Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for severe aplastic anemia (SAA), with donor sources including matched sibling donors (MSDs), haploidentical donors (HIDs), and unrelated donors (URDs). However, the optimal criteria for donor selection remain undefined. We performed a multicenter retrospective study of 795 consecutive SAA patients who underwent allo-HSCT between 2012 and 2020 across 11 transplant centers in China. The overall survival (OS), failure-free survival (FFS), and GVHD-free/FFS (GFFS) rates were 85.2%, 83.6%, and 76.1%, respectively. Donor-related variables including relationship, age, sex match, blood type, and HLA mismatches were evaluated. Multivariable Cox regression identified donor age ≥50 years as an independent risk factor for inferior GFFS (HR = 2.13), OS (HR = 2.09), and FFS (HR = 2.18) (all P < 0.001). To directly compare the prognostic weight of donor age versus HLA compatibility, we stratified patients into four subgroups according to donor type (HID vs. MSD) and donor age (<50 vs. ≥50 years). Kaplan-Meier analysis with log-rank testing revealed that recipients of haploidentical grafts from younger donors achieved superior OS and FFS compared with those transplanted from older HLA-matched sibling donors. These findings demonstrate that donor age has a greater influence on transplant outcomes than HLA matching. With continuous improvements in haploidentical transplantation techniques, selecting younger haploidentical donors may represent a more favorable strategy than choosing older matched sibling donors.

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease with limited treatment options. The COMMODORE 2 study demonstrated that the novel C5 inhibitor crovalimab had comparable safety and non-inferior efficacy to eculizumab. We evaluated the safety and efficacy of crovalimab compared with eculizumab in the Chinese subpopulation of the global COMMODORE 2 study. Adult patients with PNH without previous complement inhibitor therapy were randomized (2:1) to crovalimab or eculizumab for 24 weeks. The co-primary endpoints were the proportions of patients achieving hemolysis control from Weeks 5–25 and those with transfusion avoidance from baseline to Week 25. The secondary endpoints included the proportion of patients with breakthrough hemolysis and hemoglobin stabilization from baseline to Week 25 and the mean change from baseline in FACIT-Fatigue score at Week 25. Safety data were assessed from baseline to the clinical cut-off (16 November 2022). The demographic and baseline characteristics of the 81 patients included (eculizumab: 27; crovalimab: 54) were well-balanced. In the crovalimab and eculizumab arms, respectively, hemolysis control was achieved in 88.3% and 86.8%, transfusion avoidance in 72.2% and 74.1%, hemoglobin stabilization in 72.2% and 70.4%, and breakthrough hemolysis in 5.6% and 11.1%. The FACIT-Fatigue score improvement was greater with crovalimab. Adverse events (81.5% vs. 88.9%) and grade 3–5 adverse events (24.1% vs. 33.3%) were less frequent with crovalimab. Over 24 weeks, 91% of patients achieved complete terminal complement inhibition with crovalimab. Crovalimab demonstrated at least comparable treatment performance and acceptable safety in Chinese patients with PNH. Clinical trial registration ClinicalTrials.gov identifier NCT04434092 (study registration was first posted on 16th June 2020).

Currently, there is very limited large-scale real-world data on the use of total marrow irradiation (TMI) as conditioning for allogeneic hematopoietic stem cell transplantation (allo-HSCT). The primary objective of this study was to evaluate the real-world feasibility, efficacy, and safety of TMI-based conditioning in a large multicenter cohort. We retrospectively included consecutive patients undergoing allo-HSCT with TMI-based conditioning across four Chinese centers (2017-2024). The primary endpoint was overall survival (OS); secondary endpoints included disease-free survival (DFS), graft-versus-host disease-free/relapse-free survival (GRFS), nonrelapse mortality (NRM), graft-versus-host disease (GVHD), and safety. Among 205 patients, acute lymphoblastic leukemia (ALL) was the predominant diagnosis (81.5%). With a median follow-up of 19.3 months among survivors, 2-year OS, DFS, and GRFS were 71.7%, 60.0%, and 37.8%, respectively. One-year cumulative incidences of relapse and NRM were 20.2% and 13.8%. Day-100 grade II-IV acute GVHD occurred in 32.9%, and 1-year moderate-to-severe chronic GVHD in 19.1%. In multivariable analyses, acute myeloid leukemia (AML) diagnosis, haploidentical donor, and Eastern Cooperative Oncology Group (ECOG) performance status >1 were associated with inferior outcomes. Exploratory dose-stratified analyses were performed. Severe toxicities within 100 days were infrequent, predominantly infections (21.46%). In this large multicenter cohort, TMI-based conditioning demonstrated real-world feasibility with encouraging survival and manageable safety outcomes.

