Hyperbaric oxygen therapy (HBOT) demonstrates a promising 86.9% response rate as an adjunctive therapy for late-onset hemorrhagic cystitis (HC) following allogeneic hematopoietic stem cell transplantation (HSCT), according to a retrospective study. The findings suggest HBOT could complement existing treatment protocols, especially in cases resistant to standard conservative treatments. This offers a potential solution for patients suffering from this challenging complication post-transplant.
HBOT in Hemorrhagic Cystitis Treatment
While conservative treatments for HC show variable response rates (26-89%), HBOT has shown effectiveness in managing HC after HSCT in several retrospective studies with small sample sizes. These studies report complete response rates ranging from 57 to 94%. HBOT's effectiveness in radiation-induced HC is well-documented, leading to its recognition as a potential treatment by the European Committee for Hyperbaric Medicine and the Undersea & Hyperbaric Medical Society.
The rationale behind HBOT lies in its ability to create alternating periods of hyperoxygenation and relative hypoxia. This process establishes an oxygen gradient between healthy tissue and damaged urothelium, fostering angiogenesis, fibroblast proliferation, and vasoconstriction—all critical for tissue repair. Relative hypoxia attracts macrophages and releases growth factors like vascular endothelial growth factor (VEGF), promoting capillary proliferation. Hyperoxia stimulates fibroblast proliferation, collagen formation, and leukocyte activation. Nitric oxide (NO) downregulation leads to vasoconstriction, reducing edema without worsening ischemia due to the high oxygen levels in hyperbaric conditions.
Treatment Protocols and Outcomes
Currently, there are no established predictive factors for treatment response. However, the study indicated that a number of sessions equal to or greater than 10 were associated with more favorable response rates. HBOT was administered until macroscopic hematuria disappeared, with an average of 15.5 sessions needed for a complete response. Only two patients discontinued treatment due to a lack of clinical benefit.
Safety and Tolerability
HBOT carries potential risks, with a reported adverse effects rate of 30.1% in a meta-analysis, particularly with more than 10 sessions and chamber pressures above 2.0 ATA. In this study, the adverse effects rate was 9.8%, indicating good tolerance, even in pediatric patients. One major complication, an oxygen toxicity seizure, was observed. These events are typically self-limiting and resolve with adjustments to oxygen pressure. Incorporating a 5-minute air-break interval in treatment protocols may further decrease seizure frequency.
Limitations and Future Directions
Limitations of HBOT include its availability, treatment duration, costs, and contraindications. Access to specialized centers with hyperbaric chambers and trained professionals is essential, which can limit patient access. Contraindications include obstructive pulmonary diseases, recent thoracic surgery, uncontrolled seizures, and claustrophobia, though most are relative. The study's primary limitation is the absence of a comparative arm, restricting definitive conclusions about HBOT's efficacy compared to standard care alone. The retrospective nature introduces potential biases, such as incomplete clinical records. Future randomized controlled trials are necessary to mitigate these biases and provide more conclusive evidence.
Conducting randomized, controlled, and double-blind clinical trials for HBOT in treating late-onset HC presents significant challenges, including the rarity of the condition and ethical considerations. Collaboration across multiple centers is needed to enroll sufficient patients. Despite these challenges, the resolution of hematuria in most retrospective studies supports HBOT as a treatment strategy for HC, and it has been recognized as a therapeutic option by the ECIL.
Further research should focus on optimizing treatment protocols, conducting long-term follow-up studies, investigating physiopathological mechanisms, identifying predictive factors, and performing cost-effectiveness analyses. These advancements will enhance the understanding of HBOT's role in managing late-onset HC and guide evidence-based treatment decisions.
