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The haematological malignancies are a heterogeneous group of neoplastic disorders, which lead to almost 10,000 deaths annually in the UK. Over the past 2 decades, there has been significant progress in our understanding of the pathological mechanisms underlying these cancers, accompanied by improvements in outcomes for some patients. In particular, advances in next-generation sequencing now make it possible to define the genetic lesions present in each patient, which has led to improved disease classification, risk stratification and identification of new therapeutic targets. Here we discuss recent advances in the genomic classification and targeted treatment of haematological malignancies, focusing on acute myeloid leukaemia. Multiple novel drug classes are now on the horizon, including agents that target overactive signalling pathways, differentiation therapies and immunotherapies. By combining molecular diagnostics with targeted therapy, the management of these diseases is set to change radically over the coming years.

Background and objective There is scarce data on the treatment outcomes of B-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) in elderly patients in the era of tyrosine kinase inhibitors (TKIs), blinatumomab, and inotuzumab ozogamicin. In light of this, we aimed to address this gap in data by conducting this retrospective study. Methods Treatment outcomes were retrospectively evaluated by using data from transplant-ineligible patients aged 65 years or older with newly diagnosed B-ALL/LBL (n=29) at two hospitals in Oita, Japan between 2013 and 2023. Results The median age of the cohort was 72 (65-88) years, and 10 patients were male; 17 patients had Philadelphia chromosome (Ph)-positive ALL, and the others had Ph-negative ALL. Dasatinib combined with prednisolone was the most common induction therapy for Ph-positive ALL (88.2%). Complete response (CR) was achieved in 93.1%, and the CR rate did not differ significantly between Ph-positive ALL (100%) and Ph-negative ALL (83.3%) (p=0.16). The median observation period was 1.52 (range: 0.03-8.98) years. Overall survival (OS) and event-free survival (EFS) were significantly longer in Ph-positive ALL patients than in Ph-negative ALL patients on univariate analysis (OS: p=0.011, EFS: p=0.041). Multivariate analyses showed that the presence of Ph was significantly and independently associated with longer OS [hazard ratio (HR): 0.29, 95% confidence interval (CI): 0.10-0.87, p=0.027] and EFS (HR: 0.34, 95% CI: 0.12-0.91, p=0.03). There was no difference in relapse-free survival (RFS); 13 patients (76.5%) with Ph-positive ALL were treated with ponatinib (salvage therapy, n=7; consolidation or maintenance therapy in CR, n=6). Six of seven patients (85.7%) with ponatinib salvage therapy achieved CR, and all six patients treated with ponatinib consolidation or maintenance therapy retained CR at the last follow-up. Six patients (Ph-positive ALL: n=4; Ph-negative ALL: n=2) were treated with blinatumomab, including salvage therapy for primary refractory or relapse (n=3), and consolidation therapy due to intolerance to conventional chemotherapies (n=3). Two of three patients with blinatumomab salvage therapy achieved CR, and all three patients with blinatumomab consolidation therapy maintained CR in follow-up. Two patients (Ph-positive ALL: n=1; Ph-negative ALL: n=1) were treated with inotuzumab ozogamicin for relapsed or refractory ALL. A patient with Ph-positive ALL for the third relapse achieved CR, which was sustained for three years. The other patient with Ph-negative ALL for primary refractory achieved CR but relapsed after the fourth course of inotuzumab ozogamicin. Conclusions Elderly patients with Ph-positive ALL showed significantly longer OS and EFS than those with Ph-negative ALL in the era of molecular-targeted therapy.

Background Aplastic anemia (AA) is a rare and heterogeneous hematological disorder defined as pancytopenia with hypocellular bone marrow in the absence of abnormal infiltration or medullary fibrosis. Various causes of AA have been identified, such as autoimmune factors, bone marrow injuries, viral infections, and genetic disorders. The symptoms of AA are directly linked to pancytopenia and the most common are fatigue, recurrent infections, and bleeding problems. The treatment of AA varies according to the severity of the disease and includes immunosuppressive therapies and bone marrow transplantation. This study aims to identify the most relevant social, clinical, and demographic characteristics of patients with AA in Costa Rica. Methodology A retrospective, observational study was conducted in Costa Rica by reviewing the medical records of patients diagnosed with AA in the main hospitals of the Costa Rican Social Security Health Fund (CCSS, by its acronym in Spanish). A total of 109 patients who were evaluated between 2016 and 2018 were identified. Sociodemographic, clinical, and treatment information was collected for these patients in a database that was analyzed using statistical programs such as SPSS Statistics (version 24) and GraphPad Prism (version 8). Results Most patients were male (56%) with an average age of 32 years. Patients were classified according to the severity of the disease, and a higher mortality at 60 months was observed in those with very severe AA and in patients over 65 years old. The most commonly used first-line treatment was the combination of rabbit antithymocyte globulin (ATG) and cyclosporine (42.9%). Patients who required a greater number of blood transfusions had a more severe disease. Further, 46 patients requiring a second line of treatment were identified, and the most common treatment in this group was the combination of ATG with eltrombopag in 19.6% of the patients. The study results present the sociodemographic and clinical characteristics of patients with AA in Costa Rica. The lack of identification of a common external factor that may influence the development of the disease is highlighted. Treatment with rabbit ATG and cyclosporine demonstrated a good response in patients. The availability and cost of treatments are important considerations, especially in developing countries. Conclusions The study highlights significant progress in the understanding and treatment of AA in the Costa Rican context. The results support the efficacy of the combination of antibodies and cyclosporine as a therapeutic option. The importance of adapting treatments to the characteristics of the local population is emphasized, along with the need for further research to improve long-term outcomes.

