First Report on an Ongoing Pilot Clinical Study Incorporating Hyperbaric Oxygen into Autologous Peripheral Blood Stem Cell Transplantation

Background: High-dose chemotherapy and autologous peripheral blood stem cell (PBSC) transplantation is considered a standard of care procedure for multiple hematological malignances. Patients undergoing this procedure might face multiple morbidities including mucosal inflammation and neutropenic fever; both related to neutropenia. Based on our pre-clinical work in an umbilical cord blood (UCB) transplantation murine model, we found that hyperbaric oxygen (HBO) improved UCB CD34+ cell engraftment. As a result, we are currently conducting a pilot study exploring HBO in clinical autologous PBSC transplantation. Our primary aim is to determine the safety of HBO in this setting and secondarily to determine its efficacy in reducing time to neutrophil and platelet engraftment compared to matched historic controls. Materials/methods: Patients with multiple myeloma (MM), non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease (HD) that require autologous PBSC transplantation were included. On day 0, patients received HBO treatment consisting of exposure to 2.5 atmosphere absolutes for a total of 2 hours, in a monoplace hyperbaric chamber, breathing 100% oxygen. Six hours from the start of HBO, PBSC units were infused and patients were followed daily for toxicity and blood count recovery. A matched historic cohort was chosen based on gender, age, conditioning regimen, and disease type. Results: 16 patients were screened for this study, 13 were enrolled, and 11 were treated. One patient did not get treated because of an emergency use of the HBO chamber by another patient. The main reasons for non-enrollment were insurance denial, patient choice, and failure to meet study criteria. The treated subjects were 6 males and 5 females with median age of 63 (range: 25-67) who had MM (n=7), or NHL (n=4). For MM patients, the preparative regimen was high-dose melphalan and for NHL patients it was BEAM or BEAC. The median cell dose infused was 3.7 (2.52-6.11) X106 CD34/Kg recipient body weight. Only one patient was unable to complete the planned therapy due to ear discomfort. The rest completed therapy without subsequent treatment limiting toxicity. For the eleven patients who were assessed for engraftment, the median time to neutrophil count recovery was day 11 (10-13) and for platelet count recovery was day 16 (14-19) post-transplant. In this unplanned interim analysis, the historical control group was estimated to have a longer average time to neutrophil recovery (0.15 days with a standard error of 0.32) and a longer average log-transformed time to platelet recovery (approximately 0.16 log-days with a standard error of 0.08), which transformed into days represents about 1.2 days. Conclusion: HBO therapy prior to PBSC cell infusion appears to be well-tolerated in the setting of high-dose therapy and autologous PBSC transplantation. HBO impact on blood count recovery should be investigated further.