Clinical effects of administering leukemia-specific donor T cells to patients with AML/MDS after allogeneic transplant Article

Full Text via DOI: 10.1182/blood.2020009471 Web of Science: 000652412000010

Cited authors

  • Lulla PD, Naik S, Vasileiou S, Tzannou I, Watanabe A, Kuvalekar M, Lulla S, Carrum G, Ramos CA, Kamble R, Hill L, Randhawa J, Gottschalk S, Krance R, Wang T, Wu MF, Robertson C, Gee AP, Chung B, Grilley B, Brenner MK, Heslop HE, Vera JF, Leen AM

Abstract

  • Relapse after allogeneic hematopoietic stemcell transplantation (HCT) is the leading cause of death in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Infusion of unselected donor lymphocytes (DLIs) enhances the graft-versus-leukemia (GVL) effect. However, because the infused lymphocytes are not selected for leukemia specificity, the GVL effect is often accompanied by life-threatening graft-versus-host disease (GVHD), related to the concurrent transfer of alloreactive lymphocytes. Thus, to minimize GVHD and maximize GVL, we selectively activated and expanded stem cell donor-derived T cells reactive to multiple antigens expressed by AML/MDS cells (PRAME, WT1, Survivin, and NY-ESO-1). Products that demonstrated leukemia antigen specificity were generated from 29 HCT donors. In contrast to DLIs, leukemia-specific T cells (mLSTs) selectively recognized and killed leukemia antigen-pulsed cells, with no activity against recipient's normal cells in vitro. We administered escalating doses of mLSTs (0.5 to 10 x 10(7) cells per square meter) to 25 trial enrollees, 17 with high risk of relapse and 8 with relapsed disease. Infusions were well tolerated with no grade >2 acute or extensive chronic GVHD seen. We observed antileukemia effects in vivo that translated into not-yet-reached median leukemia-free and overall survival at 1.9 years of follow-up and objective responses in the active disease cohort (1 complete response and 1 partial response). In summary, mLSTs are safe and promising for the prevention and treatment of AML/MDS after HCT.

Publication date

  • 2021

Published in

Category

International Standard Serial Number (ISSN)

  • 0006-4971

Number of pages

  • 13

Start page

  • 2585

End page

  • 2597

Volume

  • 137

Issue

  • 19