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

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. (Korean J Hematol 2006;41:28-35.)