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.

Neutrophil to lymphocyte ratio in myelofibrosis patients treated with ruxolitinib may predict prognosis and rate of discontinuation.

BACKGROUND: Myelofibrosis (MF) is a clonal Philadelphia chromosome negative myeloproliferative neoplasm (Ph-MPN). MF is featured by an inflammatory condition that can also drive the progression of disease. Ruxolitinib (ruxo) is the-first-in-class Jak1/2 inhibitor approved for treatment of MF, proved to reduce spleen volume and decrease symptom burden. In various malignancies neutrophil-to-lymphocyte ratio (NLR) has been indicated as predictor of progression free survival (PFS) and overall survival (OS). NLR might reflect the balance between systemic inflammation and immunity and is emerging as a prognostic biomarker in several neoplasms, including the hematological ones. METHODS: We analyzed a cohort of 140 MF patients treated with ruxo to validate baseline NLR (as a continuous variable and as a cut-off 2) as predictor of OS and of ruxo treatment discontinuation. RESULTS: We found that both baseline NLR as a continuous variable [HR 0.8 (95% CI: 0.7-0.9) (p = .006)] and NLR (<2 vs. ≥2) [HR 3.4 (95% CI: 1.6-7.0) (p = .001)] were significantly associated with OS. Censoring for patients undergone allotransplant, baseline NLR <2 was predictive of an earlier ruxo any-other-cause discontinuation [HR 3.7 (95%CI 1.7-8.3) (p < .001)]. CONCLUSIONS: NLR before starting ruxo treatment may be used as a simple and early predictor of OS and earlier ruxo discontinuation in clinical practice.

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.

Early response to caplacizumab and rituximab after anaphylaxis to Octaplas plasma in a patient with thrombotic thrombocytopenic purpura.

Management of aTTP in patients who refuse or are intolerant to plasma remains challenging, but new drugs can be implemented with success. A 39-year-old woman presented to the Emergency department for bruises at the upper and lower limbs together with worsening anemia and thrombocytopenia; PLASMIC score was seven, indicative of high risk to have a thrombotic microangiopathy due to severe ADAMTS-13 deficiency: indeed, it was 1.4%. We immediately started Plasma Exchange, but after the third procedure she developed severe anaphylaxis to Octaplas plasma, so PEXs were discontinued. We proceeded to a salvage strategy with rituximab and caplacizumab that was rapidly effective to resolve symptoms and hemolysis. It has been already reported a case in which a patient developed severe reactions to fresh-frozen plasma that required discontinuation of PEX. Differently from this case, our patient was already using the less immunogenic pooled plasma units Octaplas, therefore a strategy with caplacizumab was the only available option. Moreover, rituximab is associated with a shorter time to obtain a durable remission in aTTP and a faster time (15 days) to final ADAMTS13 activity recovery >10%. To our knowledge, this is the first case of early discontinuation of caplacizumab in a patient allergic to PEX by actively monitoring ADAMTS13 activity, allowing optimization of healthcare resources during COVID-19 pandemic.

Acute Promyelocytic Leukemia After Radium-223 Exposure for Prostate Cancer in a Chemotherapy-Naïve Patient.

223Ra-dichloride is a bone-seeking targeted alpha (α)-emitting approved for bone metastases in prostate cancer. Here, we report a case of therapy-related acute promyelocytic leukemia (t-APL) following administration of 223Ra, showing some evidence of a causative relationship. A patient with metastatic prostate cancer received therapy with 223Ra, with 6 injections of the radiopharmaceutical at a standard dose of 55 kBq/kg at 4-week intervals for a cumulative administered activity of 26.3 MBq. PET/CT with 18F-methylcholine repeated 1 month after the conclusion of 223Ra was negative. After 8 months, he developed pancytopenia and we made a diagnosis of therapy-related acute promyelocytic leukemia (t-APL). We then studied the genomic locations of the breakpoints in the PML and RARA genes, which were at nucleotide positions 1708-09 of PML intron 3, respectively, outside the previously reported Topo II-associated hotspot region. t-APL was cured with all-trans-retinoic acid (ATRA) and arsenic trioxide. The type of PML/RARA rearrangement we identified, in absence of other myelotoxic treatments, is suggestive of a possible direct causal relationship with exposure to 223Ra and warrants further investigations.