OBJECTIVES:To evaluate associations between post-transplant immune reconstitution, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) DNAemia/reactivation, and survival after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS:We conducted a retrospective observational cohort study of 312 patients with hematologic malignancies who underwent allogeneic HSCT between 2016 and 2024. Bone marrow B-cell proportion and peripheral blood lymphocyte subsets were assessed longitudinally by flow cytometry. EBV and CMV reactivation was monitored by quantitative PCR and analyzed as surveillance-defined reactivation status. Landmark-based logistic regression evaluated associations between immune-reconstitution parameters and viral reactivation; receiver operating characteristic analysis assessed model discrimination, and Cox regression evaluated overall survival determinants. RESULTS:CMV and EBV DNAemia/reactivation occurred in 42.0% and 31.4% of patients, respectively, and were significantly correlated (ρ = 0.191, p = 0.028). Higher bone marrow B-cell proportion at sixmonths was associated with lower odds of CMV DNAemia/reactivation (OR = 0.947, 95% CI: 0.901-0.995, p = 0.034). For EBV, an exploratory interaction between 12-month CD8⁺ T-cell recovery and chronic GVHD was associated with EBV DNAemia/reactivation status (p = 0.039). Lower NK-cell levels were observed in patients with EBV and CMV coinfection (p = 0.021 and p = 0.036, respectively). Overall survival was mainly associated with relapse (HR = 5.5, p0.001) and conditioning regimen, whereas viral reactivation was not significantly associated with survival. DISCUSSION:Intermediate immune-reconstitution landmarks showed distinct associations with surveillance-defined viral reactivation, particularly six-month B-cell proportion for CMV and CD8⁺ T-cell recovery in the context of chronic GVHD for EBV. CONCLUSION:Longitudinal immune-reconstitution patterns may help characterize persistent post-HSCT immune vulnerability, although prospective studies incorporating viral timing and treatment-exposure data are needed for validation.

B-cell reconstitution is closely associated with prognosis, infection risk, and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the impact of different calcineurin inhibitors (CNIs) on B-cell recovery remains unclear. We retrospectively analyzed 312 allo-HSCT recipients receiving cyclosporine (CsA, n = 211) or tacrolimus (FK506, n = 101). B-cell proportions in bone marrow and peripheral lymphocyte subsets were compared, and propensity score matching was applied to balance confounders. Multivariate analysis demonstrated that FK506 was independently associated with superior B-cell reconstitution at 3 months (OR 2.93, 95

BACKGROUND:Translation inhibitors have been shown to accelerate acute myeloid leukemia (AML) cell apoptosis and regulate Akt activity and the Bcl-2 family, suggesting their potential benefit when combined with venetoclax and cytarabine in de novo AML patients. METHODS:The authors conducted a multicenter, open-label, single-arm study to assess the efficacy and safety of a venetoclax-cytarabine-based induction regimen incorporating a clinically available translation inhibitor in adult patients newly diagnosed with AML in China. RESULTS:A total of 52 cases (median age, 48.5 years; range, 18-60) were treated, with poor risk in 27% (14 of 52) of patients. The overall response rate was 90% (95% CI, 79-97) after one cycle of the regimen with 46 patients in composite complete remission. With a median follow-up of 816 days (interquartile range, 418-1143), the estimated 1-year overall survival (OS) and event-free survival (EFS) were both 81% (95% CI, 71-92). After induction chemotherapy, patients experienced decreases in CD4+ naive, CD8+ naive, Th2, and CD19+ cells, along with increases in CD4+ TEM, Th1, natural killer cells, and a higher Th1/Th2 ratio in both peripheral blood and bone marrow (BM), whereas BM-specific changes included a decrease in CD8+ naive cells and lower IL-10 levels post-treatment. CONCLUSION:This venetoclax-cytarabine regimen incorporating a translation inhibitor demonstrated efficacy and was well-tolerated in young adult patients with de novo AML, achieving high complete remission rates and encouraging OS and EFS. The induced immune-cell and cytokine shifts provide deeper insights into integrating translational inhibition with BCL2-targeted therapies and warrant further investigation in randomized controlled trials. This trial was registered at ChiCTR.org.cn as ChiCTR2100048208.

