Complete Remission Rate Research Articles

B cell-driven reduced-dose rituximab as induction therapy for 2 patients with ANCA-associated renal vasculitis: Acase series.

Antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV), a multisystem autoimmune disorder, deteriorates small vessels. Kidney involvement occurs in most affected patients and is the most common cause of rapidly progressive glomerulonephritis (RPGN). Rituximab (RTX), an anti-CD20 antibody, has been used in the induction and maintenance therapy of AAV as a non-inferior alternative to cyclophosphamide. Administration of 4 once-weekly doses of 375 mg/m2 is the common dose in remission induction therapy, referred to as a conventional regimen. Recently, it was shown that the cumulative complete remission (CR) rates did not differ between low-dose RTX (2 once-weekly doses of 375 mg/m2) and the conventional RTX regimen. We aimed to explore the effect of the B cell-driven RTX dosing regimen. Herein, we reported B cell-driven reduced-dose RTX therapies in a 71-year-old male de novo patient (case 1) and a 60-year-old female patient (case 2). Case 1, de novo diagnosed based on kidney biopsy, received 3 once-semimonthly doses of 300 mg RTX as induction therapy. Case 2, who was clinically diagnosed with ANCA-associated renal vasculitis 4 years before receiving treatment at our hospital, accepted 4 once-monthly doses of 300 mg RTX as induction therapy. Further dosages were dependent on peripheral CD19+ B-cell levels. During the course of treatment, peripheral B-cell counts of both patients turned 0, and symptoms of both patients improved, complete remission occurred in case 1, with a Birmingham vasculitis activity score (BVAS) of 0. B cell-driven reduced-dose RTX might be also effective in induction therapy for AAV. Further study is warranted to confirm the efficacy, safety, and risk of relapse of a reduced-dose RTX regimen.

A multicenter retrospective study on comparing the efficacy and safety of the therapy of intermittent cyclophosphamide and corticosteroids versus rituximab for primary membranous nephropathy.

Few clinical studies compare the long-term remission, relapse, and safety of rituximab (RTX) or a combination of intermittent intravenous infusion of cyclophosphamide (CTX) and oral corticosteroid for primary membranous nephropathy (PMN) patients. We collected multicenter retrospective data on PMN patients with nephrotic syndrome who received RTX or intermittent intravenous CTX with oral corticosteroids between 1 January 2019 and 31 January 2024. Patients were followed up until two years after receiving immunotherapy. The primary outcomes were a composite of complete or partial remission rates at 6, 12, and 24months. The secondary outcomes were the relapse and safety evaluation. Forty patients treated with RTX and 27 with the CTX regime were available for analysis. No significant difference in the remission rate at 6, 12, or 24months was observed between the two groups (p>.05). Kaplan-Meier's survival analysis showed that the relapse-free cumulative survival rate of the RTX group was superior to that of the CTX group (p=.023). Compared with baseline, both the media of urine protein and serum albumin levels in the two groups showed a significant improvement at 6months and maintained through to the second year. No significant difference in the occurrence of total side effects between the two groups (p=.160). There was no difference in remission rates and safety between RTX versus intermittent intravenous CTX combined with oral corticosteroid treatment for patients with PMN within 2years. RTX appeared to have benefits in terms of prolonging relapse-free survival.

Personalized Membrane Protein Vaccine Based on a Lipid Nanoparticle Delivery System Prevents Postoperative Recurrence in Colorectal Cancer Models

While accessing tumor neoantigens and developing effective delivery systems have posed significant challenges in therapeutic oncology vaccines, this study introduces a cost- and time-efficient personalized tumor vaccine demonstrating potent anti-tumor effects in a mouse xenograft model. This vaccine utilizes a lipid nanoparticle (C5 LNP) system loaded with membrane protein antigens (mAg) derived from surgically excised tumor tissue. Its safety and efficacy were validated in a B16-OVA murine model. C5/OVA exhibited significant uptake by dendritic cells (DCs), leading to cross-presentation, maturation, and subsequent initiation of robust cell-mediated and humoral immune responses. This resulted in clear tumor growth suppression and extended survival in the B16-OVA model. Furthermore, the personalized C5/mAg vaccine effectively inhibited tumor growth in a colorectal carcinoma model. When combined with anti-PD-1 therapy, it notably increased complete remission (CR) rates in the CT26 xenograft model. Vaccinated mice demonstrated 100% resistance to tumor rechallenge, underscoring the vaccine's ability to induce long-term immune memory. This study presents a promising personalized cancer vaccine delivery system with potential for both treatment and prevention of carcinoma in clinical applications. Statement of significanceIn this paper, we present a scheme for manufacturing personalized tumor vaccines. The vaccine component consists of lipid nanoparticles (LNPs) designated C5 and membrane protein antigens (mAg) derived from autologous tumor tissue surgically resected from the patient. Our study demonstrates that the personalized mAg-C5 vaccine for colorectal carcinoma significantly inhibits tumor growth. Furthermore, conjugation with anti-PD-1 therapy demonstrably increased the complete remission (CR) rate in the murine CT26 xenograft tumor model. Additionally, mice treated with the C5/mAg vaccine exhibited 100% resistance to tumor growth in a colon carcinoma rechallenge model, indicating the induction of immune memory by the vaccine.Our research results suggest that the mAg-LNP vaccine is a simple, cost-effective treatment that clinicians can easily and quickly integrate into routine practice.

