Secondary prophylaxis of venous thromboembolism with direct oral anticoagulants: comparison between patients with major congenital thrombophilia versus non-thrombophilic patients.

Direct oral anticoagulants (DOACs) are widely used for the treatment and secondary prophylaxis of venous thromboembolism (VTE). Congenital thrombophilia is a condition that predisposes to a higher incidence of VTE and often requires long-term anticoagulation for secondary prophylaxis. It is less clear the efficacy of DOACs in patients with major thrombophilia. The aim of our study was to evaluate the efficacy and safety of full and reduced DOACs dose for VTE secondary prophylaxis, in patients affected by major congenital thrombophilia compared to a control group of patients with idiopathic recurrent VTE without thrombophilia. We retrospectively evaluated consecutive patients who required long-term anticoagulation for recurrent VTE, treated with DOACs, and compared the outcomes between patients affected by major thrombophilia and the control group. The examined patients were 209. The median time of DOACs therapy was 20 months (range 6-90). Two (2.7%) thrombotic events were observed in the subset affected by major congenital thrombophilia (n = 72) and five (3.6%) in the control group (n = 137) (p 0.73). Four (5.5%) hemorrhagic events were reported in the group with major thrombophilia; 21 (15.3%) in the other group (p 0.039). No statistically significant differences were observed in terms of efficacy and safety between DOACs at full and reduced dose. Our data suggest that DOACs may be effective and safe in the secondary VTE prophylaxis in patients affected by major congenital thrombophilia, also at reduced dose.

Utility of procalcitonin and C-reactive protein as predictors of Gram-negative bacteremia in febrile hematological outpatients.

This study was designed to determine the utility of procalcitonin (PCT) and C-reactive protein (CRP) as predictors of Gram-negative bloodstream infection (GN-BSI) in hematological febrile outpatients at the time of the emergency unit admission. Overall, 286 febrile episodes, which included 42 GN-BSI (16%), were considered. PCT levels at patient admission were statistically higher in GNB-BSI when compared to Gram-positive bacteria BSI (median 4.06 ng/ml (range 1.10-25.04) vs 0.88 ng/ml (0.42-10), p<0.03) and to all other fever etiologies. For CRP, differences within fever etiologies were less profound but statistically significant, except for GN-BSIs vs GP BSIs (p=0.4). ROC analysis of PCT showed that an AUC of 0.85 (95%CI 0.79-0.95) discriminated GN-BSI from all other fever etiologies, with a best cut-off of 0.5 ng/ml, a negative predictive value (NPV) of 98%, and a negative likelihood ratio (negLR) of 0.1. ROC analysis of CRP showed an AUC of 0.67 (95%CI 0.53-0.81) with a best cut-off of 6.64 mg/dl, a NPV of 94%, and a negLR of 0.33. This study confirms that 0.5 ng/ml represents the PCT best cut-off to differentiate the cause of fever and rule out a GN-BSI in febrile hematologic outpatients at the time of the emergency unit admission. Therefore, introducing PCT testing could be a valid measure in order to tailor a more precise prompt antimicrobial therapy to the febrile outpatient while waiting for blood culture results.

High Basal Maximal Standardized Uptake Value (SUVmax) in Follicular Lymphoma Identifies Patients with a Low Risk of Long-Term Relapse.

BACKGROUND: Despite that the unfavorable prognostic role of a high Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma has been demonstrated, the role of SUVmax alone at baseline PET/CT could have a different prognostic role. PATIENTS AND METHODS: We performed a retrospective observational monocentric cohort study. All patients affected by FL who underwent a basal PET/CT were included. Two subgroups were identified and compared in terms of PFS and OS: (A) Basal SUVmax ≤ 6; and (B) Basal SUVmax > 6. RESULTS: Ninety-four patients were included, 34 in group A (36.2%) and 60 in group B (63.8%). The PFS at two years was comparable in the two groups (97%). The five-year PFS was 73.5% for group A and 95% for group B (p 0.005). The five-year PFS in the whole cohort was 87.5%. A clear advantage was confirmed in group A in the absence of other risk factors. Patients with SUVmax ≤ 6 and no risk factors showed a 5-year PFS of 73% against 83% for patients with SUVmax > 6 and at least two risk factors. CONCLUSION: A high FDG uptake favorably correlated with PFS. A low basal SUVmax reflected a higher rate of late relapse requiring a prolonged follow-up. The basal SUVmax is an approachable parameter with prognostic implications.

Treatment of Low-Blast Count AML using Hypomethylating Agents.

In 2002, the WHO classification reduced the proportion of blasts in the bone marrow (BM) necessary for the diagnosis of acute myeloid leukemia (AML) from 30% to 20%, eliminating the RAEB-t subtype of myelodysplastic syndromes (MDS). However, this AML subtype, defined as low-blast count AML (LBC-AML, with 20-30% BM-blasts) is characterized by peculiar features, as increased frequency in elderly individuals and after cytotoxic treatment for a different primary disease (therapy-related), poor-risk cytogenetics, lower white blood cell counts, and less frequent mutations of NPM1 and FLT3 genes. The clinical course of this entity is often similar to MDS with 10-19% BM-blasts. The hypomethylating agents azacitidine and decitabine have been shown to induce responses and prolong survival both in MDS and LBC-AML. The role of these agents has also been demonstrated in AML with >30% BM-blasts, particularly in patients with poor-risk cytogenetics and in AML with myelodysplasia-related changes. Most recent studies are evaluating strategies to improve outcome, including combinations of hypomethylating agents with immune-response checkpoint inhibitors, which have a role in cancer immune surveillance. Efforts are also ongoing to identify mutations which may predict response and survival in these patients.