Abstract
Background: Detecting the variable number of tandem repeats (VNTRs) between the recipient and the donor has already been adopted to monitor the degree of chimerism after allogeneic stem cell transplantation (SCT). In allogeneic SCT, besides MHC-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). However, the biologic effect of VNTR disparity has scarcely been studied.
Materials & Methods: Eighty-four patients receiving an SCT from HLA-identical sibling (n=68) or unrelated donors (n=16) were analyzed. The enrolled diseases included AML 48, ALL 8, CML 15, NHL 10, and high-risk MDS 3. A PCR was performed to amplify 3 VNTR regions (D1S80, D1S111, and D17S5). The disparity was classified as fully matched, partially matched, or mismatched pairs.
Results: A strong correlation was observed between the D1S80 disparity and the transplant outcomes in terms of OS (p=0.0179) and NRM (p=0.0305), yet not for the D1S111 or D17S5 disparity. The fully matched D1S80 pairs showed a better OS (72% vs 38%) and lower NRM (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 OS (p=0.03) and NRM (p=0.05). In addition, D1S80 disparity was significantly associated with the occurrence of gut chronic GVHD (p=0.05).
Conclusion: The present data suggest that disparities in D1S80 - located in chromosome 1 - seemed to be associated with an increased incidence of gut chronic GVHD and NRM.
Overall survial (A) and non-relapse mortality (B) according to D1S80 VNTR disparity
Overall survial (A) and non-relapse mortality (B) according to D1S80 VNTR disparity
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