Integrated Analysis of Polymerase Family Gene Mutations in Acute Myeloid Leukemia: Clinical Features, Prognosis, and Bioinformatics Insights

Background and Objectives: The long-term prognosis of acute myeloid leukemia (AML) is challenging due to limited understanding of the molecular markers involved in its development. This study investigates the role of DNA polymerases in AML to offer new insights for diagnosis and treatment. Materials and Methods: A retrospective study on pediatric AML patients with POL gene family mutations from 2021 to 2024 was conducted. Patients were categorized based on risk stratification criteria, and the DAH regimen was used for induction chemotherapy. Bioinformatics analysis integrated data from various databases to identify key genes and develop survival analysis plots and AUC curves. Results: The study included 59 pediatric AML patients, revealing no significant differences in demographic or clinical characteristics between those with and without POL family gene mutations. However, patients with POL gene mutations showed higher complete remission rates after initial DAH chemotherapy (91.67% vs. 59.57%, p = 0.03607), indicating a potential treatment benefit. High expression of four POL genes (POLD1, POLE, POLG, and POLQ) in bone marrow and immune cells suggests their crucial role in hematopoiesis and immune response. Survival analysis across different datasets indicated that AML patients with overexpressed POL family genes had significantly worse outcomes, proposing these genes as potential prognostic biomarkers for AML. Conclusions: This study on pediatric AML demonstrates that POL gene family mutations are associated with higher remission rates post-chemotherapy, indicating their potential as prognostic markers. Bioinformatics analysis emphasizes the significance of these mutations in AML, highlighting their impact on disease prognosis.

Salvage Therapy with Second-Generation Inhibitors for FLT3 Mutated Acute Myeloid Leukemia: A Real-World Study by the CETLAM and PETHEMA Groups

Background/Objectives: Patients with relapsed/refractory (R/R) AML with FLT3 mutation (FLT3mut) have a dismal prognosis. FLT3mut offers a target for therapy in these patients. Gilteritinib (gilter) and quizartinib (quizar) have demonstrated efficacy as single agents in two phase 3 clinical trials. Methods: We retrospectively analyzed the characteristics, treatments, and outcomes of 50 patients with R/R FLT3mut AML who received gilter or quizar as monotherapy in 27 Spanish centers before their commercial availability. Forty-four patients were treated with gilter and six with quizar. Results: The median age was 62.5 years, and 52% were women. Most patients presented with FLT3-ITD mutations (80%); 46% had refractory disease and 54% had relapsed disease at treatment initiation. First-line treatment was chemotherapy in 80% of patients, with 40% of these also receiving midostaurin. Twenty-five patients (50%) had previously received FLT3 inhibitor, and twenty-eight (56%) had received more than one line treatment before starting gilter/quizar. The rates of complete remission (CR), CR without hematological recovery (CRi), and partial remission were 22%, 18%, and 16%, respectively. The median overall survival (OS) and disease-free survival were 4.74 months and 2.99 months, respectively. We observed a significant improvement in OS in patients who had received only one prior line of therapy compared to those who had received two or more therapies (10.77 months vs. 4.24 months, p = 0.016). Multivariate analysis identified failure to achieve CR/CRi, receiving more than one prior line of therapy, age, and white blood cells count as independent prognostic factors for OS. The most common toxicities were febrile neutropenia, liver function abnormalities, and QT interval prolongation. Conclusions: Gilter/quizar monotherapy are effective and tolerable options for patients with R/R FLT3mut AML in a real-world setting. Response and toxicity rates are similar to those reported in the phase 3 trials, despite the more heterogeneous nature of the study population.

