Search Results (79)

Background and Clinical Significance: Polycythemia vera is a myeloproliferative neoplasm associated with a high thrombotic risk. Although this association is well recognized, acute coronary syndrome as the initial manifestation of polycythemia vera is rare. Case Presentation: We report the case of a previously healthy 57-year-old male with no conventional cardiovascular risk factors who presented with an anterior ST-elevation myocardial infarction. Coronary angiography revealed a subocclusive lesion in the left anterior descending artery, which was successfully treated with primary percutaneous coronary intervention. Initial laboratory testing showed markedly elevated hemoglobin (209 g/L) and hematocrit (64.9%), together with thrombocytosis (438 × 10⁹/L). In the absence of conventional risk factors, the combination of a single-vessel coronary lesion and marked hematologic abnormalities raised suspicion for polycythemia vera as a major contributor to coronary thrombosis. Subsequent work-up confirmed polycythemia vera based on the presence of a JAK2 V617F mutation and suppressed erythropoietin levels. The patient underwent therapeutic phlebotomy shortly after angioplasty and was subsequently started on hydroxyurea to maintain a hematocrit below 45%, together with dual antiplatelet therapy. Conclusions: This case highlights acute myocardial infarction as a rare initial presentation of polycythemia vera. It underscores the importance of considering polycythemia vera in patients presenting with acute coronary syndrome and unexplained erythrocytosis, while acknowledging that, in the absence of intracoronary imaging, a definitive causal link between PV and the coronary event cannot be established. Full article

Sickle cell disease (SCD) is the most common inherited clinically relevant blood disorder. Although a deceptively simple monogenetic disorder, the associated complications have multiple downstream effects. In this review, we explore the many facets of SCD, with a particular focus on its impact on the vascular system. Despite progress in understanding the underlying mechanisms of SCD, including Hemoglobin S polymerization, microvascular occlusion, and inflammation, there are still many questions surrounding the condition, especially predicting which affected individuals will acquire specific complications in order to personalize treatments. While current standard of care treatments, including hydroxyurea and chronic red blood cell transfusions, have been proven to be disease-modifying, newer therapies like crizanlizumab and voxelotor have only proven to manage symptoms. Newer gene therapies have been approved; however, it is not clear what impact these will have long-term on the end-organ complications of SCD. There is still a significant need to understand how we optimize and personalize therapies to improve outcomes for patients. This review highlights the importance of recognizing SCD as a vascular disease to understand its multi-organ complications and heterogeneity of effects. Full article

Background/Objectives: Hydroxyurea is currently the standard disease-modifying therapy for reducing sickle cell disease (SCD) complications; however, drug labels currently advise discontinuation of breastfeeding during hydroxyurea therapy due to limited human data on the risk of hydroxyurea exposure in breastfed neonates. Methods: A physiologically based pharmacokinetic (PBPK) model for hydroxyurea was built and verified with data from non-lactating adult patients with SCD. The model was then extended to predict hydroxyurea in nursing and in paediatric populations. Predictions were compared to the observed data. Results: The PBPK model predictions for hydroxyurea pharmacokinetics described the observed data in both adult and paediatric subjects with SCD. Observed concentration profiles were within the 5th–95th prediction intervals, and predicted PK parameters were within 2-fold of the observed values. The predicted milk-to-plasma ratio was 0.8. Neonatal exposure to hydroxyurea via breast milk as a percentage of maternal exposure increased from 0.6% at 1 day to 10% at the 4th week postpartum before declining to 5%, 3%, and 2% at 6, 9, and 12 months postpartum, respectively. Conclusions: About 56% of total milk hydroxyurea exposure is within the first 3 h of post-maternal dose. Disposal of this early milk would reduce the exposure of breastfed children. The reduction in exposure is especially pronounced around the first 1 month postpartum. Lactation PBPK models offer a physiological approach to assess real-life scenarios that are difficult to investigate in clinical studies and provide useful results for future clinical study design and clinical recommendations. This was exemplified with hydroxyurea in the current work. Full article

Sickle cell disease (SCD) is an inherited hemoglobinopathy in which hemoglobin S polymerization drives hemolysis and vaso-occlusion with progressive organ morbidity. Male reproductive impairment is increasingly recognized but remains underreported. This narrative review summarizes mechanistic pathways, clinical manifestations, and fertility preservation options relevant to men with SCD. PubMed, the Cochrane Library, and Medscape were searched through 31 December 2025 for human studies addressing endocrine changes, semen quality, priapism and erectile dysfunction, oxidative stress, and treatment-related gonadotoxicity. Evidence supports converging mechanisms: recurrent vaso-occlusion and chronic hypoxia may injure the seminiferous epithelium and impair Leydig cell steroidogenesis; oxidative stress and inflammation contribute to sperm DNA and membrane damage; and disease-modifying or curative therapies such as hydroxyurea and hematopoietic stem cell transplantation can further compromise spermatogenesis. Clinically, men with SCD may present with oligozoospermia, azoospermia, hypogonadism, and sexual dysfunction, particularly after recurrent ischemic priapism. Fertility preservation should be discussed early, ideally before prolonged hydroxyurea exposure or transplantation, and may include semen cryopreservation and testicular sperm extraction (TESE) with assisted reproduction when needed. Prospective longitudinal studies are required to define reproductive trajectories and optimize counseling and management. Full article

