Table 3.
Completed trials of ex vivo expansion of cord blood for hematopoietic stem cell transplantation.
| Reference | Phase of trial | Expansion method | Expanded TNC, median, ×107/kg | Expanded CD34+ cells, median, ×106/kg | Conditioning and transplant | Neutrophils engraftment time, median (range), days | Platelet engraftment time, median (range), days | Infection outcome | Survival outcome |
|---|---|---|---|---|---|---|---|---|---|
| de Lima (154) | Phase I (n=31) | MSC | 5.8 | 0.95 | MAC | 15 (9 to 42) | 42 (15 to 62) | 1-yr f/u: bacteria 9.7%, fungal 16.1% | 1-yr OS: 32.2% |
| Mehta (155) | Phase I (n=27) |
MSC | 5.7 | 1.6 | RIC | 12 (1 to 28) | 31 (9 to 25) | 5 deaths due to infection | 2-yr OS: 32% |
| Delaney (157) | Phase I (n=10) |
Notch ligand | 4.6 | 6 | MAC, co-infusion of 1u unmanipulated CB | 16 (7 to 34) | N.R. | N.R. | 1-yr OS: 70% |
| Milano (158) | Phase II (n=15) |
Notch ligand | 5.8 | 5.2 | MAC, non-HLA matched product, co-infusion with standard CB | 19 (9 to 31) | 35 (21 to 86) | N.R. | 3-yr DFS: 86% |
| Stiff (159) | Phase II/III (n=101) |
Copper chelator | 3.1 | 0.14 | MAC | 21 (95%CI 18 to 24) | 54 (95%CI 43 to 62) | 5 deaths due to infection within 100 days | 100-day OS: 84% |
| Horwitz (160) | Phase I/II (n=36) |
Nicotinamide | 4.9 | 6.3 | MAC | 11.5 (95%CI 9 to 14) | 34 (95%CI 32 to 42) | 5 deaths due to infection | 2-yr OS: 51% |
| Horwitz (34) | Phase III RCT (n=125, 1:1 assigned) |
Nicotinamide | 4.7 vs 5.0 | 9.0 vs 0.3 | MAC, omidubicel vs standard CB | 10.0 (95%CI 8 to 13), vs control 20.5 (95%CI 18 to 24) | 37.0 (95%CI 33 to 42), vs control 50 (95%CI 42 to 58) | Grade 2/3 infection 37% vs 57% in control within 100 days | 210-day NRM: 11% vs 24% |
| Wagner (161) | Phase I/II (n=17) |
SR-1 | 5 | 17.5 | MAC, co-infusion of 1u unmanipulated CB | 15 (6 to 30) | 49 (28 to 136) | N.R. | 1-yr OS: 55% |
| Cohen (162) | Phase I/II (n=22) |
UM171 | 2.92 | 0.14 | MAC | 18 (12.5 to 20) | 42 (35 to 47) | No infection related mortality | 1-yr OS: 90% |
TNC, total nucleated cells; MSC, mesenchymal stem cells; MAC, myeloablative conditioning; RIC, reduced intensity conditioning; f/u, follow up; OS, overall survival; N;R;, not reported; CB, cord blood; DFS, disease-free survival; RCT, randomized controlled trial; NRM, non-relapse mortality.