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.

Open article ↗

2026-07-06 | Modified short-course fludarabine-based conditioning regimen for salvage cord blood transplantation after graft failure.

Graft failure after allogeneic hematopoietic stem cell transplantation is a life-threatening complication requiring retransplantation. Cord blood is frequently used in this setting, although the optimal conditioning regimen remains unclear. Recently, a modified short-course fludarabine-based conditioning regimen has been used in clinical practice for salvage cord blood retransplantation in Japan.Using Japanese registry data, we analyzed 465 patients with hematologic malignancies who developed graft failure and underwent cord blood retransplantation within 2 months after allogeneic hematopoietic stem cell transplantation between 2008 and 2016. Of these, 84 patients received a modified short-course fludarabine-based conditioning regimen consisting of fludarabine 30 to 90 mg/m2 over 1 to 3 days, cyclophosphamide 2 g/m2, and low-dose total body irradiation (2 Gy).One-year overall survival and progression-free survival were higher with the modified short-course regimen than with other regimens (45.1% vs 29.9%, p = 0.028; 44.0% vs 26.8%, p = 0.008, respectively). Engraftment at day 56 did not differ significantly between groups (64.3% vs 57.4%, p = 0.178).The modified short-course regimen was associated with improved overall and progression-free survival and may represent a feasible option for salvage cord blood retransplantation after graft failure.

Open article ↗

2026-06-29 | Effect of magnesium supplementation on inflammatory factors and clinical outcomes of allogeneic hematopoietic stem cell transplantation in patients with acute leukemia receiving a neutropenic diet: a randomized clinical trial.

Transplantation-related complications remain a major clinical challenge in patients with acute leukemia, and evidence regarding high-dose oral magnesium supplementation in this setting is limited. This study investigated the effects of oral magnesium citrate on inflammatory responses and clinical outcomes, including graft-versus-host disease (GVHD), following allogeneic hematopoietic stem cell transplantation (allo-HSCT). This randomized, double-blind, placebo-controlled clinical trial was conducted at Taleghani Hospital, Tehran, Iran, and included 45 patients aged 18-60 years undergoing bone marrow transplantation. Participants, all of whom received a standard neutropenic diet, were randomly assigned to receive a neutropenic diet with magnesium supplementation (n = 23) or placebo (n = 22). The intervention group received 420 mg/day of magnesium citrate or placebo for three weeks, with follow-up at day 100. Assessments included 24-hour dietary recalls, questionnaires, clinical evaluations, and laboratory measurements of inflammatory markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The incidence of GVHD increased non-significantly in both groups during the 3-week intervention period but declined during follow-up, with a significantly greater reduction observed in the magnesium group by day 100. Fever incidence decreased in both groups at week 3, with a significantly larger reduction in the magnesium group 56.5% compared with placebo, 22.7%. ESR increased in both groups during the intervention period, with a greater rise observed in the placebo group, which was significant only in the crude model; however, by day 100, ESR had significantly decreased by 15% in the magnesium group and significantly increased by 13% in the placebo group across all models. TNF-α and IL-6 levels decreased in the magnesium group but increased in the placebo group at week 3, although these changes were not statistically significant over time in all models. Magnesium supplementation in allo-HSCT patients receiving a neutropenic diet may have a potential benefit, being associated with reductions in some clinical and inflammatory outcomes, including a lower incidence of GVHD and fever and reduced ESR. However, these findings were not consistent across all inflammatory markers and require confirmation in larger studies with longer intervention durations.Trial registration Iranian Registry of Clinical Trials. IRCT20240812062726N1. URL of trial registry record https//irct.behdasht.gov.ir/trial/78,589, Registration date 17 September 2024.

Open article ↗