Original Article

Korean J Hematol 2005; 40(4):

Published online December 30, 2005

https://doi.org/10.5045/kjh.2005.40.4.231

© The Korean Society of Hematology

조직적합형항원 일치성 동종조혈모세포이식의 성적예측인자로서 Variable Number of Tandem Repeats (VNTR) 불일치성의 임상적 의의

곽동훈, 김동환, 김시내, 안병민, 문준호, 채의수, 백진호, 김종광, 손상균, 이난영, 서장수, 이규보

경북대학교병원, 혈액종양내과, 조혈모세포이식센터

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

Dong Hoon Kwack, Dong Hwan Kim, Shi Nae Kim, Byung Min Ahn, Joon Ho Moon, Yee Soo Chae, Jin Ho Baek, Jong Gwang Kim, Sang Kyun Sohn, Nan Young Lee, Jang Soo Suh, Kyu Bo Lee

Department of Hematology, Oncology, Stem Cell Transplantation Center, Kyungpook National University Hospital, Daegu, Korea

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.

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

Article

Original Article

Korean J Hematol 2005; 40(4): 231-241

Published online December 30, 2005 https://doi.org/10.5045/kjh.2005.40.4.231

Copyright © The Korean Society of Hematology.

조직적합형항원 일치성 동종조혈모세포이식의 성적예측인자로서 Variable Number of Tandem Repeats (VNTR) 불일치성의 임상적 의의

곽동훈, 김동환, 김시내, 안병민, 문준호, 채의수, 백진호, 김종광, 손상균, 이난영, 서장수, 이규보

경북대학교병원, 혈액종양내과, 조혈모세포이식센터

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

Dong Hoon Kwack, Dong Hwan Kim, Shi Nae Kim, Byung Min Ahn, Joon Ho Moon, Yee Soo Chae, Jin Ho Baek, Jong Gwang Kim, Sang Kyun Sohn, Nan Young Lee, Jang Soo Suh, Kyu Bo Lee

Department of Hematology, Oncology, Stem Cell Transplantation Center, Kyungpook National University Hospital, Daegu, Korea

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.

Keywords: Variable number of tandem repeats, Allogeneic stem cell transplantation, Graft-versus-host disease

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