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Over the last decade, we have witnessed a massive increase in available clinical agents, both in the clinical trial setting and following commercial use approval, directed to reduced life expectancy as well as the considerable symptom, splenic and anaemia burden associated with myelofibrosis. Given the median age of onset of the disease, coupled with an ageing population globally, we will be caring for an increasingly aged myelofibrosis cohort in future years. We will need to adapt our approach, emphasizing the holistic management of the older individual with myelofibrosis accordingly. Out with the pharmacological management of the disease, consideration needs to be given to interventions based on concurrent illness, comprehensive geriatric assessments, frailty, polypharmacy and drug-drug interactions, nutritional issues, psychological concerns (depression, anxiety or distress), cognitive decline and social/economic aspects. Within this review, we summarise available data addressing these issues, outline knowledge gaps and suggest a summative and holistic approach to the older individual with myelofibrosis.
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Mielofibrose Primária , Humanos , Idoso , Mielofibrose Primária/terapia , EnvelhecimentoAssuntos
Anemia , Sobrecarga de Ferro , Inibidores de Janus Quinases , Mielofibrose Primária , Anemia/tratamento farmacológico , Anemia/etiologia , Terapia por Quelação , Humanos , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/tratamento farmacológico , Janus Quinase 2/genética , Inibidores de Janus Quinases/uso terapêutico , Mielofibrose Primária/complicações , Mielofibrose Primária/tratamento farmacológicoRESUMO
Iron chelation therapy (ICT) has become a mainstay in heavily transfused hematological patients, with the aim to reduce iron overload (IOL) and prevent organ damage. This therapeutic approach is already widely used in thalassemic patients and in low-risk Myelodysplastic Syndrome (MDS) patients. More recently, ICT has been proposed for high-risk MDS, especially when an allogeneic bone marrow transplantation has been planned. Furthermore, other hematological and hereditary disorders, characterized by considerable transfusion support to manage anemia, could benefit from this therapy. Meanwhile, data accumulated on how iron toxicity could exacerbate anemia and other clinical comorbidities due to oxidative stress radical oxygen species (ROS) mediated by free iron species. Taking all into consideration, together with the availability of approved oral iron chelators, we envision a larger use of ICT in the near future. The aim of this review is to better identify those non-thalassemic patients who can benefit from ICT and give practical tips for management of this therapeutic strategy.
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Advancements in the understanding of the pathogenesis of acute myeloid leukemia (AML) have led to the introduction and approval of a number of novel drugs in AML. Glasdegib, an oral hedgehog pathway inhibitor, was approved in 2018 in combination with low-dose cytarabine for the treatment of newly diagnosed AML in patients unfit for intensive chemotherapy. In this review, we discuss the preclinical rationale for glasdegib, important clinical trials that led to glasdegib's approval, and future trials of glasdegib in AML and other myeloid diseases. Notably, 2 large randomized, placebo-controlled phase 3 trials (AML BRIGHT 1019) are currently recruiting patients with newly diagnosed AML to evaluate glasdegib in combination with intensive chemotherapy or azacitidine, depending on the patient's ability to tolerate induction chemotherapy. While glasdegib and low-dose cytarabine have been eclipsed by venetoclax and hypomethylating agent combinations for newly diagnosed AML in the United States, we discuss other areas where glasdegib may still have an opportunity to improve outcomes in this devastating disease.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzimidazóis/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Azacitidina/uso terapêutico , Benzimidazóis/farmacologia , Linhagem Celular Tumoral , Ensaios Clínicos como Assunto , Citarabina/uso terapêutico , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Humanos , Quimioterapia de Indução/efeitos adversos , Quimioterapia de Indução/métodos , Camundongos , Compostos de Fenilureia/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor Smoothened/antagonistas & inibidores , Receptor Smoothened/metabolismo , Estados UnidosRESUMO
Myeloproliferative neoplasms (MPNs) are characterized by significant symptom burden. Integrative medicine (IM) offers unique symptom management strategies. This study describes IM interventions utilized by MPN patients and the association with symptom burden, quality of life, depression, and fatigue adjusted for lifestyle confounders. MPN patients were surveyed online for IM utilization, MPN symptom burden (MPN-Symptom Assessment Form Total Symptom Score), depression (Patient Health Questionnaire), fatigue (Brief Fatigue Inventory), and a single question on overall quality of life. Measures were compared by IM participation and adjusted for alcohol and tobacco use, BMI, diet, and MPN type using multiple linear and logistic regression. A total of 858 participants were included in the analysis. Aerobic activity (p =< 0.001) and strength training (p = 0.01) were associated with lower mean symptom burden while massage (p =< 0.001) and support groups (p =< 0.001) were associated with higher levels of symptom burden. Higher quality of life was reported in massage (p = 0.04) and support groups (p = 0.002) while lower quality of life was noted in aerobic activity (p =< 0.001) and strength training (p = 0.001). A lower depression screening score was noted in those participating in aerobic activity (p = 0.006), yoga (p = 0.03), and strength training (p = 0.02). Lower fatigue was noted in those participating in aerobic activity (p =< 0.001) and strength training (p = 0.03) while higher fatigue was noted in those participating in massage (p =< 0.001) and breathing techniques (p = 0.02). Data available on request from the authors. This international survey of MPN patients on IM usage, has shown that patients who participated in a form of IM had a pattern of decreased levels of symptom burden, fatigue, depression, and higher QoL, as adjusted for health lifestyle practices overall.
