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The article discusses the use of ruxolitinib after fedratinib failure in patients with myelofibrosis. It presents a case series of 14 patients who received ruxolitinib after fedratinib therapy, detailing their clinical outcomes and responses. The study highlights the potential clinical benefit of second-line ruxolitinib, achieving spleen and symptoms response in a subset of patients. The findings suggest that sequential use of ruxolitinib after fedratinib may be beneficial for selected patients, with no observed excess toxicity in the second-line setting. [Extracted from the article]

Ruxolitinib is beneficial in patients with myelofibrosis (MF) and polycythemia vera (PV). Information on ruxolitinib adherence is scant. The Ruxolitinib Adherence in Myelofibrosis and Polycythemia Vera (RAMP) prospective multicenter study (NCT06078319) included 189 ruxolitinib-treated patients. Patients completed the Adherence to Refills and Medications Scale (ARMS) and Distress Thermometer and Problem List (DTPL) at the earliest convenience, after registration in the study, and at later timepoints. At week-0, low adherence (ARMS > 14) and high distress (DT ≥ 4) were declared by 49.7% and 40.2% of patients, respectively. The main reason for low adherence was difficult ruxolitinib supply (49%), intentional (4.3%) and unintentional (46.7%) non-take. In multivariable regression analysis, low adherence was associated to male sex (p = 0.001), high distress (p < 0.001), and treatment duration ≥ 1 year (p = 0.03). Over time, rates of low adherence and high distress remained stable, but unintentional non-take decreased from 47.9% to 26.0% at week-48. MF patients with stable high adherence/low distress were more likely to obtain/maintain the spleen response at week-24. Low adherence to ruxolitinib represents an unmet clinical need that require a multifaceted approach, based on reason behind it (patients characteristics and treatment duration). Its recognition may help distinguishing patients who are truly refractory and those in need of therapy optimization. [ABSTRACT FROM AUTHOR]

We investigated the influence of molecular status on disease characteristics and clinical outcome in young patients (⩽40 years) with World Health Organization (WHO)-defined essential thrombocythemia (ET) or early/prefibrotic primary myelofibrosis (early-PMF). Overall, 217 patients with ET (number 197) and early-PMF (number 20) were included in the analysis. Median follow-up time was 10.2 years. The cumulative incidence of thrombosis, hemorrhages and disease evolution into myelofibrosis/acute leukemia were 16.6%, 8.6% and 3% at 15 years, respectively. No differences were detectable between ET and early-PMF patients, although the latter cohort showed a trend for worse combined-event free survival (EFS). Mutation frequency were 61% for JAK2V617F, 25% for CALR and 1% for MPLW515K, and were comparable across WHO diagnosis; however, JAK2V617F allele burden was higher in the early-PMF group. Compared with JAK2V617F-positive patients, CALR-mutated patients displayed higher platelet count and lower hemoglobin level. CALR mutations significantly correlated with lower thrombotic risk (9.1% versus 21.7%, P=0.04), longer survival (100% versus 96%, P=0.05) and better combined-EFS (86% versus 71%, P=0.02). However, non-type 1/type 2 CALR mutations ('minor' mutations) and abnormal karyotype were found to correlate with increased risk of disease evolution. At last contact, six patients had died; in five cases, the causes of death were related to the hematological disease and occurred at a median age of 64 years (range: 53-68 years). Twenty-eight patients (13%) were unmutated for JAK2, CALR and MPL: no event was registered in these 'triple-negative' patients. [ABSTRACT FROM AUTHOR]

Along with their immunogenic role, dendritic cells (DCs) are also critical in maintaining tolerance to self-antigens by inducing regulatory T cells (Tregs) via the expression of the immunomodulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO1). In turn, Tregs modulate the maturation and/or function of DCs. In immune thrombocytopenia (ITP), the interaction between DCs and Tregs has never been investigated although decreased number/function of Tregs as well as altered DCs have been described. Here, we ask whether, in ITP: (1) IDO1 expression/activity is decreased in mature DCs; (2) IDO1-mediated Treg generation is impaired; and (3) DC maturation is abnormally modulated by Tregs. We found that in ITP, DCs show reduced capability of upregulating the expression/activity of IDO1. This finding results in the reduced ability of mature DCs of converting T cells into Tregs. In turn, Tregs are characterized by decreased interleukin-10 production and show lower ability of inhibiting DC maturation. In conclusion, these data point out the role of IDO1 in the impaired regulatory T cell development of ITP patients and suggest that the cross-talk between Tregs and DCs is hampered and plays a pathogenetic role. [ABSTRACT FROM AUTHOR]

A case study of 51-year-old male patient, who experienced massive thrombocytosis during ruxolitinib therapy. Topics discussed include use of phlebotomies and low-dose acetylsalicylic acid for treatment, effect of fedratinib and ruxolitinib on platelet count, and suppression of cytokines storm and phagocytic activity.

A letter to the editor is presented about imatinib therapy for patients suffering from chronic myeloid leukemia.

Presents a letter to the editor reporting that in vivo T-cell depletion with low-dose antithymocyte globulin is effective in reducing Chronic graft versus host disease.

The article focuses on a study concerning successful treatment of severe hemorrhagic cystitis (HC) with selective vesical artery embolization. Severe HC can sometimes be life-threatening after stem cell transplantation. Late-onset HC persists as a severe complication. Possible risk factors include grade II-IV acute graft-versus-host disease, use of busulfan and/or total-body irradiation in the conditioning regimen, older age at transplant and certain viruses which can reactivate in immune deficiency conditions. Medical management of severe HC is based on hyperhydration, bladder irrigation and transfusional support, and is frequently ineffective.