Sequence matters: Total body irradiation (TBI)-based myeloablative conditioning with post-transplant cyclophosphamide may reduce the early nonrelapse mortality compared with pretransplant cyclophosphamide plus TBI.
myeloablative conditioning
nonrelapse mortality
posttransplant cyclophosphamide
total body irradiation
Journal
European journal of haematology
ISSN: 1600-0609
Titre abrégé: Eur J Haematol
Pays: England
ID NLM: 8703985
Informations de publication
Date de publication:
Jul 2023
Jul 2023
Historique:
revised:
29
03
2023
received:
17
01
2023
accepted:
31
03
2023
medline:
9
6
2023
pubmed:
15
4
2023
entrez:
14
4
2023
Statut:
ppublish
Résumé
High-dose total body irradiation (TBI) is considered a cornerstone of myeloablative conditioning for allogeneic stem cell transplantation (allo-SCT). We retrospectively compared the main outcomes of an HLA matched or 1-allele mismatched related or unrelated allo-SCT in adult patients affected by acute leukemia (AL) or myelodysplastic syndromes (MDS). Fifty-nine patients received cyclophosphamide (Cy)-TBI (13.5 Gy) and graft-versus-host disease (GVHD) prophylaxis with a calcineurin-inhibitor plus methrotrexate (CyTBI group) and 28 patients received fludarabine-TBI (8.8-13.5 Gy) and GVHD prophylaxis with PTCy and tacrolimus (FluTBI-PTCy group). Median follow-up for survivors was 82 and 22 months. The 12-month probability of overall survival and progression-free survival were similar (p = .18, p = .7). The incidence of Grades 2-4 and 3-4 acute GVHD, and the incidence of moderate-to-severe chronic GVHD were higher in the CyTBI group (p = .02, p < .01and p = .03). Nonrelapse mortality (NRM) at 12 months posttransplant was higher in the CyTBI group (p = 0.05), while the incidence of relapse was similar in both groups (p = 0.7). The number of GVHD-free and relapse-free patients without systemic immunosuppression (GRFS) at 1-year posttransplant was higher in the FluTBI-PTCy group (p = 0.01). The study confirms the safety and efficacy of a novel FluTBI-PTCy platform with reduced incidence of severe acute and chronic GVHD, and early improvement of NRM.
Substances chimiques
Cyclophosphamide
8N3DW7272P
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
146-153Subventions
Organisme : Fundació la Marató de TV3
Organisme : Instituto de Salud Carlos III, Ministerio de Economía y competitividad
ID : Tercel RD16/0011/0028
Organisme : Instituto de Salud Carlos III, Ministerio de Economía y competitividad
ID : AGAUR 2017 SGR 865
Organisme : Instituto de Salud Carlos III, Ministerio de Economía y competitividad
ID : FIS PI17/01246
Organisme : Instituto de Salud Carlos III, Ministerio de Economía y competitividad
ID : La Marató 517C/20190318/1330
Informations de copyright
© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Thomas ED, Buckner CD, Banaji M, et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. 1977;49(4):511-533. Blood. 2016;128(20):2373.
Martino R, Iacobelli S, Brand R, et al. Myelodysplastic syndrome subcommittee of the chronic leukemia working Party of the European Blood and Marrow Transplantation Group. Retrospective comparison of reduced-intensity conditioning and conventional high-dose conditioning for allogeneic hematopoietic stem cell transplantation using HLA-identical sibling donors in myelodysplastic syndromes. Blood. 2006;108(3):836-846.
Scott BL, Sandmaier BM, Storer B, et al. Myeloablative vs nonmyeloablative allogeneic transplantation for patients with myelodysplastic syndrome or acute myelogenous leukemia with multilineage dysplasia: a retrospective analysis. Leukemia. 2006;20(1):128-135.
Martino R, Valcárcel D, Brunet S, Sureda A, Sierra J. Comparable non-relapse mortality and survival after HLA-identical sibling blood stem cell transplantation with reduced or conventional-intensity preparative regimens for high-risk myelodysplasia or acute myeloid leukemia in first remission. Bone Marrow Transplant. 2008;41(1):33-38.
Gooley TA, Chien JW, Pergam SA, et al. Reduced mortality after allogeneic hematopoietic-cell transplantation. N Engl J Med. 2010;363(22):2091-2101.
Gooptu M, Kim HT, Ho VT, et al. A comparison of the Myeloablative conditioning regimen Fludarabine/Busulfan with cyclophosphamide/Total body irradiation, for allogeneic stem cell transplantation in the modern era: a cohort analysis. Biol Blood Marrow Transplant. 2018;24(8):1733-1740.
Jagasia M, Arora M, Flowers ME, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012;119(1):296-307.
Arora M, Cutler CS, Jagasia MH, et al. Late acute and chronic graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22(3):449-455.
Arai S, Arora M, Wang T, et al. Graft-vs-host disease working committee of the CIBMTR. Increasing incidence of chronic graft-versus-host disease in allogeneic transplantation: a report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2015;21(2):266-274.