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Exercício Físico , Medicina Integrativa/métodos , Massagem/métodos , Transtornos Mieloproliferativos/terapia , Treinamento Resistido/métodos , Yoga/psicologia , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/psicologia , Apoio Nutricional , Qualidade de Vida , Grupos de Autoajuda , Inquéritos e QuestionáriosRESUMO
Vitamin B6 (VB6) deficiency contributes to oncogenesis and tumor progression in certain cancers, and is prevalent in cancer patients in general. VB6 is also an essential element of heme synthesis, and deficiency can lead to anemia. Primary myelofibrosis (PMF) and secondary myelofibrosis (sMF) are myeloproliferative neoplasms often presenting with anemia along with other cytopenias. We performed a prospective study to determine whether PMF and sMF patients suffer from VB6 deficiency, and whether VB6-deficient patients show improvement of anemias with VB6 supplementation. Twelve PMF patients and 11 sMF patients were analyzed. A total of 16 of 23 patients (69.6%) were found to have VB6 deficiency, but VB6 supplementation with pyridoxal phosphate hydrate did not elevate hemoglobin levels in deficient patients. None of the patients presented with vitamin B12, iron, or copper deficiencies. Four patients showed serum folate levels below the lower limit of normal and eight patients showed serum zinc levels below the lower limit of normal; however, these deficiencies were marginal and unlikely to contribute to anemia. Compared to VB6-sufficient patients, VB6-deficient patients showed significantly lower serum folate levels and higher serum copper levels. Studies elucidating the relationship of VB6 deficiency and etiology of PMF/sMF are warranted.
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Mielofibrose Primária/sangue , Deficiência de Vitamina B 6/sangue , Adulto , Anemia , Cobre/sangue , Feminino , Ácido Fólico/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Mielofibrose Primária/etiologia , Estudos Prospectivos , Fosfato de Piridoxal/uso terapêutico , Deficiência de Vitamina B 6/tratamento farmacológicoAssuntos
Deferasirox/uso terapêutico , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Mielofibrose Primária/tratamento farmacológico , Idoso , Deferasirox/farmacologia , Feminino , Humanos , Quelantes de Ferro/farmacologia , Masculino , Mielofibrose Primária/complicações , Estudos RetrospectivosRESUMO
Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by clonal proliferation of differentiated myeloid cells leading to bone marrow fibrosis, cytopenias and extramedullary hematopoiesis. In late 2019, the FDA approved the highly selective JAK2 inhibitor, fedratinib, for intermediate-2 or high-risk primary or secondary MF, making it the second drug approved for MF after ruxolitinib, a JAK1/2 inhibitor, which was approved for MF in 2011. The approval of fedratinib was based on phase II trials and the phase III JAKARTA trial, in which the drug significantly reduced splenomegaly and symptom burden compared to placebo, including some patients previously treated with ruxolitinib. The main side effects of fedratinib include anemia, gastrointestinal symptoms, and elevations in liver transaminases. Fedratinib also has ablack box warning for encephalopathy, although this occurred only in about 1% of the treated patients, most of which were ultimately felt not to represent Wernicke's encephalopathy. Nonetheless, monitoring of thiamine levels and supplementation are recommended especially in high-risk patients. This concern has led to a prolonged clinical hold and delayed the drug approval by several years during which the drug exchanged manufacturers, highlighting the need for meticulous investigation and adjudication of serious, but rare, adverse events in drug development that could end up preventing drugs with favorable risk/benefit ratio from being approved. In this review, we discuss the pharmacokinetic data and efficacy, as well as the toxicity results of clinical trials of fedratinib. We also review ongoing trials of JAK inhibitors in MF and explore future treatment options for MF patients who are refractory to ruxolitinib.
