Predicting outcomes of HLA-identical allogeneic stem cell transplants from variable number of tandem repeat disparity between donors and recipients

Abstract

BACKGROUND AND OBJECTIVES: Detecting differences in the variable number of tandem repeats (VNTR) between a recipient and a donor has already been used to monitor the degree of chimerism after allogeneic stem cell transplantation (SCT). Alongside major histocompatibility complex disparity, the disparity of various polymorphous proteins encoded by several genes may play a critical role in the pathogenesis of graft-versus-host disease (GVHD) in allogenic SCT. However, the biological effect of VNTR disparity has scarcely been studied. BACKGROUND AND OBJECTIVES: Eighty-four patients receiving an SCT from an HLA-identical sibling (n=68) or an unrelated donor (n=16) were analyzed. The patients were transplanted because of acute myeloid leukemia (ns=48), acute lymphoblastic leukemia (n=8), chronic myeloid leukemia (n=15), non-Hodgkin's lymphoma (n=18) and myelodysplastic syndrome (n=3). Polymerase chain reaction analysis was performed to amplify three VNTR regions (D1S80, D1S111, and D17S5). These regions were classified as fully matched, partially matched, or mismatched between donors recipients. RESULTS: A strong correlation was observed between D1S80 matching status and transplant outcomes in terms of overall survival (p=0.0179) and non-relapse mortality (p=0.0305), but not for the D1S111 or D17S5 disparity. The fully matched D1S80 pairs showed a better overall survival (72% vs 38%) and lower non-relapse mortality (17% vs 50%) compared to the partially matched or mismatched pairs. In multivariate analyses, a fully matched D1S80 pair was found to be an independent favorable prognostic factor for overall survival (p=0.03) and non-relapse mortality (p=0.05). In addition, D1S80 disparity was significantly associated with the occurrence of gut chronic GVHD (p=0.05). INTERPRETATION AND CONCLUSIONS: The present data suggest that disparities in D1S80--located in chromosome 1--are associated with an increased incidence of gut chronic GVHD and non-relapse mortality.