High CD4/CD8 ratio in allografts predicts adverse outcomes in unmanipulated HLA-mismatched/haploidentical hematopoietic stem cell transplantation for chronic myeloid leukemia

Abstract

HLA-mismatched/haploidentical hematopoietic stem cell transplantation (haplo-mismatched HSCT) has improved the outcome of chronic myeloid leukemia (CML) in patients without an HLA-matched donor. To further improve the treatment outcome of haplo-mismatched HSCT in CML, a modifiable prognostic factor needs to be found. The cellular composition of grafts obtained from 75 HLA-mismatched/haploidentical related donors was prospectively correlated with the outcome of patients with CML undergoing haplo-mismatched HSCT following a modified regimen of BU/CY 2 plus antithymocyte globulin. The concentration of T-cell subsets, CD14+, and CD34+ cells and their relative proportions were analyzed. In univariate analyses, disease-free survival (DFS) and overall survival (OS) conversely correlated with the CD4/CD8 ratio in primed bone marrow graft (G-BM) (p = 0.012 and p = 0.040); similarly, CD4/CD8 ratio in total grafts was also negatively associated with DFS and OS (p = 0.018 and p = 0.020). In multivariate analyses, a CD4/CD8 ratio in G-BM higher than the median value remained the only factor negatively affecting DFS (p = 0.030; 95% confidence interval [CI], 1.166-19.341). Expectedly, high CD34+ cell dose was associated with accelerated platelet engraftment (p = 0.009; 95% CI = 1.181-3.271) after controlling for a high risk of disease. No other clinical parameter was influenced by graft composition. Our results suggest that a high CD4/CD8 ratio in allografts may predict adverse survival in patients with CML undergoing haplo-mismatched HSCT.