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Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are usually associated with poor outcomes, especially in high‐risk AML/MDS. Allogeneic hematopoietic stem cell transplantation (allo‐HSCT) is the only curative option for patients suffering from high‐risk AML/MDS. However, many patients relapse after allo‐HSCT. Novel therapy to prevent relapse is urgently needed. Both the BCL‐2 inhibitor venetoclax (VEN) and the hypomethylating agent decitabine (DEC) possess significant antitumor activity effects against AML/MDS. Administration of DEC has been shown to ameliorate graft‐versus‐host disease (GVHD) and boost the graft‐versus‐leukemia (GVL) effect post‐transplantation. We therefore conducted a prospective study (ChiCTR1900025374) to examine the tolerability and efficacy of a maintenance therapy of low‐dose decitabine (LDEC) plus VEN to prevent relapse after allo‐HSCT for high‐risk AML/MDS patients. Twenty patients with high‐risk AML (n = 17) or high‐risk MDS (n = 3) post‐transplantation were recruited. Approximately day 100 post‐transplantation, all patients received LDEC (15 mg/m2 for 3 d) followed by VEN (200 mg) on d 1‐21. The cycle interval was 2 mo, and there was 10 cycles. The primary end points of this study were rates of overall survival (OS) and event‐free survival (EFS). The secondary endpoints included adverse events (AEs), cumulative incidence of relapse (CIR), nonrelapse mortality (NRM), incidences of acute GVHD (aGVHD) and chronic GVHD (cGVHD), and incidences of viral infection after allo‐HSCT. Survival outcomes were assessed using Kaplan‐Meier analysis. The median follow‐up was 598 (149‐1072) d. Two patients relapsed, 1 died, and 1 is still alive after the second transplant. The 2‐y OS and EFS rates were 85.2% and 84.7%, respectively. The median 2‐y EFS time was 525 (149‐1072) d, and 17 patients still had EFS and were alive at the time of this writing. The most common AEs were neutropenia, anemia, thrombocytopenia, neutropenic fever, and fatigue. Grade 2 or 3 AEs were observed in 35% (7/20) and 20% (4/20) of the patients, respectively. No grade >3 AEs were observed. aGVHD (any grade) and cGVHD (limited or extensive) occurred in 55% and 20% of patients, respectively. We conclude that LDEC + VEN can be administered safely after allo‐HSCT with no evidence of an increased incidence of GVHD, and this combination decreases the relapse rate in high‐risk AML/MDS patients. This novel maintenance therapy may be a promising way to prevent relapse in high‐risk AML/MDS patients. The results of the current study suggest that maintenance treatment with LDEC combined with VEN introduced nearly 3 mo after allo‐HSCT is efficacious, with an acceptable toxicity profile and impressive long‐term disease control.

Wnt‐Fzd signalling pathway plays a critical role in acute myeloid leukaemia (AML) progression and oncogenicity. There is no study to investigate the prognostic value of Wnt and Fzd gene families in AML. Our study screened 84 AML patients receiving chemotherapy only and 71 also undergoing allogeneic haematopoietic stem cell transplantation (allo‐HSCT) from the Cancer Genome Atlas (TCGA) database. We found that some Wnt and Fzd genes had significant positive correlations. The expression levels of Fzd gene family were independent of survival in AML patients. In the chemotherapy group, AML patients with high Wnt2B or Wnt11 expression had significantly shorter event‐free survival (EFS) and overall survival (OS); high Wnt10A expressers had significantly longer OS than the low expressers (all P < .05), whereas, in the allo‐HSCT group, the expression levels of Wnt gene family were independent of survival. We further found that high expression of Wnt10A and Wnt11 had independent prognostic value, and the patients with high Wnt10A and low Wnt11 expression had the longest EFS and OS in the chemotherapy group. Pathway enrichment analysis showed that genes related to Wnt10A, Wnt11 and Wnt 2B were mainly enriched in ‘cell morphogenesis involved in differentiation’, ‘haematopoietic cell lineage’, ‘platelet activation, signalling and aggregation’ and ‘mitochondrial RNA metabolic process’ signalling pathways. Our results indicate that high Wnt2B and Wnt11 expression predict poor prognosis, and high Wnt10A expression predicts favourable prognosis in AML, but their prognostic effects could be neutralized by allo‐HSCT. Combined Wnt10A and Wnt11 may be a novel prognostic marker in AML.

Background Uric acid (UA) level is of the valuable signs of inflammation. However, the role of UA in the outcomes of hematopoietic stem cell transplantation (HSCT) such as GVHD and patients’ overall survival is still a matter of debate. In this study, we aimed to evaluate the relationship between UA levels and GVHD incidence and overall survival in allogeneic HSCT patients. Methods A total of 201 patients who were admitted for allogeneic transplantation at Taleghani hospital, Tehran, Iran, were considered for retrospective analysis. Serum UA levels from 1 week before transplantation until 2 weeks after transplantation were used to determine thresholds and find out the association of serum UA levels with GVHD and overall survival. Results We showed that the determined thresholds using receiver operating characteristic curves have poor predictive value for GVHD and overall survival. The patients with serum UA higher than 3.4 mg/dL had 37% lower odds of GVHD incidence and 35% lower hazard of death than patients with UA lower than 3.4 mg/dL. Conclusion Our results indicated that serum UA levels lower than 3.4 mg/dL could significantly increase the incidence of GVHD and hazard of death. The antioxidant functions of UA could explain the lower incidence of GVHD in hyperuricemic patients. However, the inconsistencies of the previous studies require further investigation to elucidate the role of UA in the prediction of GVHD.