Background: Mediastinal ectopic pancreas (EP) is an exceptionally rare entity that can mimic malignancy. Diagnosis is typically established post-operatively; pre-operative confirmation is challenging. Case Presentation: We describe a 28-year-old man presenting with life-threatening airway obstruction due to a progressive mediastinal mass, requiring emergency tracheal stenting. Diagnostic workup revealed a critical discordance: while CT-guided core biopsy confirmed benign ectopic pancreatic tissue, concurrent flow cytometry identified a monoclonal B-cell population with a high Ki-67 index (~86%), raising concern for a high-grade lymphoid process. However, no morphological evidence of lymphoma was found, and PET-CT showed only moderate metabolic activity (SUVmax 4.6), making an untreated aggressive lymphoma less consistent. The patient declined surgical resection. Management proceeded with a conservative strategy of structured clinical surveillance based on the benign histology. At 6-month follow-up, the patient remained clinically stable without chemotherapy, supporting the diagnosis of benign ectopic pancreas and suggesting the flow cytometric findings represented reactive “pseudo-monoclonality” secondary to inflammation. Conclusions: This case highlights mediastinal EP as a rare airway emergency and illustrates a major diagnostic pitfall: flow cytometric clonality and high proliferative fractions can occur in inflammatory settings and must not override benign architectural histology. When discordance persists and definitive tissue cannot be obtained, management should emphasize multidisciplinary review, deliberate specimen triage, and structured surveillance with predefined triggers for repeat higher-yield biopsy or surgical sampling and airway-stent reassessment.

Background:This study explores the impact of different immunoparesis states on early infection risk within 6 months of diagnosis in patients with newly diagnosed multiple myeloma (NDMM), aiming to inform clinical infection prevention strategies. Methods:A retrospective analysis was conducted on 213 NDMM patients (2016-2024). Immunoparesis was classified qualitatively (no, partial, and full immunoparesis) and quantitatively (with immunoglobulin reduction < 50% and ≥ 50%). Early infection rates and immunoparesis status were assessed using Kaplan-Meier survival curves. Cox regression models were applied to evaluate the independent prognostic effect of immunoparesis on infection risk. Results:Immunoparesis significantly increased the risk of early infections. In the qualitative analysis, infection rates were 15.8% for no immunoparesis, 53.1% for partial, and 53.8% for full immunoparesis (Log-rank P = 0.017). In the quantitative analysis, infection rates were 51.9% for < 50% immunosuppression and 54.2% for ≥ 50% immunosuppression, compared to 15.8% for no immunoparesis (Log-rank P = 0.017). Cox regression analysis showed that partial and full immunoparesis increased the risk of infection by 8.9-fold (HR = 8.9, P = 0.004) and 7.8-fold (HR = 7.8, P = 0.006), respectively. Similarly, < 50% and ≥ 50% immunosuppression increased infection risk by 8.67-fold (HR = 8.67, P = 0.005) and 7.95-fold (HR = 7.95, P = 0.005), respectively. Conclusion:Immunoparesis significantly increases early infection risk in NDMM patients. However, no significant risk gradient was observed relative to the breadth or depth of immunoparesis within this cohort. Monitoring and timely intervention for immunoparesis are essential for infection prevention.

Abstract Background The expression of the CD14 surface antigen in acute myeloid leukemia (AML) has previously been regarded as an indicator of poor overall survival. However, the existing evidence is limited, and further investigations into additional prognostic parameters are necessary. This study aimed to evaluate the impact of the CD14 antigen on survival prognosis in patients with de novo AML (dn-AML). Methods We analyzed CD14 antigen expression in diagnostic samples from 709 patients with dn-AML by flow cytometry. By utilizing a 20% positivity threshold, the cohort was stratified into CD14-positive (10.15%) and CD14-negative (89.85%) groups. We compared continuous data using the independent sample t test or Mann–Whitney U test and used the chi‒square test or Fisher’s exact test to compare categorical variables. OS and DFS were compared via Kaplan–Meier survival curve analysis and the log-rank test. Univariate and multivariate analyses were performed using the Cox proportional hazards model, and a visualized nomogram was developed to predict OS. Results Compared with the CD14-negative group, the CD14-positive group had a lower complete remission rate (P < 0.001), a higher relapse rate (P = 0.013) and a higher mortality rate (P = 0.017). According to the log-rank test, the CD14-positive group exhibited significantly shorter overall survival (OS) (P = 0.034) and disease-free survival (DFS) (P = 0.009) than the CD14-negative group did. Multivariate analysis revealed that CD14 status, TP53 mutation, European Leukemia Net (ELN) risk category, bone marrow transplant status, white blood cell (WBC) count and hemoglobin levels were independent prognostic factors associated with OS. The visualized nomogram demonstrated notable performance in predicting OS, with a C-index of 0.77. Compared with the ELN risk model, calibration plots and decision curve analyses indicated superior discrimination, calibration and net benefits. The time-dependent receiver operating characteristic (ROC) curves for 1-, 2-, and 3-year survival also performed robustly (AUC = 0.727, 0.738, and 0.753, respectively). Conclusions This study provides a comprehensive perspective on the role of the CD14 antigen as an independent prognostic marker in dn-AML patients. This prognostic model leverages readily available clinical data to increase predictive accuracy, identify potential risks and support AML therapeutic decision-making.