Background: Macrocytosis commonly develops during imatinib therapy, but its relationship with cytogenetic and molecular outcomes in chronic myeloid leukemia (CML) remains unclear. We investigated whether increases in mean corpuscular volume (MCV) during imatinib treatment are associated with response depth and treatment persistence. Methods: In this retrospective study, we analyzed 101 adults with chronic-phase CML treated with a stable imatinib dose of 400 mg/day for at least 12 months. Patients with conditions that could confound MCV (hydroxyurea exposure, megaloblastic anemia, hypothyroidism, chronic liver disease, alcoholism) were excluded. Complete cytogenetic response (CCyR) and major molecular response (MMR) were assessed by conventional karyotyping and the BCR-ABL1 International Scale, respectively. Increased MCV was defined as MCV > 100 fL after six months of therapy, persisting thereafter. Associations between MCV dynamics, response, and switching to second-generation tyrosine kinase inhibitors were evaluated. Results: Twenty patients (20%) developed increased MCV. Overall, 86 patients (85%) achieved CCyR and 70 (69%) achieved MMR. All patients with increased MCV attained CCyR, compared with 66 of 81 (81%) without MCV elevation (p = 0.037), while MMR rates were 90% versus 64% (p = 0.030). During a median follow-up of 69 months, treatment modification was required in 1 of 20 (5%) patients with increased MCV versus 25 of 81 (31%) in the non-increased group (p = 0.018). Conclusions: MCV elevation during imatinib therapy is associated with deeper molecular response and reduced need for treatment modification. MCV dynamics may serve as an inexpensive pharmacodynamic marker to support risk assessment and guide monitoring in chronic-phase CML. Full article

Background: Ropeginterferon alfa-2b (Ropeg-IFNa) is increasingly used in myeloproliferative neoplasms (MPN), particularly polycythemia vera, but real-world data across subtypes are limited. We evaluated clinical and molecular responses to Ropeg-IFNa in routine practice. Methods: We retrospectively analyzed 20 JAK2^V617F-positive MPN patients treated at a tertiary center. Baseline features, dosing, treatment line, hematologic responses, adverse events, and serial JAK2^V617F variant allele frequency (VAF) were extracted from records. Results: Median age at initiation was 53 years; 55% were ELN high-risk. Ropeg-IFNa was started first-line or after peginterferon alfa-2a, hydroxyurea, or a tapered JAK2 inhibitor. Mean treatment duration was 14 ± 11 months at 195 ± 143 µg Q2W. Hematologic control increased from 45% at the start to 60% at the last follow-up. Among patients with serial molecular monitoring (n = 11), median JAK2^V617F VAF declined from 21.2 to 12.7%. Ropeg-IFNa was generally well tolerated; adverse effects were mostly manageable, although 3/20 (15%) discontinued due to side effects, including mood disturbances, while others continued with supportive care and dose adjustments. Conclusions: In this single-center cohort, Ropeg-IFNa was tolerable and associated with improved hematologic control and modest VAF reductions, supporting its use in multi-subtype MPN cohorts. These findings underscore the value of longitudinal driver-mutation monitoring during therapy. Full article

Hydroxyurea (HU) is a cytostatic drug used in oncotherapy. The drug has inhibitory effects on bone marrow and epithelial cells and causes minor side effects in the skin, including nail deformity, alopecia, and hyperpigmentation, and severe side effects, including skin tumors and nonhealing ulcers. Herein, we report the case of a patient who received HU therapy for polycythemia vera. The patient had type 2 diabetes and atherosclerosis. Onychodystrophy and a non-healing ulcer developed. Severe deep tissue infection and osteomyelitis, rare complications of a HU-related ulcer, were also diagnosed later. Diabetes and atherosclerosis made the condition more severe. Complex systemic and local therapy led to complete healing of the ulcer and osteomyelitis. Based on the literature and our own experience, a care protocol was proposed for the dermatological follow-up of patients under HU treatment. This recommendation may be particularly useful in the treatment of patients treated with hydroxyurea who suffer from atherosclerosis, diabetes, or leg ulcers and are therefore at increased risk of severe skin and deep tissue infections. Full article

