Chronic Eosinophilic Leukemia

Our report sheds light on the distinct clinical presentations of ET patients who develop AML, characterized by different TP53 mutations and varying therapeutic outcomes when treated with decitabine. However, further studies that include a larger quantity of samples are needed to elucidate the precise underlying molecular mechanisms involved in this process.

Although rare, myeloproliferative neoplasms can involve young patients and pose unique challenges for clinicians in diagnosis and therapy. The paper aims to review the biological markers of MPNs in pediatric populations-a particular group of patients that has been poorly studied due to the low frequency of MPN diagnosis.

MPNs with JAK2 mutations are associated with SCAD in addition to usual atherosclerosis. This association needs further research.

Antiplatelet therapy was started with acetylsalicylic acid 100 mg and clopidogrel 75 mg once a day. With the recommendation of hematology, cytoreductive treatment, hydroxyurea 1000 mg twice a day, was started. The patient's complaints were resolved at the end of the second day, and the patient with minimal ataxia was discharged with recommendations. Patients with ET should be aware of ischemic cerebrovascular disease and consider antiplatelet and cytoreductive treatment options.

Till date, CEL is a very rare entity. Its presentation with cardiac and neurological manifestations is still rare.

Using a universal disease marker, carcinoembryonic antigen, as the analysis model, the signal-off sensor obtained a detection limit of 0.47 pg/mL within the detection range of 1 pg/mL - 50 ng/mL. The synthesis and application of highly stable HBOFs triggered by proteins provide a reference for the development of new reticular ECL signal labels, and electron transfer model provides flexible solutions for more sensitive sensing analysis.

P=N/A, N=5000, Recruiting, University Health Network, Toronto | Trial completion date: Oct 2025 --> Oct 2027 | Trial primary completion date: Oct 2025 --> Oct 2027

Moreover, our analysis revealed increased PD-L1 surface expression in malignant monocytes from +9p patients, while analysis of the T cell compartment unveiled elevated levels of exhausted cytotoxic T cells. Overall, here we identify a distinct novel subgroup of MPN patients, who feature a synergistic interplay between +9p and JAK2V617F that shapes immune escape characteristics and increased stemness in CD34+ cells.

Notably, no differences in neither platelet counts nor anti-thrombotic therapy was identified between patients with JAK2- and CALRmut patients. Analysis of platelet gene expression failed to identify differences in expression of relevant genes between JAK2- and CALRmut patients.

Moreover, the main objective of young MPNs therapy should be the disease outcome modification. Therefore, international collaborative work between pediatricians and "adult hematologists" is required to measure outcomes and generate protocol of management of young MPNs.

The patient was successfully treated with the JAK2 inhibitor ruxolitinib for 8 months before additional somatic mutations were acquired and the disease progressed into an acute lymphoblastic T-cell leukemia/lymphoma. The present case shows similarities to previously reported cases with PCM1::JAK2 and BCR::JAK2 with regard to disease phenotype and response to ruxolitinib, and importantly, provides an example that also patients harboring other JAK2 fusion genes may benefit from treatment with JAK2 inhibitors.

Following treatment with ruxolitinib, the patient's eosinophil levels normalized, but unfortunately, the damage to the heart was irreversible...Following the surgery, the patient successfully navigated the postoperative critical period with the support of an intra-aortic balloon pump (IABP), continuous renal replacement therapy (CRRT), and ventilator-assisted ventilation but subsequently developed an acquired Intensive care unit-acquired weakness (ICU-AW) and a depressive state. Fortunately, the patient gradually recovered from these complications.

Our patient had a prolonged course of prednisone taper treatment complicated by frequent hospitalizations, osteopenia, and insomnia. Additionally, his chronic eosinophilic pneumonia relapsed shortly after stopping steroids. In our patient, off-label treatment with mepolizumab, an interleukin-5-inhibiting monoclonal antibody, was associated with symptomatic relief, imaging findings resolution, and remission maintenance without systemic steroids.

In this article, we present a short review focused on differential diagnosis of eosinophilia and eosinophilic disorders. The diagnosis of eosinophilia is a challenge for physicians; thus this review may be useful in clinical practice.

