Essential thrombocythemia (ET) and polycythemia vera (PV) are rare in adolescent and young adult (AYA). These conditions, similar to those in older patients, are linked with thrombotic complications and the potential progression to secondary myelofibrosis (sMF). This retrospective study of ET and PV patients diagnosed before age 25 evaluated complication rates and impact of cytoreductive drugs on outcomes. Among 348 patients (278 ET, 70 PV) with a median age of 20 years, the of thrombotic events was 1.9 per 100 patient-years. Risk factors for thrombosis included elevated white blood cell count (>11 × 109/L) (HR: 2.7, p = 0.012) and absence of splenomegaly at diagnosis (HR: 5.7, p = 0.026), while cytoreductive drugs did not reduce this risk. The incidence of sMF was 0.7 per 100 patient-years. CALR mutation (HR: 6.0, p < 0.001) and a history of thrombosis (HR: 3.8, p = 0.015) were associated with sMF risk. Interferon as a first-line treatment significantly improved myelofibrosis-free survival compared to other treatments or the absence of cytoreduction (p = 0.046). Although cytoreduction did not affect thrombotic event, early interferon use reduced sMF risk. These findings support interferon use to mitigate sMF risk in AYA ET and PV patients.
- MeSH
- dospělí MeSH
- esenciální trombocytemie * farmakoterapie komplikace terapie MeSH
- kalretikulin genetika MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mutace MeSH
- následné studie MeSH
- polycythaemia vera * farmakoterapie komplikace terapie MeSH
- primární myelofibróza etiologie epidemiologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- trombóza etiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
This case report describes a case of pseudonormokalemia, true hypokalemia. Often, only laboratory values outside the normal range gain attention and false normal results are at risk of not being noticed. However, a disease state may be masked by another pathological process. Here, a 50-year old male was admitted to the Department of Internal Medicine due to sepsis from a dental infection. Initially, serum potassium measurement revealed a normal value of 4 mmol/L (reference interval 3.8-5.1 mmol/L). Thrombocyte number was above 500x109/L. Due to our policy to recommend a repeated measurement of potassium in whole blood or heparin plasma if a patient has thrombocytosis, pseudonormokalemia was identified because the heparin plasma potassium value was only 2.9 mmol/L (reference interval 3.5-4.8 mmol/L). The physiological difference between serum and plasma concentration is no more than 0.3 mmol/L. In this case, potassium concentration were falsely elevated in the serum sample, probably caused by the high number of platelets releasing potassium during clotting. Interpretative comments in patients with thrombocytosis over 500x109/L recommending plasma potassium measurement are helpful. The best way to eliminate pseudohyperkalemia and pseudonormokalemia phenomena caused by thrombocytosis is to completely change towards heparin plasma as the standard material.
- MeSH
- draslík * krev MeSH
- hypokalemie * krev diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- trombocytóza krev diagnóza MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Interferon-based therapies, such as ropeginterferon alfa-2b have emerged as promising disease-modifying agents for myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET). Current ET treatments aim to normalize hematological parameters and reduce the thrombotic risk, but they do not modify the natural history of the disease and hence, have no impact on disease progression. Ropeginterferon alfa-2b (trade name BESREMi®), a novel, monopegylated interferon alfa-2b with an extended administration interval, has demonstrated a robust and sustained efficacy in polycythemia vera (PV) patients. Given the similarities in disease pathophysiology and treatment goals, ropeginterferon alfa-2b holds promise as a treatment option for ET. The ROP-ET trial is a prospective, multicenter, single-arm phase III study that includes patients with ET who are intolerant or resistant to, and/or are ineligible for current therapies, such as hydroxyurea (HU), anagrelide (ANA), busulfan (BUS) and pipobroman, leaving these patients with limited treatment options. The primary endpoint is a composite response of hematologic parameters and disease-related symptoms, according to modified European LeukemiaNet (ELN) criteria. Secondary endpoints include improvements in symptoms and quality of life, molecular response and the safety profile of ropeginterferon alfa-2b. Over a 3-year period the trial assesses longer term outcomes, particularly the effects on allele burden and clinical outcomes, such as disease-related symptoms, vascular events and disease progression. No prospective clinical trial data exist for ropeginterferon alfa-2b in the planned ET study population and this study will provide new findings that may contribute to advancing the treatment landscape for ET patients with limited alternatives. TRIAL REGISTRATION: EU Clinical Trials Register; EudraCT, 2023-505160-12-00; Registered on October 30, 2023.
