The correlation between gut microbiota and sleep quality changes in breast cancer patients receiving postoperative chemotherapy: a longitudinal study.

Skeletal muscle mass and radiation attenuation (RA) have been shown to be associated with chemotoxicity and survival in cancer patients. However, little is known about the clinical significance of adipose tissue RA, which has been hypothesized to be associated with tissue inflammation and insulin resistance. We investigated the association between adipose tissue RA, chemotoxicity, and survival in patients with metastatic colorectal cancer (mCRC) by performing a secondary analysis using data from a randomized controlled trial. We included 104 mCRC patients treated with standard first-line chemotherapy. Using diagnostic abdominal computed tomography (CT) scans, we assessed height adjusted (cm2) area and RA of skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) at the third lumbar vertebra, and calculated SM index (SMI), VATI, and SATI as cm2/m2 based on stature. Associations between these body composition parameters and overall survival as well as chemotoxicity (NCI-CTCAE v 4.03) were evaluated using univariable and multivariable logistic and Cox regression analysis. Multivariable models evaluated body composition parameters, adjusted for age, sex, and significant clinically relevant covariates. Among the 104 patients in the cohort, 38 were female (36.5%). Mean age was 65.5 ± 9.5 years. 43 patients (41.3%) developed grade 3/4 toxicity. Pre-treatment SAT-RA was independently associated with grade 3/4 toxicities (OR = 0.78, 95% CI 0.62-0.98). Chemotherapy regimens and nutritional support were not associated with chemotoxicity. In the multivariable Cox analysis, SAT-RA (HR = 1.24, 95% CI 1.08-1.43) and SM-RA (HR = 0.74, 95% CI 0.61-0.90) were associated with shorter overall survival. Higher SAT-RA and lower SM-RA at baseline were associated with shorter overall survival of patients with mCRC, and lower SAT-RA was associated with increased chemotoxicity. These body composition alterations should be investigated in future chemotherapy related studies.

Mantle cell lymphoma (MCL) is a biologically and clinically heterogeneous B-cell malignancy with variable prognosis, ranging from indolent, asymptomatic forms to aggressive subtypes with early treatment failure. Contemporary management emphasizes risk-adapted strategies that integrate patient characteristics, clinical disease burden, and tumor biology. Prognostic tools such as the MCL International Prognostic Index (MIPI) and its biologically integrated variant (combined MIPI), alongside assessment of Ki-67 proliferation, TP53 status, and blastoid morphology, help guide treatment selection. In younger, fit patients, first-line therapy traditionally involves dose-intensified chemoimmunotherapy with high-dose cytarabine and autologous stem-cell transplantation (ASCT). The incorporation of Bruton tyrosine kinase inhibitors (BTKi), such as ibrutinib, into induction regimens has improved survival outcomes, with emerging evidence that may limit the use of ASCT to high-risk subsets. Maintenance therapy, particularly rituximab, remains crucial for durable disease control. In older or transplant-ineligible patients, bendamustine-rituximab remains a backbone therapy, with chemotherapy-free combinations incorporating BTKi, BCL2 inhibitors, and anti-CD20 antibodies offering effective, well-tolerated alternatives. High-risk patients, including those with TP53 mutations, may benefit from targeted triplet regimens or early cellular therapies. Relapsed/refractory MCL is increasingly managed with covalent and noncovalent BTKi, BCL2 inhibitors, and T-cell-redirecting therapies including chimeric antigen receptor T-cell therapy and bispecific antibodies. Ongoing trials are evaluating optimal sequencing and combination strategies to improve outcomes, particularly in high-risk and cBTKi-exposed patients. Overall, modern MCL management emphasizes individualized therapy based on biological risk, functional status, and treatment tolerability, with novel targeted and cellular approaches reshaping the frontline and relapsed treatment landscape.