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Hyperparathyroidism may be a precipitating factor to the development of myelofibrosis; however, this is extremely rare with only a few documented case reports of myelofibrosis caused by secondary hyperparathyroidism. We describe a case of a 24-year-old female who had a failed live donor renal transplant and secondary hyperparathyroidism. While on haemodialysis she became increasingly pancytopenic despite erythropoietin injections and adequate iron, vitamin B12 and folate replacement. Her secondary hyperparathyroidism evolved to tertiary hyperparathyroidism despite vitamin D supplementation and phosphate binders. In order to determine the cause of her pancytopenia, a bone marrow biopsy was performed that confirmed myelofibrosis due to her secondary hyperparathyroidism. Following a successful parathyroidectomy in a tertiary hospital, her pancytopenia resolved and she is now awaiting a second transplant.
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Medula Óssea/patologia , Hiperparatireoidismo Secundário/complicações , Falência Renal Crônica/terapia , Pancitopenia/etiologia , Feminino , Fibrose , Humanos , Hiperparatireoidismo Secundário/cirurgia , Falência Renal Crônica/complicações , Transplante de Rim , Diálise Renal , Adulto JovemRESUMO
INTRODUCTION: Treatment with ruxolitinib, a selective JAK1/2 inhibitor, has significantly improved the lives of patients with myelofibrosis. Unfortunately, this treatment is frequently limited by cytopenias, precluding a high-risk group characterized by baseline thrombocytopenia. Additionally, there are no approved treatments for patients who have progressed while receiving ruxolitinib. Pacritinib is a novel JAK2/FLT3 inhibitor associated with less treatment-related myelosuppression that has the potential to fill these unmet treatment needs. Areas covered: This review will describe the preclinical rationale for JAK2/FLT3 inhibition, review the pharmacology of pacritinib, and detail available clinical data for pacritinib treatment of myelofibrosis. The circumstances surrounding the full clinical hold temporarily placed on pacritinib will also be explored. Expert commentary: Pacritinib has demonstrated promising results in patients with myelofibrosis and thrombocytopenia. Improvements in splenomegaly and symptom burden were observed with the 200 mg twice-daily dose in PERSIST-2, including those with platelet counts <50,000 mm. Safety concerns pertaining to cardiovascular events and bleeding that arose in an early analysis of PERSIST-2 were likely related to the advanced disease state enrolled rather than clear attribution to pacritinib. The results of an ongoing dose-finding, phase II study are eagerly awaited in order to move this promising myelofibrosis therapy forward.
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Antineoplásicos/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Mielofibrose Primária/complicações , Mielofibrose Primária/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Trombocitopenia/tratamento farmacológico , Trombocitopenia/etiologia , Animais , Antineoplásicos/farmacologia , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Janus Quinase 2/antagonistas & inibidores , Mielofibrose Primária/etiologia , Mielofibrose Primária/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidoresRESUMO
Excess iron can be extremely toxic for the body and may cause organ damage in the absence of iron chelation therapy. Preclinical studies on the role of free iron on bone marrow function have shown that iron toxicity leads to the accumulation of reactive oxygen species, affects the expression of genes coding for proteins that regulate hematopoiesis, and disrupts hematopoiesis. These effects could be partially attenuated by iron-chelation treatment with deferasirox, suggesting iron toxicity may have a negative impact on the hematopoietic microenvironment. Iron toxicity is of concern in transfusion-dependent patients. Importantly, iron chelation with deferasirox can cause the loss of transfusion dependency and may induce hematological responses, although the mechanisms through which deferasirox exerts this action are currently unknown. This review will focus on the possible mechanisms of toxicity of free iron at the bone marrow level and in the bone marrow microenvironment.
