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
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.
BACKGROUND:Acute myeloid leukemia (AML) is a malignancy of the blood system. The commonly altered regions in the genome of AML encompass a multitude of gene modifications associated with epigenetic regulation. However, the prognostic significance of chromatin remodeling-related genes (CRRGs) as an overall indicator has yet to be assessed in AML. METHODS:Univariate Cox regression analysis was performed for CRRGs. Following unsupervised clustering analysis, the differentially expressed genes (DEGs) and immune cells between chromatin remodeling related subtypes in TCGA-AML were measured. Univariate Cox analysis and Least Absolute Shrinkage and Selection Operator (LASSO) analysis were used to screen prognostic biomarkers for AML, and a risk model was subsequently constructed. Gene set variation analysis (GSVA) analysis and tumor mutation burden (TMB) analysis was conducted in different risk groups. Using Tumor Immune Dysfunction and Exclusion (TIDE) score to assess patients' differences in sensitivity to immunotherapy. Additionally, the construction and verification of the nomogram were carried out. The expression of biomarkers in healthy and AML patients was analyzed by Quantitative Real-time Polymerase Chain Reaction (RT-qPCR). RESULTS:A total of 106 prognostic CRRGs were identified. Between the two clusters, 3995 genes, activated CD4 memory T cells and activated Dendritic cells were differentially expressed. A total of 6 prognostic biomarkers were identified (ARF6, ASF1B, CHD5, FLNA, KDM5B, and SPI1I), and a risk model was generated based on these biomarkers. The high-risk group exhibited higher TIDE scores. Moreover, 29 drugs showed lower IC50 values in high-risk group. We also found that risk score was an independent prognostic factor for AML. RT-qPCR results showed significant differences in expression of ARF6, KDM5B and CHD5 between healthy and AML patients. CONCLUSION:We identified six biomarkers, namely ARF6, ASF1B, CHD5, FLNA, KDM5B, and SPI1, thereby establishing a theoretical foundation for clinical diagnosis of AML.
Background:Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of non-Hodgkin's lymphoma globally. SPAG5, a mitotic spindle protein, plays a significant role in DLBCL, where its abnormal expression is often associated with tumor growth, chemotherapy resistance, local recurrence, and poor prognosis. Methods:A comprehensive analysis of SPAG5 expression across various cancer types was conducted using Timer 2.0 and Sanger Box 3.0. Subsequently, the expression levels of SPAG5 in DLBCL were investigated in comparison to normal samples. Receiver operating characteristic (ROC) curve was then generated to evaluate the diagnostic performance of SPAG5 for DLBCL. Furthermore, the functional role of SPAG5 was characterized, and its impact on the immune microenvironment of DLBCL patients was analyzed. Its potential in predicting immune checkpoint status and responses to immunotherapy was also evaluated. Results:SPAG5 expression demonstrated significant heterogeneity across various cancer types, with a marked upregulation in DLBCL. The diagnostic efficacy of SPAG5 was moderate, yielding an area under curve (AUC) of 0.75. SPAG5 exerted a multifaceted influence on DLBCL progression by regulating critical cellular processes, including cell cycle dynamics, chromosomal segregation, and DNA homeostasis. Notably, patients with elevated SPAG5 expression had poorer survival outcomes than those with low expression. Analysis of the tumor immune microenvironment revealed a distinct pattern: high SPAG5 expression correlated with increased infiltration of resting natural killer (NK) cells, while being associated with reduced presence of regulatory T cells (Tregs) and follicular helper T cells (Tfh). Conclusion:Our bioinformatics study elucidated the expression profile, diagnostic potential, and prognostic significance of SPAG5 in DLBCL, emphasizing the complex interplay between SPAG5 expression and the tumor immune landscape. Our findings suggested SPAG5 could be a candidate prognostic marker and potential therapeutic target for DLBCL.