Primary mediastinal lymphoma is rare in dogs and literature exploring this disease is limited. Therefore, the aim of this study was to describe presentation, treatment and outcome in a large cohort of dogs with mediastinal lymphoma and explore prognostic factors including chemotherapy protocol. This retrospective multi-institute study included 70 dogs with primary mediastinal lymphoma treated with lomustine-based (LOP/LOPP) or anthracycline-based (CHOP/CEOP) chemotherapy. Most immunophenotyped cases were of T-cell lineage (95.6%). The majority were substage b (90%) and hypercalcaemia was noted in 69.1% of dogs. Clinical and objective response rates to chemotherapy were 92.7% and 97.9%, respectively, with 76.6% of dogs achieving a complete response. Median progression free survival (PFS) was 132 days (95% CI 83-181), and median overall survival time (OST) was 223 days (95% CI 175-271). The 6-month, 1-year, and 2-year survival rates were 55.7%, 22.9%, and 15.7%, respectively. On multivariable analysis, factors associated with longer PFS included hypercalcaemia (p = 0.041), chemotherapy-induced neutropenia (p = 0.014) and CD4+/CD8- immunophenotype (p = 0.004). Neutropenia at diagnosis was associated with shorter PFS (p = 0.015) and OST (p = 0.004). Other factors associated with shorter OST included granular morphology (p = 0.023) and CD4+/CD8+ immunophenotype (p = 0.004). Chemotherapy-induced neutropenia was associated with improved OST (p = 0.042). Differences in outcome between anthracycline- or lomustine-based chemotherapy protocols were not statistically significant. Overall, the prognosis for primary mediastinal lymphoma in dogs is poor to fair when treated with multi-agent chemotherapy. This is the second study associating hypercalcaemia with improved PFS in dogs with non-indolent T-cell lymphoma. Results also suggest prognostic significance of specific CD4/CD8 expression patterns.

Ewing sarcoma (EWS), rhabdomyosarcoma (RMS), and osteosarcoma (OSS) are rare in adults; efficacy and feasibility of treating adults with standard paediatric protocols (PP) are uncertain as chemotherapy protocols have been extrapolated from a paediatric population. A systematic review was conducted for EWS, RMS, and OSS using the Population, Intervention, Comparison, and Outcome (PICO) framework. PICO 1 compared adults treated with PP vs personalised "adult protocols" (non-PP). PICO 2 compared adults vs children treated with PP. PP was defined as: VDC/IE, VIDE for EWS; IVA, VAC for RMS; and MAP for OSS. 14, 13 and 9 studies for EWS, RMS and OSS were identified; majority were retrospective. Compared with non-PP, PP was associated with improved survival in adults with RMS (5-year OS of 56.7% vs 39.5% in a non-metastatic cohort, multivariate analysis, p = 0.042). There was limited robust data directly comparing PP vs non-PP in adults with EWS and OSS. Acknowledging many potential confounders, adequate chemotherapy exposure may be associated with improved survival across EWS, RMS and OSS. Compared to children, adults had lower chemotherapy exposure and differential toxicities: more peripheral neuropathy, but similar or reduced haematological toxicity. The treatment of adults with EWS, RMS, and OSS remains an area of unmet need. Adequate chemotherapy exposure and inclusion of disease-specific therapeutic agents may be important elements in the optimal treatment of adults. Referral to a specialised sarcoma reference centre is strongly recommended.

A chemotherapy-free, pathological response-adapted strategy using trastuzumab-pertuzumab and T-DM1 in HER2-positive early breast cancer: the PHERGain-2 study.

How mathematical forms of chemotherapy and radiotherapy bias model-optimized predictions: Implications for model selection.

To describe the treatment pattern and outcomes for patients with extracranial, extragonadal germ cell tumors (EGCTs). We conducted a retrospective analysis of male patients with EGCT prospectively registered in the Australian GCT clinical registry (iTestis) since its inception in 2018. Demographics, clinicopathologic features, treatment characteristics, and outcomes were recorded. Data were analyzed using descriptive statistics and the Kaplan-Meier method estimates of overall survival (OS). Of 1256 patients in the iTestis registry, 33 (3%) had EGCT including 18 (55%) with mediastinal, 14 (42%) with retroperitoneal, and 1 (3%) with a lung primary. The median age was 31 years (range: 24-38), ECOG performance status was 0-1 in 26 (79%), and 21 (64%) were non-seminoma. Chemotherapy was administered upfront in 27 (82%) patients, upfront surgery in four patients (12%), and treatment was unknown in two (6%) patients. The most common chemotherapy regimen was bleomycin/etoposide/cisplatin (BEP) (n=20, 74%), followed by etoposide/ifosfamide/cisplatin (VIP) (n=5, 19%) and EP (n=2, 7%). Post-chemotherapy surgery was carried out in 16 (59%) patients, and 4 (15%) patients received second-line chemotherapy. At a median follow-up of 22.7 months (range: 0-126), no deaths were observed in individuals with retroperitoneal primary (n=14), seminoma (n=12), or International Germ Cell Cancer Collaborative Group (IGCCCG) good (n=15) and intermediate risk (n=3) disease. Three deaths occurred in patients with mediastinal non-seminoma. The estimated 24-month OS for mediastinal non-seminoma and IGCCCG poor risk disease was 71% (95% confidence interval [CI]: 27%-94%) and 79% (95% CI: 25%-95%), respectively. Incidence of EGCT in Australia is consistent with published literature. Treatment patterns reflect international practices. Primary mediastinal non-seminoma has the poorest outcomes. Primary retroperitoneal and primary mediastinal seminomas have excellent outcomes.

