Search Results (201)

Background/Objectives: Azacitidine (AZA) is the standard of care for patients with higher-risk Myelodysplastic Syndromes (MDS). There is limited real-life data, however, characterizing its efficacy and safety profile in elderly patients. Methods: We conducted a single-center retrospective cohort chart review to compare front-line AZA therapy in patients ≥75 years (elderly) vs. <75 years (younger) with higher-risk MDS treated at our cancer center. The primary endpoint was overall survival and main secondary endpoints included response, as per the 2006 International Working Group consensus criteria, leukemia-free survival, transfusion independence, and safety outcomes. Results: In total, 55 patients were elderly (median age: 79.9 years), including 27 patients >80 years, and 41 were younger (median age: 69.4 years). Baseline demographic variables were similar between both groups. The majority of elderly patients (98%) received the full dose of AZA (75 mg/m²), compared with 90% of younger patients. The median number of AZA cycles was 8 (range: 2–69) in elderly and 7.75 (range: 1–96) in younger patients. Treatment delays occurred in 36.4% of elderly and 29.3% of younger patients, most commonly due to infection complications in both groups (p = 0.076). Disease control rates (complete remission + partial remission + stable disease) were 92.9% in the younger subgroup and 96.4% in the elderly subgroup (p = 0.154). Relapse occurred in 48.8% of younger patients and 40.0% of elderly patients. Median overall survival (OS) was 17.3 months for the younger subgroup, 15.7 months for the elderly subgroup (p = 0.771), and 11.9 months among patients >80 years (p = 0.381). Mortality rates and causes of death were similar between both subgroups. Most common causes of death included disease progression, sepsis, febrile neutropenia, and pneumonia. Conclusions: AZA monotherapy resulted in a high response rate and was well-tolerated in elderly patients with higher-risk MDS. These findings remain consistent in the real-world setting despite potential confounding factors that may contribute to inferior outcomes. Full article

Background: This phase I trial aimed to assess the safety and preliminary activity of the combination of copanlisib with venetoclax in previously treated patients with B-cell non-Hodgkin lymphoma, excluding mantle-cell lymphoma patients. Methods: Intravenous copanlisib on days 1, 8, and 15 and oral venetoclax once daily (starting on day 2 of cycle 1, continuously) were administered in 28-day cycles up to a maximum of 12 cycles. Starting doses were 600 mg of venetoclax and 60 mg of copanlisib. Results: A total of seven patients were enrolled. The first two presented dose-limiting toxicities, five additional patients were treated at a lower dose level (45 mg of copanlisib and 400 mg of venetoclax), with no dose-limiting toxicities observed among three evaluable patients. The most frequent treatment-related adverse event of grade 3 or higher was neutropenia (n = 3), followed by thrombocytopenia (n = 2) and hypertension (n = 2). Four treatment-related serious adverse events occurred, including grade 3 febrile neutropenia in one patient and respiratory infections in three patients. Two patients had complete responses, and two had partial responses. Transcriptomic analysis of lymphoma samples showed enrichment of genes coding for proteins involved in B-cell receptor signaling in responding patients. The study was terminated prematurely due to a decision by the pharmaceutical company. Conclusions: Due to the limited sample size, no definite conclusions regarding safety or activity of the combination can be drawn. The two drugs could not be combined at their respective single-agent doses. Responses were observed in heavily pretreated patients. Transcriptomic analyses suggested a possible association between response and B-cell receptor signaling, which warrants further investigation. Full article

