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Long-term results of a pilot study evaluating hyperbaric oxygen therapy to improve umbilical cord blood engraftment

  • Alain Mina
  • Leyla Shune
  • Haitham Abdelhakim
  • Tara L. Lin
  • Sid Ganguly
  • Andrea Baran
  • Anurag Singh
  • Sunil Abhyankar
  • Joseph P. McGuirk
  • Dennis Allin
  • Omar S. Aljitawi
Original Article

Abstract

Umbilical cord blood (UCB) transplantation is a promising option for hematopoietic stem cell transplantation in patients with hematologic malignancies who lack an HLA-matched sibling or well-matched unrelated donor; however, it has a higher incidence of delayed or failed engraftment because cell doses are low and bone marrow homing is inefficient. We have demonstrated that pre-treating irradiated immune-deficient mice with hyperbaric oxygen (HBO) prior to UCB CD34+ cell transplantation lowered host systemic erythropoietin (EPO) and improved UCB CD34+ cell homing and engraftment. These findings suggested that EPO-EPO-R signaling plays a role in UCB CD34+ homing and engraftment. In a pilot clinical trial, we showed that recipients of HBO therapy prior to UCB cell infusion had reduced systemic EPO, which was associated with improved kinetics of blood count recovery. Although early clinical outcomes at day 100 were encouraging, with improved overall survival, the long-term effects of HBO therapy on UCB-transplanted patients were not evaluated. In this study, we examined the long-term outcome of patients in our pilot study, compared with a historic control group, and correlated their clinical outcomes to serum EPO response to HBO. While 50% of HBO-treated patients received single UCB units, ~ 90% of the control patients received double UCB units. Although HBO patients had much better rates of survival at 6 months, their 1-year survival did not significantly differ from the control group. HBO-treated patients had on average lower relapse and non-relapse mortality rates, and less chronic graft versus host disease (GVHD), but had increased acute GVHD. However, these differences were not statistically significant, probably because of the small sample size. In the HBO-treated cohort, immune reconstitution analysis showed significant improvement in early B cell recovery, with a trend toward improvement in early NK cell recovery. When we evaluated the ratio of 8 h to baseline EPO levels, we found a non-significant trend toward lower EPO values in those who neither relapsed nor died by 1 year, compared to those who died or relapsed. This result suggests that EPO response to HBO may be associated with better outcomes. Disease progression-free survival was also improved in those who had more than 80% reduction in EPO levels in response to HBO. Our study highlights the long-term safety of HBO therapy when used prior to UCB transplantation. Future UCB transplant patients who receive HBO should have their serum EPO response measured, as it may be a marker of relapse/mortality.

Keywords

Hyperbaric oxygen Umbilical cord blood transplantation Pilot study Long-term results 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committees and with the 1964 Helsinki declaration and its later amendments, or comparable ethical standards.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Alain Mina
    • 1
  • Leyla Shune
    • 2
  • Haitham Abdelhakim
    • 2
  • Tara L. Lin
    • 2
  • Sid Ganguly
    • 2
  • Andrea Baran
    • 3
  • Anurag Singh
    • 2
  • Sunil Abhyankar
    • 2
  • Joseph P. McGuirk
    • 2
  • Dennis Allin
    • 4
  • Omar S. Aljitawi
    • 5
  1. 1.Department of Internal MedicineUniversity of Kansas Medical CenterKansas CityUSA
  2. 2.Division of Hematologic Malignancies and Cellular TherapyUniversity of Kansas Medical CenterKansas CityUSA
  3. 3.BiostatisticsUniversity of Rochester Medical CenterRochesterUSA
  4. 4.Department of Emergency MedicineUniversity of Kansas Medical CenterKansas CityUSA
  5. 5.Hemagology/Oncology and Bone Marrow Transplantation ProgramUniversity of Rochester Medical CenterRochesterUSA

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