Intravascular large B-cell lymphoma (IVLBCL) presents with a wide range of clinical symptoms, making clinical diagnosis challenging. It is often misdiagnosed or overlooked, leading to delays in treatment for affected patients. We present a case of a patient exhibiting clinical symptoms such as chest tightness, dyspnea, fever, and edema, who was later diagnosed with secondary hemophagocytic syndrome (HPS). Laboratory tests indicated persistent hypoalbuminemia, significantly elevated lactate dehydrogenase levels, thrombocytopenia, and splenomegaly, with no evidence of lymphadenopathy. During the treatment for HPS, the patient developed a rash on both lower limbs and abdomen and was ultimately diagnosed as IVLBCL after a skin biopsy. Following four cycles of zanubrutinib in combination with the R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the patient achieved complete resolution of both dermatological manifestations and systemic symptoms. Laboratory parameters, including complete blood count, serum albumin levels, and lactate dehydrogenase, were normalized. Additionally, ultrasonography demonstrated a marked reduction in splenic size. However, the patient exhibited suboptimal adherence to the prescribed treatment plan and did not complete the intended number of cycles. During a subsequent telephone follow-up, the patient was confirmed to be alive; however, the status of the disease could not be evaluated. As of the latest follow-up, the patient has survived for 2 years.
Ovarian cancer (OC) peritoneal metastasis (OCPM) is a major cause of high mortality of OC, in which cancer cells incubated in ascites evolve various mechanisms to survive. Hippo/YAP singling plays multiple roles in carcinogenesis, however, its roles in OCPM have remained elusive. Here, we report that restriction of YWHAB-mediated YAP cytoplasmic retention is a critical mechanism underlying OCPM stemness maintenance. Combined tandem mass tag- and tissue microarray-based proteomic studies revealed YWHAB down-regulation in post-neoadjuvant chemotherapy OCPM tissues, which was confirmed in no-neoadjuvant-chemotherapy-response tissues, isolated OCPM stem cells, and induced cisplatin-resistant cells. Knockdown of YWHAB promoted stemness and resistance in parental complete or near-complete primary OCPM and OVCAR3 cells in vitro and in vivo. Mechanistic study showed that YWHAB directly bound to YAP and promoted YAP cytoplasmic retention and thus YWHAB restriction promoted YAP activity and stemness in OCPM in the cells in which the Hippo/YAP signaling was constitutively activated by overloaded constitutively active YAP (YAP5SA), and the effect of YWHAB knockdown was significantly abolished. The SH3 binding domain in YAP is critical for YWHAB-YAP binding. Alteration in the 5mc methylation level in the YWHAB promoter was observed in OCPM stem cells. In summary, our results reveal that restriction of YWHAB-mediated YAP cytoplasmic retention is a critical mechanism underlying OCPM stemness maintenance. Our findings suggest that YAP would be a therapeutic target for suppressing OCPM stemness caused by YWHAB restriction.
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.
To analyze the risk factors for late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors for the progression of LOHC to severe LOHC, and the effect of LOHC on survival.METHODS:The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed. The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis. Then, the differences in overall survival (OS) and progression-free survival (PFS) between different groups were analyzed.RESULTS:The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows: age≤45 years old (P =0.039), intensified conditioning regimen with fludarabine/cladribine and cytarabine (P =0.002), albumin≤30 g/L on d30 after transplantation (P =0.007), CMV-DNA positive (P =0.028), fungal infection before transplantation (P =0.026), and the occurrence of grade Ⅱ - Ⅳ aGVHD (P =0.006). In the transplant patients who have already developed LOHC, the occurance of LOHC within 32 days after transplantation (P =0.008) and albumin≤30 g/L on d30 after transplantation (P =0.032) were independent risk factors for the progression to severe LOHC. The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC (P =0.041).CONCLUSION:For the patients aged≤45 years old and with intensified conditioning regimen, it is necessary to be vigilant about the occurrence of LOHC; For the patients with earlier occurrence of LOHC, it is necessary to be vigilant that it develops into severe LOHC. Early prevention and treatment of LOHC are essential. Regular monitoring of CMV-DNA and albumin levels, highly effective antiviral and antifungal therapies, and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.
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.