Background/Objectives: Using real-world data, this study evaluates the use of ADCs over a decade across six University of California (UC) medical centers, focusing on the incidence of neutropenia-related adverse effects and associated clinical outcomes. Methods: A real-world retrospective study utilizing UC Health Data Warehouse records of patients receiving at least one dose of the ten most-used ADCs at one of the 6 UC hospitals between 2012 and 2024. The outcomes evaluated in this study were grade 3+ neutropenia and febrile neutropenia (FN) during any treatment cycle, and healthcare utilization outcomes including G-CSF prophylaxis, hospital and ICU admission, and mortality. Multivariate logistic regression was conducted to identify predictors for neutropenia-related events after the first dose of ADC. Results: Data from 3511 patients (mean ± SD age: 56.7 ± 17.6 years) were analyzed. The most commonly observed cancer types were breast cancer (43.4%), lymphoid, hematopoietic (41.8%), and urinary tract cancer (13.4%). The top three most commonly prescribed ADCs were fam-trastuzumab deruxtecan (22.6%), ado-trastuzumab emtansine (19.4%), and brentuximab vedotin (18.1%). Their respective all-cycle rates of FN were 5.4%, 1.2%, and 10.4%, while grade 3+ neutropenia rates were 16.4%, 5.1%, and 40.1%. Gemtuzumab ozogamicin and inotuzumab ozogamicin were associated with the highest rates of FN (both 18.1%), and inotuzumab ozogamicin was associated with the highest rates of hospital admissions (27.1%), ICU admissions (3.8%), and deaths (5.2%). Anemia and immunodeficiency disorders were identified as predictors for first-dose FN among patients receiving ADCs. Conclusions: Real-world data from this large multi-center cohort showed substantial variation in neutropenia-related events across ADCs. As ADC use continues to grow, these findings highlight the need for vigilant monitoring and proactive supportive care. Full article

Background: Acute lymphoblastic leukemia (ALL) requires intensive induction, but implementation of pediatric-inspired regimens in low- and middle-income countries is constrained by diagnostic gaps, procurement instability, and limited supportive-care capacity. We evaluated the feasibility, safety, and affordability of a pragmatically adapted pediatric-inspired induction regimen for adults with Philadelphia chromosome-negative Ph(−) ALL in a Pakistani tertiary hospital. Methods: In this prospective single-center cohort study at the Pakistan Institute of Medical Sciences (December 2024–June 2025), consecutive adults aged 18–50 years with newly diagnosed Ph(−)ALL received an adapted pediatric-inspired induction regimen. The primary outcome was complete remission (CR) after induction, with or without extended induction. Secondary outcomes were early mortality, treatment abandonment, grade 3–4 toxicities, and service delivery feasibility indicators. Affordability was assessed against household income. Results: Among 200 adults (mean age 30.3 ± 8.8 years; 65.5% male), 39.5% presented with WBC ≥ 30 × 10⁹/L and 88.0% with platelets < 50 × 10³/µL. CR was achieved in 83.0% of patients. Early mortality was 2.0%, and treatment abandonment was 1.5%. Grade 3–4 toxicities included febrile neutropenia (15.0%) and sepsis (7.5%). The Day-30 evaluability was high (96.5%). Observed out-of-pocket diagnostic costs were USD 119, whereas a guideline-complete diagnostic package would cost USD 929, equivalent to 3–6 months of income for households in the poorest quintile. Conclusions: This adapted pediatric-inspired induction regimen was operationally deliverable in a resource-restricted hospital and produced favorable induction-phase outcomes. Limited diagnostic capacity and a lack of financial protection for testing remain barriers to risk-adapted care. Expanding subsidies for essential diagnostics and stabilizing the procurement of critical agents may yield the greatest implementation gains. Full article

