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

OBJECTIVE: Graft-versus-host disease (GVHD) is the most prevalent long-term complication following allogeneic hematopoietic stem cell transplant (allo-HSCT). This study aimed to investigate specific posttransplant metabolic alterations in allo-HSCT recipients with acute myelogenous leukemia (AML) or myelodysplastic neoplasms (MDS). METHODS: We analyzed the global metabolic profile in serum samples from 37 patients at 3 months posttransplantation. Among these patients, 25 later developed chronic GVHD (cGVHD), and nine of these 25 patients had previously experienced acute GVHD (aGVHD). RESULTS: Principal component and hierarchical cluster analyses revealed distinct metabolic clusters associated with GVHD. Random forest analysis confirmed the distinct metabolic profile for aGVHD, with an out-of-bag accuracy of 92%. Patients with previous aGVHD exhibited elevated levels of sphingamines and bile acids, and reduced levels of corticosteroids and lysophosphatidylethanolamines. Notably, lysophosphatidic acids (LPAs) such as LPA 22:4, LPA 20:0, and LPA 16:0 were significantly lower in aGVHD patients, indicating potential disruption in LPA-mediated signaling. In contrast, no significant metabolic differences were associated with later development of cGVHD. The lack of distinct metabolic markers for cGVHD suggests that the disease's chronic nature might involve more complex and multifaceted mechanisms beyond serum metabolic alterations. CONCLUSION: Our findings indicate that aGVHD and cGVHD differ in their lipidomic profiles, with only partial overlap. This further underscores the potential of metabolomic profiling to identify biomarkers for aGVHD, while highlighting the need for larger, multicenter studies and longitudinal analyses to better understand the metabolic underpinnings of cGVHD and improve clinical outcomes.