- MeSH
- dospělí MeSH
- esenciální trombocytemie * farmakoterapie MeSH
- interferon alfa-2 * terapeutické užití škodlivé účinky MeSH
- interferon alfa * terapeutické užití škodlivé účinky MeSH
- klinické zkoušky, fáze III jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- polyethylenglykoly * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- prospektivní studie MeSH
- rekombinantní proteiny * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
The clinical course of essential thrombocythemia (ET) is complicated with thrombosis which significantly impacts patients' mortality. Studies have identified JAK2V617F mutation as an independent risk factor for thrombosis. Circulating extracellular vesicles (EVs) were evaluated in several studies regarding myeloproliferative neoplasms and thrombosis as potential biomarkers. The present study investigates the relationship between JAK2V617F mutation and EVs levels in 119 ET patients. Our analyses revealed that JAK2V617F-positive patients are at a significantly increased risk of thrombosis within five years before the ET diagnosis (hazard ratio [95% CI]: 11.9 [1.7-83.7], P = 0.013), and that JAK2V617F mutation is an independent risk factor for thrombosis at ET diagnosis or during the follow-up (hazard ratio [95% CI]: 3.56 [1.47-8.62], P = 0.005). ET patients have higher levels of platelet-EVs, erythrocyte-EVs and procoagulant activity of EVs than the healthy population. Absolute and relative counts of platelet-EVs are increased in the presence of JAK2V617F mutation (P = 0.018, P = 0.024, respectively). In conclusion, our results support the role of JAK2V617F mutation in the pathogenesis of thrombosis in essential thrombocythemia through enhancing platelet activation.
- MeSH
- esenciální trombocytemie diagnóza genetika patologie terapie MeSH
- Janus kinasa 2 genetika MeSH
- kostní dřeň patologie MeSH
- leukemie diagnóza klasifikace patologie terapie MeSH
- lidé MeSH
- mutace genetika MeSH
- myeloproliferativní poruchy * diagnóza genetika patologie terapie MeSH
- polycythaemia vera diagnóza genetika terapie MeSH
- primární myelofibróza diagnóza patologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
JAK 2-V617F mutation causes myeloproliferative neoplasms (MPNs) that can manifest as polycythemia vera (PV), essential thrombocythemia (ET), or primary myelofibrosis. At diagnosis, patients with PV already exhibited iron deficiency, whereas patients with ET had normal iron stores. We examined the influence of iron availability on MPN phenotype in mice expressing JAK2-V617F and in mice expressing JAK2 with an N542-E543del mutation in exon 12 (E12). At baseline, on a control diet, all JAK2-mutant mouse models with a PV-like phenotype displayed iron deficiency, although E12 mice maintained more iron for augmented erythropoiesis than JAK2-V617F mutant mice. In contrast, JAK2-V617F mutant mice with an ET-like phenotype had normal iron stores comparable with that of wild-type (WT) mice. On a low-iron diet, JAK2-mutant mice and WT controls increased platelet production at the expense of erythrocytes. Mice with a PV phenotype responded to parenteral iron injections by decreasing platelet counts and further increasing hemoglobin and hematocrit, whereas no changes were observed in WT controls. Alterations of iron availability primarily affected the premegakaryocyte-erythrocyte progenitors, which constitute the iron-responsive stage of hematopoiesis in JAK2-mutant mice. The orally administered ferroportin inhibitor vamifeport and the minihepcidin PR73 normalized hematocrit and hemoglobin levels in JAK2-V617F and E12 mutant mouse models of PV, suggesting that ferroportin inhibitors and minihepcidins could be used in the treatment for patients with PV.
