Korean J Hematol.  2006 Mar;41(1):28-35. 10.5045/kjh.2006.41.1.28.

T-Cell Chimerism Analysis by Mutiplex STR PCR after Non-Myeloablative Allogeneic Stem Cell Transplantation

• Goh RY
• Han JY
• Han H
• Kim JS
• Kwon HC
• Kim SH
• Kim HJ

• KMID: 2252324
• DOI: http://doi.org/10.5045/kjh.2006.41.1.28

Abstract

BACKGROUND: The ability of non-myeloablative allogeneic stem cell transplants to eradicate host neoplastic cells is based on the accumulating evidence of a graft-versus-malignancy (GVM) effect. Stable mixed chimerism (MC) is associated to the lower risk for the development of graft-versus-host diseases (GVHD), but this possibly occurs at the expense of the GVM effect. Therefore, assessment of the chimerism status is critical to allow immune intervention to maintain a state of donor-host tolerance and to prevent loss of the graft.
METHODS
Serial post-transplant peripheral blood samples were collected from 17 patients with various malignant diseases following non-myeloablative allogeneic stem cell transplantation. DNA was amplified from the T-cells, and the polymerase chain reaction (PCR) products were quantified by an automated fluorescent DNA analyzer.
RESULTS
All 17 patients showed T-cell MC at post-transplant, but this varied in degree and duration, and then 3 patterns emerged. Group 1: 5 patients experienced a short interval of T-cell MC prior to conversion to complete donor chimerism (CC) (median: 25 days). Group 2: 5 patients showed a rapid increase of host cells after a brief MC at a median of 21 days. They never achieved CC, and they relapsed or showed progressive diseases. Group 3: 7 patients showed persistent T-cell MC for 40-50 days, and they subsequently gradually converted to CC after a median of 112 days.
CONCLUSION
All the patients achieved T-cell MC in post-transplant, but the CC development differed in frequency and speed. GVHD preceded the onset of T-cell CC in the majority of the patients. Serial engraftment monitoring of the T-cell chimerism status during the first 100 days after non-myeloablative stem cell transplantation is important in aiding the clinical management of such patients.

Keyword

Non-myeloablative Allogeneic Stem Cell Transplantation; Chimerism; GVHD; STR Analysis; T-cell

MeSH Terms

Chimerism*
DNA
Graft vs Host Disease
Humans
Polymerase Chain Reaction*
Stem Cell Transplantation*
Stem Cells*
T-Lymphocytes*
Tissue Donors
Transplants
DNA

Figure

• 

  Fig. 1 Representative engraftment analysis results from the case No. 2 patient. The loci shown is penta E. Allele numbers and peak areas are designated in the boxes below each allele peak. (A) Donor. (B) Pre-transplantation patient. (C) Mixed chimerism at post-transplantation day 7. (D) Complete donor chimerism at post-transplantation day 28.

• 

  Fig. 2 Chimerism analysis result. (A) Case No. 2 patient showed a rapid conversion to CC. (B) Case No. 13 patient showed a brief interval of T-cell MC followed by a rapid loss of graft and disease relapse despite of DLI. (C) Case No. 4 patient showed a persistent T-cell MC at day 40～50 (＞15%) and later gradually converted to CC. Abbreviations: GVHD, graft-versus-host diseases; CC, complete chimerism; MC, mixed chimerism; DLI, donor lymphocyte infusion.

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