NiCord single unit expanded umbilical cord blood transplantation: Results of phase I/II trials

Background: Delayed or failed engraftment after cord blood transplantation is a major barrier to the success of the procedure, limiting its applicability as a graft source. Increasing the number of hematopoietic stem cells (HSC) within the donor graft may overcome this limitation. NiCord is an ex vivo-expanded, cryopreserved graft derived from an entire cord blood unit (CBU). In the pilot study, NiCord was transplanted with a second CBU following myeloablative conditioning (MAC) in patients with hematologic malignancies (Horwitz M, JCI 2014). Methods: We now report results of a subsequent study that explored use of NiCord as a single graft. Sixteen adult patients, median FU of 355 (232 - 373) days, with AML CR1 (5), ALL CR1/2 (5), MDS (3), CML (2), HD (1), were transplanted at 6 sites in the USA and EU. All patients received MAC with TBI/Flu ± Cy (n=8) or with thiotepa/Bu/Flu (n =8). GvHD prophylaxis consisted of tacrolimus or cyclosporine and MMF. HLA-matching was 4/6 (n=10), 5/6 (n=4) or 6/6 (n=2). NiCord median fold expansion of CD34+ cells was 104 (47-245). After expansion, the TNC and CD34+ cell doses were 3.85 x 107/kg (1.8-7.5) and 6.7 x 106/kg (3.3-14.9), respectively. Results: All patients engrafted. One patient had secondary graft failure attributed to HHV6 viremia. Neutrophil and platelet engraftment were achieved at median of 10 (6 - 26) and 32 (26 - 96) days, respectively. All engrafted patients achieved full donor myeloid and lymphoid chimerism. At day 100, median absolute lymphocyte and T cell counts were 1031.5/μl (345-1512/μl) and 285.5/μl (84 - 595μl). Non-relapse mortality was 12.5% at 100 days. Grade III-IV aGvHD was 13%. Grade III infections were observed in two patients. With a median FU of 355 (232 - 373) days, overall survival at 180 and 365 days is 81.2% and 64%, respectively. The results of this trial and the understanding of multi-site practices have provided the basis for design of the registration phase III, prospective randomized controlled study to begin in 2016. Conclusions: NiCord has the potential to broaden accessibility to HSC transplantation and become the graft of choice for patients without a timely or suitably matched adult donor.