- MeSH
- deficit železa * MeSH
- esenciální trombocytemie * genetika MeSH
- fenotyp MeSH
- hemoglobiny genetika MeSH
- Janus kinasa 2 genetika MeSH
- mutace MeSH
- myeloproliferativní poruchy * farmakoterapie genetika diagnóza MeSH
- myši MeSH
- polycythaemia vera * genetika MeSH
- železo MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- chronická myelomonocytární leukemie diagnóza patologie terapie MeSH
- esenciální trombocytemie diagnóza etiologie terapie MeSH
- lidé MeSH
- myeloproliferativní poruchy * diagnóza etiologie klasifikace terapie MeSH
- polycythaemia vera diagnóza etiologie farmakoterapie MeSH
- primární myelofibróza diagnóza etiologie patologie terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Myeloproliferative neoplasms (MPNs) are uncommon in children/young adults. Here, we present data on unselected patients diagnosed before 25 years of age included from 38 centers in 15 countries. Sequential patients were included. We identified 444 patients, with median follow-up 9.7 years (0-47.8). Forty-nine (11.1%) had a history of thrombosis at diagnosis, 49 new thrombotic events were recorded (1.16% patient per year [pt/y]), perihepatic vein thromboses were most frequent (47.6% venous events), and logistic regression identified JAK2V617F mutation (P = .016) and hyperviscosity symptoms (visual disturbances, dizziness, vertigo, headache) as risk factors (P = .040). New hemorrhagic events occurred in 44 patients (9.9%, 1.04% pt/y). Disease transformation occurred in 48 patients (10.9%, 1.13% pt/y), usually to myelofibrosis (7.5%) with splenomegaly as a novel risk factor for transformation in essential thrombocythemia (ET) (P= .000) in logistical regression. Eight deaths (1.8%) were recorded, 3 after allogeneic stem cell transplantation. Concerning conventional risk scores: International Prognostic Score for Essential Thrombocythemia-Thrombosis and new International Prognostic Score for Essential Thrombocythemia-Thrombosis differentiated ET patients in terms of thrombotic risk. Both scores identified high-risk patients with the same median thrombosis-free survival of 28.5 years. No contemporary scores were able to predict survival for young ET or polycythemia vera patients. Our data represents the largest real-world study of MPN patients age < 25 years at diagnosis. Rates of thrombotic events and transformation were higher than expected compared with the previous literature. Our study provides new and reliable information as a basis for prospective studies, trials, and development of harmonized international guidelines for the specific management of young patients with MPN.
- MeSH
- dítě MeSH
- dospělí MeSH
- esenciální trombocytemie * MeSH
- lidé MeSH
- mladý dospělý MeSH
- myeloproliferativní poruchy * komplikace diagnóza epidemiologie MeSH
- polycythaemia vera * komplikace MeSH
- primární myelofibróza * genetika MeSH
- prospektivní studie MeSH
- trombóza * etiologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- akutní lymfatická leukemie diagnóza farmakoterapie patologie MeSH
- akutní myeloidní leukemie klasifikace terapie MeSH
- anemie diagnóza etiologie patologie MeSH
- diferenciální diagnóza MeSH
- esenciální trombocytemie diagnóza terapie MeSH
- krevní nemoci * diagnóza klasifikace patologie terapie MeSH
- lidé MeSH
- lymfom diagnóza farmakoterapie klasifikace patofyziologie MeSH
- mnohočetný myelom diagnóza farmakoterapie patologie MeSH
- polycythaemia vera diagnóza patologie terapie MeSH
- Waldenströmova makroglobulinemie diagnóza farmakoterapie patofyziologie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
