Adult acute leukemia patients with gram-negative bacteria bloodstream infection: Risk factors and outcomes of antibiotic-resistant bacteria.

This study aims to analyze the risk factors for the development of multidrug-resistant (MDR) and carbapenem-resistant (CR) bacteria bloodstream infection (BSI) in a patient with acute leukemia (AL) and the mortality in gram-negative bacteria (GNB) BSI. This is a retrospective study conducted at West China Hospital of Sichuan University, which included patients diagnosed with AL and concomitant GNB BSI from 2016 to 2021. A total of 206 patients with GNB BSI in AL were included. The 30-day mortality rate for all patients was 26.2%, with rates of 25.8% for those with MDR GNB BSI and 59.1% for those with CR GNB BSI. Univariate and multivariate analyses revealed that exposure to quinolones (Odds ratio (OR) = 3.111, 95% confidence interval (95%CI): 1.623-5.964, p = 0.001) within the preceding 30 days was an independent risk factor for MDR GNB BSI, while placement of urinary catheter (OR = 6.311, 95%CI: 2.478-16.073, p < 0.001) and exposure to cephalosporins (OR = 2.340, 95%CI: 1.090-5.025, p = 0.029) and carbapenems (OR = 2.558, 95%CI: 1.190-5.497, p = 0.016) within the preceding 30 days were independently associated with CR GNB BSI. Additionally, CR GNB BSI (OR = 2.960, 95% CI: 1.016-8.624, p = 0.047), relapsed/refractory AL (OR = 3.035, 95% CI: 1.265-7.354, p = 0.013), septic shock (OR = 5.108, 95% CI: 1.794-14.547, p = 0.002), platelets < 30 × 109/L before BSI (OR = 7.785, 95% CI: 2.055-29.492, p = 0.003), and inappropriate empiric antibiotic therapy (OR = 3.140, 95% CI: 1.171-8.417, p = 0.023) were independent risk factors for 30-day mortality in AL patients with GNB BSI. Prior antibiotic exposure was a significant factor in the occurrence of MDR GNB BSI and CR GNB BSI. CR GNB BSI increased the risk of mortality in AL patients with GNB BSI.

Incidence, prognostic factors, and survival outcomes in patients with blastic plasmacytoid dendritic cell neoplasm: A retrospective study in the Surveillance, Epidemiology, and End Results database.

There are few large-scale epidemiological and prognostic studies on blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its rarity. We used the Surveillance, Epidemiology, and End Results database to investigate the incidence, clinical characteristics, prognostic factors, and survival trends of BPDCN. The age-adjusted incidence of BPDCN had a bimodal pattern with peaks in those under 20 and 60 years and older. Of 697 patients, the median age at diagnosis was 31 years. The most common primary sites were lymph nodes (59.4%), followed by bone marrow (17.1%) and skin (11.6%). Extranodal involvement (59.7%) was more common in patients aged 60 years and older, while lymph node involvement was predominant in other age groups. The 1-year, 3-year, and 5-year overall survival (OS) rates were 90.7%, 83.7%, and 82.3% in patients aged under 20, but dropped to 53.1%, 27.7%, and 20.0% in patients aged 60 and older. Multivariate Cox regression analysis revealed that age, sex, and first malignancy were independent prognostic factors for OS. Based on this regression model, a nomogram was built with high discrimination and calibration. The incidence, clinical characteristics, and prognosis of BPDCN patients vary by age group. Moreover, using the nomogram to predict OS can help guide individualized evaluations and clinical decisions.

Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials.

Objective: Bispecific antibody (BsAbs) therapy represents a promising immunotherapeutic approach with manageable toxicity and noteworthy preliminary efficacy in treating patients with relapsed or refractory multiple myeloma (RRMM). The objective of this systematic review and meta-analysis was to compare the efficacy and safety of B-cell maturation antigen (BCMA)-targeted BsAbs and non-BCMA-targeted BsAbs in the treatment of RRMM patients. Methods: PubMed/MEDLINE, Web of Science, EMBASE, Cochrane Library and meeting libraries were searched from inception to August 16th, 2023. The efficacy evaluation included the complete objective response rate (ORR), complete response (CR) rate, stringent CR (sCR) rate, partial response (PR) rate, and very good PR (VGPR) rate. The efficacy evaluation included any grade adverse events (AEs) and grade ≥ 3 AEs. Results: Fourteen studies with a total of 1473 RRMM patients were included. The pooled ORR of the entire cohort was 61%. The non-BCMA-targeted BsAbs group displayed a higher ORR than the BCMA-targeted BsAbs group (74% vs. 54%, P < 0.01). In terms of hematological AEs, BCMA-targeted BsAbs therapy exhibited higher risks of neutropenia (any grade: 48% vs. 18%, P < 0.01; grade ≥ 3: 43% vs. 15%, P < 0.01) and lymphopenia (any grade: 37% vs. 8%, P < 0.01; grade ≥ 3: 31% vs. 8%, P = 0.07). Regarding non-hematological AEs, there were no significant differences in the risks of cytokine release syndrome (CRS, any grade: 64% vs. 66%, P = 0.84; grade ≥ 3: 1% vs. 1%, P = 0.36) and infections (any grade: 47% vs. 49%, P = 0.86; grade ≥ 3: 24% vs. 20%, P = 0.06) between the two groups. However, non-BCMA-targeted BsAbs therapy was associated with a higher risk of immune effector cell-associated neurotoxicity syndrome (ICANS, any grade: 11% vs. 2%, P < 0.01) and lower risks of fatigue (any grade: 14% vs. 30%, P < 0.01) and pyrexia (any grade: 14% vs. 29%, P < 0.01). Conclusion: This analysis suggest that non-BCMA-targeted BsAbs therapy may offer a more favorable treatment response and tolerability, while BCMA-targeted BsAbs therapy may be associated with diminished neurotoxic effects. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42018090768.

