Improved GVHD-free and Relapse-free Survival After Ex Vivo αβTCR and CD19 Depleted Allogeneic HSCT Compared to T Cell Replete HSCT

Overview

Journal Bone Marrow Transplant

Specialty General Surgery

Date 2025 Mar 16

PMID 40089614

Authors

A H G Stuut

C Nijssen

L van der Wagen

A van Rhenen

L G M Daenen

A Janssen

F A Verheij

I Brinkman

F M Verduyn Lunel

H Koene

R Fijnheer

H J Prins

K Westinga

J Drylewicz

J Kuball

M A de Witte

Affiliations

Soon will be listed here.

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) aims to cure patients without inducing severe graft-versus-host disease (GVHD) or relapse. In prospective studies of mostly pediatric patients with haploidentical donors, ex vivo αβTCR/CD19 depletion has shown to have low incidences of GVHD, but data for adults with matched related (MRD) or unrelated donors (MUD) remain limited. We analyzed the outcomes of recipients who received a myeloablative regimen plus ATG, followed by an αβTCR/CD19-depleted allograft (cohort D+ATG (n = 122)), and compared outcomes to T cell-replete cohorts (cohort R (N = 60)); without ATG; R+ATG = with ATG (N = 129) in a single-center retrospective analysis. In D+ATG, the incidence of aGVHD grade III-IV was 7%, compared to 13% in R and 16% in R+ATG (p = 0.09). Extensive cGVHD was reduced from 23% in R and 10% in R+ATG to 2% in D+ATG (p < 0.001). The reduced incidence of cGVHD led to a superior GVHD-relapse-free survival (GRFS) of 56.7% in D+ATG versus 36.7% in R and 42.8% in R+ATG (p = 0.03) at 2 years. In conclusion, the combination of myeloablative conditioning, ATG, and ex vivo αβTCR/CD19 depletion appears to be a promising approach to enhance GRFS in adult patients up to 75 years of age undergoing allo-HSCT.

References

Korngold R, Sprent J . Lethal graft-versus-host disease after bone marrow transplantation across minor histocompatibility barriers in mice. Prevention by removing mature T cells from marrow. J Exp Med. 1978; 148(6):1687-98. PMC: 2185109. DOI: 10.1084/jem.148.6.1687. View

Shlomchik W . Graft-versus-host disease. Nat Rev Immunol. 2007; 7(5):340-52. DOI: 10.1038/nri2000. View

Finke J, Bethge W, Schmoor C, Ottinger H, Stelljes M, Zander A . Standard graft-versus-host disease prophylaxis with or without anti-T-cell globulin in haematopoietic cell transplantation from matched unrelated donors: a randomised, open-label, multicentre phase 3 trial. Lancet Oncol. 2009; 10(9):855-64. DOI: 10.1016/S1470-2045(09)70225-6. View

Mohty M, Labopin M, Balere M, Socie G, Milpied N, Tabrizi R . Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire. Leukemia. 2010; 24(11):1867-74. DOI: 10.1038/leu.2010.200. View

Pidala J, Tomblyn M, Nishihori T, Ayala E, Field T, Fernandez H . ATG prevents severe acute graft-versus-host disease in mismatched unrelated donor hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011; 17(8):1237-44. PMC: 5735843. DOI: 10.1016/j.bbmt.2010.12.705. View

Socie G, Schmoor C, Bethge W, Ottinger H, Stelljes M, Zander A . Chronic graft-versus-host disease: long-term results from a randomized trial on graft-versus-host disease prophylaxis with or without anti-T-cell globulin ATG-Fresenius. Blood. 2011; 117(23):6375-82. DOI: 10.1182/blood-2011-01-329821. View

Bonifazi F, Rubio M, Bacigalupo A, Boelens J, Finke J, Greinix H . 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(6):1093-1102. PMC: 7269907. DOI: 10.1038/s41409-020-0792-x. View

Penack O, Abouqateb M, Peczynski C, Boreland W, Kroger N, Stelljes M . ATG or post-transplant cyclophosphamide to prevent GVHD in matched unrelated stem cell transplantation?. Leukemia. 2024; 38(5):1156-1163. PMC: 11073959. DOI: 10.1038/s41375-024-02225-7. View

Berger M, Lanino E, Cesaro S, Zecca M, Vassallo E, Faraci M . Feasibility and Outcome of Haploidentical Hematopoietic Stem Cell Transplantation with Post-Transplant High-Dose Cyclophosphamide for Children and Adolescents with Hematologic Malignancies: An AIEOP-GITMO Retrospective Multicenter Study. Biol Blood Marrow Transplant. 2016; 22(5):902-9. DOI: 10.1016/j.bbmt.2016.02.002. View

10.

