Mediterranean Journal of Hematology and Infectious Diseases最新文献

Invasive fungal infections (IFIs) mostly affect immunocompromised hosts and are responsible for high rates of complications and mortality. Prevalence of IFIs has been reported between 7 and 15% and is evolving due to the introduction of new drugs in the prophylaxis of high-risk patients. Invasive candidiasis has become less frequent, while cases of aspergillosis are increasing. The most important risk factors for IFIs can be divided into 3 categories: those related to the hematological neoplasm, those related to the patient's lifestyle, and those dictated by the transplant characteristics. In high-risk patients, prophylaxis is driven by both local epidemiology and the timing of engraftment. During the pre-engraftment period, a wide spectrum of drugs can be chosen as antifungals, while in the post-engraftment period, posaconazole is recommended for patients presenting with GvHD who are undergoing immunosuppression. Regarding treatment, voriconazole is still the recommended drug for invasive aspergillosis, although adverse events, toxicity, and drug interactions are particularly relevant. In the management of IFIs, international guidelines recommend the best drugs for prophylaxis and treatment, but the future holds new molecules that are already demonstrating excellent efficacy and tolerability.

Background: Elderly patients with relapsed acute myeloid leukemia (AML) have limited treatment options and a poor prognosis. Venetoclax combined with azacitidine has shown promising activity in newly diagnosed or relapsed/refractory AML, but real-world data on older populations remain scarce. This study aimed to evaluate the efficacy, safety, and prognostic factors - including select blood biomarkers - of venetoclax plus azacitidine in elderly patients with relapsed AML.

Methods: We conducted a single-center retrospective review of patients aged ≥65 years diagnosed with relapsed AML who received venetoclax plus azacitidine between January 2018 and December 2022. Patient demographics, baseline disease characteristics, and treatment details were collected. Blood biomarkers, such as lactate dehydrogenase (LDH), C-reactive protein (CRP), and selected molecular markers (including FLT3-ITD and NPM1 mutations), were also assessed at baseline to evaluate their prognostic value. The primary endpoint was the overall response rate (ORR), defined as the sum of complete Remission (CR) and CR with incomplete hematologic recovery (CRi). Secondary endpoints included overall survival (OS), event-free survival (EFS), and safety. Prognostic factors were identified through univariate and multivariate analyses using Cox proportional hazards models. Survival curves were constructed via the Kaplan-Meier method.

Results: A total of 50 patients (median age, 72 years; range, 65-82) met the inclusion criteria. The ORR was 60% (40% CR and 20% CRi). The median OS was 9.2 months (95% CI: 6.8-11.5), and the median EFS was 6.0 months (95% CI: 4.2-8.3). Common Grade 3-4 adverse events included neutropenia (46%) and thrombocytopenia (32%). The 30-day treatment-related mortality rate was 4%. Elevated baseline LDH (≥ the upper limit of normal) was associated with reduced OS (p=0.03). Patients with high CRP levels and/or adverse molecular markers, such as FLT3-ITD positivity, also showed a trend toward poorer survival, which, however, did not reach statistical significance in the multivariate model. Multivariate analysis confirmed poor Eastern Cooperative Oncology Group (ECOG) performance status, baseline LDH level, and adverse cytogenetics as independent predictors of reduced OS.

Conclusion: Venetoclax combined with azacitidine demonstrated encouraging efficacy and manageable toxicity in this retrospective analysis of elderly patients with relapsed AML. Elevated LDH and adverse molecular/cytogenetic profiles were associated with worse outcomes. These findings highlight the importance of integrating blood biomarker assessment into routine evaluation and suggest venetoclax-based regimens may be a viable therapeutic option in older, relapsed AML populations. Prospective multicenter studies are warranted to confirm these results and refine patient selection.

Cuproptosis is a distinct modality of regulated cell death precipitated by an overload of intracellular copper, critically dependent on mitochondrial respiration. The underlying mechanism involves the direct interaction of copper ions with lipoylated components integral to the mitochondrial tricarboxylic acid (TCA) cycle. This binding event triggers the aggregation of these proteins, induces significant proteotoxic stress, and leads to the depletion of essential iron-sulfur cluster proteins, culminating in cell demise. Given that copper homeostasis is frequently dysregulated within cancer cells, rendering them potentially more susceptible to copper-induced toxicity, cuproptosis has rapidly become a focal point of oncological research. This systematic review meticulously analyzes and synthesizes findings from a curated collection of 45 research articles. It aims to provide a comprehensive description of the molecular intricacies of cuproptosis, explore its documented associations with a spectrum of solid tumors (including gastric, lung, liver, neuroblastoma, and ovarian cancers) and lymphoma, and examine its emerging connections with viral infections like COVID-19 and pseudorabies virus. The review elaborates on the reported prognostic significance of cuproptosis-related genes and associated pathways across various malignancies. Furthermore, it details the burgeoning therapeutic strategies designed to harness cuproptosis, encompassing the application of copper ionophores, the development of sophisticated nanomedicine platforms, and synergistic approaches that combine cuproptosis induction with immunotherapy, chemotherapy, or sonodynamic therapy. The potential clinical utility of cuproptosis-associated biomarkers for predicting patient prognosis and therapeutic response is discussed based on the evidence presented in the reviewed literature.