Acute myocardial infarction (MI) is a relatively rare but life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Information regarding the clinical characteristics, outcomes, and prognostication of post-transplant MI is lacking. We conducted a nationally representative cohort study at 34 centers in China. Patients with MI were retrospectively identified among those who underwent allo-HSCT. The diagnosis and classification of MI were reviewed according to established guidelines. One hundred thirteen patients were analyzed, including 23 patients with T1MI, 87 patients with T2MI, and three patients with T3MI. Patients with T2MI had a significantly higher mortality rate. Thrombotic microangiopathy (TMA) frequently coexisted with T2MI and adversely affected the overall survival. Disease relapse or progression, a platelet count <20 × 109/L, active TMA at MI onset, and Killip class 3-4 were identified as independent risk factors for 2-month mortality. We divided these patients into a low-risk group (without risk factors), an intermediate-risk group (1-2 risk factors), and a high-risk group (3-4 risk factors). Significantly different 2-month mortality rates were observed across these groups (11.1 %, 59.3 %, and 100.0 %, respectively). Available angiographic imaging data and antiplatelet therapy after MI onset may be associated with improved outcome, but the survival benefits and optimized medication use in patients with post-transplant MI require further validation. These findings may facilitate refined monitoring and management strategies of MI in the post-transplant population.

Hematopoietic stem cell transplantation (HSCT) remains an effective treatment for severe aplastic anemia (SAA), but the optimal conditioning regimen has yet to be established. This study aimed to evaluate the safety and efficacy of a conditioning regimen consisting of fludarabine (Flu), cyclophosphamide (Cy), and porcine anti-lymphocyte globulin (p-ATG). This prospective single-arm clinical trial enrolled 48 SAA patients who underwent HLA-matched sibling transplantation. The conditioning regimen consisted of p-ATG (120 mg/kg), Cy (120 mg/kg), and Flu (120 mg/m²). All patients achieved neutrophil engraftment (median time of 12 days), with 98

Cytomegalovirus (CMV) infection is a prevalent complication among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, posing significantly impact on clinical outcomes and healthcare costs. This study aims to assess the clinical and economic burden of CMV infection in hospitalized adult allo-HSCT recipients in China. A retrospective analysis was conducted using electronic medical records from two tertiary hospitals in China. A total of 1977 patients who underwent allo-HSCT while hospitalized between 1 January 2016 and 31 December 2021 were included in the study and followed up for 180 days. Data on CMV clinical characteristics, hospitalization duration, complications, and healthcare costs were collected and analyzed. CMV infection/disease was observed in 542 patients during the hospitalization of the allo-HSCT procedure, leading to longer hospital stays (69.36 [SD 23.15] vs 37.77 [SD 13.22] days, p < 0.001) and increased medical expenses (US$60,152.98 [SD 30,190.82] vs $34,430.88 [17,723.65], p < 0.001). Patients with CMV infection/disease had higher rates of complications, such as graft-versus-host disease (52.21% vs 19.65%, p < 0.001), and required more extensive use of granulocyte colony-stimulating factor, red blood cell and platelet transfusion, antifungals drugs, and antibacterials drugs. CMV infection/disease imposes significant clinical and economic burdens on hospitalized allo-HSCT recipients in China. Effective monitoring and prevention strategies are essential to mitigate these impacts, improve patient outcomes, and reduce healthcare costs.

Introduction: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal disorder of hematopoietic stem cells characterized by hemolysis, bone marrow failure, and thrombosis. NTQ5082, a novel oral selective inhibitor of complement factor B (CFB) with a long half life enabling once daily dosing, is currently under clinical development for PNH. Methods: This was a multicenter, open-label, phase 2 study conducted in China (NCT06764303). Adult patients aged ≥18 years with complement inhibitor-naïve PNH and signs of active hemolysis were eligible for inclusion. All patients had to be vaccinated against Neisseria meningitidis and Streptococcus pneumoniae ≥14 days before the first treatment of NTQ5082. Patients were randomized 1:1 to two cohorts. Patients in the cohort A started receiving NTQ5082 100 mg QD on Day 1 for 2 weeks. If LDH levels on Day 15 were not reduced by ≥40% from baseline, the dose was up-titrated to 300 mg QD for the remainder of the 12-week period. Patients in the cohort B received 200 mg QD for the entire 12 weeks. After the 12-week treatment period, if there were no safety issues, patients entered a long-term extension study. If failed to derive meaningful clinical benefit—defined as either a <10 g/L rise in Hb from baseline or continued transfusion dependence—entered a dose-tapering period, followed by a safety follow-up. The primary endpoint was the proportion of patients who achieved an increase in Hb concentration of ≥20 g/L compared to baseline at Week 12. Secondary endpoints included proportions of patients with Hb ≥120 g/L, patients without RBC transfusions after the first 4 weeks of dosing, and mean changes from baseline in Hb, reticulocyte count, LDH, total/indirect bilirubin and FACIT-F score. Results: A total of 25 patients (mean age 43.8 years, 13 female) were randomized to either cohort A (n=12) or B (n=13). At baseline, all patients had signs of active hemolysis (mean LDH: 1701.1 U/L) and clinically significant anemia (mean Hb: 72.7 g/L), with approximately 52% patients being transfusion-dependent. On Day 15 after treatment with NTQ5082, no patients in the cohort A required dose up-titration. Treatment with NTQ5082 resulted in a clinically meaningful improvement in Hb levels in both the cohort A (least squares [LS] mean: 53.8 g/L, 95% CI: 42.7-65.0 g/L) and the cohort B (LS mean: 49.6 g/L, 95% CI: 40.6-58.6 g/L). All treated patients remained transfusion-free up until at least Week 12. The mean percentage reductions in LDH levels from baseline by 85.9% (95% CI: 82.7%-89.1%) and 82.2% (95% CI: 77.5%-86.8%) in cohort A and cohort B, respectively. At Week 12, all 25 patients in the two cohorts achieved the primary endpoint with increases in Hb concentrations by ≥20 g/L compared with baseline. And the percentage of patients achieving Hb ≥120 g/L was 50% (6/12) in the cohort A, and 61.5% (8/13) in the cohort B at Week 12, which represents a high level among the CFB inhibitors with disclosed clinical data. Meanwhile, treatment with NTQ5082 showed consistent improvements for other markers of hemolysis. The mean (SD) percentage change from baseline in reticulocyte count was -42.6% (14.3%) in the cohort A and -46.5% (23.2%) in the cohort B. Mean (SD) percentage change from baseline in total bilirubin levels was -53.7% (13.2%) and -42.5% (29.9%), and the change in indirect bilirubin was -58.6% (19%) and -47.5% (32.1%) in the two cohorts, respectively. Furthermore, most patients showed a clinically meaningful improvement in their FACIT-Fatigue scores from baseline, with mean (SD) changes of 9.2 (7.9) points in the cohort A and 9.2 (8.8) points in the cohort B. NTQ5082 was generally well tolerated. All treatment-related adverse events (TRAEs) were mild to moderate in severity. The most common TRAEs were upper respiratory infections (16.7% in the cohort A) and headache (16.7% in the cohort A and 7.7% in the cohort B). Conclusion: NTQ5082 monotherapy at 100 mg or 200 mg once daily led to rapid and durable hemolysis control and transfusion-free improvement in Hb levels in complement inhibitor-naïve PNH patients. Both dosages of NTQ5082 were well tolerated. With its once-daily dosing regimen, robust improvement in Hb, and a favorable safety profile, NTQ5082 is positioned as a highly competitive CFB inhibitor for the treatment of PNH.