Azacitidine and venetoclax with or without pevonedistat in patients with newly diagnosed acute myeloid leukemia

This phase 2 study investigated pevonedistat + azacitidine + venetoclax (n = 83) versus azacitidine + venetoclax (n = 81) in patients with newly diagnosed acute myeloid leukemia (AML) ineligible for intensive chemotherapy. The study was stopped early following negative results from PANTHER, which evaluated pevonedistat in higher-risk myelodysplastic syndromes/chronic myelomonocytic leukemia or low-blast AML. Outcomes were analyzed up to the datacut. For pevonedistat + azacitidine + venetoclax versus azacitidine + venetoclax, the median follow-up was 8.44 versus 7.95 months; the complete remission (CR) rate was 45% versus 49%; composite CR (CCR; CR+CR with incomplete blood count recovery) was 77% versus 72%. There were no differences in event-free survival (primary endpoint; hazard ratio [HR]: 0.99; 95% confidence interval [CI]: 0.61–1.60; p = 0.477) or overall survival (HR: 1.42; 95% CI: 0.82–2.49; p = 0.896). In exploratory analyses in IDH-mutated AML, CCR rates were higher with pevonedistat + azacitidine + venetoclax versus azacitidine + venetoclax. Safety was similar between treatment arms. Efficacy/safety with azacitidine + venetoclax was consistent with the phase 3 VIALE-A study. Trial registration NCT04266795

Efficacy and safety of glucocorticoid combined with cyclophosphamide therapy on membranous nephropathy: a systematic review and meta-analysis

BackgroundThis review systematically evaluates the efficacy and safety of the combined treatment of glucocorticoids (GC) and cyclophosphamide (CTX) in patients with membranous nephropathy (MN).MethodsAs of June 2024, a comprehensive literature search was performed utilizing several reputable databases, including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang. A meta-analysis was then carried out using Review Manager 5.4 and STATA/SE-15 software.ResultsThis research evaluated a total of 22 articles involving 1,971 patients. The findings revealed that patients with MN receiving combined GC and CTX therapy had significantly higher complete remission rates (odds ratio = 1.78, p = 0.02) and total remission rates (odds ratio = 2.14, p = 0.01) when the follow-up period exceeded 12 months. Additionally, this treatment demonstrated greater efficacy in lowering serum creatinine levels compared to the control group (standardized mean difference = −0.19, p = 0.04), while its relapse rate was also lower than that of the control group (odds ratio = 0.51, p = 0.009). However, it has a high incidence of serious adverse effects (odds ratio = 2.32, p = 0.03).ConclusionOur systematic review highlights that the combination of GC and CTX demonstrates superior long-term effectiveness and reduced relapse rates in managing membranous nephropathy (MN). Furthermore, this drug combination is considered the optimal choice for normalizing serum creatinine levels. Data on the effectiveness and safety of glucocorticoids alone versus other drugs alone, and the treatment of secondary membranous nephropathy (SMN), are limited.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=566477, identifier CRD42024566477.

Long-term follow-up of a phase 2 study of all-trans retinoic acid, arsenic trioxide, and gemtuzumab ozogamicin in acute promyelocytic leukemia.

All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) combinations have produced excellent outcomes in patients with standard-risk acute promyelocytic leukemia (APL). Herein, the authors update their long-term results with the regimen of ATO-ATRA and gemtuzumab ozogamicin (GO) in standard-risk and high-risk APL. This was a phase 2 trial of patients with newly diagnosed APL. Induction comprised ATRA 45 mg/m2 and ATO 0.15 mg/kg daily. GO 6-9 mg/m2 was added for high-risk patients and for standard-risk patients who developed leukocytosis >10×109/L. Consolidation consisted of four courses of ATO-ATRA, with GO for patients who had PML::RARA persistence. One hundred forty-six patients (median age, 53.0 years; range, 19.3-83.9 years) were treated, including 106 patients (72.6%) with standard-risk APL and 40 (27.4%) with high-risk APL. GO was administered to 68 standard-risk patients (64.2%) for leukocytosis. The complete remission rate was 93.8% (95% confidence interval [CI], 92.2%-98.5%). Negative measurable residual disease status was achieved in 97.1% of patients who attained complete remission. At a median follow-up of 61.8 months (95% CI, 4.7-128.4 months), the 5-year event-free survival, disease-free survival, and overall survival rates were 92.4% (95% CI, 87.9%-97.1%), 93.6% (95% CI, 89.5%-97.8%), and 93.1% (95% CI, 88.9%-97.7%), respectively. Induction mortality was 2.7%. The most common severe adverse events were elevated transaminases in 41.0% of patients and infection in 13.7%. There were no cases of veno-occlusive disease. The combination of ATO-ATRA and GO was curative in 94% of patients who had APL with a favorable safety profile (ClinicalTrials.gov identifier NCT01409161).

