Long-term results of a pilot study evaluating hyperbaric oxygen therapy to improve umbilical cord blood engraftment

Umbilical cord blood: The promise and the uncertainty

“…Delayed engraftment and graft failure, 3,16‐18 TRM, 9,19 infection risk, 22‐24 and cost of UCB acquisition 25 remain important concerns regarding the use of UCB for transplant. Despite multiple efforts with homing, 39‐43,47 ex vivo expansion, 27‐37,46 and combined graft sources, 45 no survival benefit has been demonstrated. In addition, many of the current techniques are expensive and only available in specialized centers.…”

“…In long‐term follow‐up, overall survival at 6 months was better in patients treated with hyperbaric oxygen; however, there was no difference in overall survival between the treated patients and historical controls at 1 year. Hyperbaric oxygen‐treated patients had lower relapse, less chronic GVHD, and decreased TRM 47 . Direct intramarrow injection of the UCB had a statistically significant median time to engraftment of 23 days compared to 28 days with the intravenous administration of two units UCB.…”

“…Mesenchymal stromal cell coculture, 27,28 notch‐mediated expansion, 29 nicotinamide‐associated expansion, 30‐32 aryl hydrocarbon inhibition, 33,46 stem cell renewal agonist, 34 CD3/CD28 costimulation, 35 copper chelation, 36 and an automated continuous perfusion device 37 have been evaluated for safety, toxicity, and whether or not faster engraftment was seen with the ex vivo manipulation of the UCB unit. Homing strategies (dipeptidyl peptidase‐IV [DPP‐4], 43 complement fragment 3a, 42 fucosylation, 41 prostaglandin E2, 40 hyperbaric oxygen 39,47 ) or direct intramarrow administration of UCB 44 are additional ways being studied to possibly improve time to engraftment.…”

“…A trend toward better disease control and disease‐free survival was seen 44 . In general, homing strategies may be less complex and expensive than expansion strategies, but have not been shown to have a significant impact on survival 39‐44,47 …”

Use of hyperbaric oxygen in hematopoietic cell transplantation to aid post-transplant recovery

“…In addition, an opposite relationship has been suggested between EPO levels and HSPC bone marrow (BM) homing, which stems from the observation that soon after birth, and coinciding with the increase in blood oxygenation, circulating stem cells decline precipitously, in conjunction with a decrease in EPO blood concentration [9,10]. These observations led us to investigate a new role for EPO in HSC differentiation and BM homing that might have clinical implications on UCB transplants and engraftment outcomes [11,12]. Approximately, 20% of UCB CD34+ cells express EPO receptor (EPOR) and exposing these cells to the EPO was shown to decrease the rates of UCB stem cell in vitro transmigration toward the chemokine SDF-1 which mediates UCB HSC homing to the BM [11].…”