We describe a patient with post-essential thrombocythaemia myelofibrosis treated with intermittent hydroxyurea (Hu) therapy (20 mg/Kg, given as a single dose, thrice weekly), achieving sustained disease control and regression of bone marrow fibrosis. Additionally, we discuss the efficacy of and rationale for use of intermittent Hu therapy in patients with myeloproliferative neoplasms, including those deemed to be Hu-resistant or intolerant to the commonly used continuous therapy. Full article

Sickle cell disease (SCD) is the most common monogenic disorder worldwide and remains a major cause of morbidity and mortality. Sickle cell anemia (SCA), the homozygous HbSS genotype, represents the most severe and frequent form within the spectrum of SCD. Hydroxyurea (HU), a ribonucleotide reductase inhibitor, represents the first and most widely used disease-modifying therapy for SCA. This review summarizes current evidence on the mechanisms of action, clinical efficacy, systemic effects, and long-term safety of chronic HU therapy in patients with SCA. A comprehensive literature search was conducted in PubMed up to 2025 using the terms “sickle cell disease,” “sickle cell anemia”, “hydroxyurea,” and “children” or “paediatric.” Eligible studies included randomized controlled trials, cohort studies, and systematic reviews evaluating HU therapy in SCA. Literature analysis showed that HU exerts pleiotropic effects by inducing fetal hemoglobin (HbF) synthesis, improving red blood cell deformability, reducing leukocyte and platelet counts, and enhancing nitric oxide bioavailability. These mechanisms lead to decreased vaso-occlusive crises, acute chest syndrome, transfusion requirements, and overall mortality. Beyond hematologic improvement, HU confers neuroprotective benefits, modulates inflammatory and immune pathways, and supports normal growth and endocrine development in children. Adverse events, primarily mild bone marrow suppression, are dose-dependent and reversible with appropriate monitoring. No evidence supports an increased risk of malignancy with long-term use. In conclusion, chronic HU therapy is a safe, effective, and multifaceted treatment that substantially improves survival and quality of life in patients with SCA. Early initiation and individualized dosing maximize its therapeutic benefits and help prevent irreversible organ damage. Full article

Standard systemic treatment has not been established for refractory meningioma. This retrospective study aimed to identify prognostic factors for overall survival and document outcomes of systemic therapies. We reviewed patients with meningioma followed at CHUM hospital between 2006 and 2022. Only patients with progression after first-line treatment were included. Among 750 patients, 107 (14%) experienced progression after first-line treatment. They were divided into two groups: Group 1 (n = 69, 64%) received salvage local treatments, and Group 2 (n = 38, 36%) received additional salvage systemic treatments. The median follow-up time from diagnosis was 7.5 years. 10-year OS was 88.3% (Group 1) vs. 67.2% (Group 2) (p = 0.009). Mean survival after stopping systemic treatment was 8.94 months. Key prognostic factors for poorer survival included age ≥ 65 (HR = 2.82; p = 0.009), WHO grade 2 or 3 (HR = 4.25; p = 0.004), and progression after second-line treatment (HR = 4.77; p = 0.004). Bevacizumab was associated with a mPFS of 12 months and 1-year OS of 64,6%, whereas non-Bevacizumab treatments—including Hydroxyurea, Somatostatin, and Sunitinib—were associated with a mPFS of 7 months and 1-year OS of 52,6%. This study highlights the fatal nature of recurrent meningiomas and the urgent need for systemic treatments that can improve their survival. Full article

Background: Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by the uncontrolled proliferation of megakaryocytes and sustained thrombocytosis. Although its impact on renal function is not well established, a few case reports have described glomerular involvement and associated kidney impairment. Case Report: We present the case of a 79-year-old man with ET and stage 3b/A2 chronic kidney disease (CKD), who was admitted with severe acute kidney injury (AKI). This episode was associated with a progressive rise in platelet count, reaching 1,350,000/μL after discontinuation of anagrelide and loop diuretics. Renal biopsy (RB) revealed structural lesions compatible with a myeloproliferative neoplasm, including acute tubular necrosis (ATN), glomerulomegaly, and thrombotic microangiopathy (TMA). Cytoreductive therapy with hydroxyurea and corticosteroids was initiated, resulting in improvement of renal function and achievement of complete hematologic remission. Discussion: During follow-up, a linear correlation was observed between increasing platelet counts and declining renal function, underscoring the need for dynamic therapeutic adjustment and close monitoring to prevent progression to end-stage renal disease (ESRD). Conclusions: This case highlights the importance of nephrological evaluation in patients with ET and supports the role of cytoreductive therapy in managing ET-associated renal complications. Full article

