Bone marrow augmentation of donor-cell chimerism in kidney, liver, heart, and pancreas islet transplantation

Abstract

SummaryWe have previously postulated that donor cell chimerism in organ transplantation is needed to attain a tolerant state. Here we show that donor cell chimerism can be augmented in organ recipients if they are infused perioperatively with 3 × 10 8 per kg of unmodified donor bone marrow cells and are kept on a conventional immunosuppressive regimen of tacrolimus (FK506) and prednisolone.36 patients took part, of whom the first 18 patients have good transplanted kidney (n = 10), liver (n = 7), and heart (n = 7) function when followed up between 4 and 16 months. All patients are well. We found persistent multilineage leucocyte chimerism in blood of 17 recipients by flow cytometry and PCR techniques to detect donor alleles or Y chromosomes in female recipients of male organs. The use of the 5-antigen HLA matched same sex donor precluded detection of chimerism in one patient.

Adjuvant Bone Marrow Infusion in Clinical Organ Transplant Recipients

“…2 During the course of follow up, 28/251 (11%) of study patients have died; none due to causes uniquely related to infused BM. Similarly, 21/129 (16%) control patients have succumbed during this follow up (Fig 1B).…”

“…BM was isolated from the VB of cadaveric donors by a procedure outlined previously. 2 During the course of posttransplant follow up, serial peripheral blood samples were obtained to ascertain the presence of donor cells by flow cytometry and by molecular techniques.2 Additionally, in vitro immune monitoring was also performed to assess donor-specific modulation.…”

Bone Marrow Augmentation in Renal Transplant Recipients

“…Thus, bone marrow augmentation without recipient preconditioning was begun in December 1992, and has been done with all of the transplantable organs (kidney, pancreas, islets, liver, heart, lung, and intestine). [28][29][30][31][32] As with all of the other reported experiences, the logistic difficulties of bone marrow procurement have militated against a randomized trial, and in fact the only randomized trial of bone marrow augmentation is being performed in Miami, in liver recipients. 33 Between December 1992 and October 1996, 86 cases of bone marrow augmentation were accrued among the nearly 800 kidney transplantations at our center.…”

Perioperative donor bone marrow infusion augments chimerism in heart and lung transplant recipients

“…Details of bone marrow preparation are described elsewhere [7]. Briefly, thoracolumbar vertebrae were retrieved from the donor.…”

“…This method is more sensitive than the flow cytometric technique: it can reliably detect one donor cell within 10 4 to 10 5 recipient cells [7]. Oligonucleotides for either the sex determining region of the Y chromosome or the appropriate mismatched HLA alleles were used as primers.…”