Secondary Prophylaxis of Venous Thromboembolism (VTE) with Low Dose Apixaban or Rivaroxaban: Results from a Patient Population with More than 2 Years of Median Follow-up.

Background: Direct oral anticoagulants (DOACs) are widely used for the treatment and secondary prophylaxis of venous thromboembolism (VTE). Nowadays, DOACs represent the gold standard for long-term anticoagulation, with low-intensity DOACs administration becoming increasingly used worldwide in such scenario. Albeit low-intensity apixaban and rivaroxaban are approved for clinical usage as secondary VTE prophylaxis, there are few literature data regarding their efficacy and safety with a long follow-up. Objectives: The aim of our study was to evaluate the efficacy and safety of low-dose DOACs for VTE secondary prophylaxis in patients at high risk of VTE recurrence. Methods: We retrospectively evaluated patients who required long-term anticoagulant secondary prophylaxis to prevent recurrent VTE, treated with apixaban 2.5 mg BID or rivaroxaban 10 mg daily with a follow-up ≥ 12 months. Results: The examined patients were 323. The median low-dose DOAC administration time was 25.40 months (IQR 13.93-45.90). Twelve (3.7%) VTE recurrences were observed; 21 bleeding events were registered (6.5%), including one episode of Major bleeding (MB) (0.3%), 8 Clinically relevant nonmajor bleeding (CRNMB) (2.5%) and 12 minor bleeding (3.7%). No statistically significant difference in the rate of VTE recurrence and/or bleeding events emerged between the rivaroxaban and apixaban groups. Patients included in the study for multiple episodes of VTE presented a significantly higher risk of a new VTE recurrence during low-intensity DOAC. Conclusions: Our data suggest that low-dose DOACs may be effective and safe in secondary VTE prophylaxis in patients at high risk of VTE recurrence; however, attention might be needed in their choice in such a scenario for patients who experienced multiple episodes of VTE.

Case Report: Severe cutaneous adverse event associated with checkpoint inhibition in the setting of CAR T-cell therapy: beyond CRS.

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy actually represents the standard of care for multiple relapsed or refractory primary mediastinal B-cell lymphoma (r/r PMBCL). Checkpoint inhibitors, such as pembrolizumab, appear to be a safe and effective treatment strategy for patients who are ineligible for or resistant to autologous stem cell transplantation. Although preclinical studies suggested that checkpoint inhibitors may enhance the vitality and anti-tumor activity of CAR T cells, there are no substantial/robust clinical data about the immune-mediated toxicity of their association. We describe a case of a severe cutaneous adverse event arising immediately after Cytokine Release Syndrome (CRS) on day +6 from CAR T cells infusion in a young r/r PMBCL patient who previously received pembrolizumab. These skin lesions were interpreted as an immune mediated adverse event, considering their prompt improvement and fully recovering achieved with the addition of immunoglobulin infusion to systemic steroid therapy. This case of life-threatening cutaneous adverse event calls for further investigations about off-target immune-related adverse events deriving from the combination of CAR T cell therapy and checkpoint inhibition, whose synergic therapeutic effect is promising.

CCND2 mutations in atypical chronic myeloid leukemia: a report of two cases.

Atypical chronic myeloid leukemia (aCML) is a rare MDS/MPN disease characterized by the absence of BCR::ABL1 rearrangement and well known typical mutations associated with myeloproliferative disorders. Mutational landscape associated with this disease was recently described with frequent involvement of SETBP1 and ETNK1 mutations. CCND2 mutations have not been frequently detected in MPN or MDS/MPN patients. We describe two cases of aCML with two CCND2 mutations in 280 and 281 codons which rapidly develop progressive characteristics, and we reviewed the literature about this unfavorable association, suggesting a role as a new possible marker of aggressive disease.

Case Report: Avelumab and ruxolitinib to manage polycythemia vera and secondary metastatic Merkel cell carcinoma: a possible successful combination.

We describe a case of second primary malignancy in a 65-year-old patient affected by polycythemia vera treated with the JAK 1/2 inhibitor ruxolitinib. The latter is recognized as a risk factor for the onset of non-melanoma skin cancers in many retrospective and perspective studies, but the concomitant use of ruxolitinib with new immunotherapies is very rarely reported, and the safety of this association is still not clear. In our case, ruxolitinib combined with the anti-PD-L1 avelumab demonstrated both safety and efficacy for hematological disease control and underlying carcinoma remission.

Case Report: Infectious prophylaxis in hematological malignancies.

Patients with hematological malignancies and past serological evidence of hepatitis B are at risk for HBV reactivation. In myeloproliferative neoplasms, continuous treatment with the JAK 1/2 inhibitor ruxolitinib confers a moderate risk of reactivation (1-10%); nevertheless, no prospective randomized data are available to strongly recommend HBV prophylaxis in these patients. Here, we report a case of primary myelofibrosis and past serological evidence of HBV infection, treated with ruxolitinib and concomitant lamivudine, developing HBV reactivation due to premature withdrawal of prophylaxis. This case underlines the potential need for persistent HBV prophylaxis in the setting of ruxolitinib treatment.

Systemic mastocytosis: 2023 update on diagnosis and management in adults.

INTRODUCTION: Systemic mastocytosis (SM) is a complex and heterogeneous disease, characterized by the clonal accumulation of mast cells in one or more organs. In 2022 both the World Health Organization (WHO) and the International Consensus Classification (ICC) modified the diagnostic and classification criteria of SM. Moreover, the identification of new clinical and molecular variables has improved prognostic tools and led to increasingly individualized therapeutic strategies. AREAS COVERED: The aim of this review is to present the updates introduced by the International Consensus Classification in diagnostic criteria of SM. In addition, we report the latest data available from the most important clinical trials in patients both with non-advanced and advanced disease, including elenestinib and bezuclastinib. EXPERT OPINION: Diagnosis and classification of SM has evolved over years. The most recent WHO and ICC classification improved SM diagnostic work-up, providing clinicians with a clear and simplified diagnostic scheme. New approved targeted therapies such as midostaurin and avapritinib modified the treatment paradigm in patients in advanced stage, and next-generation inhibitors actually investigated in clinical trials are expected in the next future.

Management of Relapsed/Refractory All with Inotuzumab During COVID-19. A Case Report.

Management of patients with concomitant acute lymphoblastic leukemia (ALL) and COVID-19 infection is challenging. We describe the clinical history of a 40-year-old male with relapsed B-common ALL who developed Sars-CoV2 prior to treatment initiation with inotuzumab. Since the patient was asymptomatic for COVID-19, the first dose of inotuzumab was administered, followed by remdesivir as prophylaxis. However, a worsening in respiratory findings led to a delay in administering the following doses of inotuzumab. Interestingly, even if the patient did not receive the full inotuzumab cycle, he achieved a complete hematologic remission: furthermore, he spontaneously developed anti-sars-COV2 antibodies. COVID-19 treatment also included convalescent plasma, leading to negativization of the viral load. The patient, after COVID-19 recovery, received a second full cycle of inotuzumab, underwent allogeneic transplantation, and is currently in complete hematologic and molecular remission, in good clinical conditions, five months from allograft.