Quantitating Engraftment Of Donor Hematopoietic Cells After Transplantation

Clinical Center

Investigators

Linked publications & trials

Abstract

1. .During the past year the laboratory has implemented several technical changes to improve the sensitivity and reliability of our measurements. Most important, we have adopted a new analysis software package designated Osiris. This program was developed by NCBI for rigorous technical analysis of the capillary electrophoresis tracings generated for (STR)-based forensic DNA testing. Designed originally for forensic identification of victims after a mass-casualty disaster, Osiris uses a highly sophisticated mathematical approach to distinguish true STR peaks from noise, stutter, or multichannel compensation errors. Using this improved analytic software has improved our ability to confidently identify small donor or recipient peaks post-transplant which might suggest for early engraftment, incomplete clearance of unwanted malignant host cells post transplant. 2. In the past year, we have begun tracking engraftment in patients transplanted for cancer by Daniel Fowler and his associates using a new protocol which focuses on achieving engraftment of specially conditioned donor T-rapa T cells while deemphasizing the overall importanace of hematopoietic engraftment. Because of the choice of conditioning regimen and T cell dose, these patients manifest an unusual pattern of slow early engraftment, followed by gradual T cell emergence sometimes with late split chimerism. This protocol is clinically well tolerated, and crucial questions about the clinical graft-versus-tumor effect mediated by the engrafted T-rapa cells are currently under very active study by the NCI investigators. 3. Other NCI investigators are very actively engaged in efforts to safely allotransplant patient with congenital GATA2 and DOCK8 disorders before malignant complications associated with these lesion become life-threatening. NHLBI investigators (Barrett) continue efforts to enhance the immunotherapeutic efficacy of donor T cells engrafted during allotransplantation for leukemia. Several investigators within NHLBI and NIAID are actively engaged in studies to overcome HLA-barriers for patients who need a transplant but do not have an acceptable fully matched donor. These efforts include the use mixed haploidentical and cord blood donors (Childs), and the use of haploidentical donors with cyclosporin infusion shortly after transplant to prevent early antigraft T cell responses. These important studies require very careful monitoring because of the frequent need for early intererventions to promote successful engraftment.