Post-transplant cyclophosphamide at 80 mg/kg with low dose post-engraftment anti-thymocyte globulin in haploidentical transplantation with myeloablative conditioning.


Journal

Bone marrow transplantation
ISSN: 1476-5365
Titre abrégé: Bone Marrow Transplant
Pays: England
ID NLM: 8702459

Informations de publication

Date de publication:
10 Apr 2024
Historique:
received: 11 12 2023
accepted: 25 03 2024
revised: 13 03 2024
medline: 11 4 2024
pubmed: 11 4 2024
entrez: 10 4 2024
Statut: aheadofprint

Résumé

While post-transplant cyclophosphamide (PTCy) is commonly used as graft-versus-host disease (GvHD) prophylaxis in haploidentical stem cell transplantation (haplo-HSCT), its dose remains a matter of debate due to side effect concerns. Standard dose of 100 mg/kg associated with tacrolimus and post-engraftment anti-thymocyte globulin (ATG) was used as the reference GvHD prophylaxis in our center and had demonstrated encouraging results. Though PTCy 80 mg/kg was shown to be feasible in patients in reduced-intensity conditioning, whether it exerts equivalent GvHD prophylactic efficacy in myeloablative conditioning (MAC) setting has not been confirmed. Here, we retrospectively analyzed the efficacy and safety of PTCy 80 mg/kg combined with tacrolimus and post-engraftment ATG as GvHD prophylaxis in patients aged more than 55 years or with cardiac antecedents or HCT-CI score >2 undergoing haplo-HSCT with MAC. The cumulative incidence of grade III-IV aGvHD at day 100 and moderate-to-severe cGvHD at 1 year was 4.8% ± 3.4% and 19.9% ± 7.0%, respectively. When compared with patients receiving the reference regimen, patients from the PTCy 80 mg/kg group had similar incidence of GvHDs and survival as their younger counterparts. Thus, PTCy 80 mg/kg seems to be feasible for patients treated with MAC conditioning regimens in haplo-HSCT, inviting further investigation notably in frail patients.

Identifiants

pubmed: 38600162
doi: 10.1038/s41409-024-02277-4
pii: 10.1038/s41409-024-02277-4
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Nature Limited.

