A new approach to preventing graft-versus-host disease (GVHD) after stem cell transplants while retaining the transplants’ positive effects on fighting leukemia and lymphoma is suggested by research from an international team of researchers. The approach has potential as a curative therapy for certain hematologic malignancies.
Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for cancers of the blood and lymph system. Unfortunately, graft-versus-host disease (GVHD) is a common adverse effect of the treatment. Researchers at City of Hope, Mayo Clinic, Fred Hutchinson Cancer Research Center, and 3 Chinese medical schools reported that temporary in vivo depletion of donor T cells (CD4+) soon after infusion of donor stem cell transplants prevented GVHD while preserving strong graft-versus-leukemia (GVL) effects.
The depletion of donor CD4+ T cells increased serum IFN-γ. However, it reduced IL-2 concentrations and this led to upregulation of programmed death ligand-1 (PD-L1) expression by recipient tissues and donor CD8+ T cells. In GVHD target tissues, the interactions of PD-L1 with PD-1 on donor CD8+ T cells led to anergy, exhaustion, and apoptosis, thus preventing GVHD.
The researchers report that a clinical trial is now in the works, and if validated, this type of regimen has the potential to promote widespread application of allogenic HCT as a curative therapy for some hematologic malignancies.