Cost-effectiveness analysis of azacitidine maintenance therapy in patients with acute myeloid leukemia.

BACKGROUND: The QUAZAR AML-001 trial (NCT01757535) showed survival benefits with the maintenance treatment of oral azacitidine(CC-486) for acute myeloid leukemia(AML) in first complete remission. We conducted a cost-effectiveness analysis to explore the costs and benefits of oral azacitidine in AML. METHODS: We constructed a Markov model to evaluate the economic value of oral azacitidine. The time horizon was 10-years. The health utility scores and until prices of medical costs were acquired from previous studies and GoodRX. The transition probabilities were derived from the survival curves of the QUAZAR AML-001 study. Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). RESULTS: Compared with placebo, oral azacitidine improved 0.39 QALY, with an increasing cost of $458,928.66. The ICER of oral azacitidine is $1,176,740.15(P < 0.05). Deterministic sensitivity analysis showed that the price of oral azacitidine has a significant impact on ICERs (P < 0.05). Probability sensitivity analysis showed that the probability of cost-effectiveness for oral azacitidine is 0. CONCLUSION: In the United States, oral azacitidine is unlikely to be cost-effective for AML patients at current prices. CLINICAL TRIAL REGISTRATION: The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT01757535).

Preclinical studies of Flonoltinib Maleate, a novel JAK2/FLT3 inhibitor, in treatment of JAK2V617F-induced myeloproliferative neoplasms.

Janus kinase 2 (JAK2) hyperactivation by JAK2V617F mutation leads to myeloproliferative neoplasms (MPNs) and targeting JAK2 could serve as a promising therapeutic strategy for MPNs. Here, we report that Flonoltinib Maleate (FM), a selective JAK2/FLT3 inhibitor, shows high selectivity for JAK2 over the JAK family. Surface plasmon resonance assays verified that FM had a stronger affinity for the pseudokinase domain JH2 than JH1 of JAK2 and had an inhibitory effect on JAK2 JH2V617F. The cocrystal structure confirmed that FM could stably bind to JAK2 JH2, and FM suppressed endogenous colony formation of primary erythroid progenitor cells from patients with MPNs. In several JAK2V617F-induced MPN murine models, FM could dose-dependently reduce hepatosplenomegaly and prolong survival. Similar results were observed in JAK2V617F bone marrow transplantation mice. FM exhibited strong inhibitory effects on fibrosis of the spleen and bone marrow. Long-term FM treatment showed good pharmacokinetic/pharmacodynamic characteristics with high drug exposure in tumor-bearing tissues and low toxicity. Currently, FM has been approved by the National Medical Products Administration of China (CXHL2000628), and this study will guide clinical trials for patients with MPNs.

Nomograms for predicting survival outcomes in intensity-modulated radiotherapy era of nasopharyngeal carcinoma: A study based on Epstein-Barr virus DNA biological responses.

BACKGROUND: Treatment of nasopharyngeal carcinoma (NPC) is evolving toward Intensity-modulated radiotherapy (IMRT) era, which requires patient-specific reestimation of survival outcomes in modern health care. METHODS: A total of 488 detectable pre-treatment Epstein-Barr virus (EBV) DNA patients (stage II-IVa) treated with induction chemotherapy (IC) and IMRT were examined (training set, n = 325; validation set, n = 163). RESULTS: Concurrent chemotherapy (CC) was still an independent prognosticator for overall survival (OS) and progression-free survival (PFS). Both nomograms included age, T classification, N classification, post-IC EBV DNA, and CC. Predictions correlated well with observed 3-/5-year OS and PFS. The concordance index was 0.776 (95% confidence interval (CI) 0.69-0.86) for OS and 0.742 (95% CI 0.65-0.83) for PFS in the validation cohort. The nomograms can successfully classify patients into low- and high-risk groups. CONCLUSION: The validated nomograms provided useful prediction of OS and PFS for detectable pre-treatment EBV DNA patients with NPC in IMRT era.