Notably, increasing JAK2 allele burden was correlated with more severe symptoms, highlighting its potential role in predicting disease burden. This study emphasizes the importance of symptom assessment in MPN patients and supports the incorporation of MPN-SAF TSS in routine clinical practice to enhance patient care and management.

These networks play a role in tumorigenesis, particularly in TNBCs. Aims to deliver a thorough examination of the CmP/CmPn pathways concerning TNBCs, this paper provides a comprehensive overview of these pathways, explores their applications and highlights their significance in the context of TNBCs.

The presence of BCR::ABL1 translocation with a coexisting CALR mutation is even more uncommon. Herein, starting from a routinely diagnosed case of CALR-mutated primary myelofibrosis subsequently acquiring BCR::ABL1 translocation, we performed a comprehensive review of the literature, discussing the clinicopathologic and molecular features, as well as the outcome and treatment of cases with BCR::ABL1 and CALR co-occurrence.

Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Pemigatinib was recently approved for patients with relapsed or refractory FGFR1-rearranged neoplasms...Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. Mepolizumab, an interleukin-5 (IL-5) antagonist monoclonal antibody, is approved by the U.S Food and Drug Administration for patients with idiopathic HES. Cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. Targeted therapies such as the IL-5 receptor antibody benralizumab, IL-5 monoclonal antibody depemokimab, and various tyrosine kinase inhibitors for MLN-eo-TK, are under active investigation.

P2, N=90, Active, not recruiting, Italfarmaco | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Jun 2025 --> Dec 2026

Recent regulatory approvals in polycythemia vera (PV) include the JAK inhibitor ruxolitinib, and more recently, a novel recombinant interferon alfa-2 (IFN-α) therapeutic agent. More recently, a novel pegylated IFN-α, ropeginterferon alfa-2b, received approval for PV by the European Medicines Agency and the US Food and Drug Administration in 2019 and 2021, respectively. This article reviews the clinical research and recent advances that led to the first regulatory approval of IFN-α in a BCR/ABL-negative MPN and its future promise as a disease-modifying therapeutic agent.

Tailoring patient management on an individualized basis, favoring intensive treatment aligned with AML protocols, is crucial, regardless of blast percentage. Research on the impact of NPM1 mutations in non-acute myeloid neoplasms is ongoing, requiring challenging prospective studies with substantial patient cohorts and extended follow-up periods for validation.

P1, N=36, Completed, City of Hope Medical Center | Active, not recruiting --> Completed

Starting from the presentation of two additional cases from our routine daily practice, we focus mainly on clinical, laboratory, and bone marrow histological findings, which may represent useful clues of BCR::ABL1 and JAK2 co-occurrence. The interaction between JAK2 and BCR::ABL1 clones during the disease course as well as therapy and outcome are presented.

P1/2, N=40, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jan 2024 --> Jan 2025 | Trial primary completion date: Jan 2024 --> Jan 2025

Similar overall best response rates were observed in patients receiving induction with daunorubicin combined with cytarabine arabinoside (daunorubicin + ara-C) (74% [23/31]) or FLAG-IDA/NOVE-HiDAC (78% [39/50], p=0.78)...Mutations in TP53 (OR 8.2 [95% CI 2.01, 37.1], p=0.004) and RAS pathway (OR 5.1 [95%CI 1.2, 23.7], p=0.03) were associated with inferior treatment response for intensively-treated patients, and poorer performance status (ECOG) was associated with inferior treatment response in both intensively- (OR 10.4 [95%CI 2.0, 78.5], p=0.009) and nonintensively-treated groups (OR 12 [95%CI 2.04, 230.3], p=0.02). In patients with paired samples prior to and after therapy (N=26), there was a significant residual mutation burden remaining irrespective of response to blast-reduction therapy.

Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms. Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.

Although the patient's blood counts initially responded to ruxolitinib and hydroxyurea, the response was not durable. Early referral for allogenic bone marrow transplant appears necessary to prevent long-term complications and disease progression in myeloid neoplasms with clonal hypereosinophilia driven by noncanonical JAK2 mutations.

