2026-07-12 | Dietary stearic acid aggravates acute graft-versus-host disease by promoting oxidative stress and pro-inflammatory macrophage polarization.

Acute graft-versus-host disease (aGVHD) remains a major life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although immune activation and tissue inflammation are central to aGVHD pathogenesis, how dietary fatty acid exposure shapes inflammatory responses after transplantation remains insufficiently defined. Building on our previous finding that a high stearic acid diet (HSAD) alters the gut microbiota and aggravates aGVHD, we hypothesized that stearic acid (SA), a major saturated fatty acid, further exacerbates aGVHD by inducing oxidative stress and promoting pro-inflammatory macrophage polarization. Using a murine aGVHD model, we found that HSAD significantly increased serum SA levels and aggravated disease severity. Mechanistically, HSAD enhanced reactive oxygen species (ROS) production in splenocytes and disrupted glutathione redox homeostasis, indicating increased systemic oxidative stress. SA promoted M1-like macrophage polarization both in vivo and in vitro, without directly altering Th1 or Th17 differentiation. Pharmacological ROS scavenging with N-acetylcysteine (NAC) attenuated SA-induced ROS accumulation and M1 polarization. Additionally, SA activated mTOR signaling and promoted NLRP3 inflammasome activation in macrophages, as evidenced by increased NLRP3 expression, caspase-1 cleavage, and IL-1β maturation, which were attenuated by rapamycin. Collectively, these findings identify dietary SA as a modifiable factor that aggravates aGVHD by linking lipid metabolic stress to oxidative injury and M1 macrophage polarization. This work provides a rationale for targeting SA intake or its downstream signaling pathways as a strategy to mitigate aGVHD severity.

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2026-07-09 | Oral Sodium Butyrate Supplementation, Gut Microbiome Modulation, and Reduced Acute Graft-versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation.

Acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Disruption of the gut microbiome during transplantation has been implicated in the pathogenesis of aGVHD, yet clinically applicable strategies to modulate the microbiome in immunocompromised patients remain limited. To evaluate the association between oral sodium butyrate supplementation and the incidence and severity of aGVHD, and to investigate its impact on gut microbiome recovery following allo-HSCT. In this prospective, single-center study, 39 consecutive patients undergoing allo-HSCT received oral sodium butyrate (1,200 mg/day) from neutrophil engraftment to day +100. Outcomes were compared with 18 historical controls treated at the same institution without butyrate supplementation. The primary endpoint was the cumulative incidence of grade II-IV aGVHD by day +100. Secondary endpoints included lower gastrointestinal aGVHD and microbiome characteristics assessed using shotgun metagenomic sequencing. Competing risk analyses were performed to account for death as a competing event. Butyrate supplementation was associated with a lower incidence of grade II-IV aGVHD (30% vs 53%, p=0.028) and grade III-IV aGVHD (5% vs 34%, p=0.002). Lower gastrointestinal aGVHD occurred in 5% of the butyrate group compared with 40% of historical controls (p<0.001). In multivariable competing risk analysis, butyrate supplementation remained independently associated with reduced grade II-IV aGVHD (adjusted HR 0.31, 95% CI 0.11-0.89; p=0.029) and lower gastrointestinal aGVHD (adjusted HR 0.07, 95% CI 0.02-0.30; p<0.001). Microbiome analysis demonstrated improved recovery of gut microbial diversity at day +100 in the butyrate group, with enrichment of commensal taxa and restoration of fecal butyrate levels. Oral sodium butyrate supplementation was associated with reduced incidence and severity of aGVHD, particularly involving the gastrointestinal tract, along with improved microbiome recovery. These findings suggest a potential role for postbiotic-based microbiome modulation in GVHD prevention and warrant validation in randomized controlled trials.

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2026-07-06 | The application of rituximab during the conditioning regimen prevents Epstein - Barr virus infection following rATG-based haploidentical hematopoietic stem cell transplantation in the era of letermovir for cytomegalovirus prophylaxis.

In the era of letermovir for cytomegalovirus (CMV) prophylaxis, several centers reported that the incidence of Epstein-Barr virus (EBV) infection were significantly increased. To investigate the efficacy and safety of rituximab administration during conditioning regimen following haploidentical hematopoietic stem cell transplantation(haplo-HSCT)in the prevention of post-transplant EBV infection. We conducted a retrospective analysis of 100 patients with acute leukemia or myelodysplastic syndrome who underwent haplo-HSCT. Patients in observation group(R group) received rituximab (375 mg/m²) on day -3 before transplantation due to the presence of donor-specific antibody (MFI ≥ 2000) (n = 25) and patients in control group (C group) did not receive rituximab (n = 75) and donor-specific antibody was low (MFI < 2000). The primary objectives were the incidence of EBV-DNA viremia and PTLD within one-year post-transplantation. Secondary objectives included the incidence of CMV infection, cumulative incidence of acute graft-versus-host disease (aGVHD) and chronic GVHD, 100-day non-relapse mortality (NRM), progression-free survival (PFS), and overall survival (OS). No significant differences were observed in baseline characteristics between the two groups except for primary disease. When compared with the C group, patients in R group exhibited a lower cumulative incidence of EBV viremia within one-year post - transplantation (4.00% vs. 22.67%, P = 0.049) and a lower incidence of aGVHD (28% vs. 50.67%, P = 0.048). There was a trend toward reduction of PTLD in the R group compared with C group (0% vs. 10.67%, P = 0.089).There were no significant differences of the incidence of CMV viremia (24% vs. 13.33%, P = 0.208), cGVHD (16% vs. 12%, P = 0.607), and 100 - day NRM (4.0% vs. 10.67%, P = 0.313) between two groups. The 2-year OS rates in the R group and C group were 83.8% ± 0.086% and 81.9% ± 0.050% respectively (P = 0.360). The 2-year PFS rates in the R group and C group were 83.8% ± 0.086% and 72.6% ± 0.068% respectively (P = 0.360). The combined use of rituximab during the conditioning regimen may be regarded as an effective strategy for preventing EBV reactivation after rATG - based haplo - HSCT in the era of letermovir for CMV prophylaxis.Prospective randomized controlled trials are still required to further validate the reliability of the results.

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