Efficacy and safety of rituximab in patients with lupus nephritis: A systematic review and meta-analysis.

Our aim was to systematically evaluate the efficacy and safety of rituximab (RTX) in patients with lupus nephritis (LN). PubMed, Embase, China National Knowledge Infrastructure (CNKI), Cochrane Library, and Wanfang Databases were searched to collect literature on the efficacy and safety of RTX in patients with LN. Odds ratios (ORs), weighted mean differences (WMDs), and standardized mean differences (SMDs) were used to represent treatment efficacy and overall outcome. The outcomes included complete renal remission rate, proteinuria, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine, any adverse events and serious adverse events. We explored the heterogeneity with I2 and assessed publication bias with funnel plot and Egger's test. Nine studies involving 723 patients (254 in the RTX group and 469 in the control group) were included in our systematic review and meta-analysis. RTX resulted in a higher complete renal remission rate (OR: 2.62; 95% CI 1.43 - 4.79, p = 0.024, I2 = 54.7%) than the control group. It significantly decreased SLEDAI scores (WMD = -3.79, 95% CI: -5.78 to -1.8, p < 0.001, I2 = 94.7%) as well as proteinuria (WMD = -0.9, 95% CI: -1.6 to -0.2, p < 0.001, I2 = 97.6%). There were no significant differences in any adverse events and serious adverse events between the RTX group and control group. RTX was an effective therapeutic agent in patients with LN, and it did not increase the risk of adverse events compared to the control group.

Delineation of features, responses, outcomes, and prognostic factors in pediatric PDGFRB-positive acute lymphoblastic leukemia patients: A retrospective multicenter study.

PDGFRB fusions in acute lymphoblastic leukemia (ALL) is rare. The authors identified 28 pediatric PDGFRB-positive ALL. They analyzed the features, outcomes, and prognostic factors of this disease. This multicenter, retrospective study included 6457 pediatric patients with newly diagnosed PDGFRB fusion ALL according to the CCCG-ALL-2015 and CCCG-ALL-2020 protocols from April 2015 to April 2022 in 20 hospitals in China. Of these patients, 3451 were screened for PDGFRB fusions. Pediatric PDGFRB-positive ALL accounted for only 0.8% of the 3451 cases tested for PDGFRB. These patients included 21 males and seven females and 24 B-ALL and 4 T-ALL; the median age was 10 years; and the median leukocyte count was 29.8 × 109/L at baseline. Only one patient had eosinophilia. Three patients had an IKZF1 deletion, three had chromosome 5q31-33 abnormalities, and one suffered from a complex karyotype. The 3-year event-free survival (EFS), overall survival (OS), and cumulative incidence of relapse (CIR) were 33.1%, 65.5%, and 32.1%, respectively, with a median follow-up of 25.5 months. Twenty patients were treated with chemotherapy plus tyrosine-kinase inhibitors (TKIs) and eight were treated without TKI. Complete remission (CR) rates of them were 90.0% and 63.6%, respectively, but no differences in EFS, OS, or CIR. Univariate analyses showed patients with IKZF1 deletion or measurable residual disease (MRD) ≥0.01% after induction had inferior outcomes (p<.05). Pediatric PDGFRB-positive ALL has a poor outcome associated with high-risk features. Chemotherapy plus TKIs can improve the CR rate, providing an opportunity for lower MRD levels and transplantation. MRD ≥0.01% was a powerful adverse prognostic factor, and stratified treatment based on MRD may improve survival for these patients. Pediatric acute lymphoblastic leukemia patients with PDGFRB fusions are associated with high-risk clinical features such as older age, high white blood cell count at diagnosis, high measurable residual disease after induction therapy, and increased risk of leukemia relapse. Chemotherapy plus tyrosine-kinase inhibitors can improve the complete remission rate and provide an opportunity for lower measurable residual disease (MRD) levels and transplantation for pediatric PDGFRB-positive acute lymphoblastic leukemia (ALL) patients. The MRD level was also a powerful prognostic factor for pediatric PDGFRB-positive ALL patients.

