HIGH-DOSE DONOR BONE-MARROW INFUSIONS TO ENHANCE ALLOGRAFT SURVIVAL -THE EFFECT OF TIMING

Background. The development of strategies to enhance survival of trans planted organs and to potentially lower or even discontinue immunosupp ressive therapy would represent a significant advance in posttransplan t patient care. The aim of this clinical trial was to determine the ef fect of timing and dose of peripheral donor bone marrow cell (DBMC) in fusion on graft and patient survival after liver transplantation. Meth ods. DBMC, obtained from vertebral bodies, were administered in 101 re cipients of liver allografts (OLTX), There were 107 patients for whom DBMC could not be obtained; they received OLTX alone (controls), A tot al of 5 x 10(8)/kg DBMC were infused at day 0 (group 1; n=9); at days 0 and 11 (group 2; n=26); or at days 5 and 11 (group 3; n=26). In grou p 4 (n=40), patients received up to five infusions of 2 x 10(8)/kg DBM C at days 5, 14, 21, 28, and 90 after OLTX. Results. When the results from patients receiving two or more DBMC infusions (groups 2, 3, and 4 ) are considered, both patient and graft survival were significantly i mproved compared with the control group (P=0.02 and P=0.01, respective ly). In groups 3 and 4, 88.5% and 95% of patients were alive with mean follow-up of 536 and 265 days, respectively, compared with 77.6% of p atients in the control group (average follow-up of 452 days) (P=0.02), Graft survival was also significantly improved in groups 3 (88.5%) an d 4 (92.5%), compared with the controls (72%) (P=0.007). Conclusions. The results suggest that dose and timing of DBMC infusions may be impo rtant variables affecting allograft survival. A randomized prospective trial is now in progress to compare group 3 DBMC infusion protocol wi th controls receiving OLTX alone.