OBJECTIVE:This study aimed to investigate whether esculentoside A (EsA) alleviates airway inflammation by modulating JAK2/STAT3-mediated mitochondrial apoptosis in an ovalbumin (OVA)-induced murine model of asthma. METHODS:Female BALB/c mice were sensitized and challenged with OVA to establish the asthma model. EsA (15 mg/kg) was administered intraperitoneally from day 17 for seven consecutive days. JAK2 inhibitor (Fedratinib, 60 mg/kg) and JAK2 agonist (C-A1, 100 μg/kg) were used to further validate the involvement of the JAK2/STAT3 pathway. Histological analysis, ELISA, Western blot, TUNEL, and mitochondrial function assays were performed to evaluate inflammatory response, apoptosis, and signaling pathways. RESULTS:EsA treatment significantly alleviated airway inflammation, as shown by reduced peribronchial inflammatory infiltration and lower inflammation scores, and decreased goblet cell hyperplasia and PAS staining scores. ELISA results showed that EsA significantly reduced IL-4, IL-13, and TNF-β levels in BALF and decreased serum OVA-specific IgE. Western blot revealed that EsA downregulated phosphorylated JAK2 and STAT3 levels, as well as proapoptotic markers (Bax, Cyt C, and cleaved Caspase-3), while upregulating the antiapoptotic protein Bcl-2. These effects were comparable to those of Fedratinib and were reversed by JAK2 agonist C-A1. Furthermore, EsA restored mitochondrial membrane potential (JC-1 ratio increased) and reduced mitochondrial ROS production, indicating improved mitochondrial function. TUNEL assays corroborated the antiapoptotic effect of EsA. CONCLUSION:: EsA ameliorates OVA-induced airway inflammation in mice, likely by suppressing the JAK2/STAT3 signaling pathway and attenuating mitochondrial-dependent apoptosis. These findings suggest that EsA holds therapeutic potential as a novel anti-asthmatic agent targeting inflammatory and mitochondrial pathways.