Childhood acute lymphoblastic leukemia with CREBBP gene mutation: a clinical analysis of 14 cases

To investigate the clinical features and prognosis of childhood acute lymphoblastic leukemia (ALL) with CREBBP gene mutation. A retrospective analysis was performed for the clinical data of 14 ALL children with CREBBP gene mutation who were admitted to Children's Hospital of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023. The ALL patients with CREBBP gene mutation accounted for 1.5% (14/963) among all children diagnosed with ALL during the same period of time, among whom there were 4 boys (29%) and 10 girls (71%), with a median age of 4 years and 3.5 months. All children had an immunological type of B-cell ALL and concurrent mutations in other genes including NRAS, KRAS, ETV6, FLT3, PAX5, SH2B3, CDKN2A, and CDKN2B, and 4 children had karyotype abnormality. All 14 children received induction therapy with the VDLP regimen, with a complete remission (CR) rate of 79% (11/14) after the first course of treatment. Three children experienced bone marrow recurrence alone, with a recurrence rate of 21% (3/14), among whom 1 child achieved CR after blinatumomab therapy and 2 received bridging hematopoietic stem cell transplantation after chemotherapy for recurrence. Among the 14 children, 1 died due to treatment discontinuation and 13 achieved disease-free survival. The 5-year overall survival rate was 92%±7%, and the event-free survival rate was 73%±13%. ALL with CREBBP gene mutation is more common in girls and has a low induction remission rate and a high recurrence rate, and it is often accompanied by other types of gene mutations and abnormal karyotypes. Most children with recurrence can achieve long-term survival after immunotherapy or hematopoietic stem cell transplantation.

Prognosis and risk factors of IgA vasculitis nephritis in children

Objective: To investigate the prognosis and risk factors of IgA vasculitis nephritis (IgAVN) in children. Methods: A retrospective cohort study was conducted. Clinical data were collected from 264 children who were pathologically diagnosed with IgAVN at Department of Pediatric nephrology, Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology, between January 2011 and December 2017. All patients had a follow-up period of more than 3 years. Clinical characteristics, renal pathology, 3-year and 5-year prognosis were analyzed. The patients were grouped based on gender, age of onset (≤6 years,>6-9 years, and >9 years), pathological classification (≤Ⅲ and>Ⅲ),whether the prognosis was complete remission at 3 and 5 years. Independent sample t-tests, ANOVA or chi-squared test were used for intergroup comparisons. Spearman correlation analysis was applied for ordinal data, and multivariate Logistic regression was used to analyze factors affecting the prognosis. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of these factors. Results: Of the 264 children with IgAVN, 153 were male and 111 were female, the age of onset was 8.3 (6.7, 10.3) years, 118 patients (45%) with onset age >6-9 years accounted for the highest proportion. All patients presented with skin purpura and renal involvement, primarily manifesting as hematuria and/or proteinuria. Microscopic hematuria was observed in 253 patients (95.8%), while 246 patients (93.2%) showed proteinuria. In 256 patients (97.0%), hematuria or porteinuria urinalysis was detected within 6 months of skin purpura onset, and 243 patiauts (92.0%) underwent renal biopsy within 6 months of renal involvement. The most common clinical subtype in 264 IgAVN children was hematuria and proteinuria (204 cases, 77.3%), with grade Ⅲ being the predominant pathological classification (181 cases, 68.6%). Among children ≤6 years old, the 3-year complete remission rate was higher in males than in females (83.9% (26/31) vs. 7/16, χ²=8.12, P=0.012). Factors independently associated with poor 5-year prognosis included time from hematuria or porteinuria urinalysis to renal biopsy>6 months, elevated serum cholesterol levels, and incomplete remission 3 years post-biopsy (OR=5.41, 1.39, 6.02, 95%CI 1.40-20.86, 1.04-1.84, 2.61-13.88, all P<0.05). The serum cholesterol has a predictive value for 5-year prognosis (P=0.020, AUC=0.62, 95%CI 0.52-0.71, Youden index=0.27, cutoff=4.37). Conclusions: For children with IgAVN aged≤6 years, the 3-year prognosis is better in males than in females. Time from hematuria or porteinuria urinalysis to renal biopsy>6 months, elevated serum cholesterol levels, and incomplete remission at 3 years post-biopsy may be independent risk factors for poor 5-year prognosis in children with IgAVN.