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Medula Óssea/metabolismo , Suscetibilidade a Doenças , Ferro/metabolismo , Anemia Aplástica/complicações , Anemia Aplástica/etiologia , Anemia Aplástica/metabolismo , Anemia Aplástica/terapia , Animais , Células da Medula Óssea/metabolismo , Microambiente Celular , Células-Tronco Hematopoéticas/metabolismo , Humanos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/metabolismo , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/etiologia , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/terapia , Mielofibrose Primária/complicações , Mielofibrose Primária/etiologia , Mielofibrose Primária/metabolismo , Mielofibrose Primária/terapiaRESUMO
PURPOSE OF REVIEW: Myeloproliferative neoplasms (MPNs) are recognized for their debilitating symptom burdens. The purpose of this review is to understand the complexity of the MPN symptom burden and identify how validated MPN Patient Reported Outcome (PRO) tools may be integrated into clinical practice to assess the MPN symptom burden. RECENT FINDINGS: Significant heterogeneity exists both within and between MPN subtypes. Surrogates of disease burden such as risk scores and MPN chronicity often fail to correlate with symptomatic burden. Validated MPN PROs allow for precise and rapid assessment of the MPN symptom burden in clinical and trial settings. Their growing use among investigators has resulted in improved understanding of how the MPN disease burden and overall patient experience is impacted by novel and traditional therapies. PRO tools are an integral part of National Comprehensive Cancer Center (NCCN) guidelines for MPN treatment and should be regularly employed in disease burden assessment.
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Neoplasias Hematológicas/diagnóstico , Transtornos Mieloproliferativos/diagnóstico , Humanos , Guias de Prática Clínica como AssuntoRESUMO
Following the discovery of the JAK2V617F mutation, Janus kinase (JAK) 2 inhibitors were developed as rationally designed therapy in myeloproliferative neoplasms (MPNs). Although JAK2 inhibitors have clinical efficacy in MPN, they are not clonally selective for the JAK2V617F-mutant cells. Because activated JAK-signal transducer and activator of transcription (STAT) signaling is a common feature of MPN, JAK2 inhibitors are efficacious regardless of the specific MPN phenotypic driver mutation. The Food and Drug Administration approved the JAK1/JAK2 inhibitor, ruxolitinib, for the treatment of myelofibrosis and polycythemia vera. Additional JAK2 inhibitors are currently in advanced phased clinical trials.
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Antineoplásicos/uso terapêutico , Janus Quinase 2/antagonistas & inibidores , Terapia de Alvo Molecular , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/metabolismo , Inibidores de Proteínas Quinases/uso terapêutico , Animais , Antineoplásicos/farmacologia , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Janus Quinase 2/química , Janus Quinase 2/genética , Janus Quinase 2/metabolismo , Mutação , Transtornos Mieloproliferativos/genética , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genética , Policitemia Vera/metabolismo , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Mielofibrose Primária/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
INTRODUCTION: Imatinib mesylate is used extensively for first line treatment of Chronic Myeloid Leukemia (CML). However, not many studies have documented morphological changes in bone marrow biopsies produced during Imatinib therapy with reference to myelofibrosis. AIM: To document the morphological changes produced in the bone marrow during Imatinib therapy. MATERIALS AND METHODS: This longitudinal study followed up 75 Philadelphia Chromosome Positive Chronic Myeloid Leukemia with chronic phase(Ph+ CML- CP) patients sequentially, receiving 400-600mg Imatinib over a period of 12 or more months. Haematologic parameters were measured at admission, 2 weeks, 1 month, 3 months, 6 months and 12 or more months. Morphologic changes in bone marrow aspirate and biopsy were evaluated at admission, 6 months and ≥12 months of treatment in accordance with National Comprehensive Cancer Network(NCCN) guidelines. RESULTS: Complete Haematologic Response (CHR) was seen in 47.1%, 80%, 85.4%, 90.4% at ≥1 month, 3 months, 6 months and 12 months respectively after therapy. It was noted that patients not showing CHR by 3 months were less likely to show CHR at 6 months and beyond. Bone marrow aspirates and biopsies showed reduction in cellularity and myeloid precursors with regeneration of erythroid precursors in 70-83% at ≥12 months. A significant decrease in myelofibrosis (p-value< 0.04) was noted as early as 6 months. Mild to moderate hypoplasia was noted in 31.8% of biopsies within 6 months. Pseudo gaucher cells and benign lymphoid nodules were also seen. CONCLUSION: Sequential analysis showed that Imatinib reduced the grade of myelofibrosis significantly (p-value< 0.04). It also prevented development of myelofibrosis in patients who did not have it at presentation. Hence Imatinib is effective when used early in the course of CML-CP.