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma. Despite improved prognosis with R-CHOP, patients with high-risk features (≥2 extranodal sites, DEL, CD5+, EBV+, TP53 mutations) have poor outcomes. These patients exhibit low complete response rates and high recurrence risks when treated with R-CHOP, underscoring the urgent need for more effective therapeutic strategies. The POLARIX trial showed polatuzumab vedotin (Pola), an anti-CD79b ADC, has demonstrated a significant improvement in progression-free survival (PFS) . However, it enrolled few high-risk patients and used strict criteria, limiting generalizability to real-world populations. Real-world data on Pola-based regimens in high-risk DLBCL remain limited. Based on real-world data, this study retrospectively evaluates the efficacy and safety of Pola-based regimens specifically among molecularly and pathologically defined high-risk previously untreated DLBCL patients, providing evidence to support precision treatment decision-making. Methods A retrospective analysis was conducted on previously untreated DLBCL patients aged ≥18 years who were treated at The First Affiliated Hospital of Chongqing Medical University between April 2024 and June 2025. All patients received at least 3 cycles of Pola-based regimens, with the vast majority administered Pola-R-CHP, consisting of polatuzumab vedotin (1.8 mg/kg, intravenous [IV], day 1); rituximab (375 mg/m², IV day 1); cyclophosphamide (750 mg/m², IV, day 1); doxorubicin (50 mg/m², IV, day 1); and prednisone (100 mg,oral, days 1–5), repeated every 21 days. The primary endpoint was complete response rate (CRR) at the end of treatment (EOT). Secondary endpoints included overall response rate (ORR), incidence of adverse events (AEs) during treatment, progression-free survival (PFS), and overall survival (OS). A multivariable Cox regression–based risk scoring model was constructed based on four clinical features: cell-of-origin subtype (ABC), ≥2 extranodal sites, gastrointestinal tract involvement, and bone marrow involvement. Each variable contributed 1 point to a composite risk score. Patients were classified as high-risk (score ≥2) or low-risk, and their association with CR was analyzed using Cox proportional hazards modeling. Results 40 patients were included (median age 64, range 23–87; 70% female). According to the Hans classification, 60% of patients were classified as activated B-cell-like (ABC) lymphoma. Patients with International Prognostic Index (IPI) scores of 3–5 accounted for 57.5%, and 80.0% of Ann Arbor stage was III-IV. 72.5% of patients had extranodal involvement, 52.5% with ≥2 extranodal sites. The proportions of DEL, CD5-positive, EBV-positive, and TP53-mutated patients were 42.5%, 42.5%, 20%, and 27.5%, respectively. The median treatment cycles was 5 (range: 3–8). Among 34 EOT-evaluable patients, CRR was 64.7% and ORR 97.1%. At EOT, the CRR and ORR among patients with ≥2 extranodal sites were 63.2% and 94.7%, respectively. Corresponding values were 85.7% and 100% for DEL patients, 57.1% and 100% for EBV-positive patients, 58.8% and 94.1% for CD5-positive patients, and 70% and 100% for TP53-mutated patients. The median follow-up duration was 4 months (range: 1–13). Only two patients experienced disease progression at 3 and 7 months, respectively, and no deaths were observed over the study period. A composite score based on ABC subtype, extranodal site involvement (≥2), gastrointestinal tract involvement, and bone marrow involvement (1 point each, high-risk defined as score ≥2) showed a significant association with achieving CR at EOT. High-risk patients, as defined by this score, exhibited a significantly greater likelihood of attaining CR (HR = 3.02, 95% CI: 1.13–8.04, P = 0.0274). The most common AEs was gastrointestinal reaction (60%), followed by myelosuppression (12.5%), most of which were grade 1–2. The most common grade 3–4 AEs were myelosuppression (5%) and neutropenia (5%). No participants discontinued treatment because of adverse events. Conclusion Our findings indicate that Pola-based regimens exhibit high response rates and favorable safety profiles in newly diagnosed DLBCL patients with high-risk features in real world settings. Prospective studies with larger cohorts are needed to further validate these observations.

Multiple myeloma (MM) is a common hematologic malignancy characterized by clonal plasma cell proliferation. Despite significant therapeutic advancements with proteasome inhibitors, immunomodulatory drugs, and anti-B-cell maturation antigen (BCMA) therapies, the disease remains largely incurable. Immunoparesis, a severe state of immune dysfunction, exhibits high prevalence in MM patients and profoundly impacts prognosis. This review summarizes the pathogenic mechanisms and clinical characteristics of immunoparalysis, with a focus on its impact on prognosis and early-onset infections, the effects of contemporary drug therapies on immunoparalysis, and immune reconstitution.

Background:Multiple myeloma (MM) remains a formidable clinical challenge due to its high relapse rate and resistance to existing therapies. Estrogen-related receptor gamma (ERRγ), a nuclear receptor critical for cellular energy metabolism, has been implicated in various cancers. but its role in MM remains unclear. Methods:ERRγ expression was assessed using bioinformatics and RT-qPCR. Functional studies were conducted through siRNA-mediated ERRγ knockdown and treatment with the inverse agonist GSK5182 to examine their effects on MM cell proliferation and apoptosis. Results:ERRγ was significantly upregulated in the bone marrow of MM patients, correlating with advanced clinical stages and pathological fractures. Inhibition of ERRγ reduced MM cell expansion both in vitro and in vivo, while promoting mitochondrial-dependent apoptosis. Co-immunoprecipitation assays demonstrated a physical association between ERRγ and P65. Inhibition of ERRγ attenuated canonical nuclear factor-kappa B (NF-κB) signaling by blocking the nuclear translocation of its key effector p65. Additionally, modulation of ERRγ altered receptor activator of nuclear factor-κB ligand (RANKL) levels, implying a potential role in bone degradation observed in MM cases. Conclusion:Collectively, the data broaden understanding of ERRγ's contribution to MM development and propose it as a viable target for therapeutic intervention.

