The investigators have shown previously that after whole organ transplantation, resident bone marrow- derived """"""""passenger leukocytes"""""""" migrate out of the graft into the recipient and establish microchimerism. Furthermore, the ubiquitous presence of the donor chimeric cells in the tissues of long functioning allograft recipients, suggested that these cells may play a seminal role in graft acceptance and the induction of donor-specific tolerance. In a direct extension of this """"""""natural"""""""" phenomenon, they have augmented the leukocyte load conveyed by the transplanted organs by treating a pilot group of 89 human recipients of liver, kidney, heart, lung, and pancreas allografts with simultaneous infusion of unmodified bone marrow cells (3 - 5 x 108/kg body weight). Fifty-nine patients in whom consent to harvest donor vertebral bodies was not available, served as contemporaneous controls. The patients did not receive any cytoablative or cytoreductive conditioning prior to transplantation, and were maintained on routine immunosuppression with TacrolimusTM and steroids after transplantation. The adjuvant procedure of bone marrow augmentation was safe. The patient and graft survival, according to the investigators, was substantially improved in the augmented group as compared to the controls. The frequency and severity of rejection was also comparable in both study and control groups. Furthermore, a higher level of chimerism and increased frequency of donor-specific immune modulation was witnessed in the augmented patients. Based on these and other observations, they hypothesize that both short and long-term allograft survival and function will improve in bone marrow augmented patients. Additionally, augmentation of chimerism may also reduce the rate of chronic rejection and most importantly endow the investigators with the capacity to wean or eventually withdraw immuno-suppression. They propose a systematic evaluation of donor bone marrow augmentation in liver transplant recipients and to compare the outcome with that of non-augmented contemporaneous controls. In addition, the outcome in the bone marrow-liver cohort will be compared with that of bone marrow augmented recipients of other organs (i.e., kidney, heart, pancreas, lung, etc.); each of these will also acquire their own non-augmented organ-specific controls. The primary end-points that are to be examined are: (a) organ function and survival, (b) patient survival, and (c) the ability to reduce or withdraw immunosuppression. Secondarily, they also wish to monitor the frequency and severity of rejection, as well as that of GVHD. They will serially quantitate levels of donor cell chimerism and assess the immune status of these patients. These primary and secondary end-points will be correlated to obtain comprehensive information regarding the eventual outcome of bone-marrow augmented and control patients.
Showing the most recent 10 out of 20 publications
