Comparative Study of Chimerism Dynamics between Allogenic Bone Marrow Transplantation and Nonmyeloablative Stem Cell Transplantation.

Objective To explore whether the dynamics and outcome of chimerism are different between allogenic bone marrow transplantation (allo-BMT) and nonmyeloablative stem cell transplantation (NST) these two kinds of transplant strategies in order to define factors that significantly influence the early engraftment of donor stem cells.

Methods A retrospective comparative study was performed between 20 patients undergoing BMT and 18 patients receiving NST. There are several differences between NST and standard allo-BMT, such as conditioning regimens, the source and the quantity of hematopoietic stem cells and the protocal of GVHD prophylaxis. But component of two groups patients were similar. Sequential monitoring of chimerism were performed in 38 patients in different periods post transplantation using multiple short tandem repeat(STR) amplification by fluorescence labeling polymerase chain reaction(PCR) combined with a capillary electrophoresis.

Results

1. The median age of recipient, median quantity of MNC, CD34⁺ cells and T lymphocyte cells of NST were significantly higher compared with the BMT. The median time for absolute neutrophils recovery of NST(without G-CSF) was similar to that of BMT. While compared to BMT, NST lead to faster engraftment of platelets.

2. The establishment of full donor chimerism (FDC) of NST was much more earlier than that of BMT (1 month VS 3 months, p=0.01). In the early post-transplant period(up to day 30), there was an apparent increase in the incidence of full donor chimerism (FDC) following NST compared with BMT(38.9% VS 20%, p=0.019). Whereas a significantly lower incidence of mixed chimerism(MC) occurred in recipients of NST compare to BMT.(61.2% VS 80%, p=0.02). It suggest that in the early stage after transplantation, the engraftment of donor cells of NST was more rapid than that of BMT. The major relevant factor causing full donor chimerism formation seems to be the high quantity of donor CD34⁺ cells and T lymphocyte cells.

3. Fludarabine-based reduced-intensity conditioning didn’t result in a significant delay of donor cell engraftment compared to standard conditioning regimen.

4. The incidence of chronic GVHD was much higher in group of NST than that of BMT group(80% VS 50%, p=0.007).

This finding was related to that patients of NST group received the higher doses of CD34⁺ cells. Conclusion Factors that significantly influence the early kinetics of donor chimerism and donor cell engraftment after transplantation were the quantity of stem cell and T lymphocyte cell of grafts.