Références

Ruggeri A, Sun Y, Labopin M, Bacigalupo A, Lorentino F, Arcese W, et al. Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus-host disease prophylaxis in haploidentical transplant. Haematologica. 2017;102:401–10. https://doi.org/10.3324/haematol.2016.151779 .
doi: 10.3324/haematol.2016.151779 pubmed: 27758821 pmcid: 5286948
Shaw BE, Jimenez-Jimenez AM, Burns LJ, Logan BR, Khimani F, Shaffer BC, et al. National Marrow Donor Program-sponsored multicenter, phase II trial of HLA-mismatched unrelated donor bone marrow transplantation using post-transplant cyclophosphamide. J Clin Oncol. 2021;39:1971–82. https://doi.org/10.1200/JCO.20.03502 .
doi: 10.1200/JCO.20.03502 pubmed: 33905264 pmcid: 8260905
Sanz J, Galimard JE, Labopin M, Afanasyev B, Angelucci E, Ciceri F, et al. Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT. J Hematol Oncol. 2020;13:46. https://doi.org/10.1186/s13045-020-00882-6 .
doi: 10.1186/s13045-020-00882-6 pubmed: 32375860 pmcid: 7201995
Perez-Valencia AI, Cascos E, Carbonell-Ordeig S, Charry P, Gomez-Hernando M, Rodriguez-Lobato LG, et al. Incidence, risk factors, and impact of early cardiac toxicity after allogeneic hematopoietic cell transplant. Blood Adv. 2023;7:2018–31. https://doi.org/10.1182/bloodadvances.2022008792 .
doi: 10.1182/bloodadvances.2022008792 pubmed: 36453637
Dulery R, Mohty R, Labopin M, Sestili S, Malard F, Brissot E, et al. Early cardiac toxicity associated with post-transplant cyclophosphamide in allogeneic stem cell transplantation. JACC CardioOncol. 2021;3:250–9. https://doi.org/10.1016/j.jaccao.2021.02.011 .
doi: 10.1016/j.jaccao.2021.02.011 pubmed: 34396331 pmcid: 8352028
Yeh J, Whited L, Saliba RM, Rondon G, Banchs J, Shpall E, et al. Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era. Blood Adv. 2021;5:5599–607. https://doi.org/10.1182/bloodadvances.2021004846 .
doi: 10.1182/bloodadvances.2021004846 pubmed: 34592759 pmcid: 8714723
Ngo D, Samuels D, Chen J, Koller PB, Al Malki MM. A clinical review of the different strategies to minimize hemorrhagic cystitis associated with the use of post-transplantation cyclophosphamide in an allogeneic transplant. Transpl Cell Ther. 2022;28:349–54. https://doi.org/10.1016/j.jtct.2022.05.012 .
doi: 10.1016/j.jtct.2022.05.012
Dulery R, Goudet C, Mannina D, Bianchessi A, Granata A, Harbi S, et al. Reduced post-transplant cyclophosphamide doses in haploidentical hematopoietic cell transplantation for elderly patients with hematological malignancies. Bone Marrow Transpl. 2023;58:386–92. https://doi.org/10.1038/s41409-022-01908-y .
doi: 10.1038/s41409-022-01908-y
Dulery R, Malard F, Brissot E, Banet A, Sestili S, Belhocine R et al. Reduced post-transplant cyclophosphamide dose with antithymocyte globulin in peripheral blood stem cell haploidentical transplantation. Bone Marrow Transpl. 2023. https://doi.org/10.1038/s41409-023-02085-2 .
Spyridonidis A, Labopin M, Savani BN, Niittyvuopio R, Blaise D, Craddock C, et al. Redefining and measuring transplant conditioning intensity in current era: a study in acute myeloid leukemia patients. Bone Marrow Transpl. 2020;55:1114–25. https://doi.org/10.1038/s41409-020-0803-y .
doi: 10.1038/s41409-020-0803-y
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;123:3664–71. https://doi.org/10.1182/blood-2014-01-552984 .
doi: 10.1182/blood-2014-01-552984 pubmed: 24744269 pmcid: 4047501
Wang L, Dai B, Gao W, Wang J, Wan M, Wang R, et al. Clinical significance of haplo-fever and cytokine profiling after graft infusion in allogeneic stem cell transplantation from haplo-identical donors. Front Med. 2022;9:820591. https://doi.org/10.3389/fmed.2022.820591 .
doi: 10.3389/fmed.2022.820591
Law AD, Salas MQ, Lam W, Michelis FV, Thyagu S, Kim DDH, et al. Reduced-intensity conditioning and dual T lymphocyte suppression with antithymocyte globulin and post-transplant cyclophosphamide as graft-versus-host disease prophylaxis in haploidentical hematopoietic stem cell transplants for hematological malignancies. Biol Blood Marrow Transpl. 2018;24:2259–64. https://doi.org/10.1016/j.bbmt.2018.07.008 .
doi: 10.1016/j.bbmt.2018.07.008
Alanazi W, Chen S, Lipton JH, Kim DD, Viswabandya A, Kumar R, et al. Post-transplant cyclophosphamide combined with anti-thymocyte globulin as graft-versus-host disease prophylaxis for allogeneic hematopoietic cell transplantation in high-risk acute myeloid leukemia and myelodysplastic syndrome. Acta Haematol. 2021;144:66–73. https://doi.org/10.1159/000507536 .
doi: 10.1159/000507536 pubmed: 32428903
Dulery R, Brissot E, Mohty M. Combining post-transplant cyclophosphamide with antithymocyte globulin for graft-versus-host disease prophylaxis in hematological malignancies. Blood Rev. 2023: 101080. https://doi.org/10.1016/j.blre.2023.101080 .
Zu Y, Li Z, Gui R, Liu Y, Zhang Y, Yu F, et al. Low-dose post-transplant cyclophosphamide with low-dose antithymocyte globulin for prevention of graft-versus-host disease in first complete remission undergoing 10/10 HLA-matched unrelated donor peripheral blood stem cell transplants: a multicentre, randomized controlled trial. Bone Marrow Transpl. 2022;57:1573–80. https://doi.org/10.1038/s41409-022-01754-y .
doi: 10.1038/s41409-022-01754-y
Spyridonidis A, Labopin M, Brissot E, Moiseev I, Cornelissen J, Choi G, et al. Should anti-thymocyte globulin be added in post-transplant cyclophosphamide based matched unrelated donor peripheral blood stem cell transplantation for acute myeloid leukemia? A study on behalf of the Acute Leukemia Working Party of the EBMT. Bone Marrow Transpl. 2022;57:1774–80. https://doi.org/10.1038/s41409-022-01816-1 .
doi: 10.1038/s41409-022-01816-1
Zhang W, Gui R, Zu Y, Zhang B, Li Z, Zhang Y, et al. Reduced-dose post-transplant cyclophosphamide plus low-dose post-transplant anti-thymocyte globulin as graft-versus-host disease prophylaxis with fludarabine-busulfan-cytarabine conditioning in haploidentical peripheral blood stem cell transplantation: a multicentre, randomized controlled clinical trial. Br J Haematol. 2023;200:210–21. https://doi.org/10.1111/bjh.18483 .
doi: 10.1111/bjh.18483 pubmed: 36200642
Xue E, Lorentino F, Lupo Stanghellini MT, Giglio F, Piemontese S, Clerici DT, et al. Addition of a single low dose of anti T-lymphocyte globulin to post-transplant cyclophosphamide after allogeneic hematopoietic stem cell transplant: a pilot study. J Clin Med. 2022;11. https://doi.org/10.3390/jcm11041106 .
Gao WH, Zhu JY, Wang LN, Wan M, Wang L, Devillier R, et al. Post-transplantation cyclophosphamide combined with tacrolimus and low-dose post-engraftment anti-thymoglobulin as GVHD prophylaxis for patients undergoing peripheral blood stem cell transplantation from haploidentical family donor: A single center analysis. Front Med. 2023;10:1140217. https://doi.org/10.3389/fmed.2023.1140217 .
doi: 10.3389/fmed.2023.1140217