Background: This study aims to evaluate the real-world efficacy and safety of dalpiciclib in patients with hormone receptor-positive (HR+) advanced breast cancer and explore the impact of different clinical characteristics on treatment outcomes. Methods: This was a two-center, retrospective cohort study involving 76 patients treated with dalpiciclib between January 2022 and June 2024 at two affiliated hospitals of Anhui Medical University in China. Data on progression-free survival (PFS), adverse events, and key clinical factors were collected and analyzed. Kaplan–Meier estimates were used for statistical analysis. Results: The median PFS (mPFS) for the entire cohort was 12.00 months (95% CI: 10.09–13.91 months). Patients receiving dalpiciclib as first-line therapy had significantly better outcomes (mPFS: 17.00 months, 95% CI: 9.19–24.81 months) than those receiving later-line therapy (p < 0.001). Patients with prior exposure to cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and those with endocrine resistance had poorer outcomes. Multivariate Cox proportional hazards regression analysis confirmed that earlier treatment line (HR for second-line vs. first-line: 3.89, p = 0.015; HR for third-line or later vs. first-line: 5.56, p = 0.006) and prior CDK4/6i treatment (HR = 3.42, p = 0.040) were independent predictors of PFS. The most common adverse events were hematologic toxicities, including leukopenia (76.6%) and neutropenia (72.4%), mostly grade 1–2. No febrile neutropenia cases were reported, indicating a manageable safety profile. Conclusions: Dalpiciclib combined with endocrine therapy is associated with favorable efficacy and safety in real-world settings, with early-line treatment and lower tumor proliferative activity associated with better outcomes. While findings suggest potential for clinical application, further large-scale prospective studies are needed to validate its effectiveness in different patient subgroups and optimize treatment strategies. Full article

Purpose: A scoping review of the published risk stratification scores for febrile neutropenia (FN) was performed to provide a basis for further research and optimization of risk stratification models that can support evidence-based clinical decision-making with a combined individual patient and health resource perspective. Methods: The scoping review utilized the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR). Studies reporting risk stratification models for FN and published in the PubMed and/or Scopus databases between 2000 and 2024 were retrieved and reviewed. Study eligibility criteria were adult cancer patients and articles utilizing FN risk stratification methods. Two researchers reviewed all relevant studies separately to determine if they were eligible for inclusion and extracted the necessary data. Results: A total of 210 papers was screened by title and abstract. A further 158 were screened by retrieval and eligibility, and 14 studies were found eligible after reviewing full papers. Studies have different cohort sizes (min 31, max 4434), age and gender distributions, cancer types (1 hematological, 3 gynecological, 10 mixtures of hematological and solid cancers), definitions of FN and complication, study type (2 retrospective, 12 prospective). The resulting papers mostly focused on validating CISNE and MASCC scores. Additionally, they investigated possible improvements by evaluating revised versions of the MASCC score. Conclusions: The scoping review revealed inconsistencies in key definitions when using risk stratification scores. It is concluded that the field could benefit from more consensus in definitions and research approaches to secure the generalizability and utility of the research. Full article

Background: Empirical antibacterial therapy for febrile neutropenia requires adaptation to local epidemiology, a process that is often complex, time-consuming, and prone to human error. This study aims to address this challenge by developing a practical, data-driven tool to efficiently evaluate and adapt treatment protocols. Methods: We developed a novel, open-source computational script in Python (version 3.10), aided by large language models for code revision, to analyze antibiotic susceptibility data. The script was validated using a retrospective dataset of 237 Gram-negative bloodstream infections (BSIs) from 2015 to 2024 in cancer or hematopoietic stem cell transplant recipients at a tertiary care pediatric hospital in Italy. The script calculates efficacy metrics for both single agents and two-drug combinations. Results: Among the Gram-negative BSI strains analyzed, meropenem monotherapy demonstrated the highest efficacy (median 95.4%). In contrast, piperacillin/tazobactam and cefepime showed lower efficacy (80.3% and 81.8%, respectively). On the contrary, combination therapy, particularly with amikacin, significantly increased the efficacy of beta-lactams, elevating their effectiveness to a level comparable to meropenem. Conclusions: The developed script is a valuable tool for antimicrobial stewardship programs, offering a rapid and accessible method to validate international guidelines against local epidemiological data. While meropenem shows high efficacy, its broad use should be limited to prevent resistance. The combination of piperacillin–tazobactam and amikacin is identified as a robust and effective empirical treatment choice. Full article

