Impact of Hyperbaric Oxygen Treatment on Time to Transfusion Independency Post-UCB Transplant

Abstract Background Limitations in umbilical cord blood (UCB) transplantations result from decreased cell numbers available for infusion at time of transplant. Delayed engraftment and higher rates of engraftment failure subsequently increase the need for post-transplant growth factor use and transfusion support. Hyperbaric oxygen (HBO) has been shown to improve engraftment in an animal model of UCB transplantation. These experiments proved sufficient to initiate a first-in-human trial of HBO for UCB transplantation. Objectives This study compared growth factor use and time to packed red blood cell (PRBC) and platelet transfusion independence between the HBO study population and historical UCB cases from the same institution. The effects of conditioning regimen and the number of cord units infused at time of transplant were analyzed. Study Design Subjects underwent HBO therapy at the University of Kansas Medical Center after reduced intensity conditioning (RIC) (n=9) or myeloablative conditioning (MAC) (n=6) regimens. Six hours following HBO therapy, they received single (n=8) or double (n=7) UCB units. Charts of HBO-treated patients and historical controls (n=44) were reviewed for post-transplant growth factor use and transfusion requirements. These were further stratified by preparative regimen and number of UCB units infused. Kaplan-Meier curves were compared between HBO and control subjects using log-rank tests as some observations were right-censored if the patient experienced relapse or expired within the first 100 days post-transplant. A small quantity was imputed to values of 0 to facilitate including these subjects in the analyses. Results By days +66 and +74 post-transplant, 100% of HBO-patients were PRBC and platelet independent, respectively. This compares to incomplete platelet (88.63%) and PRBC (86.36%) independence in the control cohort at day 100. Though time to transfusion independence (TTI) for PRBCs was consistently shorter in the HBO cohort, it was only statistically significant in the RIC setting and approached significance in the single cord setting (Table-1). TTI for platelets was shorter for the HBO cohort and approached statistical significance in the single cord setting. Similarly, the consecutive days of filgrastim support post-transplant were consistently fewer for HBO patients, with values approaching statistical significance in the MAC and single cord settings. Conclusions In vitro data with HBO and UCB showed improved rates of engraftment in animal models. Similarly, data in this small pilot study suggests that HBO facilitates less growth factor use and shorter TTI. However, these effects did not reach statistical significance in all settings, most likely due to small sample size of the HBO cohort. Further studies are needed to examine the effect of HBO on growth factor use, PRBC and platelet independence post-UCB transplantation. Table 1 . A comparison of supportive transfusion means, between standard and HBO-UCB transplant recipients. These data are segregated for conditioning regimens and units of UCB infused for transplant. Group PRBC Units Platelet Units Days G-CSF Support TTI - PRBC TTI - Platelets HBO-total (n=15) 9 (p=0.30) 16.35 (p=0.31) 29.4 (p=0.08) 32.87 (p=0.07) 33.53 (p=0.11) Standard-Total (n=44) 9.29 17.14 35.02 56.09 54.8 HBO-Ablative (n=6) 5.43(p=0.23) 7.86 (p=0.16) 26.63 (p=0.07) 24 (p=0.53) 25.5 (p=0.45) Standard-Ablative (n=23) 11.93 22.29 35.65 66.13 67.78 HBO-RIC (n=9) 6.13 (p=0.66) 11.89 (p=0.78) 31.67 (p=0.44) 22.56 (p=0.02) 25.56 (p=0.11) Standard-RIC (n=21) 7.52 13.71 34.33 45.09 40.57 HBO-Single UCB (n=8) 5.43 (p=0.19) 7.87 (p=0.26) 26.63 (p=0.06) 24 (p=0.06) 25.5 (p=0.06) Standard-Single UCB (n=4) 10.25 24 36.2 74.4 70.2 HBO-Double UCB (n=7) 12.57 (p=0.87) 24.86 (p=0.95) 33.57 (p=0.70) 43 (p=0.74) 42.71 (p=0.95) Standard-Double UCB (n=40) 9.19 16.19 34.87 53.74 52.82 Disclosures No relevant conflicts of interest to declare.