Auteurs

Lining Wang (L)

Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine, Blood and Marrow Transplantation Center, Department of Hematology, Collaborative Innovation Center of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Guilin Xu (G)

Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine, Blood and Marrow Transplantation Center, Department of Hematology, Collaborative Innovation Center of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Ling Wang (L)

Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine, Blood and Marrow Transplantation Center, Department of Hematology, Collaborative Innovation Center of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Jieling Jiang (J)

Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine, Blood and Marrow Transplantation Center, Department of Hematology, Collaborative Innovation Center of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Wenhui Gao (W)

Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine, Blood and Marrow Transplantation Center, Department of Hematology, Collaborative Innovation Center of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Ming Wan (M)

Shanghai Clinical Research Center (SCRC), Fenglin International Centre, Shanghai, China.

Didier Blaise (D)

Department of Hematology, Program of Transplantation and Cell Therapy, Program of Leukemia, Centre de Recherche en Cancérologie de Marseille (CRCM), Institut Paoli-Calmettes, Aix Marseille University, Marseille, France. BLAISED@ipc.unicancer.fr.

Jiong Hu (J)

Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, National Research Center for Translational Medicine, Blood and Marrow Transplantation Center, Department of Hematology, Collaborative Innovation Center of Hematology, Ruijin Hospital affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China. hj10709@rjh.com.cn.

Classifications MeSH