Background: AMR is a public health concern which leads to high global morbidity and mortality. Immunocompromised patients, who are more susceptible to contracting potentially life-threatening infections, are faced with reduced treatment options due to emerging AMR. Ceftolozane/tazobactam is a novel β-lactam/β-lactamase inhibitor which displays effectiveness against resistant Gram-negative infections. Methods: SPECTRA was a multinational, observational study conducted in seven countries including 617 patients who received ≥48 h of ceftolozane/tazobactam. Medical-record data were collected up to 6 months before treatment and 30 days after the final dose or until death. This analysis describes clinical outcomes and healthcare resource use in patients with sepsis or who were immunocompromised, specifically in patients with hematologic malignancy with and without solid tumor, febrile neutropenia, and solid organ transplant patients. Results: Clinical success ranged from 50.0% in patients with hematologic malignancy and solid tumor to 69.4% in 38 patients with febrile neutropenia. All-cause in-hospital mortality was 23.1–42.9%, with the lowest rates in patients with solid organ transplant. ICU admission was 46.4–68.2% across subpopulations (excluding febrile neutropenia) with the lowest rates in patients with hematologic malignancy. ICU length of stay was lowest within transplant patients (9 days) and highest within the hematologic malignancy and solid tumor population (32 days). Conclusions: The results from this sub analysis of SPECTRA showed that ceftolozane/tazobactam was associated with clinical success in the selected immunocompromised and sepsis patient populations and may lead to reduced morbidity, mortality, and healthcare-resource use. Further research is required to standardize treatment protocols and improve patient outcomes. Full article

Aim: In this study, we aimed to compare patients receiving PTcy with those receiving standard graft-versus-host disease (GVHD) prophylaxis in terms of GVHD development, disease relapse, overall survival, transplant-related mortality, and infection development Methods: Data from 78 patients who underwent allogeneic stem cell transplantation (AHSCT) at Medicana Izmir Hospital between January 2022 and June 2024 were retrospectively evaluated. Results: Myeloablative-related AHSCT was performed on 38 patients (48.7%), myeloablative-unrelated AHSCT was performed on 26 patients (33.3%), and haploidentical AHSCT was performed on 14 patients (17.9%). Acute GVHD was observed in 42 patients (53.8%); it was observed significantly less frequently in the group that received PTcy (p = 0.032) In 15 patients (19.2%), chronic GVHD developed following acute GVHD. It was found that chronic GVHD occurred more frequently in those who did not receive PTcy (p = 0.0001), in sibling transplants (p = 0.037), in those without febrile neutropenia (p = 0.021), and in those with high CMV-DNA levels (p = 0.040). The median OS (months) was found to be 79.16 months. The median OS (months) was higher in patients in the good AML cytogenetic risk group (p < 0.001) and in those who underwent transplantation in first remission (p = 0.021). Conclusions: PTcy significantly reduced the development of acute and chronic GVHD. Full article

Invasive fungal disease (IFD) is one of the leading causes of morbidity and mortality in immunocompromised pediatric patients. This is a multicenter prospective cohort study with a nested retrospective analysis aimed at identifying risk factors for IFD in immunocompromised children with cancer and episodes of persistent high-risk febrile neutropenia (HRFN). One hundred and seventy-four episodes of persistent HRFN were analyzed, of which 34 (19.5%) were confirmed as IFD, 52.9% were caused by filamentous fungi, and 47.1% by yeasts. Logistic regression and survival analyses identified the following significant risk factors for IFD: male sex (OR 4.04), adolescence (OR 4.65), C-reactive protein ≥ 90 mg/L at admission (OR 3.13), and transfer to a critical care unit (OR 10.73). The predictive model demonstrated strong discriminatory capacity (AUC 0.84), with 79.4% sensitivity and 82.1% specificity. These findings highlight that adolescents, particularly males with severe clinical conditions and elevated inflammatory markers, are at the highest risk for IFD during episodes of HRFN. The proposed risk factor-based model may support early risk stratification and guide targeted antifungal prophylaxis or therapy, potentially improving outcomes in this population. Validation an external cohort is required to confirm these results and optimize clinical applicability. Full article

