A safety evaluation of ruxolitinib for the treatment of polycythemia vera.

INTRODUCTION: Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm hallmarked by deregulated proliferation of hematopoietic stem cells leading to prevalent expansion of red cell mass, increased rate of vascular events, splenomegaly, disease-associated symptoms, and risk of evolution to secondary myelofibrosis and blast phase. PV is pathogenetically associated with autonomously persistent activation of JAK2, which causes overproduction of blood cells and an inflammatory condition responsible for the clinical manifestations of the disease. Extensively supported by preclinical studies, targeting JAK2-dependent signaling represents a rational therapeutic approach to PV, finally leading to the approval of ruxolitinib, a JAK1/2 inhibitor. AREAS COVERED (LITERATURE RESEARCH): We analyzed reports of phase 2 and phase 3 trials with ruxolitinib in PV and relevant literature dealing with efficacy and safety aspects, including most recent real-world reports. EXPERT OPINION: Ruxolitinib is the only JAK2 inhibitor approved for the treatment of PV with well-known efficacy for splenomegaly, symptoms, and potentially reduction of vascular events. The treatment regimen is notably manageable and safe, with the most prevalent side effects primarily encompassing myelosuppression, hyperlipidemia, non-melanoma skin cancer and infections, mainly reactivation of Herpes Zoster. These effects necessitate ongoing surveillance and proactive preventive measures.

Fever of Unknown Origin and Multidrug Resistant Organism Colonization in AML Patients.

Background: Colonization by multidrug-resistant organisms (MDRO) is a frequent complication in hematologic departments, which puts patients at risk of life-threatening bacterial sepsis. Fever of unknown origin (FUO) is a condition related to the delivery of chemotherapy in hematologic malignancies, in which the use of antibiotics is debated. The incidence, risk factors, and influence on the outcome of these conditions in patients with acute myeloid leukemia (AML) are not clearly defined. Methods: We retrospectively analyzed 132 consecutive admissions of non-promyelocytic AML patients at the Hematology Unit of the University Tor Vergata in Rome between June 2019 and February 2022. MDRO swab-based screening was performed in all patients on the day of admission and once weekly after that. FUO was defined as fever with no evidence of infection. Results: Of 132 consecutive hospitalizations (69 AML patients), MDRO colonization was observed in 35 cases (26%) and resulted independently related to a previous MDRO colonization (p=0.001) and length of hospitalization (p=0.03). The colonization persistence rate in subsequent admissions was 64%. MDRO-related bloodstream infection was observed in 8 patients (23%) and correlated with grade III/IV mucositis (p=0.008) and length of hospitalization (p=0.02). FUO occurred in 68 cases (51%) and correlated with an absolute neutrophilic count <500µ/L at admission (0.04). Conclusion: In our experience, MDRO colonization is a frequent and difficult-to-eradicate condition that can arise at all stages of treatment. Prompt discharge of patients as soon as clinical conditions allow could limit the spread of MDRO. In addition, the appropriate use of antibiotics, especially in the case of FUO, and the contraction of hospitalization length, when feasible, are measures to tackle the further spread of MDRO.

Coexistence of T-Large Granular Lymphocyte Leukemia and Peripheral T Cell Lymphoma-NOS with Indolent Behavior.

T-cell lymphomas and leukemias are highly heterogeneous groups of rare disorders. We report a case of a 68-year-old man patient who developed two different T-cell neoplasms (Large Granular Lymphocyte Leukemia [LGLL] in 2018 and Peripheral T-cell non-Hodgkin lymphoma not otherwise specified [PTCL-NOS] in 2019) with a previous diagnosis of B-cell marginal zone lymphoma in 2010, treated with two lines of chemo-immunotherapy. The coexistence of these different T-cell neoplasms is rarely reported in the literature. Moreover, it is usually described as an LGLL transformation into PTCL-NOS; differently from these examples, herein, the simultaneous conditions appear to be driven by different T-cell clones. Furthermore, the PTCL-NOS had quite unusual behavior, with good disease control without intensive treatment. Because of these features, it could belong to a subgroup of indolent PTCL-NOS, not yet described in the WHO classification of T-cell neoplasms, which could benefit from less aggressive treatment.