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Impact of the addition of antithymocyte globulin to post-transplantation cyclophosphamide in haploidentical transplantation with peripheral blood compared to post-transplantation cyclophosphamide alone: A retrospective study on behalf of the Cellular Therapy and Immunobiology Working Party of the European Society for Blood and Marrow Transplantation

. 2025 Aug 07 ; () : . [epub] 20250807

Status Publisher Language English Country Great Britain, England Media print-electronic

Document type Journal Article

Persistent link   https://www.medvik.cz/link/pmid40772384

In the setting of haploidentical haematopoietic cell transplantation (HCT), post-transplant cyclophosphamide (PTCy) has dramatically reduced the incidence of graft-versus-host disease (GVHD) and non-relapse mortality. To further reduce GVHD incidence, the addition of antithymocyte globulin (ATG) to PTCy was evaluated in retrospective and non-comparative prospective studies showing promising results. We conducted a large retrospective analysis of the European Society for Blood and Marrow Transplantation (EBMT) registry to evaluate this approach. We analysed haploHCT with peripheral blood stem cells performed for haematological malignancies between 2014 and 2021. GVHD prophylaxis included either PTCy alone or PTCy+ATG. Four thousand five hundred and nineteen patients were analysed in the PTCy only group versus 675 with PTCy+ATG. Median follow-up was 29.80 months. In univariate analysis, 2-year GVHD-free, relapse-free survival (GRFS), relapse-free survival (RFS), overall survival (OS), cumulative incidence of relapse, non-relapse mortality (NRM) and chronic GvHD (cGVHD) were, respectively: 40.5% versus 37.5% (p = 0.098), 50.9% versus. 45.8% (p = 0.015), 56.9% versus 52.5% (p = 0.01), 24.2% versus 28.1% (p = 0.032), 25% versus 26.1% (p = 0.49) and 28.4% versus 18.5% (p < 0.001). aGVHD did not differ. After multivariable adjustment, OS and RFS were lower in the PTCy+ATG group: HR = 1.18 (p = 0.037) and HR = 1.18 (p = 0.027) and patients receiving PTCy+ATG had less cGVHD: HR = 0.68 (p = 0.004). In that retrospective analysis, the addition of ATG to PTCy for GVHD prophylaxis in haploHCT was associated with a reduction of cGVHD but also a worse OS and RFS.

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Szydlo R, Goldman JM, Klein JP, Gale RP, Ash RC, Bach FH, et al. Results of allogeneic bone marrow transplants for leukemia using donors other than HLA identical siblings. J Clin Oncol. 1997;15(5):1767–1777. https://doi.org/10.1200/JCO.1997.15.5.1767

Drobyski WR, Klein J, Flomenberg N, Pietryga D, Vesole DH, Margolis DA, et al. Superior survival associated with transplantation of matched unrelated versus one‐antigen–mismatched unrelated or highly human leukocyte antigen–disparate haploidentical family donor marrow grafts for the treatment of hematologic malignancies: establishing a treatment algorithm for recipients of alternative donor grafts. Blood. 2002;99:806–814. https://doi.org/10.1182/blood.V99.3.806

Luznik L, O'Donnell PV, Symons HJ, Chen AR, Leffell MS, Zahurak M, et al. HLA‐haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high‐dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14:641–650. https://doi.org/10.1016/j.bbmt.2008.03.005

Rashidi A, Hamadani M, Zhang MJ, Wang HL, Abdel‐Azim H, Aljurf M, et al. Outcomes of haploidentical vs matched sibling transplantation for acute myeloid leukemia in first complete remission. Blood Adv. 2019;3(12):1826–1836. https://doi.org/10.1182/bloodadvances.2019000050

Rimando J, McCurdy SR, Luznik L. How I prevent GVHD in high‐risk patients: posttransplant cyclophosphamide and beyond. Blood. 2023;141:49–59. https://doi.org/10.1182/blood.2021015129

