Abstract
Umbilical Cord Blood (UCB) represents a valid option for patients with hematopoietic malignancies lacking an HLA matched donor. To overcome the limitation of the low stem cell dose of UCB, the intrabone (IB) route has been proposed. We report the results of a prospective study on a poor-prognosis cohort of 23 patients receiving intrabone single UCB transplant (Clinicaltrials.gov NCT00886522). Cumulative incidence of hematological recovery at day 90 was 82 ± 9% (ANC > 0.5 × 109/L) and 70 ± 10% (platelet > 50 × 109/L) and correlated with CD34 + cells in the graft. NRM was 20 ± 9%. No severe aGVHD and only one extensive cGVHD occurred, with fast immune reconstitution. To test the hypothesis that the direct IB injection could affect the expression of stem cells regulatory pathways, CD34 + cells from BM aspirates at day + 10, + 20, + 30, processed in hypoxic conditions mimicking the BM-microenvironment (7%pO2), were studied for the expression of c-Mpl, Notch1 and CXCR4. We found that the expression of c-Mpl in CD34 + cells at day + 10 significantly correlated with hematological recovery. In conclusion, IB-UCB transplant success is associated with low incidence of GVHD and high-speed platelet recovery; intrabone route may preserve full hematopoietic stemness by direct delivery of UCB stem cells into the hypoxic HSC niche.
Highlights
These authors contributed : Massimiliano Bonafé, Gianluca StorciElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Umbilical Cord Blood (UCB) represents a valid option for patients needing an allotransplant but lacking a HLA matched donor
Because we here found that the level of c-Mpl in CD34 + is higher under hypoxic conditions, we surmise that the direct injection of CD34 + in the hypoxic hematopoietic stem cell (HSC) niche may contribute to the success of the IB- procedure
No severe adverse events related to IB infusion were recorded and the IB-UCB infusion were well tolerated
Summary
Double UCB transplant, one of the most popular option currently used to ameliorate the speed of engraftment, failed to demonstrate formal proof of superiority [2]. Further approaches emerged, such as ex-vivo UCB expansion by means of the administration of cytokines [3], Notch ligands [4], nicotinamide [5] or mesenchymal cells co-culture [6]. An alternative approach is to increase the seeding efficiency by bringing more cells to the physiologic place, i.e. the hematopoietic niche, as it occurs in direct intrabone (IB) injection of UCB [9]. Because we here found that the level of c-Mpl in CD34 + is higher under hypoxic conditions, we surmise that the direct injection of CD34 + in the hypoxic HSC niche may contribute to the success of the IB- procedure
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