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Ruxolitinib, an oral inhibitor of Janus kinase (JAK) 1 and 2, was associated with hematocrit control and spleen size reduction in 21% of patients with polycythemia vera who had an inadequate response to or unacceptable side effects from hydroxyurea. Polycythemia vera is a chronic clonal myeloproliferative neoplasm characterized by increased red-cell mass; elevated white-cell and platelet counts are also common. 1 Patients have an increased risk of thrombotic and cardiovascular events 2 and a substantial symptom burden that includes pruritus, fatigue, and night sweats. 3 Splenomegaly often develops as the disease progresses. 4 The main goal of therapy is to prevent thrombotic events while avoiding iatrogenic harm and minimizing the risk of transformation to post–polycythemia vera myelofibrosis or acute myeloid leukemia (AML). 5 , 6 Most patients receive low-dose aspirin and undergo phlebotomy, 7 with a goal of maintaining hematocrit values of less than 45%. Aggressive . . .

Sickle-cell anaemia is associated with substantial morbidity from acute complications and organ dysfunction beginning in the first year of life. Hydroxycarbamide substantially reduces episodes of pain and acute chest syndrome, admissions to hospital, and transfusions in adults with sickle-cell anaemia. We assessed the effect of hydroxycarbamide therapy on organ dysfunction and clinical complications, and examined laboratory findings and toxic effects. This randomised trial was undertaken in 13 centres in the USA between October, 2003, and September, 2009. Eligible participants had haemoglobin SS (HbSS) or haemoglobin Sβ 0thalassaemia, were aged 9–18 months at randomisation, and were not selected for clinical severity. Participants received liquid hydroxycarbamide, 20 mg/kg per day, or placebo for 2 years. Randomisation assignments were generated by the medical coordinating centre by a pre-decided schedule. Identical appearing and tasting formulations were used for hydroxycarbamide and placebo. Patients, caregivers, and coordinating centre staff were masked to treatment allocation. Primary study endpoints were splenic function (qualitative uptake on 99Tc spleen scan) and renal function (glomerular filtration rate by 99mTc-DTPA clearance). Additional assessments included blood counts, fetal haemoglobin concentration, chemistry profiles, spleen function biomarkers, urine osmolality, neurodevelopment, transcranial Doppler ultrasonography, growth, and mutagenicity. Study visits occurred every 2–4 weeks. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00006400. 96 patients received hydroxycarbamide and 97 placebo, of whom 83 patients in the hydroxycarbamide group and 84 in the placebo group completed the study. Significant differences were not seen between groups for the primary endpoints (19 of 70 patients with decreased spleen function at exit in the hydroxycarbamide group vs 28 of 74 patients in the placebo group, p=0·21; and a difference in the mean increase in DTPA glomerular filtration rate in the hydroxycarbamide group versus the placebo group of 2 mL/min per 1·73 m 2, p=0·84). Hydroxycarbamide significantly decreased pain (177 events in 62 patients vs 375 events in 75 patients in the placebo group, p=0·002) and dactylitis (24 events in 14 patients vs 123 events in 42 patients in the placebo group, p<0·0001), with some evidence for decreased acute chest syndrome, hospitalisation rates, and transfusion. Hydroxyurea increased haemoglobin and fetal haemoglobin, and decreased white blood-cell count. Toxicity was limited to mild-to-moderate neutropenia. On the basis of the safety and efficacy data from this trial, hydroxycarbamide can now be considered for all very young children with sickle-cell anaemia. The US National Heart, Lung, and Blood Institute; and the National Institute of Child Health and Human Development.

To compare the efficacy and safety of gecacitinib (also known as jaktinib) with hydroxyurea (HU) in treating myelofibrosis (MF) patients. In this multicenter, randomized phase 3 trial (ZGJAK016), intermediate- or high-risk primarily JAK inhibitor naïve MF patients were assigned in a 2:1 ratio to receive either gecacitinib (100 mg twice a day, BID) or HU (500 mg BID). The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) from baseline at week 24. Secondary endpoints included the best spleen response rate, the proportion of patients with a ≥50% reduction in total symptom score (TSS50), anemia improvement, and safety profile. At 24 weeks, the SVR35 was reached by 64.8% of patients on gecacitinib (46/71), compared to 26.5% on HU (9/34), P  = 0.0002. The best spleen response rates were also superior for gecacitinib at 81.7%, vs 32.4% for HU, P  < 0.0001. The TSS50 rates were 62.0% for gecacitinib- and 50% for HU-treated patients. Among non-transfusion-dependent patients with baseline hemoglobin (HGB) ≤ 100 g/L, 31.0% (13/42) in the gecacitinib group showed a ≥20 g/L increase in HGB, compared to 15.0% (3/20) in HU group. The common grade ≥ 3 treatment-emergent adverse events (TEAEs), including anemia (26.8% vs 44.1%), thrombocytopenia (15.5% vs 32.4%), leukopenia (2.8% vs 20.6%), and neutropenia (1.4% vs 20.6%), were less frequent with gecacitinib than HU. Treatment discontinuation due to TEAEs was lower in gecacitinib (7.0%) compared to HU (11.8%). Gecacitinib demonstrates superior efficacy and a more favorable safety profile compared to HU, making it a promising treatment option for managing MF, particularly in patients with anemia (This trial was registered with ClinicalTrials.gov, (NCT04617028)).

Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 Americans, primarily from underrepresented racial minority populations, and results in costly, multi-organ complications. Hydroxyurea, the primary disease-modifying therapy for SCD, is effective at reducing most complications; however, adherence to hydroxyurea remains suboptimal and is the primary barrier to clinical effectiveness. Video directly observed therapy (VDOT) has shown promise as an adherence-promoting intervention for hydroxyurea, yet previous VDOT trials were limited by high attrition from gaps in technology access, use of unvalidated adherence measures, and healthcare system limitations of delivering VDOT to patients. As such, we fostered a small business partnership to compare VDOT for hydroxyurea to attention control to address previous shortcomings, promote equitable trial participation, and maximize scalability. VDOT will be administered by Scene Health (formerly emocha Health) and adherence monitoring will be performed using a novel electronic adherence monitor developed to meet the unique needs of the target population. Adolescent and young adult patients as well as caregivers of younger patients (<11 years of age) will be recruited. In addition to visit incentives, all participants will be offered a smartphone with a data plan to ensure all participants have equal opportunity to complete study activities. The primary objectives of this pilot, multi-center, randomized controlled trial (RCT) are to assess retention and sustained engagement and to explore needs and preferences for longer-term adherence monitoring and interventions. This RCT is registered with the National Institutes of Health (NCT06264700). Findings will inform a future efficacy RCT applying VDOT to hydroxyurea to address adherence gaps and improve outcomes within this vulnerable population.

Hydroxyurea (HU) is mostly referred to as an inhibitor of ribonucleotide reductase (RNR) and as the agent that is commonly used to arrest cells in the S-phase of the cycle by inducing replication stress. It is a well-known and widely used drug, one which has proved to be effective in treating chronic myeloproliferative disorders and which is considered a staple agent in sickle anemia therapy and—recently—a promising factor in preventing cognitive decline in Alzheimer’s disease. The reversibility of HU-induced replication inhibition also makes it a common laboratory ingredient used to synchronize cell cycles. On the other hand, prolonged treatment or higher dosage of hydroxyurea causes cell death due to accumulation of DNA damage and oxidative stress. Hydroxyurea treatments are also still far from perfect and it has been suggested that it facilitates skin cancer progression. Also, recent studies have shown that hydroxyurea may affect a larger number of enzymes due to its less specific interaction mechanism, which may contribute to further as-yet unspecified factors affecting cell response. In this review, we examine the actual state of knowledge about hydroxyurea and the mechanisms behind its cytotoxic effects. The practical applications of the recent findings may prove to enhance the already existing use of the drug in new and promising ways.

A year-long, phase 3, randomized trial involving patients with sickle cell disease showed that the median number of pain crises was 25% lower and the median number of hospitalizations was 33% lower with l -glutamine supplementation than with placebo.

In a large trial conducted in four African nations, hydroxyurea was safely administered to children with sickle cell disease and led to significant increases in hemoglobin and fetal hemoglobin levels and significant reductions in the incidence of pain crises, infection, malaria, transfusion, and death.

In this yearlong trial involving patients with sickle cell disease, crizanlizumab, an antibody to P-selectin, was associated with a 45% lower rate of pain crises than placebo and a longer time to their onset. Adverse events included arthralgia, diarrhea, and pruritus. Sickle cell disease is characterized by the presence of sickle hemoglobin (HbS), chronic hemolysis, recurrent pain episodes (called sickle cell–related pain crises or vaso-occlusive crises), multiorgan dysfunction, and early death. Sickle cell–related pain crises are the primary cause of health care encounters in patients with sickle cell disease. 1 These crises result in a decrease in quality of life 2 and an increase in the risk of death. 3 Crises are thought to be caused by vascular occlusion in the microcirculation, increased inflammation, and alterations in nociception. 4 The prevention of crises could minimize or prevent tissue and organ damage and decrease the subsequent . . .

Hydroxyurea increases expression of fetal hemoglobin and decreases clinical complications in children with sickle cell anemia. A trial of a higher dose (30 mg per kg per day) as compared with a standard dose (20 mg per kg) in children in sub-Saharan Africa showed improved outcomes without increased toxicity.