BACKGROUND:Acute graft-versus-host disease (aGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of macrophages as proficient antigen-presenting cells in aGVHD is a prominent area of investigation in contemporary research. The association between long noncoding RNA nuclear enriched abundant transcript 1 (lncRNA NEAT1) and the macrophage function is of significant interest. However, the role of lncRNA NEAT1 in aGVHD needs to be further explored. METHODS:Peripheral blood mononuclear cells (PBMCs) were collected from patients with or without aGVHD (non-aGVHD) after allo-HSCT. RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were transduced with NEAT1 lentiviral vector or transfected with NEAT1 small interfering RNA to change the expression level of lncRNA NEAT1. Finally, an aGVHD mouse model was established to evaluate the role of JNK inhibitor or NLRP3 inhibitor in aGVHD. RESULTS:Compared with non-aGVHD patients, lncRNA NEAT1 was significantly up-regulated in the PBMCs of aGVHD patients. ROC and AUC analysis confirmed that the expression of lncRNA NEAT1 was correlated with the occurrence of aGVHD. The overexpression of lncRNA NEAT1 in RAW264.7 could significantly promote the proliferation, migration, and differentiation into M1 macrophages. Knockdown of lncRNA NEAT1 could significantly decrease the proportion of M1 macrophages, regulate pro-inflammatory cytokines secretion, and affect the JNK/NLRP3 pathway in lipopolysaccharides (LPS)-induced BMDMs. Correspondingly, JNK and NLRP3 inhibitors reduced LPS-induced pro-inflammatory responses in macrophages. Furthermore, JNK and NLRP3 inhibitors regulated macrophage polarization and improved symptoms in aGVHD mice. CONCLUSIONS:The aforementioned data suggest that lncRNA NEAT1 potentially plays a significant role in macrophage polarization and the secretion of inflammatory cytokines through its modulation of the JNK/NLRP3 pathway. Consequently, this study establishes a foundation for the development of novel therapeutic approaches targeting aGVHD.