Combination of rituximab and low-dose glucocorticoids for idiopathic refractory nephrotic syndrome with MCD/FSGS: a single-center prospective cohort study

Background The treatment of idiopathic refractory nephrotic syndrome (IRNS) remains a difficult problem in clinical practice. This study aims to determine the efficacy and safety of combining low-dose glucocorticoids with rituximab in IRNS treatment. Methods This prospective, single-center cohort study enrolled 60 patients who were diagnosed with refractory IRNS with minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS) and treated at First Affiliated Hospital of Sun Yat-sen University. All patients received a treatment regimen consisting of rituximab (375 mg/m2/week × 4) and low-dose glucocorticoids. Results 46 complete remissions and 4 partial remissions were observed within 6 months of treatment. Within 12 months of treatment, 48 patients achieved complete remission, and 4 achieved partial remission. The complete remission rate for steroid-dependent/frequently relapsing nephrotic syndrome was significantly higher than that for steroid-resistant nephrotic syndrome (88.24% vs. 33.33%, p < .01). Following up for 12 months, 16 patients relapsed, accounting for 30.76% of the total, with a mean time to relapse of 10.97 months. Compared with baseline data, 24-hour urine protein quantification, total cholesterol and triglycerides significantly decreased, while serum albumin, globulin and IgG significantly increased at 12 months after treatment. All follow-ups were without serious adverse events. Twenty-four patients experienced infusion-related adverse reactions, which could be relieved by slowing down the infusion rate or suspending the infusion. Nine patients experienced infection-related adverse reactions; six of them were relieved with antibiotic treatment, and 3 patients were controlled by symptomatic treatment. Conclusions Rituximab combined low-dose glucocorticoids therapy is effective and safe in idiopathic refractory nephrotic syndrome.

Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multi-center Cohort Study.

We investigated whether homoharringtonine (HHT) added to venetoclax (VEN) plus azacitidine (VA) could improve outcomes and counteract the negative effects of genetic patterns in patients with relapsed/refractory acute myeloid leukemia (RR-AML). A multi-center, retrospective, cohort study of the response and genetic patterns of response to the VA plus HHT (VAH) versus the VA regimens as salvage treatment in patients with RR-AML was performed. The endpoints were the rates of composite complete remission (CRc), measurable residual disease (MRD), event-free survival (EFS), overall survival (OS), and relapse between VAH and VA groups. A total of 321 patients (VAH, n=172; VA, n=149) were analyzed. Compared to VA, VAH significantly improved the rates of CRc (44.3% vs. 66.3%, P<0.001), MRD-negativity (34.8% vs. 59.3%, P=0.002), prolonged OS (median: 15.1 months vs. not reached, P <0.001), and EFS (median: 3.8 vs. 13.0 months, P<0.001). VAH significantly mitigated the negative impact on VA efficacy of mutated FLT3-ITD/TKD, N/KRAS, and t(8;21)/AML1-ETO, as well as the relatively unfavorable effects of the TET2 and DNMT3A mutations. VAH significantly enhanced the response of patients with non-adverse European LeukemiaNet (ELN) risk, with a trend towards improved response in those with adverse ELN risk, complex karyotype, and DNMT3A+FLT3+NPM1+. The incidence of grade 3 or higher adverse events was comparable between the two groups. Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.

Application of CAR-T cell therapy in B-cell lymphoma: a meta-analysis of randomized controlled trials.

This study aims to compare the efficacy and safety of chimeric antigen receptor T-cell (CAR-T) immunotherapy with standard treatment for B-cell lymphoma, providing evidence-based support for the more efficient use of CAR-T cell immunotherapy. We conducted a comprehensive literature search of high-quality randomized controlled trials (RCTs) on CAR-T therapy for B-cell lymphoma in the following databases: Wanfang, Web of Science, CNKI, VIP database, and PubMed, up to February 2024. The outcome measures included objective remission rate (ORR), complete remission rate (CRR), and incidence of adverse reactions. Subgroup analysis was performed based on the differences in co-stimulatory domains. Meta-analysis was conducted using Review Manager 5.4 and Stata software. A total of five RCTs involving 1670 patients were included in this meta-analysis. The results showed that the CAR-T treatment group had significantly higher ORR (RR: 1.47, 95% CI 1.23-1.76, I2 = 80%, p < 0.0001), CRR (RR: 2.19, 95% CI 2.16-3.79, I2 = 93%, p = 0.005), cytokine release syndrome (CRS) incidence (RR: 34.51, 95% CI 2.27-523.78, I2 = 98%, p = 0.01), neurotoxicity (NT) incidence (RR: 6.00, 95% CI 1.82-19.75, I2 = 80%, p = 0.003), neutropenia incidence (RR: 1.39, 95% CI 1.02-1.88, I2 = 93%, p = 0.03), leukopenia incidence (RR: 1.39, 95% CI 1.04-1.87, I2 = 61%, p = 0.03), and headache incidence (RR: 1.56, 95% CI 1.25-1.95, I2 = 34%, p < 0.0001) compared to the standard treatment group. Subgroup analysis based on co-stimulatory domains revealed that the 4-1BB subgroup had higher incidences of CRR, CRS, NT and leukopenia than the CD28 subgroup; however, the CD28 subgroup exhibited higher ORR and neutropenia than the 4-1BB subgroup. CAR-T cell immunotherapy demonstrates superior efficacy compared to standard therapy in treating B-cell lymphoma. However, CAR-T treatment can lead to adverse reactions such as CRS and NT. Infusion of an appropriate dose of CAR-T cells (e.g., 100 × 106) may be a strategy to mitigate the risk of CRS and NT.