Bruton's tyrosine kinase inhibitors (BTKis) have reshaped the management of chronic lymphocytic leukemia (CLL). The first-generation BTKi ibrutinib demonstrated significant efficacy, leading to the development of second-generation agents (acalabrutinib, zanubrutinib) with improved selectivity and safety. However, resistance-most often driven by BTK mutations at the cysteine residue at position 481 (C481S)-remains a major therapeutic limitation. Noncovalent BTKis, such as pirtobrutinib, offer effective options for patients relapsing after covalent BTKi therapy. However, the emergence of novel resistance mutations continues to limit durable responses. As insights into the molecular basis of BTK resistance evolve, routine mutation testing is poised to become integral to personalized treatment in CLL. Future clinical trials are expected to adopt mutation-driven stratification to guide therapeutic sequencing. Ultimately, overcoming BTKi resistance will require innovative strategies, including BTK degraders, bispecific antibodies, and T cell-engaging immunotherapies.

Background: To investigate the differences in clinical characteristics between Gram-positive and Gram-negative neonatal sepsis (NS).

Methods: A retrospective analysis was conducted on a total of 151 neonates admitted between March 2019 and March 2024. The 91 NS patients were divided into the Gram-negative bacteria group (n=31) and the Gram-positive bacteria group (n=60). Sixty (n=60) non-septic neonates served as controls, and general information was collected from all participants. C-reactive protein (CRP), procalcitonin (PCT) and platelets (PLT) were independent factors that influenced the differentiating infections caused by the two pathogens. The onset symptoms, strain distribution, and various biochemical parameters were compared before the treatment among the three groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy.

Results: The proportions of patients with amniotic fluid contamination and fever (body temperature ≥ 38.0 °C) were higher in the Gram-negative group than in the Gram-positive group (P=0.023, 0.049). The concentrations for CRP, PCT and PLT were P=0.019, 0.023, 0.030 respectively. ROC curve analysis revealed that the specificity of the combination of CRP, PCT and PLT in diagnosing Gram-negative bacterial infection was 100.00%, and the area under the curve (AUC) was 0.904, which was higher than those of single indicators (P=0.05).

Conclusion: There are differences in the expression of CRP, PCT and PLT between Gram-positive and Gram-negative NS. The simultaneous detection of the three has a high diagnostic value in differentiating infections caused by the two pathogens.

Background: Worldwide, glucose dysregulation (GD) and diabetes mellitus are common complications in transfusion-dependent β-thalassemia (β-TDT) patients. Impaired insulin sensitivity and insulin secretion are both involved in the deterioration of glucose tolerance from a normal to a glucose-intolerant state.

Objective: The main aim of the present study was to evaluate the plasma glucose (PG) increment (PG %) retrospectively at two h during oral glucose tolerance test (OGTT) over fasting plasma (FPG) concentration as a simple parameter to recognize early β-cell dysfunction in normoglycemic β-TDT patients with NGT and different severities of iron overload (IOL).

Patients and methods: A total of 19 β-TDT young adult patients with normal OGTT were re-evaluated according to the American Diabetes Association (ADA) guidelines. Venous blood samples were collected at baseline and at 30, 60, and 120 minutes to determine PG (mg/dL) and insulin concentrations (μIU/mL). The time required for the PG concentration to return to the fasting level was calculated by computing the percentage increment of 2-h PG with respect to FPG (PG%), using the formula [(2-h PG-FPG)/FPG]x 100. The early phase of insulin secretion (IGI) and sensitivity were assessed by validated surrogate indices calculated from parameters obtained during the four-point OGTT.

Results: The mean age of patients was 30.3 ± 5.7 (range: 23.10-44.3). The mean ± SD, median, and range of PG% increment between 2 h-PG and FPG were 35.5 ± 20.2, 38.7, and 0 - 68.2 mg/dL, respectively. The PG% increment was negatively correlated to the patient's age, FPG, and IGI, and positively correlated with 2-h PG post-glucose load. IGI was negatively correlated with 1-h and 2-h PG after post-glucose load and positively correlated with oral disposition index (oDI).

Conclusions: The PG% increment is a simple, useful screening parameter that can expand the clinical weight of OGTT and can provide valuable metabolic information on β-cell dysfunction.

Background: Emerging treatment strategies have enhanced life expectancy for cancer patients, but late complications, including vaccine-preventable infections from diminished antibody titers, are common. This study evaluates viral vaccine immunity in children post-leukemia treatment and examines the need for additional vaccine doses and their effectiveness.

Methods: Our cohort included 62 children diagnosed with acute leukemia. We recorded patients' sex, age at diagnosis, type of leukemia, risk groups, vaccination status prior to chemotherapy, and serology results for hepatitis A, hepatitis B, varicella, measles, rubella, and mumps (MMR) both at the end of chemotherapy and after vaccination following chemotherapy.

Results: Post-treatment, patients exhibited a loss of protective antibody responses: hepatitis A (44.4%), hepatitis B (67.7%), varicella (62.5%), measles (46.9%), rubella (43.5%), and mumps (50%). Notably, high-risk group acute lymphoblastic leukemia (HRG ALL) patients had a marked decrease in protective antibodies for hepatitis B, measles, rubella, and mumps compared to standard/intermediate risk group (SRG/IRG) ALL patients (p<0.05). Among the seronegative patients, following vaccination, five (15.2%) remained seronegative for varicella, one (2.2%) for hepatitis A, one (3.5%) for measles, one (3.8%) for rubella, and two (6.5%) for mumps.

Conclusion: Our study highlights a significant loss of vaccine-protective antibody responses after acute leukemia treatment, particularly among HRG. The increased vulnerability to vaccine-preventable infections, particularly hepatitis B, measles, rubella, mumps, and varicella, in HRG ALL patients highlights the importance of ongoing monitoring of immunization status and potential revaccination strategies to ensure adequate protection against infectious diseases.