myeloproliferative syndrome treatment

INTRODUCTION: Porto-sinusoidal vascular syndrome is characterised by specific histological changes that do not include cirrhosis, with or without portal hypertension. Patients are usually asymptomatic until development of portal hypertension complications. CASE DESCRIPTION: A 69-year-old female with history of JAK2 positive essential thrombocythemia (ET) was referred to internal medicine consultation due to elevated liver enzymes. The patient had no previous history of liver disease...

INTRODUCTION: Sweet syndrome (SS) is well-known to be associated with underlying hematologic malignancies. The incidence and qualities of SS among novel targeted therapies for acute myeloid leukemia (AML) have not yet been described. METHODS: Through retrospective review of 19432 patients diagnosed with acute/chronic leukemia or myelodysplastic syndromes/ myeloproliferative neoplasms (MDS+/-MPN) over 28 years, we calculated the incidence of SS in the setting of select hematologic malignancies and described the clinicopathologic characteristics of SS in patients with onset of SS after initiation of novel AML-targeted therapies...

BACKGROUND: Chronic myelomonocytic leukemia (CMML) is a rare, malignant, clonal hematopoietic disorder with features of both myelodysplastic syndrome (MDS) and myeloproliferative neoplasm (MPN). It is classified as MDS/MPN overlap syndrome by the World Health Organization (WHO), and the prognosis is generally poor. Solid tumors are rarely associated with or are secondary to CMML. CASE DESCRIPTION: We here reported a case of a 75-year-old female patient with persistent peripheral blood monocytosis and bone marrow blasts ≤20%...

The Omicron variant of SARS-CoV-2 has rapidly become the dominant strain worldwide due to its high transmissibility, although it appears to be less pathogenic than previous strains. However, individuals with hematological malignancy (HM) and COVID-19 remain susceptible to severe infection and mortality, especially those with chronic lymphocytic leukemia (CLL) and those undergoing chimeric antigen receptor T-cell (CAR-T) treatment. Hematologists should thoroughly assess the severity of the patient's hematological disease and the potential risk of SARS-CoV-2 infection before initiating chemotherapy or immunosuppressive treatment...

We describe the case of a patient with extreme thrombocytosis whose evolution was rapidly fatal. No cause of secondary thrombocytosis was found. There was no sign of myelofibrosis but the megakaryocytes were small and dysplastic. The patient presented a calreticulin (CALR) variant in exon 3 (C105S), as well as concomitant mutations of ASXL1, U2AF1, and EZH2. This variant of CALR has never been described before, and after sorting, all identified mutations were found in myeloid cells but not in lymphoid cells...

Myelodysplastic syndromes and myeloproliferative neoplasms both represent hematologic diseases associated with bone marrow failure often resulting in anemia. For those patients, transfusion of red blood cell (RBC) units is essential but results in iron overload (IOL) that may affect various organ functions. Therefore, iron chelation therapy plays a major role in anemic patients, not only because it reduces IOL, but also because it may improve hematopoietic function by increasing hemoglobin or diminishing the requirement for RBC transfusions...

Hypereosinophilic syndrome (HES) is a myeloproliferative disorder characterized by persistent hypereosinophilia that is associated with multi-organ damage. Eosinophilic endocarditis is a serious complication of HES. The exact prevalence of the disease is unknown, and it is characterized by a persistently elevated eosinophil count, resulting in multi-organ involvement due to eosinophilic infiltration. We present a case of a 65-year-old Caucasian male patient who presented with one-week symptoms of feeling unwell and intermittent pleuritic chest pain...

INTRODUCTION: Neutrophilic panniculitis (NP) is a rare subtype of neutrophilic dermatosis, a group of neutrophil-rich inflammatory skin disorders that can present in association with myeloid neoplasms. NP is defined by the presence of a neutrophilic infiltrate in the fat lobules of the subcutis in the absence of either infection or vasculitis. We herein describe a 65-year-old woman with a recent diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm overlap syndrome (MDS/MPN) who abruptly developed painful, pruritic nodules consistent with NP...

The utility of CD19-targeted chimeric antigen receptor T-cell (CAR-T cell) therapy in the management of refractory/relapsed B-cell malignancies has increased tremendously in recent times. In addition to cytokine release syndrome (CRS), neurotoxicity, and infections, CAR-T cell patients develop cytopenias, with about 15% of the patients continuing to have severe cytopenias up to three months after treatment. Retrospective reviews have reported the development of myelodysplastic syndrome (MDS) in patients undergoing CAR-T cell therapy...

Despite recent advancements, treatment of cytopenia due to bone marrow failures (BMF) and myeloid neoplasms remains challenging. Androgens promote renewal and maturation of blood cells and may be beneficial in these forms. Here we report a systematic review of androgens use as single agent in hematologic conditions. Forty-six studies, mainly retrospective with various androgen types and doses, were included: 12 on acquired aplastic anemia (AA), 11 on inherited BMF, 17 on myelodysplastic syndromes (MDS), and 7 on myelofibrosis...