Chemotherapy-induced peripheral neuropathy (CIPN) is a complication caused by some drugs used to treat cancers including metastatic spine and malignant nerve tumors. Debilitating denervation may result from such tumors directly or from their surgical resection. The inhibitory effects of adjuvant chemotherapy on nerve regeneration in peripheral neurotization surgeries are poorly understood and must be inferred from known mechanisms of CIPN. This narrative review aims to create an index of chemotherapeutics that may cause chemotherapy-associated neurotization failure (CANF) to better inform preoperative counseling, operative timing, and postoperative prognostication by peripheral nerve surgeons. A narrative review of published English-language literature on CIPN was performed, focusing on its known pathogenic mechanisms and its clinical manifestations including onset, duration of dysfunction, and effect size. The literature was also searched for existing evidence on the effects of the same agents on nerve regeneration and outcomes after peripheral nerve surgery. CIPN can manifest with sensory, motor, and/or autonomic dysfunction. Platinum-based compounds, taxanes, vinca alkaloids, antimetabolites, and proteasome inhibitors are implicated drug classes, all of which have distinct neurotoxicity profiles. CIPN phenotypes vary in timing, severity, and nerve modalities affected. Some agents are associated with a "coasting" phenomenon, where neuropathy persists even after the offending drug's discontinuation. The neurotoxic milieu induced by chemotherapy likely impairs nerve regeneration, but this has not been addressed in the literature. Data on neurotoxic chemotherapy agents were synthesized and used to create an index and risk-stratified decision tree based on inferred likelihood of CANF. Denervated patients on neurotoxic adjuvant chemotherapy regimens pose unique challenges to peripheral nerve surgeons. At least a cursory understanding of CIPN-implicated drugs, mechanisms of neurotoxicity, presentations, and the inferred risk of CANF is recommended before pursuing neurotization surgery. This index serves as a resource for peripheral nerve surgeons in this clinical conundrum.

Chemoimmunotherapy efficacy in patients with and without liver metastases: A systematic review and meta-analysis.

Canine lymphoma is a heterogenous group of diseases. The most common subtype is diffuse large B cell lymphoma (DLBCL), though definitive diagnosis beyond non-indolent = multicentric B cell lymphoma is not often achieved in clinical practice as it requires histopathology. Most dogs respond well to standard-of-care multiagent chemotherapy (CHOP) but relapse and eventual CHOP-resistance is likely. Less commonly there is a lack of complete response to initial CHOP treatment. CHOP-resistant cases are treated with rescue chemotherapy protocols, of which many are published, but the most effective is unknown. In this systematic review we aimed to determine the most effective rescue chemotherapy protocol for dogs with multicentric non-indolent B cell lymphoma resistant to initial chemotherapy with a CHOP-based protocol. After initial screening, 65 full-text articles were reviewed. However, outcomes for the population of interest could not be identified in any, leaving our research question unanswered. Future publications of rescue treatment for canine lymphoma should report outcomes separately for groups of dogs where disease characteristics and prior treatment may affect outcome.

