Original Article
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Korean J Hematol 2011; 46(1):
Published online March 31, 2011
https://doi.org/10.5045/kjh.2011.46.1.18
© The Korean Society of Hematology
Lineage-specific chimerism analysis in nucleated cells, T cells and natural killer cells after myeloablative allogeneic hematopoietic stem cell transplantation
1Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, Korea.
2Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
Correspondence to : Correspondence to Jin-Yeong Han, M.D., Ph.D. Department of Laboratory Medicine, Dong-A University College of Medicine, 1, 3-ga, Dongdaesin-dong, Seo-gu, Busan 602-715, Korea. Tel: +82-51-240-5323, Fax: +82-51-255-9366, jyhan@dau.ac.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
Chimerism analysis is an important tool for assessing the origin of hematopoietic cells after allogeneic stem cell transplantation (allo-SCT) and can be used to detect impending graft rejection and the recurrence of underlying malignant or nonmalignant diseases.
Methods
This study included 24 patients who underwent myeloablative allo-SCT. DNA was extracted from nucleated cells (NCs), T cells, and natural killer (NK) cells, and the chimerism status of these cell fractions was determined by STR-PCR performed using an automated fluorescent DNA analyzer.
Results
Twenty-three out of the 24 patients achieved engraftment. Mixed chimerism (MC) in NCs, but not in T cells and NK cells, was significantly correlated with disease relapse. MC in all cell fractions was correlated with mortality. Ten patients (41.6%) developed extensive chronic GVHD. Six patients had MC in T cells, and 3 of them had chronic GVHD. Four patients with MC and relapse received donor lymphocyte infusion (DLI), and among them, 3 had secondary relapse. Further, the chimerism status differed among different cell lineages in 6 patients with myeloid malignancies.
Conclusion
The implications of MC in lymphocyte subsets are an important area for future research. Chimerism analysis in lineage-specific cells permits detection of relapse and facilitates the monitoring of therapeutic interventions. These results can provide the basic data for chimerism analysis after myeloablative SCT.
Keywords Lineage-specific chimerism, Myeloablative stem cell transplantation, T cells, Natural killer cells
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Original Article
Korean J Hematol 2011; 46(1): 18-23
Published online March 31, 2011 https://doi.org/10.5045/kjh.2011.46.1.18
Copyright © The Korean Society of Hematology.
Lineage-specific chimerism analysis in nucleated cells, T cells and natural killer cells after myeloablative allogeneic hematopoietic stem cell transplantation
Ri-Young Goh1, Sung-Hyun Kim2, and Jin-Yeong Han1*
1Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, Korea.
2Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.
Correspondence to: Correspondence to Jin-Yeong Han, M.D., Ph.D. Department of Laboratory Medicine, Dong-A University College of Medicine, 1, 3-ga, Dongdaesin-dong, Seo-gu, Busan 602-715, Korea. Tel: +82-51-240-5323, Fax: +82-51-255-9366, jyhan@dau.ac.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Chimerism analysis is an important tool for assessing the origin of hematopoietic cells after allogeneic stem cell transplantation (allo-SCT) and can be used to detect impending graft rejection and the recurrence of underlying malignant or nonmalignant diseases.
Methods
This study included 24 patients who underwent myeloablative allo-SCT. DNA was extracted from nucleated cells (NCs), T cells, and natural killer (NK) cells, and the chimerism status of these cell fractions was determined by STR-PCR performed using an automated fluorescent DNA analyzer.
Results
Twenty-three out of the 24 patients achieved engraftment. Mixed chimerism (MC) in NCs, but not in T cells and NK cells, was significantly correlated with disease relapse. MC in all cell fractions was correlated with mortality. Ten patients (41.6%) developed extensive chronic GVHD. Six patients had MC in T cells, and 3 of them had chronic GVHD. Four patients with MC and relapse received donor lymphocyte infusion (DLI), and among them, 3 had secondary relapse. Further, the chimerism status differed among different cell lineages in 6 patients with myeloid malignancies.
Conclusion
The implications of MC in lymphocyte subsets are an important area for future research. Chimerism analysis in lineage-specific cells permits detection of relapse and facilitates the monitoring of therapeutic interventions. These results can provide the basic data for chimerism analysis after myeloablative SCT.
Keywords: Lineage-specific chimerism, Myeloablative stem cell transplantation, T cells, Natural killer cells
Fig 1.
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Chimerism results of unique patient number (UPN) 5 and UPN 11 after donor lymphocyte infusion (DLI). Four patients who received DLI (excluding UPN 11) showed mixed chimerism or relapse. UPN 11 maintained 100% donor chimerism during 867 days. UPN 5 had acute graft-versus-host disease after DLI. Abbreviations: DLI, donor lymphocyte infusion; GVHD, graft-versus-host disease; NCs, nucleated cells; NK, natural killer.
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Table 1 . Patient characteristics and their clinical outcomes after transplantation..
Abbreviations: UPN, unique patient number; CD34+, positive selection of CD34 cells; DLI, donor leukocyte infusion; M, male; BM, bone marrow; MC, mixed chimerism; CC, complete chimerism; PBSC, peripheral blood stem cell; F, female; SAA, severe aplastic anemia; MDS, myelodysplastic syndrome; PNH, paroxysmal nocturnal hemoglobinuria..
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Table 2 . Chimerism analysis of relapsed time after transplantation..
Abbreviations: NCs, nucleated cells; NK cells, natural killer cells; UPN, unique patient number; NA, not applicable..
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Table 3 . Correlation between the lineage-specific mixed/100% recipient chimerism and clinical outcome..
The Pearson chi-square test was used to analyze the relationship of donor-type chimerism with relapse and mortality after allogeneic stem cell transplantation..
Abbreviations: NCs, nucleated cells; NK cells, natural killer cells; GVHD, graft-versus-host disease; NS, not significant..
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Table 4 . Results of lineage-specific chimerism analysis of UPN 19..
Abbreviations: NCs, nucleated cells; NK cells, natural killer cells; NA, not applicable..
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