Three-Month Posttransplant Lipidomic Profile Reflects Acute GVHD but Not Chronic GVHD Risk in Allogeneic Stem Cell...

Area of Science:

• Biochemistry and Molecular Biology
• Immunology
• Oncology

Background:

• Graft-versus-host disease (GVHD) is a major long-term complication of allogeneic hematopoietic stem cell transplant (allo-HSCT).
• Understanding post-transplant metabolic alterations is crucial for managing GVHD, particularly in patients with acute myelogenous leukemia (AML) or myelodysplastic neoplasms (MDS).

Purpose of the Study:

• To investigate specific posttransplant metabolic alterations in allo-HSCT recipients.
• To identify potential metabolic biomarkers differentiating acute GVHD (aGVHD) and chronic GVHD (cGVHD).

Main Methods:

• Serum samples from 37 allo-HSCT recipients were analyzed for global metabolic profiles at 3 months post-transplantation.
• Statistical analyses including principal component, hierarchical cluster, and random forest analyses were employed.
• Patients were categorized based on the development of aGVHD and/or cGVHD.

Main Results:

• Distinct metabolic clusters were associated with GVHD, with a 92% accuracy for aGVHD prediction using random forest analysis.
• Patients with prior aGVHD showed elevated sphingamines and bile acids, and reduced corticosteroids and lysophosphatidylethanolamines.
• Significantly lower levels of specific lysophosphatidic acids (LPAs) were observed in aGVHD patients, suggesting LPA-mediated signaling disruption. No distinct metabolic markers were found for cGVHD.

Conclusions:

• Acute GVHD and cGVHD exhibit distinct lipidomic profiles with limited overlap.
• Metabolomic profiling shows promise for identifying aGVHD biomarkers.
• Larger, multicenter studies are needed to elucidate cGVHD metabolic underpinnings and improve clinical outcomes.