OBJECTIVE:To investigate the efficacy and safety of matched sibling donor allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of young patients with multiple myeloma (MM).METHODS:The clinical data of 8 young patients (median age:46 years) with MM who underwent allo-HSCT from HLA-indentical sibling donors in the First Affiliated Hospital of Chongqing Medical University from June 2013 to September 2021 were collected, and their survival and prognosis were retrospectively analyzed.RESULTS:All the patients were successfully transplanted, and 7 patients could be evaluated the efficacy after transplantation. The median follow-up time was 35.2 (2.5-84.70) months. The complete response (CR) rate was 2/8 before transplantation and 6/7 after transplantation. Acute GVHD developed in 2 cases and extensive chronic GVHD developed in 1 case. Within 100 days, 1 case died of non-recurrent events, and 1-year and 2-year disease-free survival were 6 and 5 cases, respectively. At the end of follow-up, all the 5 patients who survived for more than 2 years survived, and the longest disease-free survival time has reached 84 months.CONCLUSION:With the development of new drugs, HLA-matched sibling donor allo-HSCT may be a curable treatment for young patients with MM.
Patterns of hepatitis B virus reactivation (HBV-R) in HBsAg (-)/HBcAb (+) patients with B-cell non-Hodgkin lymphoma (NHL) receiving rituximab based immunochemotherapy have not been well described. The retrospective study included 222 HBsAg (-)/HBcAb (+) NHL patients as training cohort and 127 cases as validation cohort. The incidence of HBV-R in HBsAg (-)/HBcAb (+) B-cell NHL patients was 6.3% (14/222), of which that in HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was 23.7% (9/38). Multivariate analysis showed that HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) correlated with a high risk of HBV-R in B-cell lymphoma patients (training phase hazard ratio [HR], 10.123; 95% confidence interval [CI], 3.389-30.239; p < 0.001; validation phase HR, 18.619; 95% CI, 1.684-205.906; p = 0.017; combined HR, 12.264; 95% CI, 4.529-33.207; p < 0.001). In the training cohort, the mortality rate of HBsAg (-)/HBcAb (+) B-cell NHL caused by HBV-R was 14.3% (2/14) while that for HBV reactivated HBsAg (-)/HBsAb (-)/HBeAg (-)/HBeAb (+)/HBcAb (+) population was up to 44.4% (4/9). As a high incidence of HBV-R and high mortality after HBV-R was found in HBsAg (-)/HBsAb (-)/HBcAb (+)/HBeAg (-)/HBeAb (+) patients with B-cell NHL receiving rituximab based immunochemotherapy, prophylactic antiviral therapy is recommended for these patients.
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.
目的 探讨中高危骨髓增生异常综合征(MDS)患者的化学药物治疗(简称化疗)方案及预后.方法 选取医院血液内科2015年1月至2020年10月收治的MDS国际预后评分系统(IPSS)危险分层为中高危的MDS患者71例,按治疗方案的不同分为接受去甲基化药物(HMA)治疗组(HMA组)和HMA联合化疗组(联合化疗组)的,回顾性分析患者的临床资料,并进行疗效评估及生存分析.结果 与HMA组比较,联合化疗组患者治疗前的IPSS危险分层更严重,骨髓原始细胞百分比更高(P<0.05),疗效、总生存率(OS)、无白血病生存率(LFS)无显著差异(P>0.05).初诊时髓系原始细胞百分比小于分界值[4.395%,由接收者操作特征(ROC)曲线得到]的非化疗组患者的OS比化疗组更高(P=0.0256),在髓系原始细胞百分比<10%的患者中得到相似结果.结论 部分MDS患者初诊时IPSS危险分层及骨髓原始细胞百分比较高,其可能需要行HMA联合化疗,但对于初诊时髓系原始细胞百分比小于4.395%的患者,化疗前需谨慎评估.