Mussetti A, Greco R, Peccatori J, Corradini P . Post-transplant cyclophosphamide, a promising anti-graft versus host disease prophylaxis: where do we stand?. Expert Rev Hematol. 2017; 10(5):479-492. DOI: 10.1080/17474086.2017.1318054. View

11.

Uygun V, Karasu G, Daloglu H, Ozturkmen S, Caki Kilic S, Hazar V . Haploidentical hematopoietic stem cell transplantation with post-transplant high-dose cyclophosphamide in high-risk children: A single-center study. Pediatr Transplant. 2019; 23(7):e13546. DOI: 10.1111/petr.13546. View

12.

Sharma A, Rastogi N, Chatterjee G, Kapoor R, Nivargi S, Yadav S . Haploidentical Stem Cell Transplantation With Post-transplant Cyclophosphamide for Pediatric Acute Leukemia is Safe and Effective. J Pediatr Hematol Oncol. 2020; 43(7):e1033-e1036. DOI: 10.1097/MPH.0000000000002030. View

13.

Broers A, de Jong C, Bakunina K, Hazenberg M, van Marwijk Kooy M, de Groot M . Posttransplant cyclophosphamide for prevention of graft-versus-host disease: results of the prospective randomized HOVON-96 trial. Blood Adv. 2022; 6(11):3378-3385. PMC: 9198908. DOI: 10.1182/bloodadvances.2021005847. View

14.

Bolanos-Meade J, Hamadani M, Wu J, Al Malki M, Martens M, Runaas L . Post-Transplantation Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis. N Engl J Med. 2023; 388(25):2338-2348. PMC: 10575613. DOI: 10.1056/NEJMoa2215943. View

15.

Finazzi M, Boschini C, Craddock C, Rambaldi A, Ward J, Malladi R . Characteristics of graft-versus-host disease occurring after alemtuzumab-containing allogeneic stem cell transplants: incidence, organ involvement, risk factors and survival. Br J Haematol. 2019; 188(4):550-559. DOI: 10.1111/bjh.16200. View

16.

Nijssen K, Westinga K, Stuut A, Janssen A, van Rhenen A, van der Wagen L . Graft engineering: how long can you wait, how low can you go, and pandemic readiness. Bone Marrow Transplant. 2023; 58(7):820-822. PMC: 10069722. DOI: 10.1038/s41409-023-01976-8. View

17.

Locatelli F, Merli P, Pagliara D, Li Pira G, Falco M, Pende D . Outcome of children with acute leukemia given HLA-haploidentical HSCT after αβ T-cell and B-cell depletion. Blood. 2017; 130(5):677-685. DOI: 10.1182/blood-2017-04-779769. View

18.

Bethge W, Eyrich M, Mielke S, Meisel R, Niederwieser D, Schlegel P . Results of a multicenter phase I/II trial of TCRαβ and CD19-depleted haploidentical hematopoietic stem cell transplantation for adult and pediatric patients. Bone Marrow Transplant. 2021; 57(3):423-430. PMC: 8702395. DOI: 10.1038/s41409-021-01551-z. View

19.

Leahy A, Li Y, Talano J, Elgarten C, Seif A, Wang Y . Unrelated donor α/β T cell- and B cell-depleted HSCT for the treatment of pediatric acute leukemia. Blood Adv. 2021; 6(4):1175-1185. PMC: 8864664. DOI: 10.1182/bloodadvances.2021005492. View

20.

de Witte M, Janssen A, Nijssen K, Karaiskaki F, Swanenberg L, van Rhenen A . αβ T-cell graft depletion for allogeneic HSCT in adults with hematological malignancies. Blood Adv. 2021; 5(1):240-249. PMC: 7805311. DOI: 10.1182/bloodadvances.2020002444. View