Bone Marrow Transplantation最新文献

The gut microbiota has emerged as a critical factor influencing outcomes following allogeneic hematopoietic cell transplantation (alloHCT). Notably, disruptions to the intestinal microbiome-referred to as dysbiosis-have been strongly linked to the development of acute graft-versus-host disease (aGVHD). The gut microbiome interacts closely with the host immune system, influencing both immune reconstitution and alloHCT complications. As a result, microbiome-targeted strategies are being investigated to improve outcomes and include antibiotic stewardship, prebiotic and diet intervention, probiotics including fecal microbiota transfer (FMT) and postbiotics. These approaches are being investigated not only as a therapeutic intervention in particular for aGVHD, but also as preventive strategies.

Anti-T-lymphocyte globulin (ATLG) is commonly administered to reduce graft-versus-host disease (GVHD) in allogeneic stem cell transplantation (allo-SCT). However, the optimal ATLG dose in matched-sibling-donor (MSD) peripheral blood stem-cell transplantation (PBSCT) remains uncertain. We compared two ATLG doses (15 mg/kg vs. 30 mg/kg) in the MSD-PBSCT setting to assess allo-SCT outcomes. In this single-center retrospective study, we included 165 consecutive patients with hematologic malignancies who underwent MSD-PBSCT. Of these, 71 received 15 mg/kg ATLG (ATLG-15), and 94 received 30 mg/kg ATLG (ATLG-30). ATLG-15 was associated with earlier leukocyte (median 11 vs. 12 days, p = 0.004) and platelet engraftment (median 12 vs. 15 days, p = 0.0002). Moderate/severe chronic GVHD at 2 years was significantly higher with ATLG-15 (43% vs. 28%, p = 0.045), with no difference in OS, PFS, NRM, or CIR. In multivariable analysis, ATLG-30 was associated with improved GRFS (HR 0.47, p = 0.02). After propensity score matching, GRFS and all-grade cGVHD remained significantly better with ATLG-30 (p = 0.047), with a trend toward reduced moderate/severe cGVHD (p = 0.067). In AML/MDS patients not receiving TBI (n = 108), moderate/severe cGVHD remained lower with ATLG-30 (19% vs. 38%, p = 0.039). Our study suggests that ATLG-30 in MSD-PBSCT reduces moderate/severe cGVHD and improves GRFS.

SOS/VOD is a life-threatening complication of hematopoietic stem cell transplantation, especially in children, with incidences reaching up to 15-20%. Despite efforts, SOS/VOD remains unpredictable with significant morbidity and mortality. High-risk criteria are clearly defined, and the pediatric EBMT diagnostic criteria have improved sensitivity, reducing treatment delays and enhancing outcomes. A meta-analysis combining retrospective and prospective studies found a risk ratio of 0.30 for SOS/VOD with defibrotide (DF) prophylaxis. Additionally, two prospective trials were conducted: the pediatric prevention trial (NCT00272948) and the Harmony Trial (NCT02851407), involving adults and children, with primary outcomes of incidence and SOS/VOD-free survival, respectively. The trials produced conflicting results regarding the effectiveness of prophylactic DF. Despite significant limitations of the Harmony trial, a direct healthcare professional communication (DHPC) from the European Medicines Agency (EMA) advised against prophylactic DF. This recommendation has serious consequences for children, especially infants, who are among the most vulnerable groups receiving HSCT. Therefore, a panel of experts issued guidelines for children at high risk for SOS/VOD, in which DF prophylaxis is considered justified. These guidelines include a weighted scoring system based on all relevant high-risk criteria to predict SOS/VOD, supporting decisions regarding the use of prophylactic DF in children.

Background: Transplantation-associated thrombotic microangiopathy (TA-TMA) confers high mortality after allogeneic hematopoietic stem cell transplantation (HSCT). While characteristics are established in pediatric populations, real-world data on adults-particularly regarding standardized diagnostics and risk stratification-remain scarce.

Methods: This multicenter, retrospective cohort study analyzed 113 Asian adult patients diagnosed per international consensus criteria (median onset: 60 days post-HSCT). Outcomes were assessed using Jodele and harmonized risk tools, treatment responses, and biomarker profiles (cytokines, aGVHD, proteinuria, sC5b-9, D-dimer).

Results: The 6-month post-TMA and 1-year post-HSCT survival rates were 30.5% and 31.6%, respectively. High-risk classification by Jodele criteria (33.6% of patients) predicted significantly inferior 6-month survival (10.5% vs. 38.3%, p = 0.001). All patients met harmonized high-risk criteria. Immune reconstitution was severely impaired, especially in higher Jodele risk categories. Proteinuria (HR = 3.55, p = 0.027), multi-organ dysfunction syndrome (MODS; HR = 0.06, p < 0.001), and elevated IL-10 (HR = 0.24, p = 0.025) were independent predictors of reduced survival. Eculizumab yielded higher response rates than plasma exchange (57.1% vs. 31.3%).

Conclusion: This study validates harmonized diagnostic criteria and Jodele risk stratification in Asian adults with TA-TMA, and identifies proteinuria, MODS, and IL-10 as prognostic biomarkers. The universal high-risk classification underscores disease severity in this population. Early complement inhibition and cytokine-targeted therapies merit further investigation.