Abstract
Background: Umbilical cord blood (UCB) transplantation is associated with delayed blood count recovery and engraftment. We have demonstrated that pre-treatment with hyperbaric oxygen (HBO) therapy to the recipient mice improved engraftment of intravenously infused human UCB CD34+ in a murine transplant model. Further studies from our laboratory attribute HBO effects on engraftment to HBO-induced low erythropoietin (EPO) state in the host, resulting in early UCB CD34+ cell bone marrow homing and an increase in myeloid to erythroid differentiation. These results lead to the first in-human pilot clinical trial investigating the safety of HBO in the setting of UCB transplantation and secondarily evaluating time to blood count recovery. Herein, we report the final results of this study in comparison to our historic institutional data to determine the impact of HBO on blood count recovery and day +100 survival.Materials/methods: Enrolled patients had hematologic malignancies that required reduced intensity conditioning (RIC) or myeloablative conditioning (MAC) and UCB transplantation. They received HBO therapy on day 0 consisting of exposure to 2.5 atmosphere absolutes for a total of 2 hours, in a single hyperbaric chamber, breathing 100% oxygen. Six hours from the start of HBO, single or double UCB units were intravenously infused and patients were followed daily for toxicity and blood count recovery. Serum EPO levels were measured by enzyme-linked immunosorbent assay (ELISA). Mycophenolate mofetil and cyclosporine were used for GVHD prophylaxis. Charts of 48 patients who received UCB transplantation at our institution for hematologic malignancies between 2008 and 2013 were reviewed for comparison.Results: 15 patients, 9 males (60%) and 6 females (40%), with a median age of 44 years (17-70) were treated. One patient had lymphoma and 14 patients had acute leukemia; 10 in first remission and 4 in second remission. Eight patients received one UCB unit and 7 received two units. Patients received a median total nucleated cell dose of 3.02(1.67-4.51) ×107/Kg recipient body weight (BWT), a median CD34 cell dose of 1.2 (0.7-6.5) ×105/Kg recipient BWT, and 9/15 patients received RIC. 14/15 treated patients completed the planned therapy, while one patient did not finish the last 15 minutes due to nausea. None of the patients experienced an unexpected toxicity. All patients engrafted except for one patient who demonstrated prompt autologous blood count recovery. Full donor chimerism was achieved in 7/8 (88%) of engrafted RIC patients 30 days post-transplant. Eleven of the 15 (67%) patients developed acute graft versus host disease at time of engraftment; 36% developed grade I, 54% had grade II and 9% had grade III. On average, EPO levels 8-hours post HBO were 56 (27-92) % of their pre-HBO values. Median time to neutrophil count recovery, median time to platelet count recovery, day +100 survival (Figure-1), percentage of patients who achieved neutrophil recovery and platelet count recovery in the HBO and historic cohorts are summarized in table-1.Conclusions: HBO therapy prior to UCB cell infusion appears to be safe and well-tolerated in the setting of clinical UCB transplantation. Given the potential benefits of relatively fast recovery and lack of toxicity, HBO should be further evaluated as a strategy to promote engraftment in UCB transplantation.Table 1Summary of transplant outcomes in HBO and historic cohorts.AllMACRICHBO (n=15)Historic (n=48)P valueHBO (n=6)Historic (n=21)P valueHBO (n=9)Historic (n=27)P valueDay 100 survival (n/%)No- (0%)11 (24%)0.051- (0%)10 (48%)0.03- (0%)1 (4%)NSYes15 (100%)34 (76%)6 (100%)11 (52%)9 (100%)23 (96%)Neutrophil recovery (n/%)No- (0%)6 (12%)NS- (0%)4 (19%)NS- (0%)2 (7%)NSYes15 (100%)42 (88%)6 (100%)17 (81%)9 (100%)25 (93%)Platelet recovery (n/%)No- (0%)15 (31%)0.013- (0%)11 (52%)0.023- (0%)4 (15%)NSYes15 (100%)33 (69%)6 (100%)10 (48%)9 (100%)23 (85%)Median time to neutrophil recovery (Range)14 (6-45)20.5 (5-71)NS24.5 (16-45)33 (13-71)NS7 (6-17)14 (5-28)NSMedian time to platelet recovery (Range)37.5 (0-85)38 (0-161)NS54.5 (30-84)50 (29-161)NS32 (0-85)38 (0-112)NS [Display omitted] DisclosuresNo relevant conflicts of interest to declare.
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