Organ failure, including; liver toxicity, renal failure, and neurotoxicity, are frequent complications following HSCT which can affect the transplant outcome, morbidity, and mortality of allo-HSCT recipients: A retrospective study of 206 allo-HSCT patients was conducted to determine the frequency of organ failure and overall survival in patients receiving allo-HSCT. Liver toxicity, renal failure, and neurotoxicity were diagnosed according to clinical and laboratory records pre and post-allo-HSCT. A total of 33 patients (16%) developed organ failure within 200 days after allo-HSCT. Liver toxicity was diagnosed in 12% of patients, and the median time of its occurrence was 22 days (range: 0-207 days) post-allo-HSCT. Two percent (6 of 206) of allo-HSCT recipients presented renal failure. Renal failure was developed within the median time of 33 days (range: 5-88 days). Neurological involvement occurred in 0.9% of patients. Among 206 patients, the frequency of complications such as veno-occlusive disease (VOD) and graft-versus-host disease (GVHD) was 1.4% and 16.01%, respectively. One-year overall survival of patients who had organ failure was 24%, and the mean survival determined 329±99.58 days. Three-month overall survival of patients who developed liver injury and renal failure were 78% and 33%, respectively. Organ failure remains a common complication in patients who received allo-HSCT. Patients with GVHD and two or multi-organ involvement seem to have lower overall survival.

[This corrects the article DOI: 10.3389/fmed.2025.1626325.].

This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine and donor lymphocyte infusion (DLI) in treating patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-six AML patients who relapsed after allo-HSCT were enrolled and treated with venetoclax plus azacitidine and DLI. Complete remission with incomplete recovery (CRi), partial remission (PR), and objective remission rate (ORR) were assessed, and then event-free survival (EFS) and overall survival (OS) were evaluated. Besides, adverse events were documented. Additionally, whole exome sequencing was performed in bone marrow samples. The CRi, PR, and ORR rates were 26.9%, 34.6%, and 61.5%, respectively. The median time of EFS and OS was 120 (95% CI: 71–610) days and 284.5 (95% CI: 81–610) days, respectively. The most common adverse events were hematologic system adverse events including agranulocytosis, anemia, and thrombocytopenia, while the adverse events of other systems were relatively less and milder. In addition, no serious adverse events existed. Of note, there were 6 (23.1%) patients who developed GVHD. As for gene mutation, 49 mutated genes were found, which were categorized as first-, second-, and third-class mutations, and then further analysis revealed that the first-class mutations were not correlated with EFS or OS. Additionally, the most frequent mutated genes were FLT3, CEBPA, DNMT3A, KIT, KRAS, and NRAS. Venetoclax plus azacitidine and DLI is efficient and tolerant in treating patients with relapsed AML after allo-HSCT, implying this combined therapy as a potential treatment option in the studied patients.

Growing evidence suggests that highly intestinal microbiota diversity modulates host inflammation and promotes immune tolerance. Several studies have reported that patients undergoing allo-HSCT have experienced microbiota disruption that is characterized by expansion of potentially pathogenic bacteria and loss of microbiota diversity. Thus, the primary aim of this meta-analysis was to determine the association of intestinal microbiota diversity and outcomes after allo-HSCT, and the secondary aim was to analyze the associations of some specific microbiota abundances with the outcomes of allo-HSCT. Electronic databases of Pubmed, Embase, Web of Science, and Cochrane Library were searched from inception to August 2023, and 17 studies were found eligible. The pooled estimate suggested that higher intestinal microbiota diversity was significantly associated with overall survival (OS) benefit (HR = 0.66, 95% CI: 0.55–0.78), as well as decreased risk of transplant-related mortality (HR = 0.56, 95% CI: 0.41–0.76), and lower incidence of grade II-IV aGVHD (HR = 0.41, 95% CI: 0.27–0.63). Furthermore, higher abundance of Clostridiales was associated with a superior OS (HR = 0.40, 95% CI: 0.18–0.87), while higher abundance of Enterococcus (HR = 2.03, 95% CI: 1.55–2.65), γ-proteobacteria (HR = 2.82, 95% CI: 1.53–5.20), and Candida (HR = 3.80, 95% CI: 1.32–10.94) was an adverse prognostic factor for OS. Overall, this meta-analysis highlights the protective role of higher intestinal microbiota diversity on outcomes after allo-HSCT during both pre-transplant and post-transplant periods. Some specific microbiota can be useful in the identification of patients at risk of mortality, offering new tools for individualized pre-emptive or therapeutic strategies to improve allo-HSCT outcomes.

Cellular based therapies, such as bispecific T-cell engagers (TCE), have changed the landscape of myeloma treatment, but to the present day little is known about the use of these therapies in patients with prior allogeneic hematopoietic stem cell transplantation (allo-HSCT). In this case report, we present a patient with multi-refractory multiple myeloma (MM), who relapsed after allo-HSCT and anti-SLAMF-7-CART-cell-therapy and was ultimately successfully treated with teclistamab, a BCMA-directed TCE, and we discuss theoretical considerations based on present literature about possible underlying immunological mechanisms, that might have contributed to a long enduring treatment response.

Uncommon manifestations of graft-versus-host disease are a clinical challenge due to the absence of clear diagnostic criteria and treatment strategies. Herein, we present the case of a patient with neurological manifestations of GVHD that successfully resolved after extracorporeal photopheresis.