Clinical and immunologic impact of CCR5 blockade in graft-versus-host disease prophylaxis

Ryan H. Moy, Austin P. Huffman, Lee P. Richman, Lisa Crisalli, Ximi K. Wang, James A. Hoxie, Rosemarie Mick, Stephen G. Emerson, Yi Zhang, Robert H. Vonderheide, David L. Porter and Ran Reshef

Key Points

  • CCR5 blockade decreases peripheral T-cell activation, gut GVHD biomarkers, and acute GVHD incidence in allo-HSCT recipients.

  • CXCR3-mediated lymphocyte trafficking may represent an important resistance mechanism to CCR5 blockade in GVHD prophylaxis.


Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Lymphocyte trafficking via chemokine receptors such as CCR5 plays a critical role in alloreactive responses, and previous data suggest that CCR5 blockade with maraviroc results in a low incidence of visceral GVHD. However, the full scope of clinical and immunologic effects of CCR5 blockade in HSCT has not been described. We compared a cohort of patients enrolled on a trial of reduced-intensity allo-HSCT with standard GVHD prophylaxis plus maraviroc to a contemporary control cohort receiving standard GVHD prophylaxis alone. Maraviroc treatment was associated with a lower incidence of acute GVHD without increased risk of disease relapse, as well as reduced levels of gut-specific markers. At day 30, maraviroc treatment increased CCR5 expression on T cells and dampened T-cell activation in peripheral blood without impairing early immune reconstitution or increasing risk for infections. Patients who developed acute GVHD despite maraviroc prophylaxis showed increased T-cell activation, naive T-cell skewing, and elevated serum CXCL9 and CXCL10 levels. Collectively, these data suggest that maraviroc effectively protects against GVHD by modulating alloreactive donor T-cell responses, and that CXCR3 signaling may be an important resistance mechanism to CCR5 blockade in GVHD.

  • Submitted August 18, 2016.
  • Accepted December 20, 2016.
View Full Text