Interim Analysis of a Randomized Phase II Study Evaluating the Efficacy of Hyperbaric Oxygen in Improving Engraftment in Umbilical Cord Blood Transplantation

Introduction Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cells (HSC) for transplantation in patients who lack HLA-matched donors. UCB transplantation (UCBT) advantages include availability for immediate use and lower incidence of chronic GvHD. Pitfalls include delayed engraftment and graft failure which can translate into higher infection rates especially early post UCBT. Strategies to overcome defects in homing and engraftment are needed. Prior preclinical studies made by our group showed that lower erythropoietin (EPO) levels favor UCB CD34+ engraftment by positively affecting homing and differentiation of HSCs. Hyperbaric oxygen (HBO) reduces systemic EPO and can be safely administered to patients undergoing HSCT. We present the safety interim analysis of a phase II study evaluating the efficacy of HBO in improving engraftment in patients undergoing reduced intensity conditioning (RIC) followed by UCBT at our institution. Methods Patients with hematological malignancies aged 18 to 75 years old with adequate system function to be eligible for RIC transplant were enrolled. RIC regimens included Fludarabine (Flu), Cyclophosphamide (Cy) and 200Gy of total body irradiation (TBI) with and without Thiotepa (TT). Patients were randomized to Arm A (HBO treatment) or Arm B (no HBO treatment). For patients in Arm A, 1-time HBO treatment was administered in the morning of UCB infusion. This consisted of exposure to hyperbaric conditions (100% oxygen at 2.5 ATA) for approximately 90 minutes. Mycophenolate mofetil and cyclosporine were used for GvHD prophylaxis. An interim analysis to assess safety was conducted once 100-day follow ups were completed for the first 16 randomized subjects. Results A total of 16 patients were randomized and underwent RIC UCBT. Eight patients were randomized to receive HBO therapy prior to RIC UCBT but only 6 received it due to exclusion criteria. A total of 8 patients were randomized to the non-HBO group. There were no primary or secondary graft failures in either group. As-treated safety analysis showed 2 deaths in the group treated with HBO and who received the treatment. Deaths were due to disease relapse/progression and transplant-related mortality. Five deaths occurred in the non-HBO group (2 related to disease progression/relapse and 3 were transplant-related). Median overall survival (OS) in the HBO-treated group was not reached, 95% CI= [2.30 months, not estimated] while in non-HBO group, median OS was 5.52 months, 95% CI= [3.11 months, not estimated]. Conclusion We present the initial results of the safety interim analysis of a phase II trial evaluating the efficacy of HBO in improving engraftment in patients undergoing RIC followed by UCBT at our institution. Improved median OS is reported in the arm treated with HBO compared to the arm that was not treated with HBO prior to UCBT. No events of graft failure were seen in either group.