Our ongoing efforts monitoring chimerism in patients undergoing bone marrow transplantation at the NIH provide timely data for physicians managing patients and for clinical investigators planning research protocols or gathering data for retrospective analysis. A retrospective study published this year in collaboration with Dr. Childs? laboratory at the NHLBI has analyzed the impact of prior chemotherapy and of the dose of CD34 cells administered on the speed of engraftment in a group of patients undergoing allotransplantation for treatment of cancer. Chimerism data from our lab helped to demonstrate the important impact of prior chemotherapy and CD34 dose on engraftment. In attempting to reduce the incidence of acute graft versus host disease in patients transplanted for chronic myelogenous leukemia, Dr. John Barrett (NHLBI) has explored the usefulness of reducing the number of donor T cells infused into patients at the time of transplant, using chimerism assays to determine when later donor lymphocyte infusions are needed to accelerate later donor T cell engraftment. In retrospective review, Dr Barrett has found that this approach produces very low levels of acute graft versus host disease without compromising patient outcome from infection or tumor recurrence. Subsequent studies will further exploit this approach. We have also recently collaborated with the laboratory of Douglas Hale (NIDDK), who is using cynomologus monkeys to study the value of concurrent low dose bone marrow infusion as a strategy for reducing rejection after solid organ transplantation. To evaluate the potential risks of unwanted donor stem cell expansion, Dr. Hale needed to monitor donor chimerism in the blood of transplanted animals. Since other methods were not available, we adapted commercially available kits (designed to detect microsatellite polymorphisms in man) for measurement of chimerism in cynomologus monkeys. This approach proved very useful in establishing the safety of bone marrow infusions in this animal model. A publication describing this approach is in press. The data obtained provides support for planned clinical studies using an analogous approach.
