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

Premal D. Lulla, Swati Naik, Spyridoula Vasileiou, Ifigeneia Tzannou, Ayumi Watanabe, Manik Kuvalekar, Suhasini Lulla, George Carrum, Carlos A. Ramos, Rammurti Kamble, La Quisa Hill, Jasleen Randhawa, Stephen Gottschalk, Robert Krance, Tao Wang, Mengfen Wu, Catherine Robertson, Adrian P. Gee, Betty Chung, Bambi GrilleyMalcolm K. Brenner, Helen E. Heslop, Juan F. Vera, Ann M. Leen

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Relapse after allogeneic hematopoietic stem cell 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 × 107 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. This trial is registered at www.clinicaltrials.com as #NCT02494167.

Original languageEnglish (US)
Pages (from-to)2585-2597
Number of pages13
JournalBlood
Volume137
Issue number19
DOIs
StatePublished - May 13 2021

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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