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Myelofibrosis (MF) is the most severe among the classical Philadelphia-negative myeloproliferative neoplasms that also include essential thrombocytemia and polycythemia vera. Myelofibrosis is characterized by numerous genetic lesions, often variously associated with each other, and by an aggressive clinical phenotype leading to severely reduced survival. Also, the inflammatory microenvironment plays a key role in disease initiation and progression. Because of the complexity of its pathogenesis and the variability of clinical features, MF is a disease that requires a personalized approach and remains orphan of curative treatments besides allogeneic transplantation. JAK2 inhibitors have marked a remarkable progress, because they alleviate systemic symptoms and reduce splenomegaly but have a limited effect on survival, on mutation load, and on marrow fibrosis. Here, we review the main contributing factors to MF pathogenesis and prognosis, focusing on how these factors relate to therapeutic choices. We discuss results from ongoing studies of JAK2 inhibitors and report on new therapeutic strategies that proved effective in early preclinical and clinical trials, including combination treatments, antifibrotic agents, and telomerase inhibitors.
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Mielofibrose Primária/terapia , Quimioterapia Combinada , Humanos , Janus Quinase 2/antagonistas & inibidores , Mielofibrose Primária/etiologia , Mielofibrose Primária/genética , Mielofibrose Primária/mortalidade , Prognóstico , Telomerase/antagonistas & inibidoresRESUMO
An important pathogenetic distinction in the classification of myeloproliferative neoplasms (MPNs) is the presence or absence of the BCR-ABL fusion gene, which encodes a unique oncogenic tyrosine kinase. The BCR-ABL fusion, caused by the formation of the Philadelphia chromosome (Ph) through translocation, constitutes the disease-initiating event in chronic myeloid leukemia. The development of successive BCR-ABL-targeted tyrosine-kinase inhibitors has led to greatly improved outcomes in patients with chronic myeloid leukemia, including high rates of complete hematologic, cytogenetic, and molecular responses. Such levels of treatment success have long been elusive for patients with Ph-negative MPNs, because of the difficulties in identifying specific driver proteins suitable as drug targets. However, in recent years an improved understanding of the complex pathobiology of classic Ph-negative MPNs, characterized by variable, overlapping multimutation profiles, has prompted the development of better and more broadly targeted (to pathway rather than protein) treatment options, particularly JAK inhibitors. In classic Ph-negative MPNs, overactivation of JAK-dependent signaling pathways is a central pathogenic mechanism, and mutually exclusive mutations in JAK2, MPL, and CALR linked to aberrant JAK activation are now recognized as key drivers of disease progression in myelofibrosis (MF). In clinical trials, the JAK1/JAK2 inhibitor ruxolitinib - the first therapy approved for MF worldwide - improved disease-related splenomegaly and symptoms independent of JAK2 (V617F) mutational status, and prolonged survival compared with placebo or standard therapy in patients with advanced MF. In separate trials, ruxolitinib also provided comprehensive hematologic control in patients with another Ph-negative MPN - polycythemia vera. However, complete cytogenetic or molecular responses with JAK inhibitors alone are normally not observed, underscoring the need for novel combination therapies of JAK inhibitors and complementary agents that better address the complexity of the pathobiology of classic Ph-negative MPNs. Here, we discuss the role of tyrosine-kinase inhibitors in the current MPN-treatment landscape.
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Myelofibrosis (MF) and myelodysplastic syndrome (MDS) are hematopoietic stem cell disorders associated with cytopenias and red blood cell (RBC) transfusion dependence. Iron overload (IO) as a consequence of RBC transfusion dependence and its effect on outcomes in MF has not been formally studied. However, IO is a demonstrated poor prognostic feature in patients with MDS and congenital or acquired chronic anemias. Evidence that iron chelation therapy (ICT) reduces the deleterious effects of IO in MDS has led to speculation of benefit in MF. However, data supporting the use of ICT in MF is lacking. Neither disease has clear consensus guidelines for the use of ICT. Moreover, JAK-STAT inhibition, the cornerstone of MF treatment, often contributes to anemia and transfusional requirements. This manuscript reviews known and potential implications of IO in MF and highlights the need for prospective clinical investigations of ICT with consideration in the setting of JAK2 inhibitor therapy.
