Retrospective Comparison between Multiple Hyperbaric Oxygen, Single Hyperbaric Oxygen Treatments and No Hyperbaric Oxygen Treatments in Patients with Multiple Myeloma Undergoing High-Dose Therapy and Autologous Hematopoietic Cell Transplants

Hyperbaric oxygen (HBO) therapy is being explored as a strategy to improve hematopoietic recovery after autologous HCT (auto-HCT) in multiple myeloma (MM). Serum erythropoietin (EPO) negatively impacts hematopoietic stem/progenitor cell (HSPC) homing and engraftment, and preclinical models showed HBO lowers EPO and accelerates hematopoietic recovery and immune reconstitution. A phase II randomized trial found single HBO treatment (s-HBOT) on Day 0 reduced EPO, improved absolute lymphocyte count (ALC) recovery, and T cell reconstitution. A pilot study of multiple HBO treatments (m-HBOT, Days 0,+1,+2) showed sustained EPO suppression, low platelet transfusion needs, and encouraging responses. The impact of m-HBOT on Auto-HCT remains to be confirmed. We retrospectively compared hematopoietic recovery, immune-reconstitution and outcomes related to immune-reconstitution among MM patients who received s-HBOT, m-HBOT, or no HBO. A total of 125 patients were included (47 no HBO, 52 s-HBOT, 26 m-HBOT). On Day 1, EPO was reduced with s-HBOT versus no HBO (p<0.0001), while m-HBOT showed sustained suppression through Day +2, followed by EPO rebound by Day +7 through Day +15. Neutrophil recovery was universal (median 12 to 12.5 days; p=0.80). Median ALC recovery was 13 days with no HBO, 12 days with s-HBOT (HR 1.54 vs no HBO), and 14.5 days with m-HBOT (HR 0.65 vs no HBO), p=0.01. Platelet recovery by Day 15 occurred in 43%, 35%, and 55%, respectively, and platelet transfusions were required in 54%, 65%, and 39% (p=0.08). Length of stay (median 13 to 14 days), G-CSF use (about 6 days), and RBC transfusions (median 0 units) were similar between all groups. Neutropenic fever occurred in 74%, 81%, and 42% (p=0.004), and bloodstream infections in 23%, 16%, and 4% (p=0.13), respectively. At Day 15, NK cells (CD16+CD56+) differed across arms (p=0.008); s-HBOT was higher and m-HBOT was lower compared to no HBO. NKT cells (CD3+CD16+CD56+) were numerically higher in both HBO cohorts versus no HBO, with m-HBOT greater than s-HBOT. Both HBO cohorts had non-significantly improved CD4+ T-cell (p=0.051) and CD8+ T-cell recovery (p=0.13) versus no HBO. By Day +100, CR or better was achieved in 26%, 49%, and 52% (p=0.03), respectively. Both s-HBOT and m-HBOT demonstrated biologic signals of potential benefit in MM auto-HCT. s-HBOT was associated with early EPO suppression and faster ALC recovery, while m-HBOT showed sustained EPO suppression, fewer infections, lower platelet transfusion needs, and possibly higher Day +100 CR rates. These exploratory findings suggest that HBO, particularly m-HBOT, may enhance immune recovery and early disease response, supporting further prospective evaluation.