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Single UM171 expanded cord blood transplant is feasible and safe, accelerates engraftment, reduces hospitalization length and most importantly improves HLA matching

      Cord blood (CB) transplants are hampered by low cell dose and high transplant related mortality (TRM). UM171, a potent agonist of hematopoietic stem cell (HSC) self-renewal could solve this limitation, allowing for CB’s important qualities as lower risk of chronic GVHD and relapse to prevail. Hence, we initiated a clinical trial to test UM171 expanded CB (eCB). The procedure was designed to be non-labor intensive and of short duration for it to be clinically viable. Patients (pts) received a myeloablative conditioning regimen. On day(D)-7 of transplant, CB was CD34+ selected. The CD34- component was cryopreserved and infused at transplant. The CD34+ component was placed in a closed culture system with UM171 and media was injected once a day until D0. This culture system allowed for small culture volumes, saving cost and labor. Between 9/16-3/17, 7 adult pts received a single eCB. Median final culture volume was 713mL. Median net CD34 fold expansion was 35. Median 1st day of 100 and 500 neutrophils (N) were D+10 and D+18, respectively. As infused (i) CD34 dose is the best predictor of N engraftment with non eCB, an algorithm can predict engraftment based on iCD34. We therefore inferred that N engraftment improved by a median of 4 days. However, more importantly, patients who did not have a N recovery by day 12, had 100 N by day 10 and had clear clinical benefit once 100 N were reached with disappearance of fever and earlier hospital discharge. In addition, because cell dose requirements were lower, half received a better HLA matched CB. There has been no TRM or relapse. Full donor chimerism was achieved in all cell subsets. These results favorably compare to other expansion trials which utilize much larger (up to 30L) and longer (up to 21 days) cultures. Moreover and in contrast to others, we have now initiated a dose reduction study with smaller, better HLA matched CBs, proven to reduce TRM. Despite very preliminary data, a 7 day UM171 single eCB protocol appears feasible and provides clinical benefit beyond faster engraftment with fewer infectious complications and better HLA matching, all the while saving production and hospitalization costs.