The Hematology Molecular Diagnostics Laboratory routinely measures donor T cell and myeloid chimerism in patients undergoing stem cell allo-transplantation using a variety of investigator-specific preparative regimens. Based on our accumulated experience we can now recognize several discrete patterns of donor engraftment: 1) Patients undergoing non-myeloablative conditioning and T cell-rich stem cell infusions undergo rapid donor engraftment but more delayed myeloid engraftment. In an analysis done with Dr. Childs and his associates (in press), we could identify a number of factors which influence the speed of engraftment in this setting. These include the underlying diagnosis, the level of prior chemotherapy, and the level of concurrent immunosuppression post transplant. 2) Patients undergoing myeloablative conditioning with T cell-depleted stem cells demonstrate the opposite pattern i.e. rapid myeloid engraftment with much later donor T cell engraftment. 3) Patient undergoing myeloablative conditioning with T cell replete grafts engraft both cell types quickly. Because of these profound protocol-specific differences, the criteria for successful engraftment vary depending upon the details of each transplantation protocol. To help us in interpreting this heterogeneous engraftment data, we monitor engraftment data for each protocol group separately, and notify individual investigators on an ongoing basis of patients with atypical patterns of engraftment, In recent monitoring of chimerism patterns, we could identified early in their clinical course, two individual who ultimately required emergent infusion of additional stem cells and/or T cells for graft salvage, and several other patients with very slow or incomplete engraftment. Poor engraftment in transplant patients could reflect suboptimal stem cell or T cell dose, unrecognized technical problems during pheresis and cell freezing, or underlying subtle immune abnormalities in the donor or recipient. In the coming year we will be working with the cell processing unit in Department of Transfusion Medicine focusing on engraftment problems early in the post-transplant period i.e. days 15 through 60 post-transplant. By evaluating in detail the properties of cells administered and in some cases by retrospective evaluation of the function of aliquots of the donor cells which were infused using the ELISPOT methods under development in this laboratory, we hope to identify factors underlying instances of poor engraftment, and perhaps develop a strategy for avoiding them in the future.