Chakupurakal G, Freudenberger P, Skoetz N, Ahr H, Theurich S. Polyclonal anti‐thymocyte globulins for the prophylaxis of graft‐versus‐host disease after allogeneic stem cell or bone marrow transplantation in adults. Cochrane Database Syst Rev. 2023;2023(6):CD009159. https://doi.org/10.1002/14651858.CD009159.pub3/full

Bonifazi F, Rubio MT, Bacigalupo A, Boelens JJ, Finke J, Greinix H, et al. Rabbit ATG/ATLG in preventing graft‐versus‐host disease after allogeneic stem cell transplantation: consensus‐based recommendations by an international expert panel. Bone Marrow Transplant. 2020;55:1093–1102. https://doi.org/10.1038/s41409‐020‐0792‐x

Duléry R, Ménard A‐L, Chantepie S, el‐Cheikh J, François S, Delage J, et al. Sequential conditioning with thiotepa in T cell‐replete hematopoietic stem cell transplantation for the treatment of refractory hematologic malignancies: comparison with matched related, haplo‐mismatched, and unrelated donors. Biol Blood Marrow Transplant. 2018;24(5):1013–1021. https://doi.org/10.1016/j.bbmt.2018.01.005

Salas MQ, Law AD, Lam W, Al‐Shaibani Z, Loach D, Kim DD, et al. Safety and efficacy of haploidentical peripheral blood stem cell transplantation for myeloid malignancies using post‐transplantation cyclophosphamide and anti‐thymocyte globulin as graftversus‐host disease prophylaxis. Clin Hematol Int. 2019;113:105–113. https://doi.org/10.2991/chi.d.190316.003

Duléry R, Bastos J, Paviglianiti A, Malard F, Brissot E, Battipaglia G, et al. Thiotepa, busulfan, and fludarabine conditioning regimen in t cell‐replete hlahaploidentical hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019;25(7):1407–1415. https://doi.org/10.1016/j.bbmt.2019.02.025

Peric Z, Mohty R, Bastos J, Brissot E, Battipaglia G, Belhocine R, et al. Thiotepa and antithymocyte globulin‐based conditioning prior to haploidentical transplantation with posttransplant cyclophosphamide in high‐risk hematological malignancies. Bone Marrow Transplant. 2020;55(4):763–772. https://doi.org/10.1038/s41409‐019‐0726‐7

Salas MQ, Atenafu EG, Law AD, Lam W, Pasic I, Chen C, et al. Experience using anti‐thymocyte globulin with post‐transplantation cyclophosphamide for graft‐versus‐host disease prophylaxis in peripheral blood haploidentical stem cell transplantation. Transplant Cell Ther. 2021;27(5):428.e1–428.e9. https://doi.org/10.1016/j.jtct.2021.02.007

Li X, Yang J, Cai Y, Huang C, Xu X, Qiu H, et al. Low‐dose anti‐thymocyte globulin plus low‐dose post‐transplant cyclophosphamide‐ based regimen for prevention of graft‐versus‐host disease after haploidentical peripheral blood stem cell transplants: a large sample, long‐term follow‐up retrospective study. Front Immunol. 2023;14:1252879. https://doi.org/10.3389/fimmu.2023.1252879

Alfaro Moya T, Salas MQ, Santos Carreira A, Atenafu EG, Law AD, Lam W, et al. Dual T cell depletion for graft versus host disease prevention in peripheral blood haploidentical hematopoietic cell transplantation for adults with hematological malignancies. Bone Marrow Transplant. 2024;59:534–540. https://doi.org/10.1038/s41409‐024‐02216‐3

Battipaglia G, Labopin M, Blaise D, Diez‐Martin JL, Bazarbachi A, Vitek A, et al. Impact of the addition of antithymocyte globulin to post‐transplantation cyclophosphamide in haploidentical transplantation with peripheral blood compared to post‐transplantation cyclophosphamide alone in acute myelogenous leukemia: a retrospective study on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Transplant Cell Ther. 2022;28(9):587.e1–587.e7. https://doi.org/10.1016/j.jtct.2022.06.006

Armand P, Kim HT, Logan BR, Wang Z, Alyea EP, Kalaycio ME, et al. Validation and refinement of the disease risk index for allogeneic stem cell transplantation. Blood. 2014;123:3664–3671. https://doi.org/10.1182/blood‐2014‐01‐552984