Introduction Acute myocardial infarction (MI) is a rare but life-threatening complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several transplant-related conditions are recognized as cardiovascular risk factors, whether and how these factors are associated with the occurrence of post-transplant acute MI (PT-MI) remain unclear. The management of MI among transplant recipients is challenging given the frequent occurrence of anemia and increased bleeding risk, and prognostic information in this population is limited. We conducted a multicenter cohort study to investigate the clinical manifestations, causes, and outcomes in patients with PT-MI. Methods Patients who developed acute MI after transplantation were retrospectively identified among those receiving allo-HSCT between April 2015 and March 2025 from 43 centers in China. The diagnosis and classification of MI were reviewed according to the 4th universal definition. Potential causes of type 2 MI (T2MI) were classified according to the 2020 ESC Guidelines. Categorical variables were compared using the Fisher’s exact test. Continuous variables were compared using the Mann-Whitney U test and were dichotomized according to cutoff values with the optimal Youden index if applicable. Candidate predictors for 2-month mortality after PT-MI (a univariate logistic p value of <0.1) were included in the multivariate analysis using a forward stepwise logistic regression model. Variables remaining in the final model with a p value of <0.05 were determined to be independent prognostic risk factors. The study protocol was approved by the central institutional review board of Peking University People's Hospital. Results One hundred thirteen (113) patients with PT-MI were identified, including 23 (20.4%) with type 1 MI (T1MI), 87 (77.0%) with T2MI, and three (2.7%) with type 3 MI. Patients developed PT-MI at a median age of 52.5 (IQR, 40.75-60) years, and 84 of them were male. The median time of onset was significantly shorter for patients with T2MI than for those with T1MI (121 vs. 425 days after HSCT, p = 0.005). Patients with T2MI had a significantly higher mortality rate than those with T1MI (73.6% vs. 24.8%, p = 0.001). The most frequently reported potential causes of T2MI included anemia (93.1%), sepsis (29.9%), and hypoxemia (29.9%). Concomitant thrombotic microangiopathy (TMA) was frequently observed in patients with T2MI (49.4%). In these patients, MI was among the early end-organ manifestations of TMA (median time of onset: three days after TMA diagnosis for MI, one day for acute kidney injury, 3.5 days for CNS involvement, one day for gastrointestinal bleeding, and five days for polyserositis). Patients complicated with TMA showed poor overall survival (log rank p < 0.001). Among patients with T1MI and T2MI, 62 (56.4%) died within two months of MI onset. Disease relapse or progression (p = 0.004), a platelet count of < 20×109/L (p = 0.019), active TMA at MI onset (p = 0.016), and Killip class 3-4 (p < 0.001) were identified as independent risk factors for 2-month mortality. We divided these patients into a low-risk group (without risk factors, n = 27), an intermediate-risk group (1-2 risk factors, n = 59), and a high-risk group (3-4 risk factors, n = 24). Significantly different 2-month mortality rates were observed across the three risk groups (11.1%, 59.3%, and 100.0%, respectively). The median survival was also well separated between patients in the intermediate-risk group and those in the high-risk group (29 vs. 3 days, respectively). ConclusionsPT-MI is rare but potentially fatal. Compared with T1MI, T2MI is more common and has significantly worse outcomes. TMA is frequently complicated with T2MI and adversely affects the overall survival. Prognostic risk factors were identified, and a preliminary prognostication was explored for patients with PT-MI.

Metabolic reprogramming is a key focus of targeted therapies in acute myeloid leukemia (AML). The mitochondrial sirtuin SIRT5 removes succinyl groups from specific lysines and impacts cell metabolism, but its role in AML tumorigenesis has not been extensively explored. A recent study highlighted that SIRT5 regulates AML cell activity by modulating glutamine metabolism, but its molecular targets in AML remain unclear. This study aims to identify the substrates of SIRT5 in AML. It was found that a total of 83 proteins with 121 lysine (K) residues showed increased succinylation after SIRT5 knockdown, as determined by succinylome analysis of MOLM-13 cells. SIRT5 was validated to interact with HADHA, a key molecule in the fatty acid oxidation pathway. Knockdown of SIRT5 resulted in hypersuccinylation and reduced enzymatic activity of HADHA. Mimetic mutations of lysine indicated that SIRT5 desuccinylates HADHA at K644. Inhibiting SIRT5 or HADHA increased sensitivity to venetoclax (VEN) in both VEN-sensitive and VEN-resistant cell lines. SIRT5 knockdown enhanced VEN-mediated suppression of mitochondrial metabolism and improved the survival of AML-transplanted NSG mice when combined with VEN. This study reveals the role of SIRT5 in AML metabolic regulation and provides valuable insights for developing SIRT5-targeted drugs and combination therapies with metabolic inhibitors.

