In a new study from Reshef and colleagues, locking lymphocyte chemotaxis with an oral inhibitor of the CCR5 receptor was associated with reduced incidence of visceral graft-versus-host disease (GVHD) in patients undergoing reduced-intensity conditioned allogeneic hematopoietic stem-cell transplantation.
Acute graft-versus-host disease (GVHD) is a major cause of death and complications after hematopoietic stem-cell transplantation (HSCT).
• How common is GVHD?
The condition occurs in 30 to 50% of patients receiving HLA-matched transplants from a related donor and in 50 to 70% of those receiving transplants from an unrelated donor.
• What is the pathogenesis of GVHD, and side effects of current treatment modalities?
The pathogenesis of GVHD is multifactorial, but ultimately, donor-derived T cells recognize recipient antigens as foreign,
resulting in activation, expansion, and cytokine release and leading to destruction of host tissues. Therapies for GVHD target T cells and cytokines, often antagonize T-cell-mediated graft-versus-tumor responses, and delay immune reconstitution. Preventing GVHD without intensive immune suppression would represent a major advance for HSCT
Morning Report Questions
Q: What were the results of chemotaxis blockade by maraviroc early after allogeneic HSCT with respect to GVHD in this study?
A: The addition of maraviroc (a CCR5 or chemokine [C-C motif] receptor antagonist that decreases chemotaxis) to standard GVHD prophylaxis resulted in a low incidence of GVHD in high-risk patients with hematologic cancers after allogeneic HSCT. Although cases of skin GVHD were still observed at expected rates, the addition of maraviroc
was associated with an absence of liver and gut (visceral) GVHD through day 100, leading to a low incidence of severe (grade III or IV) GVHD.
Q: What side effects were associated with the administration of maraviroc?
A: Maraviroc had few documented toxic effects. Administration of the drug was briefly suspended in 7 patients because of grade 3 abnormalities on liver-function testing (in two patients) or grade 3 or 4 mucositis (in five). CCR5 blockade with maraviroc did not disrupt hematopoietic engraftment or lead to a higher-than-expected incidence of relapse or infectious complications.