Ex vivo mesenchymal progenitor cell-based cord blood cell expansion and exofucosylation to enhance transplant engraftment.

Abstract

Umbilical cord blood (CB) transplantion is limited by slower engraftment and higher failure rates compared to other allografts. We hypothesized that ex vivo expansion of CB using mesenchymal progenitor cells (MPCs) and exofucosylation to enforce expression of osteotropism-mediating sLeX would shorten engraftment time. Six patients with hematologic malignancies underwent transplantation with two CB units (CBUs). Five received one unmanipulated CBU and one MPC-expanded, exofucosylated CBU. Median neutrophil engraftment, platelets >20,000/µL, and platelets >50,000/µL were 29, 45, and 55 days, respectively. A sixth received one exofucosylated CBU and one MPC-expanded CBU, achieving neutrophil engraftment, platelets >20,000/µL, and platelets >50,000/µL in 34, 53, and 57 days, respectively. Acute GVHD occurred in 4/6 patients, including one grade III/IV case. Three were alive without disease relapse at a median of 43.6 months post-transplant. Deaths in three patients were due to relapse, COVID, and GVHD. Thus, these approaches were safe, but did not improve engraftment.