Multiple myeloma (MM), a prevalent plasma cell malignancy, represents a life-threatening hematological disorder with significant clinical morbidity. Despite its recognized impact on global health burdens, the precise molecular pathogenesis underlying disease progression remains incompletely elucidated. Transcriptomic profiling via RNA sequencing revealed significant upregulation of cyclin-dependent kinase regulatory subunit 2 (CKS2) in multiple myeloma. Clinical validation was performed through quantitative analysis of CKS2 expression in patient-derived specimens. Two established MM cell models (MM.1S and RPMI-8226) were selected for functional characterization. Cellular proliferation dynamics were quantified using CCK-8 metabolic assays and EdU DNA incorporation analysis, with flow cytometric evaluation employed to assess apoptotic indices. A xenograft mouse model was established to investigate CKS2-mediated tumorigenesis in vivo, complemented by western blot analysis of pathway-associated protein expression. Bioinformatic interrogation of the HumanBase database identified putative CKS2 interactomes, subsequently validated through co-immunoprecipitation assays and confocal immunofluorescence microscopy. Structural modeling via AlphaFold2 predicted molecular interaction interfaces, with three-dimensional visualization achieved through PyMOL rendering. In this study, we demonstrated that CKS2 knockdown in MM.1S and RPMI-8226 cell lines significantly inhibited cellular proliferation and induced apoptosis. Conversely, CKS2 overexpression enhanced malignant proliferation while suppressing apoptotic processes, establishing its functional role in myeloma pathogenesis. Mechanistic investigations revealed that CKS2 depletion modulates cell proliferation and apoptosis via PTEN/AKT/mTOR signaling axis. Notably, co-immunoprecipitation assays demonstrated direct protein-protein interaction between CKS2 and thioredoxin (TXN), with subsequent functional validation suggesting TXN appears to function as a key upstream regulatory factor governing CKS2 stability. These findings establish CKS2 as a critical regulator of myeloma cell homeostasis and identify it as a promising therapeutic target warranting further preclinical validation.

Objective: This study aims to examine the incidence of post-chemotherapy perianal infection and its influencing factors in patients with acute leukemia. Methods: A total of 243 patients with acute leukemia who underwent chemotherapy in the Three Gorges Hospital affiliated to Chongqing University, China, between January 2019 and December 2020 were selected as study subjects. In the present retrospective study, patients with post-chemotherapy perianal infection were monitored, and the perianal infection rate and clinical features of perianal infection were determined. Categorical variables were compared using the Chi-square test, and the influencing factors of post-chemotherapy perianal infection in patients with acute leukemia were evaluated using logistic analysis. Results: A total of 24 patients (9.88%) with acute leukemia suffered post-chemotherapy perianal infection. Age, basic perianal disease (hemorrhoids) history, constipation, diarrhea, duration of agranulocytosis, and length of hospital stay were compared among the patients. Perianal disease classification, perianal ultrasound, colonoscopy, postoperative pathology, and other clinical data were compared and discussed in relation to the occurrence and development of the disease. The results showed that there were no significant differences in perianal infection degrees between genders and among different types of leukemia (p > 0.05). There were no statistically significant differences in age, pain score, minimum white blood cell count, deficiency duration, and length of hospital stay among patients with different degrees of infection. The Spearman rank correlation test showed that the perianal infection degree was positively correlated with the highest hypersensitive C-reactive protein (hs-CRP) level (p < 0.05). The difference was statistically significant; the higher the maximum hs-CRP/procalcitonin levels, the more serious the perianal infection. Conclusions: Perianal infections are common in the procession of chemotherapy or myelosuppression. This is worthy of clinical recognition. Early recognition of perianal infection and the strengthening of infection risk factor control may be beneficial to improving the subjective feelings of patients with acute leukemia undergoing chemotherapy.

Background. The immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for preventing infections and relapse and enhancing graft-versus-tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo-HSCT has not been well studied. Methods. In this study, we analyzed the dynamics of B cells in 252 patients who underwent allo-HSCT for 2 years and assessed the impact of factors on B-cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood. Results. We found that the B-cell reconstitution in the bone marrow was consistent with the peripheral blood (p = 0.232). B-cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft-versus-host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post-1-year B-cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age-B cells-survival axis and found that B-cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival (p = 0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation (p = 0.037). Conclusion. Our findings provide valuable insights for optimizing the management of B-cell reconstitution and improving the efficacy and safety of allo-HSCT.

