Adverse impact of deletion of the chromosome 6 on clinical outcomes after allogeneic hematopoietic transplantation

Graft-versus-leukemia (GVL) effect is mainly mediated by alloreactive T and NK cells through human leukocyte antigen (HLA). Although most HLA genes are located on the short arm of chromosome 6, the clinical significance of deletion of the short arm of chromosome 6 (del6p) which could attenuate the GVL effect has not been elucidated. We investigated impact of del6p at the diagnosis of hematological malignancies on allogeneic cell transplantation, using a Japanese registry database. Del6p was highly associated with additional chromosomal abnormalities. In the univariate analysis, the del6p group showed a higher incidence of relapse at 2 years among the entire cohort (2y-relapse 48.3% vs 25.7%, P <0.001). Multivariate analysis confirmed that del6p was significantly associated with an increased risk of relapse (HR 1.30 [95% CI: 1.02-1.65], P = 0.036). The del6p group also tended to be associated with relapse, when focusing on patients with complex karyotype (HR 1.25 [95% CI: 0.97-1.60], P = 0.079). Additionally, the impact of del6p on relapse was more evident in the HLA-mismatched than in the HLA-matched cohort. These results suggest that del6p at diagnosis might attenuate the GVL effect through HLA status.