Korean J Hematol.  2005 Dec;40(4):231-241. 10.5045/kjh.2005.40.4.231.

Variable Number of Tandem Repeats (VNTR) Disparity between Donor and Recipient has a Potential to Predict the Outcomes of HLA-identical Allogeneic Stem Cell Transplantation

• Kwack DH
• Kim DH
• Kim SN
• Ahn BM
• Moon JH
• Chae YS
• Baek JH
• Kim JG
• Sohn SK
• Lee NY
• Suh JS
• Lee KB

• KMID: 2083461
• DOI: http://doi.org/10.5045/kjh.2005.40.4.231

Abstract

BACKGROUND
Detection of variable number of tandem repeats (VNTR) between recipient and donor has 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 been scarcely studied.
METHODS
We analyzed 84 patients receiving SCT from HLA-identical sibling (n=68) or unrelated donors (n=16). Enrolled diseases included AML 48, ALL 8, CML 15, NHL 10, and high-risk MDS 3. The PCR was performed to amplify 3 VNTR regions (D1S80, D1S111, and D17S5).
RESULTS
We observed strong correlation between the D1S80 disparity and transplant outcomes in terms of OS (P=0.0179) or non-relapse mortality (NRM) (P=0.0305), but not for D1S111 or D17S5 disparity. The D1S80-fully matched pair showed a better OS (72% vs 38%) and lower NRM (17% vs 50%) compared to partially matched or mismatched pairs. In multivariate analyses, D1S80-fully matched pair was found to be independent favorable prognostic factor for OS (P=0.03) or NRM (P=0.05). In addition, the D1S80 disparity was significantly associated with the myeloid engraftment speed (P=0.01) or the occurrence of gut chronic GVHD (P=0.05).
CONCLUSION
Our data suggest that disparities in D1S80-located on chromosome1-seemed to be associated with increased incidence of gut chronic GVHD and NRMs, thus suggesting the existence of unknown genes of minor histocompatibility antigens targeting gut or cytokine/cytokine receptor on chromosome 1.

Keyword

Variable number of tandem repeats; Allogeneic stem cell transplantation; Graft-versus-host disease

MeSH Terms

Chimerism
Chromosomes, Human, Pair 1
Graft vs Host Disease
Humans
Incidence
Minisatellite Repeats*
Minor Histocompatibility Antigens
Mortality
Multivariate Analysis
Polymerase Chain Reaction
Siblings
Stem Cell Transplantation*
Stem Cells*
Tissue Donors*
Unrelated Donors
Minor Histocompatibility Antigens

Figure

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  Fig. 1. The cumulative incidence of non-relapse mortality (A) and occurrence of gut-involved chronic GVHD (B,C) according to the D1S80 disparity.

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