Background: Teicoplanin is widely used for the empirical and targeted treatment of febrile neutropenia in patients with hematological malignancies. However, the pathophysiological alterations typical of this population may substantially affect drug exposure. The aim of this study was to develop and validate a population pharmacokinetic (PopPK) model of teicoplanin in adult hematological patients and to propose individualized dosing strategies. Methods: A retrospective, single-center study including 151 patients and 263 serum concentrations was conducted, with participants assigned to development (n = 100) and validation (n = 51) cohorts. Concentrations were quantified using a turbidimetric immunoassay, and the PopPK model was developed in NONMEM using FOCE-I. Results: Teicoplanin pharmacokinetics were described by a one-compartment model with first-order elimination. Ideal body weight, estimated glomerular filtration rate, and age were identified as significant predictors of clearance. Internal and external validation confirmed the robustness and predictive performance of the model. Monte Carlo simulations showed that conventional regimens (6 mg/kg every 12 h for three loading doses, followed by 6 mg/kg once-daily, or 600 mg every 12 h for three loading doses, followed by 600 mg once-daily) are insufficient to achieve therapeutic trough concentrations (≥15–20 mg/L) within the first 72 h, particularly in patients with preserved renal function or higher body weight. An intensified regimen consisting of five loading doses of 12 mg/kg every 12 h, followed by 12 mg/kg once-daily, enabled rapid attainment and maintenance of trough concentrations ≥ 20 mg/L in patients with lower to intermediate ideal body weight. Conclusions: These findings underscore the importance of intensified dosing strategies and covariate-guided individualization supported by therapeutic drug monitoring to achieve optimal teicoplanin exposure in this vulnerable patient group. Full article

Background: The UGT1A1 gene is associated with the toxicity caused by SN38, the cytotoxic component of Sacituzumab govitecan (SG) used in the treatment of metastatic triple-negative breast cancer (mTNBC), among other approved indications. In this study, we aimed to analyze the effect of UGT1A1*28 allele on the safety and, secondarily, the effectiveness of SG in mTNBC. Methods: This was a multicenter, ambispective study that included patients treated with SG for mTNBC. Genotyping for UGT1A1*28 was performed using real-time polymerase chain reaction (PCR). Adverse events (AEs) of grade ≥ 2 during the first three cycles were compared between patients who were homozygous mutant (UGT1A1*28/*28) and those with wild-type (WT) or heterozygous genotypes. Effectiveness between the two groups was also compared using progression-free survival (PFS) and overall survival (OS) assessed with the Kaplan–Meier method. Results: A total of 81 patients were included: 37.0% were WT, 55.6% heterozygous, and 7.4% homozygous mutant. All UGT1A1 *28/*28 patients experienced grade ≥ 2 AEs (100% vs. 69.3%; p = 0.109), with a statistically significant association in the case of febrile neutropenia (33.3% vs. 6.7%; p = 0.025), and a trend towards higher rates of anemia and diarrhea (50.0% vs. 17.3%; p = 0.053). Genotype did not influence PFS or OS; however, dose reductions were associated with better survival outcomes. Conclusions: This real-world study shows a correlation between toxicity and the presence of the UGT1A1*28 mutation in patients treated with SG for mTNBC. Improving treatment tolerability through dose reductions may enhance SG effectiveness. These findings support the implementation of UGT1A1 genotyping in routine clinical practice. Full article

Background and Objectives: Febrile neutropenia (FN) is a potentially life-threatening complication in children undergoing cancer treatment. Immediate initiation of empirical antibiotic treatment (EAT) has improved the prognosis and outcomes of FN. Although the ideal timing for initiating EAT is clear, the optimal timing for EAT discontinuation remains debatable. Early hospital discharge (EHD) with continuation of oral antibiotics has also been proposed as an alternative strategy. This narrative review aims to present a comprehensive overview of the evidence on early discontinuation of EAT or EHD in children with FN and cancer. Materials and Methods: A comprehensive literature search was performed to identify relevant studies assessing early EAT discontinuation or EHD in children with cancer and FN. Extracted data included the safety outcomes, the benefits for the patients and the cost for healthcare systems. Results: Thirty-one studies were included; twenty-one investigated the early discontinuation of EAT and ten studies evaluated EHD. Most studies reported early discontinuation of EAT or EHD as a safe FN treatment approach with potential benefits for the patients, especially when applied to selected low-risk FN cases. Reported benefits included shorter hospitalization duration and reduced antibiotic use, with additional economic advantages in several studies. Conclusions: Early discontinuation of EAT appears to be a safe and beneficial management approach for children with FN and cancer by reducing the length of hospital stay and the duration of antibiotic use. EHD with oral therapy continuation also appears to be safe but less beneficial than early discontinuation of EAT. High-quality evidence and standardized criteria are needed to support broader implementation of these strategies in routine clinical practice. Full article