The optimal adjuvant alkylating chemotherapy regimen for high-risk WHO grade 2 glioma in the molecular era remains uncertain. We evaluated real-world treatment patterns, toxicity, and outcomes following radiotherapy with adjuvant temozolomide (TMZ) or procarbazine, lomustine, and vincristine (PCV) in a multicentre Canadian cohort. PROTECT is a retrospective multicentre cohort study including adults with clinically defined high-risk WHO grade 2 diffuse glioma treated with radiotherapy and adjuvant alkylating chemotherapy. Clinical, molecular, treatment delivery, toxicity, surveillance, and survival data were collected. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test and Cox regression. A total of 116 patients were included, with a median follow-up of 71 months. Isocitrate dehydrogenase (IDH) mutation was present in 84.6% of evaluable cases, and 1p/19q codeletion in 56.6% of tested tumours. Median OS was not reached, with estimated 3- and 5-year OS rates of 97.3% and 94.1%, respectively. Median PFS was 8.4 years, with 3- and 5-year PFS rates of 83.6% and 77.9%, respectively. In multivariable analysis, IDH status was the only independent predictor of PFS (HR = 3.54, 95% CI 1.12-11.15; p = 0.03). Among patients with IDH-mutant tumours, PFS did not differ significantly between TMZ and PCV, including in analyses stratified by 1p/19q status. PCV was associated with higher rates of dose modification, treatment delays, and hematologic toxicity. In high-risk WHO grade 2 glioma, outcomes were favorable with radiotherapy and adjuvant alkylating chemotherapies, with greater toxicity associated with PCV compared to TMZ. IDH mutational status emerged as the dominant prognostic factor. Prospective, molecularly stratified trials are necessary to characterize comparative effectiveness of regimens.

Mutations in Fms-like tyrosine kinase 3 (FLT3) are strongly associated with relapse and resistance in acute myeloid leukemia (AML) patients, and the treatment of relapsed or refractory AML (R/R AML) remains a major clinical challenge. We previously conducted a prospective clinical trial on R/R AML with chemotherapy regimen BHA (bortezomib, homoharringtonine and cytarabine), which demonstrated promising efficacy in patients with FLT3-mutated R/R AML. However, the therapeutic mechanism remains unclear. In this study, we aim to elucidate the therapeutic mechanism of BHA regimen on the basis of its efficacy for FLT3-mutated R/R AML. We retrospectively analyzed twenty-nine patients with R/R AML, after one course of therapy, patients harboring FLT3 mutations had a significantly higher complete remission/complete remission with incomplete hematologic recovery rate than those without FLT3 mutations (46.67% vs. 7.14%, respectively; P = 0.035). To further explore the underlying mechanisms, we conducted combination index analysis, inhibition of proliferation and apoptosis assays. Compared with 293T-FLT3 cells, 293T-FLT3-ITD cells were more sensitive to bortezomib, with significantly lower IC50 values. Bortezomib in combination with homoharringtonine had a synergistic effect on FLT3-ITD cells. Moreover, compared with monotherapy, the combination of bortezomib (4nM) and homoharringtonine (1nM) markedly increased total cell death in FLT3-ITD cell lines (MV4-11 and Molm-13). Mechanistically, bortezomib promoted the degradation of FLT3-ITD protein, and the degradation of FLT3-ITD protein was further enhanced by homoharringtonine. Notably, this degradation effect was partially reversed by chloroquine. These findings demonstrate that bortezomib and homoharringtonine have synergistic effects and lead to degradation of FLT3-ITD oncoprotein, potentially contributing to a higher complete remission rate in FLT3-ITD R/R AML.

Taxane chemotherapy promotes response to TIM-3 checkpoint blockade via STING-mediated ER stress and HMGB1 secretion.