Vacuolar ATPase (V-ATPase) is regarded as a possible target in cancer treatment. It is expressed in primary acute myeloid leukemia cells (AML), but the expression varies between patients and is highest for patients with a favorable prognosis after intensive chemotherapy. We therefore investigated the functional effects of two V-ATPase inhibitors (bafilomycin A1, concanamycin A) for primary AML cells derived from 80 consecutive patients. The V-ATPase inhibitors showed dose-dependent antiproliferative and proapoptotic effects that varied considerably between patients...

Myeloid neoplasms represent a broad spectrum of hematological disorders for which somatic mutation status in key driver genes is important for diagnosis, prognosis and treatment. Here we summarize the findings of a targeted, next generation sequencing laboratory developed test in 24,639 clinical myeloid samples. Data were analyzed comprehensively and as part of individual cohorts specific to acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Overall, 48,015 variants were detected, and variants were found in all 50 genes in the panel...

Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are hematological disorders characterized by both proliferative and dysplastic features. According to the 2022 International Consensus Classification (ICC), MDS/MPN consists of clonal monocytosis of undetermined significance (CMUS), chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), MDS/MPN with SF3B1 mutation (MDS/MPN-T-SF3B1), MDS/MPN with ring sideroblasts and thrombocytosis not otherwise specified (MDS/MPN-RS-T-NOS), and MDS/MPN-NOS...

KEY CLINICAL MESSAGE: Hypomethylating agents may be useful in some but not all cases of myelodysplastic syndromes. In some versions of these conditions, this treatment may yield deleterious results. ABSTRACT: Chronic myelomonocytic leukemia (CMML) is considered to be a heterogeneous group of hematopoietic neoplasms. Usually it shares the features of myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS) and is known as MDS/MPN. It occurs mostly in the elderly and has an inherent tendency to transform to acute myeloid leukemia...

ETV6-ABL1 gene fusion is a rare genetic rearrangement in a variety of malignancies, including myeloproliferative neoplasms (MPN), acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML). Here, we report the case of a 16-year-old male diagnosed with a MPN, 7 months post-completion of treatment for Burkitt leukaemia. RNA sequencing analysis confirmed the presence of an ETV6-ABL1 fusion transcript, with an intact, in-frame ABL tyrosine-kinase domain. Of note, secondary ETV6-ABL1 -rearranged neoplastic diseases have not been reported to date...

SLN124, an N-acetylgalactosamine conjugated 19-mer short interfering RNA, is being developed to treat iron-loading anemias (including beta-thalassemia and myelodysplastic syndromes) and myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting and silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This is the first clinical report of an siRNA targeting a component of iron homeostasis. This first-in-human, phase 1 study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of SLN124 (1...

Objective Azacitidine (AZA) has been the standard of care for elderly patients with high-risk myelodysplastic syndromes (MDS). However, reliable clinical predictors of outcome have yet to be identified. The prognostic value of fetal hemoglobin (HbF) levels has been reported for decitabine therapy. We evaluated pretreatment HbF levels in AZA monotherapy as a prognostic marker in MDS/acute myeloid leukemia (AML). Methods This study included chemotherapy-naïve patients who had received seven-day treatment schedules of AZA and whose HbF levels were measured at the onset of treatment between March 2011 and July 2020...

INTRODUCTION: Hypereosinophilic syndrome is a rare clinical condition, and cardiac involvement confers a poor prognosis. Hypereosinophilic myocarditis is a medical emergency and targeted treatment should be started promptly even before a definitive diagnosis could be made. CASE PRESENTATION: A 27-year-old female patient is hospitalized for exertional dyspnea, chest pain, and fatigue for the past 2 weeks. She also describes left leg paresthesias. Clinical examination was in normal limits...

BACKGROUND: Transient abnormal myelopoiesis (TAM) is characterized by leukocytosis with increased circulating megakaryoblasts that harbor N-terminal truncating mutations in the GATA1 gene. Approximately 10% of affected patients experience early death. OBSERVATIONS: A 2-month-old boy with Down syndrome was diagnosed with TAM and followed without treatment. Although the blasts in the peripheral blood disappeared, liver failure progressed. A pathological examination revealed liver fibrosis, and double-immunostaining for full-length GATA1 and CD42b identified megakaryocytes with a GATA1 mutation...

Hypereosinophilic syndrome requires a peripheral absolute eosinophil count of ≥1.5 × 109 /L with clinical manifestations attributable to peripheral or tissue hypereosinophilia. Clinical manifestations can vary greatly, with the majority of patients relatively asymptomatic and the eosinophilia detected incidentally. However, in a minority of hypereosinophilia cases, they may present with severe lifethreatening organ dysfunction affecting skin, lung, heart, gastrointestinal tract, and nervous system...