Essential thrombocythemia (ET) is a rare myeloproliferative neoplasm characterized by excessive platelet production and a predisposition to thrombotic or hemorrhagic complications. We report a case of a 62-year-old male with no conventional cardiovascular risk factors who presented with a non-ST-segment elevation myocardial infarction (NSTEMI). Initial coronary angiography showed isolated proximal LAD stenosis. Laboratory tests revealed marked thrombocytosis (>1,000,000/μL) and a CALR mutation, confirming a diagnosis of ET. The patient was treated with percutaneous coronary intervention (PCI), dual antiplatelet therapy, and cytoreductive therapy with hydroxyurea, leading to a favorable outcome. This case illustrates how ET, particularly CALR-mutated subtypes, can manifest as acute coronary syndrome in the absence of atherosclerosis and underscores the need to consider hematologic malignancies in atypical presentations of myocardial infarction. Full article

Hydroxyurea is effective in reducing the severity of Sickle cell anemia (SCA) symptoms, yet adherence remains challenging, particularly in resource-limited settings. Bugando Medical Centre, a major healthcare provider, faces undocumented adherence issues among its pediatric SCA patients. This study aims to evaluate the adherence rate to hydroxyurea therapy among caregivers of children with SCA at Bugando Medical Centre and identify factors contributing to non-adherence. This analytical cross-sectional study involved 172 participants. Data were analyzed using Stata version 15 and modified Poisson regression determined the association between exposures and adherence to hydroxyurea treatment. More than half (68.6%) of the children were aged between 1 and 10 years, with a median age of 8 years (IQR: 5–12). Good adherence to hydroxyurea was observed in 23.8% of participants, while 76.2% showed moderate to poor adherence. Children aged 1–10 years were twice as likely to have good adherence compared to those aged 11–17 years (aPR = 2.98, 95% CI = 1.18, 7.47). Children of caregivers with secondary education had a 41% higher chance of good adherence (aPR = 1.41, 95% CI = 1.19, 2.87) compared to those with primary education. Additionally, children of caregivers with college/university education had a 92% higher chance of good adherence (aPR = 1.92, 95% CI = 1.09, 4.63) compared to those with primary education. Participants with good knowledge of hydroxyurea had a 55% higher chance of good adherence (aPR = 1.55, 95% CI = 1.10, 4.78) compared to those with poor knowledge. Factors such as the child’s age and caregiver’s educational level are associated with good adherence to hydroxyurea treatment. Despite these associations, overall adherence rates are low, highlighting the need for targeted interventions to enhance knowledge and awareness about the importance of adherence to hydroxyurea treatment. Full article

Kidney disorders significantly contribute to morbidity and mortality in sickle cell disease (SCD). Acute kidney injury (AKI), a major risk factor for chronic kidney disease (CKD), often arises from intravascular hemolysis, where plasma cell-free heme drives AKI through inflammatory and oxidative stress mechanisms. Hydroxyurea (HU), a well-established SCD-modifying therapy, improves clinical outcomes, but its effects on systemic heme and inflammatory mediators of kidney injury remain underexplored. This study evaluated HU’s impact on plasma heme, pro-inflammatory mediators, kidney injury, and renal histopathology in a sickle cell mouse model. Townes humanized sickle cell mice (HbSS) and non-sickle (HbAA) controls were treated with HU or vehicle for two weeks. HU significantly reduced total plasma heme, lactate dehydrogenase, and pro-inflammatory cytokines (CXCL10, VEGF-A, IFN-γ) in HbSS mice. HU reduced renal injury biomarkers (cystatin C, NGAL) and improved renal histopathology, evidenced by reduced vascular congestion, glomerulosclerosis, and tubular damage. Interestingly, HU did not alter the levels of kidney repair biomarkers (clusterin and EGF). These findings suggest that HU mitigates kidney injury by reducing the deleterious effects of circulating heme and inflammation, supporting its potential to slow or prevent progressive kidney injury in SCD. Full article

Hydroxyurea (HU), a cornerstone treatment for myeloproliferative disorders, is associated with a wide range of cutaneous side effects, from xerosis and hyperpigmentation to more severe conditions like dermatomyositis-like eruptions (DM-LE) and nonmelanoma skin cancers (NMSC), particularly squamous cell carcinoma (SCC). In this review, we present a unique case of HU-induced DM-LE with histological evidence of keratinocyte dysplasia and p53 overexpression, followed by a systematic analysis of similar cases. Our findings reveal that the clinical presentation of DM-LE, while typically considered benign, shares clinical and histological features with hydroxyurea-associated squamous dysplasia (HUSD), a precancerous condition that may progress to SCC in chronically exposed patients. Key insights include the characteristic histopathological findings of DM-LE, the role of chronic HU therapy and UV-induced damage in promoting p53 overexpression, and the overlap between DM-LE and HUSD. Regular dermatologic monitoring, patient education on photoprotection, and the careful assessment of skin lesions in long-term HU users are essential for the early detection and prevention of malignancies. This review underscores the importance of distinguishing between DM-LE, HUSD, and SCC to optimize management and minimize risks associated with HU therapy. Full article