Introduction: Delayed platelet (PLT) recovery is a common complication following haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Improved platelet recovery may reduce the need for transfusions and improve transplant outcomes. Thrombopoietin receptor agonists (TPO-RAs) have been used in various types of thrombocytopenic disorders, including prolonged thrombocytopenia after allo-HSCT. Our previous retrospective study revealed the safety and efficacy of avatrombopag, a TPO-RA, in the treatment of primary delayed platelet engraftment and secondary failure of platelet engraftment after haplo-HSCT. However, prospective evidence is limited. In this study, we performed a randomized, double-blind, multicenter, placebo-controlled trial to investigate the safety and efficacy of avatrombopag in enhancing platelet recovery after haplo-HSCT. This study is registered at ClinicalTrials.gov as NCT06202625. Methods: This prospective multicenter trial were performed in 10 centers in China and included patients 18–65 years old who underwent haplo-HSCT. Patients were excluded if they had active infection; liver or kidney injury (ALT or AST>3 ULN, or total Bil>2 ULN, or Ccr<50 mL/min); a history of arteriovenous thrombosis or cardiovascular disease; a history of drug use to promote platelet production two weeks before enrollment, including but not limited to TPO-RAs; or secondary or multiple HSCTs. Patients known to be allergic to avatrombopag and any of its excipients were also excluded. The enrolled patients received avatrombopag 20 mg/day or placebo on a 1:1 randomization schedule starting on Day 7. The primary objective was to assess the proportion of participants who achieved a PLT count of ≥50×10⁹/L and remained independent of PLT transfusion for ≥7 consecutive days by Day 60. Key secondary endpoints included: the proportions of participants with a PLT count of ≥50×10⁹/L and ≥20×10⁹/L on Day 30; and the proportion of participants with a PLT count of ≥100×10⁹/L on Day 60 who remained free from PLT transfusion for ≥7 consecutive days. Avatrombopag 20 mg/d or placebo was taken orally from +D7 after haplo-HSCT until reaching the adjustment indication or to Day 60 after haplo-HSCT. Results: From March 1st, 2024, to July 21st, 2025, 100 patients (50 in the avatrombopag group and 50 in the control group) were included. The median time to platelet recovery (>20×109/L) was 13 days for patients treated with avatrombopag and 14 days for controls (P= 0.087). Compared with patients in the control group, significantly more patients in the avatrombopag group achieved a PLT level ≥50×109/L without the need for PLT transfusion for ≥7 consecutive days by Day 30 (78.0% vs. 56.0%, P=0.019). On Day 60, 74.0% of patients in the avatrombopag group had a platelet count of ≥50×10⁹/L and did not require platelet transfusion for 7 or more consecutive days, whereas 60.0% of patients in the control group did (P=0.164). The proportion of participants whose PLT level ≥20×109/L or ≥100×109/L on Day 60, PLT≥50×109/L or PLT≥100×10^9/L on Day 90 after haplo-HSCT independent of PLT transfusion for ≥7 consecutive days were comparable between the avatrombopag group and the control group . No patients in either group experienced grade ≥3 adverse events. The number of platelet transfusions received, overall survival, progression-free survival, GVHD rate, relapse rate, and nonrelapse mortality were similar between the two groups. Conclusion: Overall, this represents the first randomized, double-blind, multicenter, placebo-controlled trial to confirm that avatrompag is effective and safe in improving platelet recovery after haplo-HSCT.

BackgroundThe emergence of carbapenem-resistant organisms (CROs) poses a major challenge to clinical infection control in hospitals. Patients undergoing hematopoietic stem cell transplants (HSCTs) infected with CROs are at high risk of mortality. Proactive screening of HSCT patients for CRO colonization may enable early and accurate preemptive anti-CRO therapy, reduce the probability of secondary infections, and contribute to infection prevention and control measures. However, screening CRO colonization with stool/rectal swab culture and sensitivity has a low positivity rate with a long turnaround time, which limits the effectiveness of the interventions. A more rapid and accurate method to detect CRO colonization is urgently needed. Xpert Carba-R assay provides a rapid and accurate detection of carbapenemase types, enabling targeted anti-infective therapy selection based on the identified resistance mechanism.MethodsWe conducted a historically controlled prospective study at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between August 2021 and July 2022. The study population comprised adult HSCT patients (≥18 years old) who received preemptive anti-CRO therapy based on rectal culture and Xpert Carba-R screening during this period. A total of 381 patients who underwent HSCT from August 2020 to July 2022 were included in the study, and CRO colonization screening was performed on admission and weekly thereafter. In the historic control group from August 2020 to July 2021, HSCT patients were screened only by rectal swab traditional CRO culture, and CRO colonization was determined if the rectal culture was positive. In the study group from August 2021 to July 2022, two rectal swab specimens were collected from HSCT patients for both CRO traditional culture (RS-culture) and Xpert Carba-R testing (RS-Carba-R). CRO colonization was determined if either of the screening methods was positive. CRO-active antibiotics were immediately provided on the first febrile episode of neutropenia (FN) in CRO-colonized patients. Clinical outcome data for the CRO monthly colonization rate and anti-infection efficiency were collected and contrasted between the two groups.ResultsIn the historic group, 47 out of 197 patients (23.9%) were identified as colonized with CRO, detected only by RS-culture. In the study group, 41 out of 184 patients (22.3%) were identified as colonized with CRO, detected by either RS-culture or RS-Carba-R; among them, Escherichia coli was the most common CP-CRO strain, and the most prevalent carbapenemase type was NDM. This indicated a slightly lower annual detection rate of CRO gut colonization in the study group compared to the historic group, but no significant difference was observed (22.3% vs. 23.9%, p = 0.715). The incidence of CRO-related bloodstream infections (CRO-BSI) was significantly lower in the study group compared to the historic group (4.8% vs. 25.5%, p = 0.012), and the CRO-related mortality in colonized patients decreased from 19.4% in the historic group to 2.4% in the study group (p = 0.046). The monthly detection rate of CRO gut colonization by RS-culture in the historic group remained steady, with no significant fluctuation (19.7% in the first month and 18.8% in the last month). In contrast, the monthly detection rate of CRO gut colonization by either RS-culture or RS-Carba-R in the study group was higher in the first month compared to the historic group (21.2% in August 2021 vs. 18.8% in July 2021). However, a gradual decline in the monthly detection rates of CRO gut colonization by RS-culture and/or RS-Carba-R was observed in the study group, dropping from 21.2% in the first month to 2.9% in the last month. The univariate and multivariate analyses indicated that the study group had a shorter length of hospitalization (OR = 0.94, 95% CI 0.88–0.99, p = 0.038) and CRO-related mortality (OR = 0.12, 95% CI 0.01–0.75, p = 0.021) than the historic group.ConclusionsOur study showed a positive effect of more rapid CRO colonization screening using rectal swabs with Xpert Carba-R and culture, which can guide potent CRO preemptive therapy for subsequent infections based on the detected carbapenemase mechanism, thereby reducing mortality and the spread of CRO infection in HSCT patients.Clinical Trial Registrationchictr.org, identifier ChiCTR2100041976.