This study aimed to characterize the longitudinal and dynamic changes of gut microbiota in patients with nasopharyngeal carcinoma (NPC) during radiotherapy, to inform the development of strategies for maintaining gut microbiota homeostasis. Thirty-one newly diagnosed NPC patients were recruited from the Department of Radiotherapy, First Affiliated Hospital of Guangxi Medical University, and 31 age-matched healthy controls from the same Hospital Physical Examination Center between August and December 2023. Fecal samples were collected from NPC patients at three key time points, including days 1-3 pre-radiotherapy (T0), days 14-18 of mid-radiotherapy (T1), and days 28-32 at end of radiotherapy (T2). Meanwhile, fecal samples from healthy controls were collected on the morning of their physical examination. 16S rDNA sequencing, combined with bioinformatics and statistical analyses, was used to compare the structural characteristics and dynamic changes of gut microbiota in NPC patients during radiotherapy. Alpha diversity analysis showed significantly lower Shannon and Chao1 indices in NPC patients compared with healthy controls. Beta diversity analysis based on the Bray-Curtis distance revealed distinct gut microbial community structures between NPC patients and healthy controls. In this intergroup comparison, a total of 16 core differentially abundant taxa were consistently identified by two complementary analytical methods (LEfSe and ALDEx2). Linear mixed-effects models demonstrated that the Chao1 index at T0 was significantly lower than at T1 and T2 in NPC patients. Following adjustment for multiple confounding variables, mucositis grade was the only factor significantly associated with gut microbiota alpha diversity during radiotherapy. Radiotherapy time points, treatment regimen, and most clinical and demographic variables showed no such association. Beta diversity analyses based on the Bray-Curtis and unweighted Unifrac distances revealed significant compositional and structural differences linked to radiotherapy time points (T0/T1/T2) in the gut microbiota of NPC patients. This temporal variation was abrogated by stratification according to chemotherapy regimen. Beta diversity based on Bray-Curtis distance showed no significant differentiation across time points in either the concurrent chemotherapy (CCRT) alone cohort or the induction chemotherapy plus CCRT cohort. LEfSe and ALDEx2 concordantly identified seven core differentially abundant taxa across all NPC patients in the longitudinal T0 vs. T1 vs. T2 analysis. Stratification by chemotherapy regimen revealed such core taxa in the CCRT alone cohort, whereas no core differentially abundant taxa were detected by either method in the induction chemotherapy plus CCRT cohort. Our findings demonstrate that NPC patients exhibit significant gut microbial dysbiosis compared with healthy controls, characterized by reduced alpha diversity and altered genus-level composition. Longitudinal analyses further revealed that radiotherapy is associated with dynamic alterations in gut microbial diversity, composition, and structure in NPC patients. Notably, these temporal shifts in the gut microbiota are strongly stratified by chemotherapy regimen, with pronounced changes observed in patients receiving CCRT alone but a stable microbial profile in those receiving induction chemotherapy followed by CCRT. Collectively, these results highlight the profound impact of oncological treatment on the gut microbiome in NPC patients and identify treatment regimen as a critical modifier of microbial dynamics during radiotherapy.

Background. Among the factors contributing to unsuccessful treatment outcomes in patients with drug-resistant pulmonary tuberculosis-particularly multidrug-resistant tuberculosis (MDR-TB)-considerable importance is attributed to interindividual variability in pharmacological response, which is largely determined by patients’ genetic characteristics. Recent advances in MDR-TB chemotherapy are closely associated with the introduction of bedaquiline. Bedaquiline is primarily metabolized by the cytochrome P450 enzyme CYP3A4; however, the impact of CYP3A4 gene polymorphisms on bedaquiline pharmacokinetics and treatment efficacy in patients with drug-resistant TB remains insufficiently studied. Personalized therapy based on a patient’s genetic profile represents a key strategy for optimizing dosing regimens, improving treatment efficacy, and reducing the risk of developing further drug resistance. Aims — to evaluate the influence of CYP3A4 polymorphic alleles (*1B/rs2740574 and *1G/rs2242480) on bedaquiline pharmacokinetic parameters and chemotherapy efficacy in patients with drug-resistant pulmonary tuberculosis, including those with MDR-TB. Methods. A prospective, observational cohort study was conducted involving 143 patients with pulmonary tuberculosis and confirmed drug-resistant Mycobacterium tuberculosis (including MDR, pre-XDR, and XDR-TB) treated at the Central TB Research Institute (CTRIT), Russia, between 2022 and 2024 (66 women and 77 men). Three observation groups were formed based on genotype: Group 1 — wild-type CYP3A4*1 (n = 99); Group 2 — *1B (rs2740574) carriers (n = 10); Group 3 — *1G (rs2242480) carriers (n = 34). Genotyping was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). Bedaquiline was administered as part of individualized chemotherapy regimens at a dose of 400 mg once daily for 2 weeks, followed by 200 mg three times weekly for up to 6 months. Bedaquiline pharmacokinetic parameters were assessed in 30 patients using high-performance liquid chromatography. Treatment efficacy was evaluated based on sputum culture conversion by month 6. Statistical analysis employed nonparametric Kruskal–Wallis and Mann–Whitney tests for group comparisons. Results. Patients carrying the CYP3A4 *1G (rs2242480) allele showed significantly higher bedaquiline exposure compared to wild-type individuals: AUC₀–₂₄ (49.06 vs. 41.99 µg·h/mL; p 0.05), Cmax (3.13 vs. 2.21 µg/mL; p 0.05), and AUC₀–₂₄/MIC ratio (196.24 vs. 167.94; p 0.05), suggesting reduced metabolic clearance. In contrast, the *1B variant was associated with lower AUC₀–₂₄. Although culture conversion rates at 6 months did not differ significantly (p = 0.87), a trend toward higher efficacy was observed in *1G carriers (95.8%) versus wild-type patients (84.5%). Conclusion. The CYP3A4 *1G (rs2242480) polymorphism is associated with decreased bedaquiline metabolism, leading to increased systemic drug exposure and a potential improvement in treatment response. These findings highlight the role of CYP3A4 genetics in bedaquiline pharmacokinetics and support the integration of CYP3A4 genotyping into personalized MDR-TB treatment strategies. The *1G allele may serve as a promising pharmacogenetic biomarker for optimizing bedaquiline dosing in drug-resistant tuberculosis.

