Impact of Post-transplant Cyclophosphamide (PTCy)-based Prophylaxis in Matched Sibling Donor Allogeneic Haematopoietic Cell Transplantation for Patients with Myelodysplastic Syndrome: a Retrospective Study on Behalf of the Chronic Malignancies...

Overview

Journal Bone Marrow Transplant

Specialty General Surgery

Date 2024 Jan 22

PMID 38253869

Authors

Maria Queralt Salas

Diderik-Jan Eikema

Linda Koster

Johan Maertens

Jakob Passweg

Jurgen Finke

Annoek E C Broers

Yener Koc

Nicolaus Kroger

Zubeyde Nur Ozkurt

Maria Jesus Pascual-Cascon

Uwe Platzbecker

Gwendolyn Van Gorkom

Thomas Schroeder

Jose Luis Lopez-Lorenzo

Massimo Martino

Patrizia Chiusolo

Martin Kaufmann

Francesco Onida

Carmelo Gurnari

Christof Scheid

Joanna Drozd-Sokolowska

Kavita Raj

Marie Robin

Donal P McLornan

Affiliations

Soon will be listed here.

Abstract

We retrospectively compared outcomes of 404 MDS patients undergoing 1st matched sibling donor allo-HCT receiving either PTCy-based (n = 66) or other "conventional prophylaxis" (n = 338; mostly calcineurin inhibitor + methotrexate or MMF). Baseline characteristics were balanced, except for higher use of myeloablative regimens in the PTCy group (52.3% vs. 38.2%, p = 0.047). Incidences of neutrophil (Day +28: 89% vs. 97%, p = 0.011) and platelet (Day +100: 89% vs. 97%, p < 0.001) engraftment were lower for PTCy-based. Day +100 cumulative incidences of grade II-IV and III-IV aGVHD, and 5-year CI of extensive cGVHD were 32%, 18% and 18% for PTCy-based and 25% (p = 0.3), 13% (p = 0.4) and 31% (p = 0.09) for the conventional cohort. Five-year OS (51% vs. 52%, p = 0.6) and GRFS (33% vs. 25%, p = 0.6) were similar between groups. Patients receiving PTCy had a trend to a lower cumulative incidence of relapse (20% vs. 33%, p = 0.06), not confirmed on multivariable analysis (p = 0.3). Although higher NRM rates were observed in patients receiving PTCy (32% vs. 21%, p = 0.02) on univariate analysis, this was not confirmed on multivariate analysis (HR 1.46, p = 0.18), and there was no resultant effect on OS (HR 1.20, p = 0.5). Based on these data, PTCy prophylaxis appears to be an attractive option for patients with MDS undergoing MSD allo-HCT.

References

Stern M, de Wreede L, Brand R, van Biezen A, Dreger P, Mohty M . Sensitivity of hematological malignancies to graft-versus-host effects: an EBMT megafile analysis. Leukemia. 2014; 28(11):2235-40. DOI: 10.1038/leu.2014.145. View

Passweg J, Baldomero H, Ciceri F, Corbacioglu S, de la Camara R, Dolstra H . Hematopoietic cell transplantation and cellular therapies in Europe 2021. The second year of the SARS-CoV-2 pandemic. A Report from the EBMT Activity Survey. Bone Marrow Transplant. 2023; 58(6):647-658. PMC: 9987384. DOI: 10.1038/s41409-023-01943-3. View

Forcade E, Chevret S, Finke J, Ehninger G, Ayuk F, Beelen D . Impact of in vivo T-cell depletion in patients with myelodysplastic syndromes undergoing allogeneic hematopoietic stem cell transplant: a registry study from the Chronic Malignancies Working Party of the EBMT. Bone Marrow Transplant. 2022; 57(5):768-774. DOI: 10.1038/s41409-022-01620-x. View

Alanazi W, Chen S, Lipton J, Kim D, Viswabandya A, Kumar R . 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. 2020; 144(1):66-73. DOI: 10.1159/000507536. View

Kanakry C, ODonnell P, Furlong T, De Lima M, Wei W, Medeot M . Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014; 32(31):3497-505. PMC: 4209101. DOI: 10.1200/JCO.2013.54.0625. View

Ruggeri A, Labopin M, Bacigalupo A, Afanasyev B, Cornelissen J, Elmaagacli A . Post-transplant cyclophosphamide for graft-versus-host disease prophylaxis in HLA matched sibling or matched unrelated donor transplant for patients with acute leukemia, on behalf of ALWP-EBMT. J Hematol Oncol. 2018; 11(1):40. PMC: 5855999. DOI: 10.1186/s13045-018-0586-4. View