A phase 1/2 study of gilteritinib in combination with chemotherapy in newly diagnosed patients with AML in Asia.

This interim analysis of a phase 1/2, open-label, single-arm study assessed the safety, efficacy, and pharmacokinetics of gilteritinib plus chemotherapy in adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia. In sequential phase 1 and 2 studies, induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: idarubicin/cytarabine once daily; consolidation: cytarabine twice daily) was followed by maintenance gilteritinib 120 mg/day monotherapy. Endpoints included maximum tolerated dose (MTD), recommended expansion dose (RED), and dose-limiting toxicity (phase 1), and complete remission (CR) rate following induction therapy (primary endpoint), overall survival (OS), safety, and pharmacokinetics (phase 2). In phase 1, MTD was not reached and RED was 120 mg/day. In phase 2, the CR rate was 50.0% after induction (90% confidence interval [CI] 40.4, 59.6); however, the lower confidence limit did not exceed the pre-defined 55% benchmark. Composite CR (CRc) rates were high following induction (86.6%, 95% CI [77.3, 93.1]), consolidation, and maintenance therapy (87.8%, 95% CI [78.7, 94.0], each). The probability of OS was 86.6% at 12 months. No new safety findings were reported. In this interim analysis, gilteritinib 120 mg/day in combination with chemotherapy was well tolerated, with similar CRc rates to previous studies.

Delaying pegaspargase during induction in adults with acute lymphoblastic leukaemia is associated with lower risk of high-grade hepatotoxicity without adversely impacting outcomes.

Pegaspargase is a key drug for the treatment of younger adults with acute lymphoblastic leukaemia (ALL). Pegaspargase-associated hepatotoxicity is most common during induction, and its incidence increases with age and body mass index (BMI). We hypothesized that the delayed administration of pegaspargase during induction is associated with lower risk of hepatotoxicity while retaining efficacy. We retrospectively reviewed 141 adult patients with newly diagnosed ALL who received pegaspargase during induction from November 2013 to February 2024. There were 78 (55.3%) patients who received early pegaspargase (EP) on day 4 and 63 (44.7%) patients who received delayed pegaspargase (DP) on day 15. High-grade hepatotoxicity (grade ≥ 3 transaminitis and/or hyperbilirubinaemia) occurred more frequently in the EP group (p = 0.06). Rates of complete remission and negative minimal residual disease post induction were not different between cohorts. Univariate logistic regression analysis showed that BMI and age significantly predicted an increased risk of high-grade hepatotoxicity while DP was associated with a lower risk (odds ratio = 0.44; p = 0.04). Overall survival and event-free survival were not significantly different between cohorts. Delaying pegaspargase administration from day 4 to day 15 during induction cycle in adults with ALL might reduce the risk of high-grade hepatotoxicity without adversely impacting clinical efficacy outcomes.

Remission rate, toxicity and pharmacokinetics of venetoclax-based induction regimens in untreated pediatric acute myeloid leukemia

The efficacy and safety of venetoclax in newly diagnosed pediatric acute myeloid leukemia (AML) are not well-established as they are in adults. Children newly diagnosed with AML were recommended for induction therapy with venetoclax and chemotherapy or hypomethylating agents (HMAs) as per for the ChiCTR1900027146 trial. Venetoclax was administered at a consistent dose of 200 mg/m2/day for 28 days, with adjustments when used concurrently with azoles. The study measured both the remission rates and the safety assessments of venetoclax. We enrolled 45 newly diagnosed pediatric patients with AML. The complete remission rates were 94.7% in the low/middle-risk group and 80.8% in the high-risk group; MRD-negative rates were 52.6% and 38.5% in the low/middle-risk group and high-risk group, respectively. Venetoclax based combination therapy was well tolerated by the majority of patients. The median duration of venetoclax dosing was 18 days (range 9–28), with hematological toxicity and infection being the most common adverse events. Venetoclax-based induction regimens demonstrated a high response rate and safety profile in newly diagnosed pediatric AML cases. This underscores the significance of venetoclax as a viable treatment option for untreated AML, extending beyond its role as salvage therapy for refractory/relapsed AML.

