Simrit Parmar1, Marcelo Fernandez-Vina, Marcos de Lima. 1. Department of Stem Cell Transplantation and Cell Therapy, University of Texas, M D Anderson Cancer Center, Houston, Texas 77005, USA. sparmar@mdanderson.org
Abstract
PURPOSE OF REVIEW: This review summarizes the recent developments in the clinical research and therapeutic applications for prevention and treatment of postallogeneic stem cell transplant (SCT) relapse. Specifically, we address various maneuvers to optimize the graft-versus-leukemia (GVL) effect while preventing graft-versus-host-disease (GVHD). RECENT FINDINGS: Alloreactive natural killer (NK) cells can be recruited to mediate GVL effect by careful mismatching on the killer-cell immunoglobulin-like receptors (KIRs) ligand. Donor posttransplant NK cell infusions have led to remission in poor-risk acute myeloid leukemia (AML). Donor lymphocyte infusions may also be used both prophylactically or at the time of leukemia relapse. Posttransplant hypomethylating agents have emerged as promising therapies to safeguard against relapse. Prevention of GVHD while preserving GVL effect using third-party regulatory T cells is under investigation. Adoptive T-cell transfer against specific leukemic antigens and immunotherapy exploiting the marrow microenvironment seem promising as well. SUMMARY: In the setting of allogeneic SCT, cellular and immunotherapy needs to be thoroughly investigated for its potential to fight minimal residual disease. The tight balance between GVL and GVHD needs to be harnessed in an optimal fashion to lead to long-term durable remission.
PURPOSE OF REVIEW: This review summarizes the recent developments in the clinical research and therapeutic applications for prevention and treatment of postallogeneic stem cell transplant (SCT) relapse. Specifically, we address various maneuvers to optimize the graft-versus-leukemia (GVL) effect while preventing graft-versus-host-disease (GVHD). RECENT FINDINGS: Alloreactive natural killer (NK) cells can be recruited to mediate GVL effect by careful mismatching on the killer-cell immunoglobulin-like receptors (KIRs) ligand. Donor posttransplant NK cell infusions have led to remission in poor-risk acute myeloid leukemia (AML). Donor lymphocyte infusions may also be used both prophylactically or at the time of leukemia relapse. Posttransplant hypomethylating agents have emerged as promising therapies to safeguard against relapse. Prevention of GVHD while preserving GVL effect using third-party regulatory T cells is under investigation. Adoptive T-cell transfer against specific leukemic antigens and immunotherapy exploiting the marrow microenvironment seem promising as well. SUMMARY: In the setting of allogeneic SCT, cellular and immunotherapy needs to be thoroughly investigated for its potential to fight minimal residual disease. The tight balance between GVL and GVHD needs to be harnessed in an optimal fashion to lead to long-term durable remission.
Authors: Aude G Chapuis; Daniel N Egan; Merav Bar; Thomas M Schmitt; Megan S McAfee; Kelly G Paulson; Valentin Voillet; Raphael Gottardo; Gunnar B Ragnarsson; Marie Bleakley; Cecilia C Yeung; Petri Muhlhauser; Hieu N Nguyen; Lara A Kropp; Luca Castelli; Felecia Wagener; Daniel Hunter; Marcus Lindberg; Kristen Cohen; Aaron Seese; M Juliana McElrath; Natalie Duerkopp; Ted A Gooley; Philip D Greenberg Journal: Nat Med Date: 2019-06-24 Impact factor: 53.440