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Transfusão de Sangue/métodos , Sobrecarga de Ferro/terapia , Síndromes Mielodisplásicas/tratamento farmacológico , Mielofibrose Primária/terapia , Quelantes de Ferro/uso terapêutico , Prognóstico , Resultado do TratamentoRESUMO
The JAK1 and JAK2 inhibitor ruxolitinib has approved indications in myelofibrosis, a BCR-AB1-negative myeloproliferative neoplasm associated with progressive bone marrow fibrosis and shortened survival. In Phase III clinical studies, ruxolitinib provided rapid and durable improvement of myelofibrosis-related splenomegaly and symptoms irrespective of mutation status, and was associated with a survival advantage compared with placebo or best available therapy. Because of dose-dependent cytopenias, blood count monitoring and dose titration are important to optimize therapy. Specific precautions apply to the treatment of patients with or at risk of serious infections. Discontinuation of ruxolitinib generally leads to symptom return within 1 week. Ruxolitinib also is approved for treatment of patients with polycythemia vera who have had an inadequate response to or are intolerant of hydroxyurea.
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Antineoplásicos/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirazóis/uso terapêutico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Janus Quinases/antagonistas & inibidores , Nitrilas , Mielofibrose Primária/etiologia , Mielofibrose Primária/mortalidade , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/química , Pirazóis/farmacologia , Pirimidinas , Resultado do TratamentoRESUMO
Iron chelation therapies (ICTs) can help eliminate iron surplus in erythrocyte transfusion-dependent (TD) patients with myelofibrosis (MF). The study assessed adjusted incidence rate ratios (aIRRs) of MF-related complications and resource utilization (RU) and adjusted mean monthly inpatient cost differences in patients with TD MF treated with versus without ICT (ICT+ vs. ICT-) using data from two healthcare claims databases. Patients with ≥ 2 MF International Classification of Diseases, 9th Revision (ICD-9) diagnosis codes ≥ 30 days apart were included. Among 571 patients with TD MF, 103 (18%) were ICT+ and 468 (82%) were ICT-. ICT+ patients had lower rates of thrombocytopenia (aIRR: 0.55; p < 0.001), pancytopenia (0.53; p < 0.001), emergency room visits (0.84 [95% confidence interval: 0.74-0.96]) and inpatient stays (0.75 [0.64-0.87]), but higher rates of outpatient visits (1.21 [1.18-1.23]). Adjusted mean complication-related inpatient cost difference per month was lower in ICT+ patients (-$1804 [$570]; p = 0.004). ICT+ patients had significantly lower rates of acute care, but higher rates of outpatient care.
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Transfusão de Sangue , Terapia por Quelação , Custos de Cuidados de Saúde , Recursos em Saúde , Quelantes de Ferro , Mielofibrose Primária/complicações , Mielofibrose Primária/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue/economia , Terapia por Quelação/economia , Bases de Dados Factuais , Transfusão de Eritrócitos/efeitos adversos , Transfusão de Eritrócitos/economia , Feminino , Recursos em Saúde/economia , Humanos , Incidência , Seguro Saúde , Quelantes de Ferro/economia , Quelantes de Ferro/uso terapêutico , Masculino , Pessoa de Meia-Idade , Prevalência , Mielofibrose Primária/terapia , Estudos Retrospectivos , Reação Transfusional , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: Myelofibrosis (MF) is characterized by shortened survival and a greatly compromised quality of life. Weight loss and cachexia seem to be the most important factors influencing survival in patients with MF. The aim of this study was to assess the efficacy of an integrated supportive therapy in improving cachexia and MF-related symptoms. METHODS: We reported on a case of a patient with MF who presented with weight loss and cachexia associated with severe anemia, fatigue, fever, and bone pain. The circulating levels of inflammatory, oxidative stress parameters, hepcidin, and erythropoietin were evaluated and were above normal ranges. The patient was treated with a multitargeted approach specifically developed for cachexia including oral l-carnitine, celecoxib, curcumin, lactoferrin, and subcutaneous recombinant human erythropoietin (EPO)-α. RESULTS: Surprisingly, after 1 y, cachexia features improved, all MF symptoms were in remission, and inflammatory and oxidative stress parameters, hepcidin, and EPO were reduced. CONCLUSIONS: Because our protocol was targeted at inflammation and the metabolic state, its effectiveness may emphasize the role of inflammation in the pathogenesis of MF symptoms and demonstrates a need for the study of new integrated therapeutic strategies.