Acute myeloid leukemia (AML) can manifest as de novo AML (dn-AML) or secondary AML (s-AML), with s-AML being associated with inferior survival and distinct genomic characteristics. The underlying reasons for this disparity remain to be elucidated. In this multicenter study, next-generation sequencing (NGS) was employed to investigate the mutational landscape of AML in 721 patients from June 2020 to May 2023.Genetic mutations were observed in 93.34% of the individuals, with complex variations (more than three gene mutations) present in 63.10% of them. TET2, ASXL1, DNMT3A, TP53 and SRSF2 mutations showed a higher prevalence among older individuals, whereas WT1 and KIT mutations were more commonly observed in younger patients. BCOR, BCORL1, ZRSR2, ASXL1 and SRSF2 exhibited higher mutation frequencies in males. Additionally, ASXL1, NRAS, PPMID, SRSF2, TP53 and U2AF1 mutations were more common in patients with s-AML, which PPM1D was more frequently associated with therapy-related AML (t-AML). Advanced age and hyperleukocytosis independently served as adverse prognostic factors for both types of AML; however, s-AML patients demonstrated a greater number of monogenic adverse prognostic factors compared to dn-AML cases (ASXL1, PPM1D, TP53 and U2AF1 in s-AML vs. FLT3, TP53 and U2AF1 in dn-AML). Age and sex-related gene mutations suggest epigenetic changes may be key in AML pathogenesis. The worse prognosis of s-AML compared to dn-AML could be due to the older age of s-AML patients and more poor-prognosis gene mutations. These findings could improve AML diagnosis and treatment by identifying potential therapeutic targets and risk stratification biomarkers.

OBJECTIVE:To explore the effects of pre-transplant controlling nutritional status (CONUT) and post-transplant minimal residual disease (MRD) on prognosis of patients with multiple myeloma (MM) after autologous hematopoietic stem cell transplantation (auto-HSCT). METHODS:The clinical data of 79 patients who received auto-HSCT from 2011 to 2020 in The First Affiliated Hospital of Chongqing Medical University were retrospectively analyzed. The patients were divided into Low-CONUT group (n=62) and High-CONUT group (n=17) according to whether the CONUT score was less than 5. The differences in clinical features, hematopoietic reconstruction, adverse reactions, efficacy and survival between the two groups were compared. In addition, the prognostic risk factors were analyzed and verified by time-dependent ROC curve. RESULTS:The proportions of male patients and bone marrow plasma cells>30% at initial diagnosis in High-CONUT group were both higher than those in Low-CONUT group (both P <0.05). While, there were no significant differences in hematopoietic reconstruction and adverse reactions (>grade 2) between the two groups. The complete response (CR) rate and CR+very good partial response (VGPR) rate before transplantation in Low-CONUT group were both significantly higher than those in High-CONUT group (both P <0.05). After 3 months of transplantation, the CR+VGPR rate still remained an advantage in Low-CONUT group compared with High-CONUT group (P <0.01), but CR rate did not(P >0.05). The overall survival (OS) and progression-free survival (PFS) in Low-CONUT group were both superior to those in High-CONUT group (both P <0.05). Low CONUT score (0-4) before transplantation and negative MRD at 6 months after transplantation were favorable factors affecting OS and PFS (both P <0.05), while the International Myeloma Working Group (IMWG) high-risk at initial diagnosis and lactate dehydrogenase (LDH) level>250 U/L before transplantation were only risk factors for PFS (both P <0.05). Time-dependent ROC curve analysis showed that pre-transplant CONUT score and MRD status at 6 months after transplantation could independently or jointly predict 1- and 2-year OS and PFS, and the combined prediction was more effective. CONCLUSION:The combination of pre-transplant CONUT and post-transplant MRD can better predict the prognosis of MM patients.

The immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is crucial for preventing infections and relapse and enhancing graft-versus-tumor effects. B cells play an important role in humoral immunity and immune regulation, but their reconstitution after allo-HSCT has not been well studied. In this study, we analyzed the dynamics of B cells in 252 patients who underwent allo-HSCT for 2 years and assessed the impact of factors on B-cell reconstitution and their correlations with survival outcomes, as well as the development stages of B cells in the bone marrow and the subsets in the peripheral blood. We found that the B-cell reconstitution in the bone marrow was consistent with the peripheral blood ( p  = 0.232). B-cell reconstitution was delayed by the male gender, age >50, older donor age, the occurrence of chronic and acute graft-versus-host disease, and the infections of fungi and cytomegalovirus. The survival analysis revealed that patients with lower B cells had higher risks of death and relapse. More importantly, we used propensity score matching to obtain the conclusion that post-1-year B-cell reconstitution is better in females. Meanwhile, using mediation analysis, we proposed the age-B cells-survival axis and found that B-cell reconstitution at month 12 posttransplant mediated the effect of age on patient survival ( p  = 0.013). We also found that younger patients showed more immature B cells in the bone marrow after transplantation ( p  = 0.037). Our findings provide valuable insights for optimizing the management of B-cell reconstitution and improving the efficacy and safety of allo-HSCT.

Background: Myeloid neoplasms (MN) tend to relapse and deteriorate. Exploring the genomic mutation landscape of MN using next-generation sequencing (NGS) is a great measure to clarify the mechanism of oncogenesis and progression of MN.Methods: This multicenter retrospective study investigated 303 patients with MN using NGS from 2019 to 2021. The characteristics of the mutation landscape in the MN subgroups and the clinical value of gene variants were analyzed.Results: At least one mutation was detected in 88.11% of the patients (267/303). TET2 was the most common mutation in the cohort, followed by GATA2, ASXL1, FLT3, DNMT3A, and TP53. Among patients with myeloid leukemia (ML), multivariate analysis showed that patients aged & GE;60 years had lower overall survival (OS, p = 0.004). Further analysis showed TET2, NPM1, SRSF2, and IDH1 gene mutations, and epigenetic genes (p < 0.050) presented significantly higher frequency in older patients. In patients with myelodysplastic syndrome (MDS) and myelodysplastic neoplasms (MPN), univariate analysis showed that BCORL1 had a significant impact on OS (p = 0.040); however, in multivariate analysis, there were no factors significantly associated with OS. Differential analysis of genetic mutations showed FLT3, TP53, MUC16, SRSF2, and KDM5A mutated more frequently (p < 0.050) in secondary acute myeloid leukemia (s-AML) than in MDS and MPN. TP53, U2AF1, SRSF2, and KDM5A were mutated more frequently (p < 0.050) in s-AML than in primary AML. KDM5A was observed to be restricted to patients with s-AML in this study, and only co-occurred with MUC16 and TP53 (2/2, 100%). Another mutation was MUC16, and its co-occurrence pattern differed between s-AML and AML. MUC16 mutations co-occurred with KDM5A and TP53 in 66.7% (2/3) of patients with s-AML and co-occurred with CEBPA in 100% (4/4) of patients with AML.Conclusions: Our results demonstrate different genomic mutation patterns in the MN subgroups and highlight the clinical value of genetic variants.

多发性骨髓瘤(MM)是血液系统恶性肿瘤,即使患者在治疗后达到深度缓解,最终仍会复发,这可能与克隆异质性和克隆演变有关.克隆异质性是MM的特征,在骨髓微环境和抗肿瘤治疗的选择压力下,亚克隆遵循不同的进化模式发生演变,如分支进化模式、线性进化模式、中性进化模式等,克隆演变贯穿于MM各个阶段,推动着MM的发生、耐药及复发.该文对MM克隆异质性、克隆演变及临床意义进行综述,以期为临床治疗决策提供新思路.