Mycophenolate mofetil (MMF) is widely used in lupus nephritis (LN), but interindividual variability in pharmacokinetics and pharmacogenetics may affect treatment response. This study investigated the relationship between MMF pharmacokinetics, key genetic polymorphisms, and therapeutic response in Egyptian female LN patients. In this prospective study, 53 female patients with active LN (ISN/RPS class III-IV) maintained on 2g/day MMF were enrolled at the Urology and Nephrology Center, Mansoura University, Egypt. Baseline clinical, laboratory, and histopathological data were collected. Serial blood samples were obtained over 8h for mycophenolic acid (MPA) quantification by LC/MS. Genomic DNA was extracted for UGT2B7 (rs7438135) and SLCO1B1 (rs183624077) genotyping using TaqMan real-time PCR assays. Treatment response was classified as complete or partial remission versus non-response at 6 months. Population pharmacokinetics were analyzed using Monolix 2020R1. Considerable variability in MPA exposure was observed (mean AUC₀-₈: 22.4 ± 12.9µg·h/mL; mean Cmax: 12.9 ± 5.5µg/mL). Responders exhibited higher median AUC₀-₈ than non-responders (23.1 vs. 16.2µg·h/mL; p = 0.039). SLCO1B1 and UGT2B7 genotypes did not differ significantly between responders and non-responders, though TT carriers showed lower MPA AUC₀-₈. Multivariate analysis identified biopsy class (III vs. IV), induction therapy with MMF, and higher MPA AUC₀-₈ as independent predictors of response. MMF exposure, biopsy class, and induction regimen significantly influence therapeutic response in LN. Pharmacokinetic monitoring of MPA may help optimize MMF therapy, while common UGT2B7 and SLCO1B1 variants showed limited predictive value in this cohort.

Plasmablastic lymphoma (PBL) is a rare CD20-negative aggressive lymphoma with poor prognosis when treated with standard treatment options. Although PBL is associated with HIV infection and other immunosuppressed states, it can also affect immunocompetent individuals. The diagnosis of PBL requires a high clinical suspicion and pathological confirmation. EBV-encoded RNA (EBER) expression and MYC gene rearrangements are frequently detected in the malignant cells. The differential diagnosis includes EBV+ diffuse large B-cell lymphoma (DLBCL), extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B-cell lymphoma, among others. Age ≥ 60 years, advanced clinical stage, and high International Prognostic Index scores are associated with worse survival. Combination chemotherapy regimens, such as infusional EPOCH, are recommended. The addition of bortezomib or daratumumab might improve outcomes. B-cell maturation antigen-targeted therapies have shown early efficacy. The participation of patients with PBL in prospective clinical trials is warranted.

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

Chemotherapeutic agents can induce morphologic changes in erythrocytes, leukocytes, and platelets in peripheral circulation. However, the cytomorphologic alterations associated with chemotherapy administration in circulating hemic cells are minimally characterized in dogs. Study objectives were to (1) assess differences in erythrocyte, leukocyte, and platelet morphologies and CBC metrics between healthy matched control dogs and dogs with multicentric lymphoma and (2) evaluate alterations in hemic cell morphology and CBC metrics in dogs with multicentric lymphoma being treated with multiagent CHOP chemotherapy regimen. Dogs with multicentric lymphoma (n = 20) had no differences in frequency and magnitude of hemic cell cytomorphology compared to control dogs (n = 20). However, lymphoma dogs had higher leukocyte, neutrophil, and monocyte counts. As dogs with lymphoma progressed through CHOP therapy, no differences in leukocyte or platelet cytomorphology were observed. The frequency and magnitude of erythrocyte polychromasia and were different between multiple chemotherapy timepoints. No morphologies consistent with dysplastic change were observed for any lineages. Differences in several erythrocyte, leukocyte, and platelet CBC indices were also observed. Atypical cytomorphologic abnormalities in circulating erythrocytes, leukocytes, and platelets, with the exception of leukemic cells, may be infrequent findings in dogs with multicentric lymphoma being treated with CHOP chemotherapy.