Three critically ill, chemotherapy-refractory patients with diffuse large B-cell lymphoma (DLBCL) received loncastuximab tesirine in conjunction with standard therapies for secondary malignancy-associated hemophagocytic lymphohistiocytosis (Mal-HLH). All patients were treated inpatient, with one requiring intubation on the day of administration. Each patient had an H-score >238, indicating a >98% probability of HLH. A significant reduction in ferritin levels was observed in two patients, and one patient achieved a complete response (CR). Loncastuximab tesirine demonstrated promise in managing Mal-HLH where previous treatments had failed. This study suggests that loncastuximab tesirine exhibits favorable activity and should be considered a valuable addition to the treatment options for Mal-HLH driven by DLBCL.

Polycythemia vera (PV) is a primary acquired marrow condition that causes erythrocytosis. It may present with erythromelalgia, pruritus, splenomegaly, and thrombotic events. Secondary causes of polycythemia should be ruled out before labeling a patient as having PV. Serum erythropoietin (EPO) level helps distinguish primary and secondary polycythemia, but it should be aided by further testing such as the JAK-2 gene mutation test. We present a case of a previously healthy 47-year-old female who came to the hospital with a headache and transient left-sided body weakness. She had no similar episodes in the past. Her initial workup showed a high hemoglobin and a high hematocrit level. A plan computed tomography (CT) scan of the head showed evidence of a thalamo-capsular infarct. The serum EPO level was elevated, and a bone marrow biopsy returned positive for JAK-2 mutation indicating the diagnosis of polycythemia vera despite the high EPO level. The World Health Organization (WHO) consensus criteria for diagnosing PV demand the presence of two major criteria and one minor criterion or the presence of the first major criterion and two minor criteria. Decreased EPO is considered a minor WHO criterion for PV diagnosis. A low EPO is also used to discriminate PV from secondary thrombocytosis, as it might be low, as expected, or elevated. Phlebotomy primarily treats PV with low risk with a target hematocrit of less than 45%. PV patients with high risk can benefit from low-dose aspirin. Anticoagulation may be added for patients with thromboembolism. Patients with polycythemia vera can present with a high or low serum EPO level. Further diagnostic tests are usually required to confirm the final diagnosis.

A kind of hemoglobinopathy known as sickle cell anemia (SCA) is characterized by aberrant hemoglobin molecules. The most frequent neurological side effects linked to SCA include neurocognitive dysfunction, asymptomatic cerebral infarction, and ischemic stroke. This study aims to investigate the relationship between SCA and cognitive dysfunction. We systematically searched electronic databases like PubMed, MEDLINE, Science Direct, and Scopus. Two independent reviewers screened and extracted data from eligible studies. Eighteen studies, including 2,457 participants in total and nearly half of them 1,151 (46.8%) were males, were included in our data. The prevalence of cognitive dysfunction in the adult population ranged from 11.5% to 70%. Cognitive dysfunction among adults was significantly associated with poorer educational status, reduced family income, decreased kidney function, older age, stroke history, and vasculopathy. The prevalence of cognitive dysfunction in children ranged from 10.2% to 68.2%. The decline in cognitive function among adults was significantly associated with children over the age of four, abnormal transcranial Doppler and previous stroke, school absence, age beyond 13, and increased BMI. Cognitive function deficiencies are a defining feature of SCA that affects people of all ages. These findings suggest that if cognitive decline is not slowed down, or better still, stopped, medical interventions targeting a variety of sequelae in this population will be ineffective. Future analyses of this population's cognition should evaluate the environmental and other biological variables.

Mutations in the BRCA1 tumor suppressor gene, such as 5382insC (BRCA1insC), give carriers an increased risk for breast, ovarian, prostate, and pancreatic cancers. We have previously reported that, in mice, Brca1 deficiency in the hematopoietic system leads to pancytopenia and, as a result, early lethality. We explored the cellular consequences of Brca1-null and BRCA1insC alleles in combination with Trp53 deficiency in the murine hematopoietic system. We found that Brca1 and Trp53 codeficiency led to a highly penetrant erythroproliferative disorder that is characterized by hepatosplenomegaly and by expanded megakaryocyte erythroid progenitor (MEP) and immature erythroid blast populations. The expanded erythroid progenitor populations in both BM and spleen had the capacity to transmit the disease into secondary mouse recipients, suggesting that Brca1 and Trp53 codeficiency provides a murine model of hematopoietic neoplasia. This Brca1/Trp53 model replicated Poly (ADP-ribose) polymerase (PARP) inhibitor olaparib sensitivity seen in existing Brca1/Trp53 breast cancer models and had the benefits of monitoring disease progression and drug responses via peripheral blood analyses without sacrificing experimental animals. In addition, this erythroid neoplasia developed much faster than murine breast cancer, allowing for increased efficiency of future preclinical studies.