Infusion of Non-HLA-Matched Off-the-Shelf Ex Vivo Expanded Cord Blood Progenitors in Patients Undergoing Cord Blood Transplantation: Result of a Phase II Clinical Trial

F Milano, L A Thur, J Blake, C Delaney, F Milano, L A Thur, J Blake, C Delaney

Abstract

Recipients of myeloablative cord blood transplants (CBT) are known to experience delayed hematopoietic recovery and an increased risk of transplant related mortality (TRM). We developed methods for ex vivo expansion and cryopreservation of CB stem and progenitor cells. 15 patients with hematologic malignancies were enrolled in this single center phase II trial between September 2010 and August 2012 to assess the safety of infusing a non-HLA-matched expanded CB product to bolster a conventional CBT. On the day of transplant, an infusion of the expanded CB product followed the primary graft (1 or 2 unmanipulated CB units). All patients engrafted. Median time to neutrophil and platelet recovery was 19 and 35 days, respectively. Early myelomonocytic recovery was almost entirely due to cells arising from the non-HLA-matched expansion product and were no longer detected at day 14 in all but 2 patients. The probability of 3-years disease free survival was 86%. No TRM was observed throughout the study period, and only 2 patients relapsed. All patients presented with grade II acute graft-versus-host disease (aGVHD) at a median time of 32 days, with no grade III-IV aGVHD observed. At 2 years only 2 patients remain on immunosuppressive therapy for mild chronic GVHD. This phase II safety study demonstrate that infusion of an off-the-shelf non-HLA-matched expanded CB product in addition to a conventional CB graft was safe and led to sustained myeloid recovery. Based on these encouraging results, a prospective multicenter randomized trial utilizing this product has been conducted and results will be soon released. ClinicalTrials.gov Identifier: NCT01175785.

Keywords: allogeneic transplantation; cellular therapy; cord blood; expansion stem cells; hematopoietic recovery.

Conflict of interest statement

CD and JB are employed at and have equity in Deverra Therapeutics that now holds the exclusive license from the Fred Hutch to the technology used to manufacture the expanded progenitor cell product (EPC). At the time of this study’s completion the technology had not yet been licensed and Deverra was not an entity. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Milano, Thur, Blake and Delaney.

Figures

FIGURE 1
FIGURE 1
Treatment plan.
FIGURE 2
FIGURE 2
A total of 15 patients who received 1 or 2 unmanipulated CB units along with a randomly selected non-HLA-matched expanded CB unit. Figure 2A shows the cumulative incidence of neutrophil recovery. Figure 2B shows the cumulative incidence of platelet recovery.
FIGURE 3
FIGURE 3
Persistence in peripheral blood of cells derived from the expanded cell graft at day 7 (Figure 3A) and at day 14 (Figure 3B).
FIGURE 4
FIGURE 4
Disease free survival at 10 years: recipients ex-vivo expanded cells 86% (95% CI: 56–96) (Figure 4A). Cumulative incidence relapse (Figure 4B).

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