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      GVHD occurrence does not reduce AML relapse following PTCy-based haploidentical transplantation: a study from the ALWP of the EBMT

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          Abstract

          The association between graft-versus-host disease (GVHD) occurrence and acute myeloid leukemia (AML) relapse in patients treated with HLA-haploidentical allogeneic hematopoietic stem cell transplantation (Haplo-HCT) with post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis has remained debated. Here, we addressed this issue in patients with active AML at transplantation. 2-year cumulative incidences of relapse and leukemia-free survival (LFS) were 49% and 32.3%, respectively. There were no associations between acute nor chronic GVHD of any grade and lower relapse incidence. However, grade I acute GVHD was associated with better LFS (HR = 0.71, 95% CI 0.51–0.99, P = 0.04). In contrast, grade III–IV acute (HR = 3.09, 95% CI 1.87–5.12, P < 0.0001) as well as extensive chronic (HR = 3.3, 95% CI 1.81–6.04, P = 0.0001) GVHD correlated with higher nonrelapse mortality leading to lower LFS (HR = 1.36, 95% CI 0.99–1.86, P = 0.056 and HR = 1.97, 95% CI 1.35–2.89, P = 0.0004, respectively). In conclusion, these data suggest a dissociation of graft-versus-leukemia effects from GVHD in patients with active AML treated with PTCy-based Haplo-HCT.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s13045-023-01403-x.

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          Graft-versus-leukemia reactions after bone marrow transplantation.

          M Horowitz, R P Gale, P Sondel … (1990)
          To determine whether graft-versus-leukemia (GVL) reactions are important in preventing leukemia recurrence after bone marrow transplantation, we studied 2,254 persons receiving HLA-identical sibling bone marrow transplants for acute myelogenous leukemia (AML) in first remission, acute lymphoblastic leukemia (ALL) in first remission, and chronic myelogenous leukemia (CML) in first chronic phase. Four groups were investigated in detail: recipients of non--T-cell depleted allografts without graft-versus-host disease (GVHD), recipients of non--T-cell depleted allografts with GVHD, recipients of T-cell depleted allografts, and recipients of genetically identical twin transplants. Decreased relapse was observed in recipients of non--T-cell depleted allografts with acute (relative risk 0.68, P = .03), chronic (relative risk 0.43, P = .01), and both acute and chronic GVDH (relative risk 0.33, P = .0001) as compared with recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect of GVHD. AML patients who received identical twin transplants had an increased probability of relapse (relative risk 2.58, P = .008) compared with allograft recipients without GVHD. These data support an antileukemia effect of allogeneic grafts independent of GVHD. CML patients who received T-cell depleted transplants with or without GVHD had higher probabilities of relapse (relative risks 4.45 and 6.91, respectively, P = .0001) than recipients of non--T-cell depleted allografts without GVHD. These data support an antileukemia effect independent of GVHD that is altered by T-cell depletion. These results explain the efficacy of allogeneic bone marrow transplantation in eradicating leukemia, provide evidence for a role of the immune system in controlling human cancers, and suggest future directions to improve leukemia therapy.
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            Antileukemic effect of chronic graft-versus-host disease: contribution to improved survival after allogeneic marrow transplantation.

            R Storb, N Flournoy, P Weiden … (1981)
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              The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

              Xiao-hui Zhang, Jing Chen, Ming-Zhe Han … (2021)
              The consensus recommendations in 2018 from The Chinese Society of Hematology (CSH) on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation (allo-HSCT) facilitated the standardization of clinical practices of allo-HSCT in China and progressive integration with the world. There have been new developments since the initial publication. To integrate recent developments and further improve the consensus, a panel of experts from the CSH recently updated the consensus recommendations, which are summarized as follows: (1) there is a new algorithm for selecting appropriate donors for allo-HSCT candidates. Haploidentical donors (HIDs) are the preferred donor choice over matched sibling donors (MSDs) for patients with high-risk leukemia or elderly patients with young offspring donors in experienced centers. This replaces the previous algorithm for donor selection, which favored MSDs over HIDs. (2) Patients with refractory/relapsed lymphoblastic malignancies are now encouraged to undergo salvage treatment with novel immunotherapies prior to HSCT. (3) The consensus has been updated to reflect additional evidence for the application of allo-HSCT in specific groups of patients with hematological malignancies (intermediate-risk acute myeloid leukemia (AML), favorable-risk AML with positive minimal residual disease, and standard-risk acute lymphoblastic leukemia). (4) The consensus has been updated to reflect additional evidence for the application of HSCT in patients with nonmalignant diseases, such as severe aplastic anemia and inherited diseases. (5) The consensus has been updated to reflect additional evidence for the administration of anti-thymocyte globulin, granulocyte colony-stimulating factors and post-transplantation cyclophosphamide in HID-HSCT.
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                Author and article information

