Peripheral Blood CD38 Bright CD8+ Effector Memory T Cells Predict Acute Graft-versus-Host Disease

• CD38 bright CD8+ effector memory T cells increase a median of 8 days before acute graft-versus-host disease
• Absolute CD38 bright CD8+ effector memory T cells > 35/μL predict acute graft-versus-host disease
• CD38 upregulation could be a marker of trafficking activated T cells

Acute graft-versus-host disease (aGVHD) is mediated by allogeneic T cell responses. We hypothesized that increases of peripheral blood–activated CD8+ effector memory T (TEM) cells would be observed after hematopoietic stem cell transplantation (HSCT) before onset of aGVHD symptoms. Blood was collected twice weekly after HSCT for 7 weeks in 49 consecutive pediatric and adult HSCT recipients. Samples were incubated with fluorochrome-conjugated antibodies against CD45, CD3, CD8, CD38, CD45RA, and CCR7 and analyzed using flow cytometry. TEM cells were defined as CD3+ CD8+CCR7− CD45RA− lymphocytes. CD38 expression was used as a marker of T cell activation. Patients were followed for 100 days for development of aGVHD. Twenty-three patients developed grade 1 to 4 aGVHD at a median of 37 days (range, 15 to 79 days) after HCST. Absolute CD38 bright CD8+ TEM of > 35 cells/μL predicted aGVHD at a median of 8 days (range, 1 to 34) before aGVHD onset with a sensitivity of 82.6% and specificity of 91.6%. The cumulative incidence of aGVHD was 90% in patients with absolute CD38 bright CD8+ TEM >35 cells/μL and 15% in patients without (P < .0001). Quantification of CD38 bright CD8+ TEM cells may predict aGVHD in children and young adult HSCT recipients.