Background: Febrile neutropenia (FN) is a serious chemotherapy-related complication in patients with solid tumors. Identifying simple and accessible biomarkers that can predict prolonged hospitalization may support early risk stratification and clinical decision-making. Methods: This retrospective study included 169 adults hospitalized with FN between January 2023 and January 2025. Immunonutritional indices, including the Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) score, the Prognostic Nutritional Index (PNI), and the C-reactive protein/albumin ratio (CAR), as well as the Clinical Index of Stable Febrile Neutropenia (CISNE) score were calculated. HALP and PNI were categorized using ROC-derived cut-offs based on the Youden Index. Prolonged hospital stay was defined as a binary variable based on the cohort median (>9 days). Spearman correlation, univariate and multivariate logistic regression were performed to identify predictors of prolonged hospitalization. Results: HALP showed a significant negative correlation with hospitalization duration (r = −0.469; p < 0.001), as did serum albumin (r = −0.184; p = 0.017) and PNI (r = −0.273; p < 0.001). CAR (p = 0.617) and neutrophil count (p = 0.955) demonstrated no correlation. In univariate logistic regression, low HALP (p < 0.001), low PNI (p = 0.001), intermediate CISNE (p = 0.002), high CISNE (p < 0.001), microbiological culture positivity (p < 0.001), and sex (p = 0.015) were significantly associated with prolonged hospitalization. Age, comorbidity status, metastatic stage, and CAR were not significant. In the multivariate model, low HALP (p < 0.001), intermediate CISNE (p = 0.007), high CISNE (p < 0.001), and culture positivity (p < 0.001) remained independent predictors. PNI (p = 0.400) and sex (p = 0.176) did not retain significance. Conclusions: A Low HALP score, higher CISNE risk categories, and microbiological culture positivity independently predicted prolonged hospitalization in FN. HALP, as a simple and inexpensive immunonutritional marker, may enhance early FN risk assessment when used alongside validated clinical tools such as CISNE or MASCC. Full article

Background: Decitabine efficacy in acute myeloid leukemia (AML) may be enhanced by the pharmacologic upregulation of microRNA miR-29b, a regulator of DNA methyltransferase (DNMT) expression. Bortezomib and sorafenib have been shown preclinically to increase miR-29b levels, providing a biologically informed strategy to sensitize leukemic blasts to DNMT inhibition. Objectives: To evaluate the safety, tolerability, biological activity, and preliminary efficacy of combining bortezomib and sorafenib followed by decitabine in patients with newly diagnosed or relapsed/refractory AML. Methods: This phase I, dose-escalation study enrolled 15 patients (11 untreated, 4 relapsed/refractory) who received fixed-dose bortezomib and sorafenib across three dose levels prior to decitabine. Dose escalation was guided by dose-limiting toxicities (DLTs) and an increase in miR-29b expression. Results: The regimen was generally well tolerated with the most frequent grade ≥3 adverse events of hypertension and febrile neutropenia. At the highest dose level, a ≥2-fold increase in miR-29b expression was observed in two of the six evaluable patients. The overall response rate was 33.3%, with clinical responses observed in both newly diagnosed and relapsed/refractory patients. However, changes in miR-29b expression did not consistently correlate with clinical response. Conclusions: Sequential treatment with bortezomib and sorafenib followed by decitabine is feasible and demonstrates acceptable safety in AML. Although the biologic modulation of miR-29b was variable, this trial provides a proof of concept for pharmacodynamic-guided dose finding in epigenetic therapy combinations. Full article