Cohort-Controlled Comparison of Umbilical Cord Blood Transplantation Using Carlecortemcel-L, a Single Progenitor–Enriched Cord Blood, to Double Cord Blood Unit Transplantation

Abstract

Umbilical cord blood (UCB) transplantation has a high early mortality rate primarily related to transplanted stem cell dose. To decrease early mortality and enhance engraftment, a portion of selected cord blood units (20% to 50%) was expanded with cytokines and the copper chelator tetraethylenepentamine (carlecortemcel-L) and transplanted with the unmanipulated fraction after myeloablative conditioning. The primary endpoint was 100-day survival, which was compared with a contemporaneous double-unit cord blood transplantation (DUCBT) group. We enrolled 101 patients at 25 sites; the DUCBT comparison (n = 295) was selected from international registries using study eligibility criteria. Baseline carlecortemcel-L study group unit nucleated cell (NC) and CD34 were 3.06 × 10 cell dose/kg and 1.64 × 10 cell dose/kg. Median NC and CD34 fold expansion were 400 and 77, with a mean total CD34 infused of 9.7 × 10/kg. The 100-day survival was 84.2% for the carlecortemcel-L study group versus 74.6% for the DUCBT group (odds ratio, .50; 95% CI, .26 to .95; P = .035). Survival at day 180 was similar for the 2 groups; the major cause of death after day 100 was opportunistic infections. Faster median neutrophil (21 days versus 28 days; P < .0001), and platelet (54 days versus 105 days; P = .008) engraftment was seen in the carlecortemcel-L study group; acute and chronic graft-versus-host disease rates were similar. In this multinational comparative study, transplanting expanded CD34 stem cells from a portion of a single UCB unit, with the remaining unmanipulated fraction improved 100-day survival compared with DUCBT control patients while facilitating myeloid and platelet engraftment. This trial was registered at www.clinicaltrials.gov as #NCT00469729.

Current and future perspectives on allogeneic transplantation using ex vivo expansion or manipulation of umbilical cord blood cells

“…Acute and chronic graft-versus-host disease rates were similar. The study suggests that transplanting expanded CD34+ stem cells from a portion of single UCB unit along with unmanipulated portion improved 100-day survival while improving neutrophil and platelet engraftments [16].…”

Hematopoietic Niche – Exploring Biomimetic Cues to Improve the Functionality of Hematopoietic Stem/Progenitor Cells

“…With this product, a fraction of a single UCB unit is expanded for 21 days with cytokines and TEPA, and infused in patients along with the unmanipulated cell fraction. Gamida Cell launched a multinational phase II/III registration trial (NCT00469729, http://clinicaltrials.gov website accessed on 3rd May, 2017) and concluded that transplanting a StemEx® graft improves a number of important clinical endpoints …”

Expansion or Incubation? Which is Better to Manipulating Stem Cells for Improving the Effects of Umbilical Cord Blood Transplantation

“…Fourteen phase I/II clinic trials [11,[14][15][16][17][18][19][20][21][22][23][24][25][26] and one phase II/III clinic trials [27] were included and their characteristics were presented in Table 1. One study [14] had a randomized control group while fourteen studies [11,[15][16][17][18][19][20][21][22][23][24][25][26][27] were single arm clinic trials for using historical controls. It's worth mentioning that the historical controls were well matched for transplantation conditioning, disease status, age, graft size, HLA matching and performance score criteria.…”

“…Children and adult patients were both included in eight studies [11, 15-17, 21, 24, 26, 27] while six studies [18-20, 22, 23, 25] only focused on adult patients. Twelve studies [11,15,17,18,[20][21][22][23][24][25][26][27] used myeloablative conditioning whereas only one study [19] used nonmyeloablative regimens, and two [14,16] used both of them. One manipulated UCB unit and one unmanipulated unit were co-infused to patients in eleven studies [14,[16][17][18][19][20][21][22][23][24][25].…”