BackgroundRelevant studies have demonstrated the poor treatment outcomes and prognosis for double-expressor diffuse large B cell lymphoma (DE-DLBCL) in the rituximab era. Zanubrutinib plus R-CHOP (rituximab, cyclophosphamide, doxorubicin/liposomal doxorubicin, vincristine, prednisone; ZR-CHOP) has shown efficacy in untreated non-GCB DLBCL patients with extranodal involvement. However, its efficacy in newly diagnosed DE-DLBCL remains uncertain.ObjectiveThis retrospective study sought to assess the efficacy and safety of ZR-CHOP in comparison to R-CHOP in treatment-naïve patients with DE-DLBCL.MethodThis study assessed 78 patients with newly diagnosed DE-DLBCL who were admitted between June 2017 and January 2024. Among them, 55 patients received the R-CHOP regimen, while 23 patients were treated with the ZR-CHOP regimen. The clinical characteristics were well balanced between the two groups.ResultsThe complete response rates (CRR) were higher in the ZR-CHOP group than the R-CHOP group, regardless of whether patients completed 4 or 6 treatment cycles (P= 0.019; P= 0.025). ORR in the ZR-CHOP group showed a higher trend than that in the R-CHOP group (P= 0.624; P= 0.219). The median follow-up period was 23.3 months, and the predicted median progression free survival (PFS) in the R-CHOP group was 22.8 months, whereas the median PFS in the ZR-CHOP group was not reached. The 1-, 2-, and 3-year PFS rates in the ZR-CHOP group showed a beneficial trend compared with the R-CHOP group, but there was no statistical difference (P= 0.072). However, the PFS of the ZR-CHOP group was longer than that of the R-CHOP group in patients with Ki67 index >75% (P= 0.034) and p53 expression >50% (P= 0.0033). The predicted median overall survival (OS) in the ZR-CHOP and R-CHOP groups were not reached. The 1-, 2- and 3-year OS rates were not significantly different between the two groups (P= 0.29). The most common adverse event in both groups was hematotoxicity, but there was no significant difference in the incidence of all adverse events between the two groups.ConclusionFirst-line treatment with the ZR-CHOP regimen improved CRR in the untreated patients with DE-DLBCL and prolonged PFS in the Ki67 index >75% subgroup and the p53 expression >50% subgroup.

Objective: Mucosa-associated lymphoid tissue (MALT) lymphoma represents a distinct subtype among marginal zone lymphomas (MZL). The stomach is the most frequently involved site in MALT lymphoma, but the disease can occur in mucosa-associated lymphoid tissue of all organs, including the orbit, lung, and salivary glands. Current clinical studies indicate BTK inhibitors exhibit promising efficacy in MZL. As a novel BTK inhibitor, Orelabrutinib reduces adverse reactions associated with off-target effects and improves patient tolerance. Nevertheless, clinical data on Orelabrutinib combined with Anti-CD20 monoclonal antibody for treating MALT lymphoma remains insufficient. Therefore, this study aims to evaluate the effectiveness and safety of the Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen in treating MALT lymphoma through a single-center retrospective analysis. Methods: Clinical data of MALT lymphoma patients diagnosed and treated with the Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology between June 2023 and April 2025 were retrospectively analyzed. Treatment efficacy was assessed based on PET-CT/CT imaging or gastrointestinal endoscopy results before and after medication. Primary endpoints included: objective response rate (ORR), complete response rate (CR), progression-free survival (PFS), overall survival (OS), and incidence of adverse events. Results: Baseline Characteristics By April 2025, this study enrolled 12 evaluable MALT lymphoma patients, comprising 4 males and 8 females. The median age was 61 years (range 30-73). Among them, 25% (3/12) had Ann Arbor stage III-IV disease, with 1 case presenting bone marrow involvement. Primary sites included gastric (n=4) and non-gastric (n=8), with non-gastric subtypes comprising pulmonary MALT lymphoma (n=4), orbital MALT lymphoma (n=2), parotid MALT lymphoma (n=1), and colonic MALT lymphoma (n=1). According to MALT-IPI stratification, 8 cases (66.7%) were low-risk and 4 cases (33.3%) were intermediate-low risk. Ten treatment-naïve MALT lymphoma patients received the Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen as first-line treatment. One treatment-naïve patient received it as second-line therapy due to prior chemotherapy intolerance, while one refractory patient received this regimen as second-line treatment. Efficacy and safety The ORR for the entire cohort was 100%, with a CR rate of 75% (9/12). The gastric MALT lymphoma subgroup comprised 4 patients with a median follow-up of 11 months. All patients received first-line treatment, achieving a CR rate of 75% (3/4). The non-gastric MALT lymphoma subgroup included 8 patients with a median follow-up of 13 months, attaining a CR rate of 87.5% (7/8). All four pulmonary MALT lymphoma patients achieved a 100% CR rate. Among them: one patient was assessed as PR after 4 cycles of R-miniCDOP regimen but switched to Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen due to chemotherapy intolerance, subsequently achieving CR after 4 cycles; another patient showed progressive disease after 2 cycles of R-CDOP regimen but attained CR after switching to 4 cycles of Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen. Both orbital MALT lymphoma patients achieved 100% CR. The single colonic MALT lymphoma patient reached 100% CR. One parotid MALT lymphoma patient was preliminarily assessed as PR after 2 treatment cycles. No disease progression, relapse, or death occurred among all patients; therefore, OS and PFS were not evaluated. Hematological adverse events were observed in 25% (3/12) of cases, including two grade 1 leukopenia events and one grade 2 thrombocytopenia event. No non-hematological adverse events were reported. Conclusion: Despite the limited sample size in this retrospective study, the results indicate that the Orelabrutinib combined with Anti-CD20 monoclonal antibody regimen demonstrates favorable safety and efficacy in MALT lymphoma patients, providing an effective and safe treatment option for this population.