Luznik L, O'Donnell PV, Symons HJ, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641-650.
Prem S, Atenafu EG, Al-Shaibani Z, et al. Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants. Eur J Haematol. 2019;102(6):486-493.
García-Cadenas I, Awol R, Esquirol A, et al. Incorporating posttransplant cyclophosphamide-based prophylaxis as standard-of-care outside the haploidentical setting: challenges and review of the literature. Bone Marrow Transplant. 2020;55(6):1041-1049.
Mielcarek M, Furlong T, O'Donnell PV, et al. Posttransplantation cyclophosphamide for prevention of graft-versus-host disease after HLA-matched mobilized blood cell transplantation. Blood. 2016;127(11):1502-1508.
McCurdy SR, Kasamon YL, Kanakry CG, et al. Comparable composite endpoints after HLA-matched and HLA-haploidentical transplantation with post-transplantation cyclophosphamide. Haematologica. 2017;102(2):391-400.
Lorentino F, Labopin M, Ciceri F, et al. Acute leukemia working party (ALWP) and cellular therapy and Immunobiology working party (CTIWP) of the European Society for Blood and Marrow Transplantation (EBMT). Post-transplantation cyclophosphamide GvHD prophylaxis after hematopoietic stem cell transplantation from 9/10 or 10/10 HLA-matched unrelated donors for acute leukemia. Leukemia. 2021;35(2):585-594.
Ruggeri A, Labopin M, Bacigalupo A, et al. 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.
Sabloff M, Chhabra S, Wang T, et al. Comparison of high doses of total body irradiation in myeloablative conditioning before hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2019;25(12):2398-2407.
Bornhäuser M, Kienast J, Trenschel R, et al. Reduced-intensity conditioning versus standard conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: a prospective, open-label randomised phase 3 trial. Lancet Oncol. 2012;13(10):1035-1044.
Fasslrinner F, Schetelig J, Burchert A, et al. Long-term efficacy of reduced-intensity versus myeloablative conditioning before allogeneic haemopoietic cell transplantation in patients with acute myeloid leukaemia in first complete remission: retrospective follow-up of an open-label, randomised phase 3 trial. Lancet Haematol. 2018;5(4):e161-e169.
Kim HJ, Min WS, Cho BS, et al. Successful prevention of acute graft-versus-host disease using low-dose antithymocyte globulin after mismatched, unrelated, hematopoietic stem cell transplantation for acute myelogenous leukemia. Biol Blood Marrow Transplant. 2009 Jun;15(6):704-717.
Shi L, Lu X, Deng D, et al. The safety and efficacy of a novel hypo-fractionated total marrow and lymphoid irradiation before allogeneic stem cell transplantation for lymphoma and acute leukemia. Clin Transl Radiat Oncol. 2020;12(26):42-46.
Monaco F, Scott BL, Chauncey TR, et al. Total body irradiation dose escalation decreases risk of progression and graft rejection after hematopoietic cell transplantation for myelodysplastic syndromes or myeloproliferative neoplasms. Haematologica. 2019;104(6):1221-1229.
García-Cadenas I, Rivera I, Martino R, et al. Patterns of infection and infection-related mortality in patients with steroid-refractory acute graft versus host disease. Bone Marrow Transplant. 2017;52(1):107-113.
Przepiorka D, Weisdorf D, Martin P, et al. 1994 consensus conference on acute GVHD grading. Bone Marrow Transplant. 1995;15(6):825-828.
Filipovich AH, Weisdorf D, Pavletic S, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11(12):945-956.
Valcárcel D, Martino R, Caballero D, et al. Chimerism analysis following allogeneic peripheral blood stem cell transplantation with reduced-intensity conditioning. Bone Marrow Transplant. 2003;31(5):387-392.
Scott BL, Pasquini MC, Fei M, et al. Myeloablative versus reduced-intensity conditioning for hematopoietic cell transplantation in acute myelogenous leukemia and myelodysplastic syndromes-long-term follow-up of the BMT CTN 0901 clinical trial. Transplant Cell Ther. 2021;27(6):483.e1-483.e6.
Bento L, Bastida JM, García-Cadenas I, et al. Thrombopoietin receptor agonists for severe thrombocytopenia after allogeneic stem cell transplantation: experience of the Spanish group of hematopoietic stem cell transplant. Biol Blood Marrow Transplant. 2019;25(9):1825-1831.
Penack O, Peczynski C, Mohty M, et al. How much has allogeneic stem cell transplant-related mortality improved since the 1980s? A retrospective analysis from the EBMT. Blood Adv. 2020;4(24):6283-6290.
Styczyński J, Tridello G, Koster L, et al. Infectious diseases working party EBMT. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020;55(1):126-136.
Spyridonidis A, Labopin M, Savani BB, et al. Retrospective comparison between 12-gray and 8-gray Total body irradiation (TBI) before allogeneic hematopoietic cell transplantation in patients with acute lymphoblastic leukemia in first complete remission. Blood. 2021;138(Supplement 1):1783.