Keywords: Graft versus host disease (GvHD); acute leukemia (AL); anti-thymocyte globulin (ATG); haploidentical stem cell transplantation (HSCT); peripheral blood stem cells (PBSCs); post-transplantation cyclophosphamide (PTCy).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Cumulative incidence (CI) of graft-versus-host disease (GvHD) according to treatment groups; (A) CI of grade II–IV acute GvHD; (B) CI of grade III–IV acute GvHD; (C) CI of extensive chronic GvHD.
Figure 2
Figure 2
Probability of survival according to treatment groups: (A) Kaplan–Meier estimates of overall survival; (B) Kaplan–Meier estimates of disease-free survival; (C) Kaplan–Meier estimates of GvHD-free, relapse-free survival.
Figure 3
Figure 3
CI of relapse and non-relapse mortality (NRM) according to treatment groups: (A) CI of relapse; (B) CI of NRM.
See this image and copyright information in PMC

References

    1. Gratwohl A, Pasquini MC, Aljurf M, Atsuta Y, Baldomero H, Foeken L, et al. . One million haemopoietic stem-cell transplants: a retrospective observational study. Lancet Haematol (2015) 2(3):e91–e100. doi: 10.1016/S2352-3026(15)00028-9 - DOI - PubMed
    1. Apperley J, Niederwieser D, Huang XJ, Nagler A, Fuchs E, Szer J, et al. . Haploidentical hematopoietic stem cell transplantation: a global overview comparing Asia, the European union, and the united states. Biol Blood Marrow Transpl (2016) 22:23–6. doi: 10.1016/j.bbmt.2015.11.001 - DOI - PubMed
    1. Passweg JR, Baldomero H, Bader P, Bonini C, Duarte RF, Dufour C, et al. . Use of haploidentical stem cell transplantation continues to increase: the 2015 European society for blood and marrow transplant activity survey report. Bone Marrow Transpl (2017) 52(6):811–7. doi: 10.1038/bmt.2017.34 - DOI - PMC - PubMed
    1. Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, et al. . Haploidentical vs identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood (2015) 125:3956–62. doi: 10.1182/blood-2015-02-627786 - DOI - PubMed
    1. Arcuri LJ, Aguiar MTM, Ribeiro AAF, Pacheco AGF. Haploidentical transplantation with post-transplant cyclophosphamide versus unrelated donor hematopoietic stem cell transplantation: A systematic review and meta-analysis. Biol Blood Marrow Transpl (2019) 25(12):2422–30. doi: 10.1016/j.bbmt.2019.07.028 - DOI - PubMed

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