Risk of Bleeding Associated With Ibrutinib in Patients With B-Cell Malignancies: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Ibrutinib is an oral covalent Bruton's tyrosine kinase inhibitor that has been approved for chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia and some other B-cell malignancies. Some studies have found an increased risk of bleeding with ibrutinib. Some studies, however, found no significant differences in the risk of major bleeding between patients treated with ibrutinib and those with other regimens. So, a systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to estimate the risk of bleeding associated with ibrutinib in patients with B-cell malignancies. Methods: A systematic search of PUBMED, EMBASE, Central Register of Controlled Trials, and ClinicalTrials.gov was conducted from January 2000 to February 2020 to identify RCTs by comparing ibrutinib with other agents or placebo in B-cell malignancies. The RevMan software (version 5.3) was used to carry out this analysis, and the analyzed data were represented by risk ratios (RR) and 95% confidence intervals (CI). Results: There were 11 eligible RCTs (4,288 patients). All studies reported major bleeding, and seven studies reported overall bleeding (any-grade bleeding). Ibrutinib was associated with a significantly increased risk of bleeding (overall bleeding and major bleeding) in patients with B-cell malignancies [RR = 2.56, 95% CI 1.68-3.90, p < 0.0001 and RR = 2.08, 95% CI 1.36-3.16, p = 0.0006, respectively]. The bleeding (overall bleeding and major bleeding) risk in patients with CLL was more obvious [RR = 3.08, 95% CI 2.07-4.58, p < 0.00001 and RR = 2.46, 95% CI 1.37-4.41, p = 0.003, respectively]. There were no statistically significant differences for risk of bleeding between the subgroups based on dose and treatment setting. Conclusion: Ibrutinib was associated with a significantly higher risk of bleeding (both overall bleeding and major bleeding) in patients with B-cell malignancies, especially in CLL.

Comparison of GP and TPF induction chemotherapy for locally advanced nasopharyngeal carcinoma.

OBJECTIVES: This study aims to compare two induction chemotherapy regimens, TPF and GP, for patients with locally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: We analyzed patients with newly diagnosed stage III-IVA NPC (excluding T3/T4N0, AJCC) between December 2010 and May 2015 who were treated with TPF or GP induction chemotherapy (IC) followed with concurrent chemoradiotherapy (CCRT) and those treated with CCRT alone. Treatment compliance, survival outcomes and grade 3-4 side effects were compared among these three groups. RESULTS: A total of 189 patients were eligible for this study, with 87 (46.0%), 71 (37.6%) and 31 (16.4%) in the TPF, GP and CCRT alone groups. All patients were followed for 3 years. There was no difference in the 3-year survival rate between GP- and TPF-treated patients. Disease-free survival (DFS) and overall survival (OS) were significantly improved in both IC groups compared with those in the CCRT alone group. Multivariable analysis suggested that patients with N3 had a higher risk of distant metastasis than those with N1-2. GP is not inferior to TPF regardless of different N categories. There were significant more grade 3-4 treatment-related toxicity in TPF group than in GP group. CONCLUSION: Our study found that in locally advanced NPC, the GP induction chemotherapy regimen is equivalent to TPF in treatment outcomes, but with significant less grade 3-4 acute toxicity. Further studies are needed to validate our findings.

A multidimensional nomogram combining overall stage, dose volume histogram parameters and radiomics to predict progression-free survival in patients with locoregionally advanced nasopharyngeal carcinoma.

OBJECTIVES: To develop a multidimensional nomogram for predicting the progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) (stage III-IVa). MATERIALS AND METHODS: A total of 224 patients with locoregionally advanced NPC (training cohort, n = 149; validation cohort, n = 75) were retrospectively included. We extracted 260 radiomic features from the primary tumor and lymph nodes on the axial contrast-enhanced T1 weighted and T2 weighted MRI. Radiomic signatures of the gross tumor volume (RSnx) and lymph node (RSnd), Dose Volume Histogram (DVH) signature reflecting planning score (PS), and clinical characteristics were included as potential predictors of PFS. The least absolute shrinkage and selection operator (LASSO) regression were applied for feature selection and data dimension reduction. A nomogram was developed by incorporating the selected predictors. The C-index and calibration curve were used to assess discrimination and calibration power of the nomogram, respectively. RESULTS: RSnd, PS, and tumor-node-metastasis (TNM) stage were the independent predictors for PFS (all p < 0.05). The nomogram integrating the three factors achieved a C-index of 0.811 (95% CI: 0.74-0.882) in the validation cohort for predicting PFS, which outperformed than that of the TNM stage alone (C-index, 0.613, 95% CI: 0.532-0.694). Subgroup analysis showed Epstein-Barr virus (EBV) DNA status improved the predictive accuracy of the nomogram (C-index, 0.86, 95% CI: 0.787-0.933). CONCLUSIONS: The multidimensional nomogram incorporating RSnd, PS, and TNM stage showed high performance for predicting PFS in patients with locoregionally advanced NPC.

