Effects of Omega-3 Fatty Acids on Acute Graft-versus-Host Disease After Allogeneic Stem Cell Transplantation.

This study evaluates the therapeutic potential of Omega-3 polyunsaturated fatty acids (PUFAs) in the context of acute graft-versus-host disease (aGVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Omega-3 fatty acids have demonstrated beneficial effects on cardiovascular health, regulation of immune responses, and modulation of inflammatory pathways. Given that current immunosuppressive therapies for aGVHD are often associated with significant side effects and limited efficacy, the development of safer and more effective interventions is urgently needed.

The investigators have previously established robust research platforms, including HTLV-1 detection methods, infection and disease models (such as humanized mice and Diannan small-eared pig models), as well as multi-omics technologies covering virology, immunology, genomics, and epigenetics. Building on this foundation, the present trial aims to:

Conduct integrative analyses of viral genomic characteristics and host genetic susceptibility to construct a risk prediction model for ATL development, providing data support for clinical prevention and treatment strategies.

Characterize the dynamic spatial and temporal changes of the host immune microenvironment at the single-cell level after HTLV-1 infection, and elucidate key nodes of virus-host interaction that contribute to aGVHD pathogenesis.

Establish and optimize therapeutic strategies targeting the NPM1/B23-sHBZ interaction, and evaluate the specificity, efficacy, and safety of Omega-3 PUFA-based immunotherapy alone or in combination with agents such as PD-1 antibodies, chidamide, and DNA methyltransferase inhibitors.

Assess treatment outcomes by monitoring virological suppression, tumor burden, immune and metabolic microenvironment alterations, epigenetic modifications, incidence and severity of cytokine release syndrome (CRS), hematological parameters, and overall survival.

This proof-of-concept study is expected to provide important scientific evidence for the development of novel immunotherapy approaches targeting ATL, with the potential to improve prognosis and expand therapeutic options for patients undergoing allo-HSCT.

• Omega-3 Lipid Emulsion (Drug), also known as ω-3 Lipid Emulsion, Omega-3 PUFA, Omega-3 Fatty Acid Emulsion: Intravenous Omega-3 lipid emulsion administered at a dose of 2 mL/kg/day (equivalent to 0.2 g/kg of fish oil), starting from the conditioning phase prior to hematopoietic stem cell infusion and continuing daily until neutrophil and platelet engraftment or up to Day +35 post-transplantation. The emulsion is infused over 4-6 hours and combined with medium- and long-chain triglyceride emulsion as part of parenteral nutrition.

Primary outcomes

• Incidence and Severity of Acute Graft-versus-Host Disease (aGVHD) Within 100 Days After Allogeneic Hematopoietic Stem Cell Transplantation [Within 100 days post-transplantation]: The primary outcome is to assess the incidence and clinical severity of acute graft-versus-host disease (aGVHD) occurring within 100 days following allogeneic hematopoietic stem cell transplantation. aGVHD will be diagnosed and graded based on standard clinical criteria involving skin, liver, and gastrointestinal tract involvement, using established staging and grading systems.

Secondary outcomes

• Progression-Free Survival (PFS) at Day 100 Post-Transplantation [100 days post-transplantation]: Progression-Free Survival (PFS) is defined as the time from transplantation to disease relapse, progression, or death from any cause, whichever occurs first. Participants who are alive and without disease progression at Day 100 will be considered progression-free.

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

1. Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT)
2. Age 18 to 65 years (inclusive)
3. Male or female
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3
5. Expected survival of at least 100 days
6. Willingness to participate and provide written informed consent

Exclusion Criteria:

1. History of solid organ transplantation
2. Serum triglycerides ≥ 7.9 mmol/L
3. Uncontrolled diabetes
4. Severe dyslipidemia (e.g., LDL-C ≥ 4.9 mmol/L)
5. Contraindications to parenteral nutrition (e.g., severe electrolyte imbalance, acidosis)
6. Severe hepatic impairment (AST/ALT > 3× ULN)
7. Creatinine clearance < 15 mL/min
8. Known allergy to Omega-3, fish, or egg protein
9. Significant psychiatric illness or substance abuse interfering with study compliance
10. Participation in another clinical trial or receipt of other experimental treatments during the study

• Ting Yang, MD, PhD, Principal investigator, First Affiliated Hospital of Fujian Medical University