                Contributors
                Frédéric Baron: f.baron@ulg.ac.be , f.baron@uliege.be
                Myriam Labopin: myriam.labopin@upmc.fr
                Johanna Tischer: Johanna.Tischer@med.uni-muenchen.de
                Anna Maria Raiola: annamaria.raiola@hsanmartino.it
                Jan Vydra: Jan.Vydra@uhkt.cz
                Didier Blaise: blaised@ipc.unicancer.fr
                Patrizia Chiusolo: Patrizia.Chiusolo@unicatt.it
                Friedrich Stölzel: friedrich.stoelzel@uksh.de
                Renato Fanin: renato.fanin@uniud.it
                Patrice Chevallier: patrice.chevallier@chu-nantes.fr
                Arnon Nagler: Arnon.Nagler@sheba.health.gov.il
                Fabio Ciceri: ciceri.fabio@hsr.it
                Mohamad Mohty: mohamad.mohty@inserm.fr
                Journal
                Journal ID (nlm-ta): J Hematol Oncol
                Journal ID (iso-abbrev): J Hematol Oncol
                Title: Journal of Hematology & Oncology
                Publisher: BioMed Central (London )
                ISSN (Electronic): 1756-8722
                Publication date (Electronic): 13 February 2023
                Publication date PMC-release: 13 February 2023
                Publication date Collection: 2023
                Volume: 16
                Electronic Location Identifier: 10
                Affiliations
                [1 ]GRID grid.4861.b, ISNI 0000 0001 0805 7253, Laboratory of Hematology, GIGA-I3, , University of Liege and CHU of Liège, ; Sart-Tilman, 4000 Liège, Belgium
                [2 ]GRID grid.492743.f, EBMT Paris Study Office/CEREST-TC, ; Paris, France
                [3 ]GRID grid.412370.3, ISNI 0000 0004 1937 1100, Department of Hematology, , Saint Antoine Hospital, ; Paris, France
                [4 ]GRID grid.7429.8, ISNI 0000000121866389, INSERM UMR 938, ; Paris, France
                [5 ]GRID grid.462844.8, ISNI 0000 0001 2308 1657, Sorbonne University, ; Paris, France
                [6 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Department of Internal Medicine III, , LMU, University Hospital of Munich, ; Campus Grosshadern, Munich, Germany
                [7 ]GRID grid.410345.7, ISNI 0000 0004 1756 7871, IRCCS Ospedale Policlinico San Martino, ; Genoa, Italy
                [8 ]GRID grid.419035.a, Institute of Hematology and Blood Transfusion, ; Prague, Czech Republic
                [9 ]GRID grid.5399.6, ISNI 0000 0001 2176 4817, Programme de Transplantation et d’immunothérapie Cellulaire, Management Sport Cancer Lab, Institut Paoli Calmettes, , Aix Marseille University, ; Marseille, France
                [10 ]GRID grid.414603.4, Dipartimento di Diagnostica per Immagini, Radioterapia Oncologica ed Ematologia, , Fondazione Policlinico Universitario A. Gemelli IRCCS, ; Rome, Italy
                [11 ]GRID grid.4488.0, ISNI 0000 0001 2111 7257, University Hospital Dresden, Medizinische Klinik und Poliklinik, , TU Dresden, ; Dresden, Germany
                [12 ]GRID grid.412468.d, ISNI 0000 0004 0646 2097, University Hospital Schleswig-Holstein, ; Kiel, Germany
                [13 ]GRID grid.5390.f, ISNI 0000 0001 2113 062X, Division of Hematology, , Azienda Ospedaliero Universitaria di Udine, ; Udine, Italy
                [14 ]GRID grid.277151.7, ISNI 0000 0004 0472 0371, Dept. D`Hematologie, , CHU Nantes, ; Nantes, France
                [15 ]GRID grid.413795.d, ISNI 0000 0001 2107 2845, Division of Hematology and Bone Marrow Transplantation, , The Chaim Sheba Medical Center, ; Tel-Hashomer, Ramat-Gan, Israel
                [16 ]GRID grid.18887.3e, ISNI 0000000417581884, Haematology and BMT, , Ospedale San Raffaele S.R.L., ; Milan, Italy
                Article
                Publisher ID: 1403
                DOI: 10.1186/s13045-023-01403-x
                PMC ID: 9923893
                PubMed ID: 36782226
                SO-VID: e42c8cb0-3f75-49bf-b7cf-8e6b76f1d34f
                Copyright © © The Author(s) 2023
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                Date received : 5 December 2022
                Date accepted : 20 January 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100002661, Fonds De La Recherche Scientifique - FNRS;
                Award ID: Senior research associate
                Award Recipient :
                Categories
                Subject: Correspondence
                Custom metadata
                issue-copyright-statement © The Author(s) 2023

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: aml,acute myeloid leukemia,hla-haploidentical,mismatched unrelated donor,post-transplant cyclophosphamide,ptcy
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: aml, acute myeloid leukemia, hla-haploidentical, mismatched unrelated donor, post-transplant cyclophosphamide, ptcy

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