[Disease burden of lung cancer in Jinchang cohort].

OBJECTIVE: To understand the current status of lung cancer disease burden in Jinchang cohort. METHODS: In this historical cohort study, the mortality data of the lung cancer from 2001 to 2013 and medical records of the lung cancer cases from 2001 to 2010 in Jinchang cohort were used, analyze mortality, direct economic burden, potential years of life lost (PYLL) and working PYLL (WPYLL) associated with lung cancer. RESULTS: A total of 434 lung cancer deaths occurred in Jinchang cohort from 2001 to 2013. The crude mortality rate of lung cancer was 78.06 per 100,000 from 2001 to 2013, with the increasing rate of 4.77%. The mortality rate of lung cancer in males and females were about 108.90 per 100,000 and 26.08 per 100,000 with the increasing rate of 4.24% and 6.91%, respectively. During the thirteen years, the PYLL and average PYLL (APYLL) of lung cancer were 3 721.71 person-years and 8.58 years. The APYLL of lung cancer in females (15.94 years) was higher than that in males (7.87 years). The WPYLL and the average WPYLL (AWPYLL) of lung cancer were 1161.00 person-years and 2.68 years, respectively. The AWPYLL of lung cancer was also higher in females than in males. The direct economic burden of lung cancer from 2001 to 2010 in Jinchang cohort was 6309.39 Yuan per case with no increased trend. CONCLUSION: Lung cancer is the main health problem in Jinchang cohort, causing heavy disease burden.

[Disease burden of liver cancer in Jinchang cohort].

OBJECTIVE: To understand the current status of the disease burden of liver cancer in Jinchang cohort. METHODS: All the liver cancer death data from 2001 to 2013 and medical records of liver cancer cases from 2001 to 2010 in Jinchang cohort were collected for the analyses of the mortality, standardized mortality, potential years of life lost (PYLL) and working PYLL (WPYLL) associated with liver cancer. Spearman correlation and the average growth rate were used to analyze the trends. RESULTS: A total of 207 liver cancer deaths occurred in Jinchang cohort from 2001 to 2013, accounting for 16.68% of total cancer deaths. There were 259 liver cancer inpatients, accounting for 6.79% of the total cancer cases inpatients, in which 83 died (32.05%). Liver cancer death mainly occurred in males, accounting for 88.89%, and the liver cancer deaths in females accounted for 11.11%. The standardized mortality rate was 42.32/100,000 in males and 15.31/100,000 in females. The growth rate of liver cancer mortality was 5.62% from 2001 to 2013. Liver cancer deaths mainly occurred in age groups 60-69 years (26.57%) and 50-59 years (24.15%). The PYLL was 2906.76 person-years, the average PYLL was 14.04 years. The WPYLL was 1477.00 person-years and the average WPYLL was 7.14 years. The direct economic burden of liver cancer was 6270.78 Yuan per person, 301.75 Yuan per day. The average stay of hospitalization was 21.32 days. CONCLUSION: The mortality rate of liver cancer is increasing and the disease burden is still heavy.

[Disease burden of colorectal cancer in Jinchang cohort].

OBJECTIVE: To evaluate the disease burden of colorectal cancer in Jinchang cohort, and provide evidence for preventing colorectal cancer and reducing the disease burden of colorectal cancer in the cohort. METHODS: The colorectal cancer mortality data from 2001 to 2013 and the medical records of colorectal cancer patients from 2001 to 2010 were collected for this retrospective cohort study. The colorectal cancer disease burden was described by using mortality rate, standardized mortality rate, medical expenditure, potential years of life lost (PYLL), average potential years of life lost (APYLL), working potential years of life lost (WPYLL), and average working potential years of life lost (AWPYLL). The development trend in disease burden of colorectal cancer was analyzed by using Spearman correlation and the average growth rate. RESULTS: The crude mortality rate of colorectal cancer from 2001 to 2013 was 9.53/100,000 with the average annual growth rate of 12.89%. The PYLL, APYLL, WPYLL and AWPYLL of colorectal cancer were 485.00 person-years, 9.15 years, 253.00 person-years, and 4.77 years, respectively. The direct medical expenditure due to colorectal cancer was 7064.38 Yuan per case and 408.43 Yuan per day. There was no increasing trend in the direct medical expenditure due to colorectal cancer. CONCLUSION: Colorectal cancer mortolity rate was on the rise and it caused heavy disease burden in Jinchang cohort.