title: Harnessing the power of alloreactivity without triggering graft-versus-host disease: how non-engrafting alloreactive cellular therapy might change the landscape of acute myeloid leukemia treatment.
abstract: Human leukocyte antigen-mismatched leukocyte infusions outside of the context of transplantation are a promising strategy for acute myeloid leukemia. Recent studies using such non-engrafting alloreactive cellular therapy (NEACT) revealed that survival of elderly patients increased from 10% to 39% when NEACT was given following chemotherapy, and that durable complete remissions were achieved in about a third of patients with relapsed or chemorefractory disease. We review the clinical reports of different NEACT approaches to date and describe how although T-cell and NK alloreactivity could generate immediate anti-leukemic effects, long-term disease control may be achieved by stimulating recipient-derived T-cell responses against tumor-associated antigens. Other variables likely impacting NEACT such as the release of pro-inflammatory cytokines from donor-host bidirectional alloreactivity and the choice of chemotherapeutics as well as future avenues for improving NEACT, such as optimizing the cell dose and potential synergies with adjuvant pharmacologic immune checkpoint blockade, are discussed.
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Hôpital Maisonneuve-Rosemont Research Center, Université de Montréal, 5415 de l'Assomption, Montreal, Quebec, H1T 2M4, Canada. Electronic address: elizabeth.krakow@umontreal.ca.
authors.forename: Elizabeth F
authors.initials: EF
authors.lastname: Krakow
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Hôpital Maisonneuve-Rosemont Research Center, Université de Montréal, 5415 de l'Assomption, Montreal, Quebec, H1T 2M4, Canada. Electronic address: juliebergeron.hmr@ssss.gouv.qc.ca.
authors.forename: Julie
authors.initials: J
authors.lastname: Bergeron
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Hôpital Maisonneuve-Rosemont Research Center, Université de Montréal, 5415 de l'Assomption, Montreal, Quebec, H1T 2M4, Canada. Electronic address: silvy.lachance@umontreal.ca.
authors.forename: Silvy
authors.initials: S
authors.lastname: Lachance
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Hôpital Maisonneuve-Rosemont Research Center, Université de Montréal, 5415 de l'Assomption, Montreal, Quebec, H1T 2M4, Canada. Electronic address: denis-claude.roy@umontreal.ca.
authors.forename: Denis-Claude
authors.initials: DC
authors.lastname: Roy
authors.affiliation: Department of Medicine, Division of Hematology and Oncology, Hôpital Maisonneuve-Rosemont Research Center, Université de Montréal, 5415 de l'Assomption, Montreal, Quebec, H1T 2M4, Canada. Electronic address: js.delisle@umontreal.ca.
authors.forename: Jean-Sébastien
authors.initials: JS
authors.lastname: Delisle
mesh_terms: D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods*; D015470:Leukemia, Myeloid, Acute / Q000276:immunology* / Q000628:therapy*; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
keywords: Alloreactivity; Cytokines; Graft vs host disease; Immunotherapy; Natural killer cells; Relapsed acute myeloid leukemia (AML); T cells; Transplantation; Tumor-associated antigen