Background: 20-30% of de novo acute myeloid leukemia (AML) patients still do not achieve complete remission (CR) using standard induction regimens. Homoharringtonine (HHT) has been extensively applied in the therapy of hematological diseases in China for more than 50 years. Recent clinical trials have shown that venetoclax combined with intensive chemotherapy including FLAG-IDA, CLIA, and DA induction achieved a 90% CR rate in de novo adult AML and was well-tolerated. Whether veneclax combined with HHT and cytarabine (HAV) can synergistically improve the remission rate of de novo AML patients and reduce adverse events deserves further exploration. Aims: To investigate the safety and efficacy of HAV regimen (HHT and cytarabine combined with venetoclax) in adult patients with de novo AML. We evaluated patients’ characteristics, overall response (ORR = CRc + MLFS), composite CR (CRc = CR + CRi + CRp), the negativity rates of MRD (MFC, <0.1%), venetoclax pharmacokinetics, relapse-free survival (RFS), overall survival (OS), non-hematological toxicities, and the mortality rates during the first two months. Methods: Single-arm, prospective clinical trial conducted in the First Affiliated Hospital of Chongqing Medical University and Southwest Hospital, Third Military Medical University (Army Medical University). Eligible patients (18-60 years old) with de novo AML (exclude acute promyelocytic leukemia) were enrolled since April 1, 2021, with final follow-up in Feb 26, 2023. Patients were treated with HHT 2-2.5mg/m2 on days 1-3 (d1-3) and cytarabine 100-200 mg/m2/d on d1-7 plus venetoclax 100mg/d on d1-14 (coadministration with oral Posaconazole 200mg three times a day). No additional molecular inhibitors were administered. No G-CSF was used during the induction therapy. The trial was registered in the Chinese Clinical Trial Register (ChiCTR2100048208). Results: Thirty-six patients were enrolled, and 34 cases were evaluated as 2 patients died of severe infections shortly after HAV regimen initiated. The median age was 47.5 years old (range, 18-57), with poor risk in 35.3% (12/34) of patients (European Leukemia Net 2022 risk). The most common gene mutations were FLT3 20.6% (7/34), AML1/ETO 14.7% (5/34), NPM1 17.6% (6/34), NRAS 11.8% (4/34), KRAS 11.8% (5/34), DNMT3A 11.8% (4/34), IDH1 5.9% (2/34), and IDH2 5.9% (2/34). Other characteristics of patients were listed in Table 1. Both ORR and CRc rates were 97.1% (33/34). 11 out of 12 (91.7%) patients with poor risk achieved CRc. Only one poor-risk patient with PTPN11 mutation failed to achieve CR and died of severe infection. MRD negativity was confirmed in 48.5% (16/33) of CRc patients. Blast count reduction to <5% was observed in 53.8% (7/13) on day 14 and in 97.1% (33/34) on day 30 by bone marrow evaluations. 13 patients underwent allo-HSCT and 4 of them died of severe aGVHD (n=3) or leukemia relapse (n=1). 2 patients underwent auto-HSCT. After 10.6 months of median follow-up, the median OS and RFS have not been reached (Figure 1). The most common grade 3-5 non-hematological adverse events were febrile neutropenia (97.1%, 33/34) and bacteremia/sepsis (14.7%, 5/34). The incidence of septic shock, severe pneumonia, and intra-abdominal infection were 11.8%, 14.7%, and 11.7%, respectively. Day 30 and day 60 mortality rates were 0% (0/34) and 2.9% (1/34), respectively. The mean blood concentration of venetoclax (Cmax/Cmin) was 1329.4/844.3 ng/ml (range, 594-2580/324-1630) on day 4 and 1584.4/1148.8 ng/ml (range, 952-2190/534-1690) on day 9. Summary/Conclusion: HAV was effective and well-tolerated in young adult patients with de novo AML, producing high rates of CR and encouraging OS and RFS.Keywords: Acute myeloid leukemia

To explore the clinical significance and prognosis of acute myeloid leukemia (AML) patients with WT1 mutations.In total, the clinical data of 269 adult patients with non-M3 AML were considered retrospectively. From these patients, 153 carried WT1 mutation whereas 116 were negative. WT1 mutation positive patients were further divided into WT1 low expression and high expression groups base on the expression level of WT1 by qPCR at diagnosis (cut off: 170500). Survival and therapeutic effect analysis were performed for the above patients with different interfering factors such as co-mutations, the extent of WT1 log reduction and the chemotherapy regimens. Patients with high WT1 expression have higher rate of relapse. We can accurately identify patients with inferior outcomes when we take the following factors into consideration: the WT1 expression level at diagnosis; different prognostic factors including co-mutations (especially NPM1 and FLT3-ITD); the log reduction of WT1 after induction therapy and the risk of stratification. Idarubicin + Cytarabine (IA) regimen could reduce the expression level of WT1 after treatment, and Allo-HSCT played an important role in improving the prognosis of patients with WT1 high expression and patients with WT1 negativity. Among the relapsed patients, there existed a rising trend of WT1-MRD in advance than MFC-MRD and that of patients with continuous complete remission (CR). Different clinical background should be taken into consideration when we judge the prognosis and therapeutic effect of patients with WT1 mutations. In addition, WT1 may be an optional MRD marker, which needs regular monitoring.