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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.
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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.
Table 1.
The PowerPlex16 System locus-specific informations
Abbreviations: STR, short tandem repeats; TH1, throsine hydroxylase theta l; FGA, alpha chain fibrinogen; TPOX, thyroid peroxidase; vWA, von willebrand factor; CSF1PO, c-fms-proto-oncogene for CSF-1 receptor; TMR, carboxy-tetramethylrhodamine; FL, fluorescein; JOE, 6-carboxy-4', 5'- dichloro-2', 7'-dimethoxyfluorescein; NA, not applicable.
Table 2.
Clinical and hematologic findings in 17 patients
Table 3.
Follow-up informations
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