Nicord® Expanded Hematopoietic Progenitor Cells (HPC) Are Capable of Outcompeting the Unmanipulated (UM) Cord Blood Unit and of Prolonged Myeloid and Lymphoid Engraftment Following Myeloablative Dual Umbilical Cord Blood (UCB) Transplantation

Human transplantation of expanded HPCs resulting in durable, robust donor myeloid and T-cell engraftment has yet to be reported. A pilot study of myeloablative dual UCB transplantation where one UCB unit is expanded ex vivo using NiCord technology has completed accrual. The NiCord UCB graft consisted of an expanded CD133+ and an unexpanded CD133- T-cell fraction. HPCs were expanded for 21 days in media containing cytokines supplemented with nicotinamide (NAM). All patients were conditioned with TBI (1350cGy), fludarabine 160mg/m2 ±cyclophosphamide 120mg/kg (n=2). GvHD prophylaxis consisted of tacrolimus and MMF. Eleven patients (med. age 45; range 21-61) with high-risk malignancies received NiCord and an UM graft (Table). Both units were comparably HLA-matched with the recipient; 4/6 (n=7), 5/6 (n=3) or 6/6 (n=1) vs. 4/6 (n=8), 5/6 HLA (n=3), respectively. However, the UM unit contained a larger pre-cryopreserved cell dose (3 x 107/kg [range 1.9-3.9] vs. 2.5 x 107/kg [range 1.7-3.8]). After expansion (CD133+ fraction), NiCord contained a median TNC and CD34+ cell dose of 2.7 x 107/kg (1.0-6.4) and 3.5 x 106/kg (0.9-18.3), respectively. The NiCord T-cell dose was substantially smaller than the UM graft. Eight patients engrafted with NiCord (one of which is a mixed donor chimera) and two with the UM graft (Table). One patient experienced primary graft failure. The median time to neutrophil engraftment was 12.5 days (7-26) for the entire cohort, and 10.5 (7-18) days for those engrafting with NiCord. Three patients experienced grade I/II acute GvHD. There were no cases of Grade III/IV acute GvHD. No safety concerns were raised. The estimated 100-day treatment-related mortality is 10%. With a median follow-up of 8 months, the progression-free and overall survival are both 90%. NiCord expanded HPC's are capable of out-competing those from the UM unit and predominate in the majority of patients. NiCord expanded HPC's reduce the time to hematopoietic recovery and are capable of long term (>22 months) neutrophil and T-cell engraftment. Stem cell transplantation using NiCord is feasible, and may provide a potent cord blood graft enabling transplantation of a single expanded unit, without co-infusion of UM cells.TablePatient NumberDisease Stage/AgeEngrafted CBUEngraftment DayNiCord Chimerism∗Performed at date of last follow-up from peripheral blood.Months post TransplantANC >500Platelet >20,000CD15 (%)CD3 (%)1AML (CR1)/61NiCord + UM1433422222MDS (Int-2)/43NiCord1130100100173MDS (Int-2)/59NiCord10309793154AML (CR2)/41UM183600145AML (CR1)/57UM264900116AML (CR2)/45NiCord1030100% (Whole Blood)87HL/21NiCord + UM7261003168NHL/46Graft failure----5‡Re-transplanted with haploidentical donor.9AML(CR1)/45NiCord14419761210AML (PR)/59NiCord18->98 (Whole Blood)2†Death Day 47 Pneumonia.11ALL (CR1)/44NiCord7N/A1001001∗ Performed at date of last follow-up from peripheral blood.† Death Day 47 Pneumonia.‡ Re-transplanted with haploidentical donor. Open table in a new tab