Bailen R, Pascual-Cascon M, Guerreiro M, Lopez-Corral L, Chinea A, Bermudez A . Post-Transplantation Cyclophosphamide After HLA Identical Compared to Haploidentical Donor Transplant in Acute Myeloid Leukemia: A Study on Behalf of GETH-TC. Transplant Cell Ther. 2022; 28(4):204.e1-204.e10. DOI: 10.1016/j.jtct.2022.01.020. View

Bolanos-Meade J, Reshef R, Fraser R, Fei M, Abhyankar S, Al-Kadhimi Z . Three prophylaxis regimens (tacrolimus, mycophenolate mofetil, and cyclophosphamide; tacrolimus, methotrexate, and bortezomib; or tacrolimus, methotrexate, and maraviroc) versus tacrolimus and methotrexate for prevention of graft-versus-host disease.... Lancet Haematol. 2019; 6(3):e132-e143. PMC: 6503965. DOI: 10.1016/S2352-3026(18)30221-7. View

Battipaglia G, Labopin M, Hamladji R, Blaise D, Chevallier P, Brissot E . Post-transplantation cyclophosphamide versus antithymocyte globulin in patients with acute myeloid leukemia undergoing allogeneic stem cell transplantation from HLA-identical sibling donors: A retrospective analysis from the Acute Leukemia Working.... Cancer. 2020; 127(2):209-218. DOI: 10.1002/cncr.33255. View

10.

Lazzari L, Balaguer-Rosello A, Montoro J, Greco R, Hernani R, Lupo-Stanghellini M . Post-transplant cyclophosphamide and sirolimus based graft-versus-host disease prophylaxis after allogeneic stem cell transplantation for acute myeloid leukemia. Bone Marrow Transplant. 2022; 57(9):1389-1398. PMC: 9439951. DOI: 10.1038/s41409-022-01725-3. View

11.

Marco-Ayala J, Sanz J, Gomez-Segui I, Balaguer-Rosello A, Montoro J, Guerreiro M . Impact of Post-Transplantation Cyclophosphamide on Transfusion Requirements in HLA-Matched Sibling Peripheral Blood Stem Cell Transplantation. Transplant Cell Ther. 2023; 29(5):313.e1-313.e10. DOI: 10.1016/j.jtct.2023.01.009. View

12.

Lin C, Vader J, Slade M, Dipersio J, Westervelt P, Romee R . Cardiomyopathy in patients after posttransplant cyclophosphamide-based hematopoietic cell transplantation. Cancer. 2017; 123(10):1800-1809. DOI: 10.1002/cncr.30534. View

13.

Yeh J, Whited L, Saliba R, Rondon G, Banchs J, Shpall E . Cardiac toxicity after matched allogeneic hematopoietic cell transplant in the posttransplant cyclophosphamide era. Blood Adv. 2021; 5(24):5599-5607. PMC: 8714723. DOI: 10.1182/bloodadvances.2021004846. View

14.

Dulery R, Mohty R, Labopin M, Sestili S, Malard F, Brissot E . Early Cardiac Toxicity Associated With Post-Transplant Cyclophosphamide in Allogeneic Stem Cell Transplantation. JACC CardioOncol. 2021; 3(2):250-259. PMC: 8352028. DOI: 10.1016/j.jaccao.2021.02.011. View

15.

Bacigalupo A, Ballen K, Rizzo D, Giralt S, Lazarus H, Ho V . Defining the intensity of conditioning regimens: working definitions. Biol Blood Marrow Transplant. 2009; 15(12):1628-33. PMC: 2861656. DOI: 10.1016/j.bbmt.2009.07.004. View

16.

Sorror M, Maris M, Storb R, Baron F, Sandmaier B, Maloney D . Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005; 106(8):2912-9. PMC: 1895304. DOI: 10.1182/blood-2005-05-2004. View

17.

Harris A, Young R, Devine S, Hogan W, Ayuk F, Bunworasate U . International, Multicenter Standardization of Acute Graft-versus-Host Disease Clinical Data Collection: A Report from the Mount Sinai Acute GVHD International Consortium. Biol Blood Marrow Transplant. 2015; 22(1):4-10. PMC: 4706482. DOI: 10.1016/j.bbmt.2015.09.001. View

18.

Jagasia M, Greinix H, Arora M, Williams K, Wolff D, Cowen E . National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2014; 21(3):389-401.e1. PMC: 4329079. DOI: 10.1016/j.bbmt.2014.12.001. View

19.

Glucksberg H, Storb R, Fefer A, Buckner C, Neiman P, Clift R . Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974; 18(4):295-304. DOI: 10.1097/00007890-197410000-00001. View

20.

Moiseev I, Pirogova O, Alyanski A, Babenko E, Gindina T, Darskaya E . Risk-adapted GVHD prophylaxis with post-transplantation cyclophosphamide in adults after related, unrelated, and haploidentical transplantations. Eur J Haematol. 2018; 100(5):395-402. DOI: 10.1111/ejh.13030. View