Graftversusleukemia

Graft-versus-leukemia (GVL) refers to the immunologic effect whereby donor immune cells attack residual leukemic cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVL is a major contributor to disease control and potential cure in several hematologic malignancies. It is primarily mediated by donor T cells, with contributions from natural killer (NK) cells and other immune effectors.

Mechanism and relationship to GVHD: The donor immune system recognizes leukemia-associated antigens and minor histocompatibility antigens on host leukemic cells, initiating cytotoxic responses that kill malignant cells. The GVL effect often coexists with graft-versus-host disease (GVHD), an adverse reaction against normal host tissues; while GVHD and GVL can be correlated, they are distinct phenomena and GVHD is not required for GVL.

Clinical implications: GVL reduces relapse risk after allo-HSCT in acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myeloid leukemia (CML), among others. The strength of GVL varies with disease, conditioning, graft source, and immune matching. When relapse occurs, donor lymphocyte infusions (DLI) or adoptive immunotherapy can enhance GVL, sometimes at the cost of GVHD.

Challenges and research: Balancing GVL efficacy with GVHD toxicity remains a central goal. Monitoring strategies include chimerism analysis and measurable residual disease. Ongoing work seeks to optimize donor selection and graft engineering, utilize NK cell alloreactivity, selectively deplete or modulate alloreactive T cells, and combine with targeted therapies to enhance GVL while minimizing GVHD.