Allogeneic Hematopoietic Stem Cell Transplantation (Allo-HSCT) with Human Placenta-Derived Stem Cells (HPDSC) Combined with Unrelated Cord Blood (UCB) for Malignant and Non-Malignant Disorders (IND 14949)

Background MAC or RTC followed by UCB donor allo-HSCT in children with malignant and non-malignant diseases is safe and effective (Geyer/Cairo, BJH 2011). However, concentration of CD34+ HPCs in UCB is low, leading to delayed hematopoietic reconstitution and high incidence of engraftment failure (Satwani/Cairo, BBMT 2013). HPDSCs are rich in HPCs, low in HLA Class I/II expression and T-cells, and have regenerative, anti-inflammatory, and immunosuppressive properties (Liao/Cairo, Stem Cells Trans Med 2018). Objective To determine the safety and efficacy of HPDSCs plus UCB for allo-HSCT in children. Design/Method UCB with TNC ≥ 5 × 107/kg (4/6 HLA match) or ≥ 3.5 × 107/kg (5-6/6 HLA match) were included. Patients received MAC or RTC followed by UCB plus HPDSC infusion. GVHD prophylaxis consisted of tacrolimus and MMF as previously described (Bhatia/Cairo, BBMT 2009). Results Twenty-eight patients ≤18 years were enrolled, 15 males. Mean age± SD was 6.8±5.5 years, (4 months-12 years). There were 12 patients with non-malignant diseases including ALD (2), CAT (1), CGD (1), SCID (2), DC (1), CN (1), SAA (2), LCH (1), and SDS (1) and 16 patients with malignant diseases including B-ALL- CR1 (4), B-ALL - CR2 (4), T-ALL – CR1 (1), AML-CR1 (4), JMML-CR1 (1), TLL - CR1 (1), and BL - CR2 (1). There were 13, 9, and 5 patients with 6/6, 5/6, and 4/6 HLA match, respectively. Mean UCB TNC±SD and CD34+ cell dose±SD infused were 0.77±0.5 × 108/kg and 0.48±0.59 × 106/kg, respectively. Mean HPDSC TNC±SD and CD34+ cell±SD dose were 0.96±3.51 × 108/kg and 0.05±0.05 × 106/kg, respectively. There were no SAEs associated with HPDSC infusions. Four patients were withdrawn for administration of alternative therapy after engraftment failure (3) or relapse (1). Probability of neutrophil engraftment by day 42 was 78.6%, median day 22 (13-53). Probability of platelet engraftment by day 100 in neutrophil engrafted patients was 86.4%, median day 42 (35-98) (Figure 1). Mean UCB chimerism was 92, 99, 96 and 99% at day 30, 60, 100 and 180, respectively. Average HPDSC chimerism was Conclusions These results suggest that UCB plus HPDSCs for Allo-HSCT is safe and well tolerated. Median day to platelet engraftment was lower than previously reported using UCB alone (Geyer/Cairo.BJH 2011). Probability of Grade 2-4 aGVHD was lower than previously reported using UCB alone, possibly due to the immunomodulatory effect of HPDSCs (Geyer/Cairo.BJH 2011). A larger cohort and longer follow-up is required to determine clinical significance.