The close correlation shown between IL-18 and cfDNA levels, together with the finding of enhanced DNA-triggered IL-18 release from monocytes, suggest that cfDNA promotes inflammation, at least in part, through inflammasome activation. This work highlights cfDNA, the inflammasome and IL-18 as additional players in the complex inflammatory circuit that fosters MF progression, potentially providing new therapeutic targets.

This retrospective analysis provides insights into hematologic outcomes under the current first-line treatment paradigm for MF in clinical practice. Many pts who initiated RUX were anemic and/or thrombocytopenic at baseline, and incidences of anemia and thrombocytopenia as well as RBC transfusion burden increased over time. These results highlight the continued need for treatments that address the underlying hematologic burden, including anemia and thrombocytopenia, of pts with MF.

Our ET patient population had high prevalence of MPL (Pro106Leu) mutation which may be germ line in nature as previously reported, and correspondingly lowered the prevalence of JAK2V617F and CALR mutations in our cohort. Thrombosis developed in 26. 8% patients.

Most patients with PV receive phlebotomy and low-dose aspirin to prevent thrombosis...Treatment-naïve patients and those pretreated with hydroxyurea (HU) will be included...General statistical summaries will be applied to primary and secondary endpoints. For categorical variables, frequency and percentage will be presented with a 95% confidence interval.

Involvement of additional Italian labs is already planned, and further implementation within the ECNM will be proposed. Definition of common SOPs, uniform sample requirements and web-based reporting following the GIMEMA LabNet model will be pursued.

Here, we report a very unusual case of myeloid/lymphoid neoplasm with ETV6::FLT3 fusion with a nodal presentation without associated eosinophilia. Our case draws attention to diagnostic pitfalls in these rare entities.

Thus, individuals with high JAK2V617F variant allele frequency (≥50% VAF) presented more thrombo-hemorrhagic events and manifestations of splenomegaly compared with those with low JAK2V617F variant allele frequency (1 variant in the JAK2 gene, especially rs2230722, rs2230724, and rs77375493 variants, and those with high JAK2V617F VAF show alterations in the clinical-laboratory profile compared with those with low JAK2V617F VAF.

Ruxolitinib, a JAK2 inhibitor, provided a promising therapeutic effect in a phase II study...Anti-CD52 antibody, alemtuzumab, or anti-IL-5 antibody, mepolizumab, are promising drugs to control symptoms that are associated with hypereosinophilic syndrome. Allo-SCT is anticipated as a curative treatment for CEL, but the evidence of Allo-SCT for CEL is still limited. Further study is required to define the treatment strategy.

In summary, the presence of CHIP, with or without neoplasia, can be associated with autoimmune manifestations and thrombosis. In the presence of these manifestations, it is necessary to consider a "disease-modifying therapy" that may either reduce the clonal burden or inhibit the clonally activated JAK pathway.

Treatment with rusfertide resulted in rapid, robust, and sustained reduction in HCT levels in PV patients with elevated HCT levels at baseline. Treatment resulted in normalization of iron parameters as noted by increases in ferritin, and normalization of serum iron and MCV in patients who were iron deficient at baseline. Improvements in iron deficiency following rusfertide are suggestive of clinical benefits and merit further investigation.

Lastly, 96.7% of the patients were treated with hydroxyurea, which corrected cellular alterations and laboratory abnormalities found in AvWS... AvWS can be found in patients with platelet counts below 1,000 x103/µL, especially among those with PV with elevated Hb and Hct levels. This may deem it necessary to carry out diagnostic tests in patients with MPN and any degree of thrombocytosis. To our knowledge, this is the most comprehensive study among latin american patients that describes the coexistence of PMF and AvWS; even though the mechanism by which some PMF patients develop AvWS is not perfectly understood.

P2, N=10, Recruiting, William Shomali | N=25 --> 10 | Trial completion date: Oct 2023 --> Nov 2025 | Trial primary completion date: Apr 2023 --> Nov 2025

Improvements favored momelotinib versus danazol for each MFSAF individual item, and greater improvements were observed for disease- and cancer-related fatigue and physical functioning at week 24, with significant results for multiple items/domains across the 3 assessments. These findings are consistent in demonstrating that momelotinib provides substantial symptom benefit.