Transarterial Infusion Chemotherapy and Embolization for Patients With Unresectable Advanced Cancer of Stomach or Gastroesophageal Junction: A Retrospective Study.

The feasibility of transarterial infusion chemotherapy and embolization (TAICE) in the treatment of advanced gastric cancer remains unclear. This study explored the value of TAICE in patients with unresectable locally advanced or metastatic cancer of stomach or gastroesophageal junction (GEJ). Patients with unresectable gastric cancer who received TAICE for tumor hemorrhage cessation were enrolled in this retrospective study. TAICE was performed using the Seldinger method. The tumor feeding artery was selected for infusion chemotherapy and then was embolized by microspheres or gelatin sponge. Patients involved in this study received one to four cycles TAICE with one to three drugs in the regimen. The possibility of surgery was evaluated after TAICE. Objective response rate (ORR), disease control rate (DCR), R0 resection rate, pathological complete remission (pCR) rate, major pathological remission (MPR) rate, progression-free survival (PFS), overall survival (OS), and safety were analyzed. Between January 2015 and December 2020, a total of 27 patients received a median of 2 (range, 1-4) cycles of TAICE. ORR and DCR were 33.3% and 74.0%, respectively. Eighteen patients received surgery, and 15 of them underwent gastrectomy and D2 lymph node dissection, with an R0 resection rate of 83.3% (15/18). Four (26.7%, 4/15) patients achieved MPR, but none achieved pCR. The median PFS was 19.8 months (95%CI, 12.1-40.0), and the median OS was 36.1 months (95%CI, 21.0-not reached). Patients with gastrectomy had significantly longer PFS (40.0 vs. 9.5 months, p < 0.0001) and OS (not reached vs. 16.6 months, p < 0.0001) than those without gastrectomy. All the TAICE-related adverse events were manageable, with the most common being fatigue (100%), nausea (63.0%), and vomiting (55.6%). No severe surgical complications occurred. TAICE was well-tolerated and could be a potential therapy to provide opportunity of surgery for patients with unresectable advanced gastric or GEJ cancer.

Exploring the Rarity: Insights into Primary Diffuse Large B Cell Lymphoma of the Prostate from a Global Retrospective Analysis

PurposeThe purpose of this study is to comprehensively analyze cases of P-DLBCL-P from a global perspective, aiming to understand the disease's characteristics, treatment responses, and outcomes. By doing so, we seek to establish a valuable reference for the clinical management of this rare malignancy. Materials and methodsThis study conducted a retrospective review of P-DLBCL-P cases reported worldwide, utilizing various online databases including PubMed, Scopus, and other English databases, as well as WanFang Data and China National Knowledge Infrastructure (CNKI) in Chinese, collecting clinical pathology information, treatment modalities, and prognosis of patients, and conducted survival analysis using the Kaplan-Meier method. ResultsA cohort comprising 68 patients was enrolled in this study. Lower urinary tract symptoms (LUTS) were prevalent in 90.63% of cases. Furthermore, 89.5% of patients exhibited prostate-specific antigen (PSA) levels below the threshold of 4 ng/mL. Prostate biopsy was the most commonly used method, accounting for 52.38% of cases, followed by Transurethral Resection of the Prostate (TURP) at 33.33%. Approximately 33.90% of patients diagnosed with prostate lymphoma experienced stage IV disease, with the bladder or ureter being the organs most frequently involved (53.33%). Surgical procedures were associated with an elevated risk of uncontrollable hemorrhage. Notably, chemotherapy demonstrated a positive therapeutic response, resulting in a complete remission (CR) rate of 50.94% and a partial remission (PR) rate of 28.30%. A subsequent follow-up study revealed a one-year survival rate of 73.08% and a three-year survival rate of 65.38%. ConclusionThe symptoms of P-DLBCL-P are often atypical, leading to many patients being diagnosed at a later stage of the disease. Through a global study of cases, we have confirmed the efficacy of the R-CHOP regimen as the preferred treatment option. Surgical intervention is typically only used for diagnostic purposes or to relieve organ obstruction.