**7. Conclusions**

*Advances in Hematologic Malignancies*

cohorts, respectively (log rank *p* < 0.0001).

**5. HBO and stem cell mobilization**

**6. Current and future prospective**

64.2%, *p* < 0.01).

Encouraged by the results of HBO in UCB transplantation, the same group conducted a pilot study in Auto-HSPC transplantation. A total of 20 patients were treated on the Auto-HSPC transplant study. HBO therapy was very well tolerated as 19 completed full therapy [40]. For efficacy comparison, HBO subjects were matched to historical controls from the same institution based on gender, age (within 5 years), disease type (multiple myeloma or lymphoma), and preparative regimen. The median time to neutrophil count recovery was 11 days in both cohorts, the HBO and control cohorts. However, time to neutrophil recovery was approximately 1 day sooner for HBO than historical controls taking into account the full distribution estimates of Kaplan-Meier estimator (log rank *p* = 0.005). The median time to platelet count recovery was 16 versus 18 days for the HBO and control

In a separate analysis, HBO effects on other outcomes of post-autologous transplantation were evaluated. In this analysis, the HBO cohort patients who completed HBO therapy (*n* = 19) were compared with historic patients (*n* = 225) [40]. The average days of GCSF use were 6 days in the HBO cohort compared to 8 days in controls (*p* < 0.01). Also, HBO patients had significantly less mucositis (26.3 versus

In the previous section, the effects of HBO on stem cell homing and engraftment posttransplant were reviewed. Interestingly, HBO can also help with stem cell/progenitor cell mobilization from the bone marrow [41]. However, the mobilized stem/ progenitor cells exhibited characteristics of endothelial progenitor cells [42].

Incorporating HBO into HCT backbone represents a new direction in the field of HCT aiming at improving the outcome of HCT by improving HSPC homing and subsequent engraftment. Accumulated data suggest improvement in immune reconstitution too. Targeting EPO at the time of HSPC infusion represents a new understanding of EPO role in basic HSCP functions, including cell differentiation, transmigration, homing, and engraftment. Though these studies represent an early attempt at understanding EPO role in HSCP biologic functions and HBO's role in blocking EPO/EPOR signaling in HCT transplantation, the accumulated data seem to be promising. Currently, a phase II study investigating HBO in Auto-HCT is open for enrollment (ClinicalTrials.gov Identifier: NCT03398200). Another phase II study investigating HBO in UCB transplantation is expected to be open for enrollment in early 2019 (ClinicalTrials.gov Identifier: NCT03739502). Both of these studies are randomized prospective clinical trials that focus on investigating HBO effects on time to neutrophil recovery, platelet count recovery, blood and platelet transfusion requirements, and growth factor use. Additionally, both studies will be evaluating disease response posttransplant. Immune reconstitution will be examined in an attempt to correlate that to disease response posttransplant, hypothesizing that HBOT improves immune reconstitution which in turn will result in improved disease response to transplant. Finally, these studies will examine HBO effects on EPO and IL-15 levels posttransplant. The study in UCB transplantation will also focus on time to achieving full-donor chimerism as that might influence

**4.3 HBO in autologous HCT**

**158**

Targeting EPO using HBO in hematopoietic cell transplantation is a new direction in the HCT field which will potentially have major impact on the outcome of HCT. By improving HSPC homing, engraftment, and immune reconstitution, HBO therapy will have the potential to improve the outcome of HCT by improving patient recovery and by reducing posttransplant complications related to infections. Overall, that might reduce the cost of HCT. Though data from pre-clinical and pilot clinical studies are encouraging, data from current and future phase II studies might show more definitive data in support of this application. Also future studies will be needed to examine HBO effects on bone marrow microenvironment elements.