The predictive performance of the Molecular International Prognostic Scoring System (IPSS-M) for high-risk myelodysplastic syndromes (MDS) patients undergoing transplantation remains uncertain. We retrospectively analyzed 86 MDS patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center from 2016 to 2023. According to IPSS-M, patients were classified as Low (n = 3), Moderate-Low (n = 9), Moderate-High (n = 15), High (n = 28), and Very-High risk (n = 31). The IPSS-M did not demonstrate good prognostic accuracy for overall survival (OS) (P = 0.227) and disease-free survival (DFS) (P = 0.095) in these 86 patients. We then divided the patients into three groups based on their IPSS-M scores: IPSS-M < 0.56 (n = 28), IPSS-M 0.56-1.75 (n = 30), and IPSS-M>1.75 (n = 28). There was a significant difference in the long-term OS (P = 0.010) and DFS among the three groups (P < 0.001). This indicates that, based on the original IPSS-M scores, we may be able to find a more precise risk stratification for high-risk MDS patients undergoing allo-HSCT. Compared with TP53 wild-type and TP53 monoallelic mutations, TP53 biallelic mutations have a significant negative impact on OS and DFS (P = 0.016, P = 0.006). It is crucial to identify TP53 allelic status at diagnosis to distinguish these patients and determine the need for early involvement in clinical trials.

The combined use of quantitative real-time polymerase chain reaction (qPCR) and next-generation sequencing (NGS) to detect molecular measurable residual disease (mMRD) has been shown to have prognostic value for patients undergoing matched-hematopoietic stem cell transplantation (HSCT). However, there have been no related studies in the context of haploidentical HSCT (haplo-HSCT). We included 148 acute myeloid leukemia (AML) patients who were in first complete remission (CR1) and underwent HSCT at Union Hospital (Wuhan, China) between 2019 and 2023. Among them, 28 patients were mMRD (+) before transplantation according to PCR/NGS. Then, on the basis of the 2017 European Leukemia Net (ELN) risk stratification, we randomly enrolled 56 mMRD (–) patients at a 1:2 ratio. Finally, we compared the outcomes, including overall survival (OS), cumulative incidence of relapse (CIR), leukemia-free survival (LFS), and nonrelapse mortality (NRM), between the two groups. Persisting mMRD predicts worse long-term clinical outcomes in AML patients who received haplo-HSCT. The 2-year OS and LFS between the mMRD (+) and mMRD (–) groups were 77.1

Graft-versus-host disease (GVHD) remains a major concern following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Two principal in vivo T-cell depletion (TCD) strategies-post-transplant cyclophosphamide (PTCY)-based and anti-thymocyte globulin (ATG)-based GVHD prophylaxis-have effectively mitigated this challenge. In recent years, PTCY has expanded beyond haploidentical HSCT to include matched related donor (MRD), matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HSCT, resulting in favorable outcomes. ATG-based regimens have been optimized in terms of dosing and timing across various transplant settings. Individualized ATG administration shows potential in overcoming the highly heterogeneous pharmacokinetics. Some prospective studies have explored the combined use of ATG and PTCY in haploidentical and MUD HSCT. Only a few randomized controlled trials (RCTs) have compared ATG and PTCY head-to-head, and high-level evidence remains scarce. Ongoing clinical trials are expected to clarify which in vivo T-cell depletion protocol is better, and whether adjustments in timing, dose, or combination can yield better outcomes for patients.

