Occurrence and Severity of Donor Lymphocyte Infusion-Associated Chronic Graft-versus-Host Disease Influence the Clinical Outcomes in Relapsed Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract

The aim of this study was to investigate the occurrence and severity of chemotherapy plus donor lymphocyte infusion (Chemo-DLI)-associated chronic graft-versus-host disease (cGVHD) in a consecutive cohort of patients with acute leukemia who experienced relapse after allogeneic hematopoietic stem cell transplantation (n = 104). The 5-year cumulative incidence of complete remission after Chemo-DLI was 81.0% (95% CI, 73.3% to 88.7%) and 84.6% (95% CI, 74.5% to 94.7%) in the moderate and severe cGVHD groups, respectively, which was significantly higher than that of the mild cGVHD group at 40.9% (95% CI, 29.3% to 52.5%) and non-cGVHD group at 29.2% (95% CI 23.1% to 35.3%). The cumulative incidence of nonrelapse mortality was comparable between patients with and without cGVHD. The 5-year probabilities of progression-free survival after Chemo-DLI were 42.9% (95% CI, 26.2% to 70.2%) and 34.6% (95% CI, 15.3% to 78.2%) in the moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD group at 9.1% (95% CI, 2.4% to 34.1%) and non-cGVHD group at 8.3% (95% CI 3.3% to 21.3%). The 5-year probabilities of overall survival after Chemo-DLI were 56.7% (95% CI, 38.9% to 82.7%) and 43.1% (95% CI, 22.1% to 84.0%) in the moderate and severe cGVHD groups, respectively, which were both significantly higher than those of the mild cGVHD group at 9.1% (95% CI 1.8% to 47.1%) and non-cGVHD group at 14.9% (95% CI, 7.3% to 30.2%). Our observations highlight the close relationship between cGVHD and immune-mediated graft-versus-leukemia (GVL) effect in patients with relapse receiving Chemo-DLI; however, mild cGVHD may not be associated with a sufficiently strong GVL effect to induce remission and improve survival.

Keywords: Acute leukemia; Chronic graft-versus-host disease; Donor lymphocyte infusion; Hematopoietic stem cell transplantation; National Institutes of Health consensus criteria.