OBJECTIVE:To explore the risk factors of cytomegalovirus (CMV) and refractory CMV infection (RCI) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their influences on survival.METHODS:A total of 246 patients who received allo-HSCT from 2015 to 2020 were divided into CMV group (n=67) and non-CMV group (n=179) according to whether they had CMV infection. Patients with CMV infection were further divided into RCI group (n=18) and non-RCI group (n=49) according to whether they had RCI. The risk factors of CMV infection and RCI were analyzed, and the diagnostic significance of Logistics regression model was verified by ROC curve. The differences of overall survival (OS) and progression-free survival (PFS) between groups and the risk factors affecting OS were analyzed.RESULTS:For patients with CMV infection, the median time of the first CMV infection was 48(7-183) days after allo-HSCT, and the median duration was 21 (7-158) days. Older age, EB viremia and gradeⅡ-Ⅳacute graft-versus-host disease (aGVHD) significantly increased the risk of CMV infection (P=0.032, <0.001 and 0.037, respectively). Risk factors for RCI were EB viremia and the peak value of CMV-DNA at diagnosis≥1×104 copies/ml (P=0.039 and 0.006, respectively). White blood cell (WBC)≥4×109/L at 14 days after transplantation was a protective factor for CMV infection and RCI (P=0.013 and 0.014, respectively). The OS rate in CMV group was significantly lower than that in non-CMV group (P=0.033), and also significantly lower in RCI group than that in non-RCI group (P=0.043). Hematopoietic reconstruction was a favorable factor for OS (P<0.001), whereas CMV-DNA≥1.0×104 copies/ml within 60 days after transplantation was a risk factor for OS (P=0.005).CONCLUSION:The late recovery of WBC and the combination of EB viremia after transplantation are common risk factors for CMV infection and RCI. CMV-DNA load of 1×104 copies/ml is an important threshold, higher than which is associated with higher RCI and lower OS risk.
Abstract Autologous stem cell transplantation (ASCT) is an important treatment for Peripheral T-cell lymphoma (PTCL) patients both during front and salvage therapy. We retrospectively compared the outcomes of 52 PTCL patients treated with CEAC (n=28), BEAM (n=14) and IEAC (n=10) regimens followed by ASCT at our center between 2012 and 2021. Although the time of neutrophil engraftment in CEAC group was earlier than that in IEAC group (P=0.042) and platelet infusion in BEAM group was significantly more than CEAC group (P=0.042), there were no significant difference in platelet engraftment, hematopoietic engraftment and red blood cells infusion among the 3 groups. The transplantation related mortality rate (TRM) and the early overall response rate (ORR) was 3.8% and 85.7% respectively. The 5-year OS and PFS was 62.8% (95% CI: 54.8%-70.8%) and 61.0% (95% CI: 53.1%-68.9%) respectively. There was no significant difference in TRM, ORR and survival among the 3 groups. Univariate and multivariate analysis showed that high PIT score (>1) and non-CR at 3 months after ASCT were common risk factors for OS (P=0.036 and 0.007) and PFS (P=0.021 and 0.012). In conclusion, CEAC and IEAC regimen can be used as alternative conditioning regiments for ASCT in PTCL patients, and their efficacy and safety are comparable to BEAM regiment. Patients with high PIT score and failure to reach CR early after ASCT had worse outcomes.
OBJECTIVE To evaluate the clinical effect of haploid allogeneic hematopoietic stem cell transplantation(haplo-HSCT) in the treatment of severe aplastic anemia (SAA), and to explore the efficacy different between post-transplant cyclophosphamide (PT/Cy) and standard-dose ATG. METHODS The clinical data of 38 patients with SAA in our hospital from January 2012 to December 2019 were collected and retrospectively analyzed. The efficacy was evaluated. The patients with haplo-HSCT were divided into low-dose ATG combined with PT/Cy group and standard-dose ATG group, and the blood cell hematopoietic reconstruction time, GVHD incidence, mortality and survival time of the patients in the two groups was compared. RESULTS Among the 32 patients, hematopoietic reconstitution were detected in 9375%(30/32) recipients. The median time of neutrophil and platelet engraftment was 15(10-22) days and 13(7-30) days, respectively. The incidence of GVHD was 21.89%, the incidence of infection was 93.75%, and the 2-year overall survival rate was 84.38%. The hematopoietic reconstitution time, incidence of GVHD, mortality rate and survival time were no statistical differences between the patients in the two groups(all P>0.05). CONCLUSION Haplo-HSCT is an effective method for the treatment of SAA,low-dose ATG combined with PT/Cy can lighten the economic burden on patients, it would be a feasible treatment plan for SAA with light side effect.