Background Bone marrow (BM) aspiration is essential for monitoring post-transplant relapse in AML/MDS and is typically performed unilaterally under the assumption of even blast distribution. However, our clinical observations revealed cases of asymmetric blast distribution, leading to inconsistent cytologic results and potential diagnostic errors. To address this, we conducted a prospective study using bilateral BM aspiration of posterior superior iliac spine (PSIS) to investigate the spatial distribution pattern of blasts. Method A total of 57 patients undergoing HSCT were enrolled, with 98 bilateral BM aspirations performed. Inclusion criteria were as follows: 1. Patients with AML or MDS who had post-transplant relapse or suspected relapse; 2. Provision of written informed consent; 3. Following bilateral BM aspiration, cases were included if the proportion of blasts exceeded 5% in any side of PSIS, or proportion was between 0–5% with MRD+ on any side. Exclusion criteria were as follows: 1. Patients with diseases other than AML or MDS; 2. Patients were unwilling or unable to tolerate bilateral aspirations; 3. Patients without evidence of relapse after bilateral aspiration or with factors (e.g., BM necrosis) that hindered blast quantification were excluded. The study is registered at ChiCTR.org.cn (ChiCTR2100045918). Result A total of 22 patients undergoing 36 bilateral BM aspirations were included in the analysis. Asymmetric distribution (Asy-distribution) was defined as a blast percentage <5% on one side and ≥5% on the other, or a ≥1.5-fold difference between sides (n=17); others were classified as symmetric (Sy-distribution, n=19). Patients exhibiting ≥1 Asy-distribution were assigned to the Asy-group (n=11), others to the Sy-group (n=11). Among Asy-distribution, 6 cases showed <5% blasts on one side with ≥5% on the contralateral side (6/17; 6/11 patients). In each cytology pair, the side with higher blast proportion was defined as “high-side,” the other as “low-side.” In Asy-distribution, lymphocyte proportion was significantly lower in the high-side (P=0.0081, Wilcoxon matched-pairs test), while no such difference was observed in Sy-distribution. Single-cell RNA-seq was performed on 3 Asy- and 2 Sy-distribution pairs. In Asy-samples, compared with low-side, leukemia cells from the high-side showed upregulation of histone/chromatin genes (e.g., H3-3A, H3-3B, H1-10) and mitochondrial genes (MT-ND2, MT-ND4, MT-ND5), while inflammatory genes (S100A8, S100A9, NLRP3) were downregulated. GSEA revealed activation of E2F targets, G2/M checkpoint, and MYC targets, with suppression of apoptosis, IL-2–STAT5, and IL-6–JAK–STAT3 signaling pathways. Similarly, compared with Sy-distribution, blast cells from Asy-distribution samples displayed similar DEG and pathway patterns to those from the high-side. CD8⁺ T cells in both high-side and Asy-distribution exhibited reduced expression of cytotoxic genes (GZMB, PRF1, NKG7, CXCR4), as did NK cells (CXCR4). GSEA indicated suppression of immune effector pathways, including IFN-γ signaling, suggesting an immune-evasive phenotype in regions with higher leukemia burden. No significant differences were found between the Asy- and Sy-groups in demographics, overall survival, leukemia-free survival, or aGVHD incidence. Notably, the Asy-group showed a significantly higher 1-year cumulative incidence of cGVHD (45% vs 0%, P=0.013), but the correlation between asymmetric distribution and occurrence of cGVHD before relapse did not reach statistical significance (P=0.059). Conclusion This study revealed asymmetric distribution of blasts in the bone marrow, accompanied by reduced lymphocyte proportions and immune transcriptional differences. In both high-side vs. low-side and Asy- vs. Sy-distribution comparisons, blasts from the high-side or Asy-distribution consistently exhibited enriched proliferative signatures, suppressed apoptotic and inflammatory pathways, and impaired immune cytotoxicity. Despite a limited cohort, nearly half of the patients exhibited asymmetry. While uneven HSC distribution post-transplant has been suggested, its mechanisms remain unclear. Whether asymmetry is driven by leukemia, immune-mediated, or influenced by cGVHD remains unknown. These findings underscore a clinically overlooked phenomenon and suggest that unilateral marrow sampling may be inadequate for relapse assessment in post-transplant AML/MDS. Larger studies are warranted to elucidate underlying mechanisms.

Background. Acute graft-versus-host disease (aGVHD) mediated by alloreactive T cells remains a serious and life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). The contribution of the different CD4 + T helper cell subtypes to the pathogenesis and regulation of aGVHD is a central point in current research. The specialized effector subsets of T cells that differentiate from naive T cells into mature cells are closely related to scaffold/matrix-associated region-1–binding protein (SMAR1). However, the role of SMAR1 in aGVHD is unclear. Methods. Peripheral blood was collected from the patients with or without aGVHD after allo-HCT. The differences in CD4 + T cells transduced with the SMAR1 lentivirus vector and empty vector were analyzed. A humanized aGVHD mouse model was constructed to evaluate the function of SMAR1 in aGVHD. Results. The expression of SMAR1 was significantly reduced in the CD4 + T cells from aGVHD patients and related to the occurrence of aGVHD. SMAR1 overexpression in human CD4 + T cells regulated CD4 + T-cell subsets differentiation and inflammatory cytokines secretion and inhibited the Janus kinase/signal transducer and activator of transcription pathway. Moreover, SMAR1 changed chromatin accessibility landscapes and affected the binding motifs of key transcription factors regulating T cells. Additionally, upregulation of SMAR1 expression in CD4 + T cells improved the survival and pathology in a humanized aGVHD mouse model. Conclusions. Our results showed that upregulation of SMAR1 regulated the CD4 + T-cell subpopulation and cytokines secretion and improved survival in a humanized aGVHD mouse model by alleviating inflammation. This study provides a promising therapeutic target for aGVHD.