Management of mixed cryoglobulinemia with rituximab: evidence and consensus-based recommendations from the Italian Study Group of Cryoglobulinemia (GISC).

Cryoglobulinemic vasculitis (CV) or mixed cryoglobulinemic syndrome (MCS) is a systemic small-vessel vasculitis characterized by the proliferation of B-cell clones producing pathogenic immune complexes, called cryoglobulins. It is often secondary to hepatitis C virus (HCV), autoimmune diseases, and hematological malignancies. CV usually has a mild benign clinical course, but severe organ damage and life-threatening manifestations can occur. Recently, evidence in favor of rituximab (RTX), an anti-CD 20 monoclonal antibody, is emerging in CV: nevertheless, questions upon the safety of this therapeutic approach, especially in HCV patients, are still being issued and universally accepted recommendations that can help physicians in MCS treatment are lacking. A Consensus Committee provided a prioritized list of research questions to perform a systematic literature review (SLR). A search was made in Medline, Embase, and Cochrane library, updated to August 2021. Of 1227 article abstracts evaluated, 27 studies were included in the SLR, of which one SLR, 4 RCTs, and 22 observational studies. Seventeen recommendations for the management of mixed cryoglobulinemia with rituximab from the Italian Study Group of Cryoglobulinemia (GISC) were developed to give a valuable tool to the physician approaching RTX treatment in CV.

Predicting failure of hematopoietic stem cell mobilization before it starts: the predicted poor mobilizer (pPM) score.

Predicting mobilization failure before it starts may enable patient-tailored strategies. Although consensus criteria for predicted PM (pPM) are available, their predictive performance has never been measured on real data. We retrospectively collected and analyzed 1318 mobilization procedures performed for MM and lymphoma patients in the plerixafor era. In our sample, 180/1318 (13.7%) were PM. The score resulting from published pPM criteria had sufficient performance for predicting PM, as measured by AUC (0.67, 95%CI: 0.63-0.72). We developed a new prediction model from multivariate analysis whose score (pPM-score) resulted in better AUC (0.80, 95%CI: 0.76-0.84, p < 0001). pPM-score included as risk factors: increasing age, diagnosis of NHL, positive bone marrow biopsy or cytopenias before mobilization, previous mobilization failure, priming strategy with G-CSF alone, or without upfront plerixafor. A simplified version of pPM-score was categorized using a cut-off to maximize positive likelihood ratio (15.7, 95%CI: 9.9-24.8); specificity was 98% (95%CI: 97-98.7%), sensitivity 31.7% (95%CI: 24.9-39%); positive predictive value in our sample was 71.3% (95%CI: 60-80.8%). Simplified pPM-score can "rule in" patients at very high risk for PM before starting mobilization, allowing changes in clinical management, such as choice of alternative priming strategies, to avoid highly likely mobilization failure.

Neurological symptoms in essential thrombocythemia: impact of JAK2V617F mutation and response to therapy.

Patients with essential thrombocythemia (ET) often suffer from neurological symptoms (NS) not ever resulting from previous thrombotic cerebral events (TCE). We reported NS occurred in 282 patients, in order to identify the factors influencing ET-related NS in the absence of TCE, and the response to therapy. Overall, 116 of 282 patients (41%) presented NS; 101 of them (87%) reported subjective transient and fluctuating NS, without concurrent TCE, which we defined as ET-related NS, by frequency: cephalalgia, chronic paresthesias, dizziness or hypotension, visual disturbances, and tinnitus. In univariate analysis, ET-related NS resulted more frequently in young people (P = 0.017) and in females (P = 0.025). We found a higher prevalence of JAK2V617F mutation in ET-related NS patients (P = 0.021). In multivariate analysis, gender (P = 0.024) and JAK2V617F mutation (P = 0.041) remained significantly associated with the development of ET-related NS, with a risk of about four times higher for JAK2V617F-mutated patients (OR = 3.75). Ninety-seven of 101 patients with ET-related NS received an antiplatelet (AP) agent at the time of NS, whereas only selected high-risk ET-related NS patients were treated with a cytoreductive drug, according to the published guidelines and similarly to patients without NS. We observed that only 32 of 97 (33%) patients with ET-related NS achieved a complete response after AP treatment. Among the 65 non-responder patients, 36 (55.4%) improved NS after the introduction of cytoreductive therapy; therefore, the addition of cytoreductive treatment should be considered in this setting.

Peripheral blood lymphocyte/monocyte ratio predicts outcome in follicular lymphoma and in diffuse large B-cell lymphoma patients in the rituximab era.

BACKGROUND: Diffuse large B-cell lymphoma is an aggressive lymphoma and a large number of studies have therefore focused on the search for prognostic factors. The same interest concerns FL, for which identification of patients candidates for watch and wait (W&W) strategy is still an option. Studies about the number and type of lymphocytes and monocytes detectable in patients with Hodgkin and non-Hodgkin lymphomas indicate they might affect the pathogenesis and prognosis of these diseases. LMR is recently under investigation as a new prognostic parameter in DLBCL; the role of this ratio in FL in the rituximab era is unknown. PATIENTS AND METHODS: We retrospectively analyzed 137 DLBCL and 132 FL patients referred to our institution; among FL pts, a W&W approach was performed at diagnosis for 42 patients. The remaining patients were treated with rituximab-containing therapy. We analyzed different LMR cutoff values at diagnosis and we wanted to investigate the prognostic effect among DLBCL and FL. RESULTS: We found that the most discriminative LMR was 2.4 for DLBCL and 2 for FL. Among DLBCL patients, an LMR value < 2.4 was associated with a worse 2-year progression-free survival (PFS), and we observed no difference in overall survival and complete response rate. Considering FL patients, LMR > 2 was associated with a longer time to treatment start compared with the LMR < 2 group (P = .0096). Among the 92 patients treated with rituximab chemotherapy, 2-year PFS was superior in the LMR > 2 group. CONCLUSION: LMR at diagnosis is a simple tool to better define long-term outcome of DLBCL and FL patients. The use of this tool might better define selection in FL of ideal candidates for W&W strategy.