Saccardi R, Putter H, Eikema D‐J, Busto MP, McGrath E, Middelkoop B, et al. Benchmarking of survival outcomes following haematopoietic stem Cell transplantation (HSCT): an update of the ongoing project of the European Society for Blood and Marrow Transplantation (EBMT) and Joint Accreditation Committee of ISCT and EBMT (JACIE). Bone Marrow Transplant. 2023;58(6):659–666. https://doi.org/10.1038/s41409‐023‐01924‐6

Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, et al. 1994 Consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15(6):825–828.

Lee SJ, Vogelsang G, Flowers MED. Chronic graft‐versus‐host disease. Bone Marrow Transplant. 2003;9(4):215–233. https://doi.org/10.1053/bbmt.2003.50026

Battipaglia G, Ruggeri A, Labopin M, Volin L, Blaise D, Socié G, et al. Refined graft‐versus‐host disease/relapse‐free survival in transplant from HLA identical related or unrelated donors in acute myeloid leukemia. Bone Marrow Transplant. 2018;53(10):1295–1303. https://doi.org/10.1038/s41409‐018‐0169‐6

White IR, Royston P. Imputing missing covariate values for the cox model. Stat Med. 2009;28(15):1982–1998. https://doi.org/10.1002/sim.3618

Passweg JR, Baldomero H, Ciceri F, de la Cámara R, Glass B, Greco R, et al. Hematopoietic cell transplantation and cellular therapies in Europe 2022. CAR‐T activity continues to grow; transplant activity has slowed: a report from the EBMT. Bone Marrow Transplant. 2024;59(6):803–812. https://doi.org/10.1038/s41409‐024‐02248‐9

Anasetti C, Logan BR, Lee SJ, Waller EK, Weisdorf DJ, Wingard JR, et al. Peripheral‐blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367(16):1487–1496. https://doi.org/10.1056/NEJMoa1203517

Ruggeri A, Labopin M, Bacigalupo A, Gülbas Z, Koc Y, Blaise D, et al. Bone marrow versus mobilized peripheral blood stem cells in haploidentical transplants using posttransplantation cyclophosphamide. Cancer. 2018;124(7):1428–1437. https://doi.org/10.1002/cncr.31228

Soiffer RJ, Lerademacher J, Ho V, Kan F, Artz A, Champlin RE, et al. Impact of immune modulation with anti‐T‐cell antibodies on the outcome of reduced‐intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies. Blood. 2011;117(25):6963–6970. https://doi.org/10.1182/blood‐2011‐01‐332007

Remberger M, Ringdén O, Hägglund H, Svahn BM, Ljungman P, Uhlin M, et al. A high antithymocyte globulin dose increases the risk of relapse after reduced intensity conditioning HSCT with unrelated donors. Clin Transplant. 2013;27(4):E368–E374. https://doi.org/10.1111/ctr.12131

Modi D, Kim S, Surapaneni M, Ayash L, Ratanatharathorn V, Uberti JP, et al. Absolute lymphocyte count on the first day of thymoglobulin predicts relapse‐free survival in matched unrelated peripheral blood stem cell transplantation. Leuk Lymphoma. 2020;61:3137–3145. https://doi.org/10.1080/10428194.2020.1805114

Zhou X, Cai Y, Yang J, Tong Y, Qiu H, Huang C, et al. Lower absolute lymphocyte count before conditioning predicts high relapse risk in patients after haploidentical peripheral blood stem cell transplantation with low dose anti‐thymocyte globulin/post‐transplant cyclophosphamide for GvHD prophylaxis. Cell Transplant. 2022;31:9636897221079739. https://doi.org/10.1177/09636897221079739

Jin F, He J, Jin C, Fan W, Shan Y, Zhang Z, et al. Antithymocyte globulin treatment at the time of transplantation impairs donor hematopoietic stem cell engraftment. Cell Mol Immunol. 2017;14(5):443–450. https://doi.org/10.1038/cmi.2015.92

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