No abstract

Lymphoma represents a heterogeneous hematological malignancy (HM), which is characterized by severe immunosuppression. Patients diagnosed of coronavirus disease (COVID-19) during the course of HM have been described to have poor outcome, with only few reports specifically addressing lymphoma patients. Here, we investigated the clinical behaviour and clinical parameters of a large multicenter cohort of adult patients with different lymphoma subtypes, with the aim of identifying predictors of death. The study included 856 patients, of whom 619 were enrolled prospectively in a 1-year frame and were followed-up for a median of 66 days (range 1-395). Patients were managed as outpatient (not admitted cohort, n=388), or required hospitalization (n=468), and median age was 63 years (range 19-94). Overall, the 30- and 100-days mortality was 13% (95%CI 11-15%) and 23% (95%CI 20-27%), respectively. Anti-lymphoma treatment, including anti-CD20 containing regimens, did not impact on survival. Patients with Hodgkin's lymphoma had the more favourable survival, but this was partly related to significantly younger age. The time interval between lymphoma diagnosis and COVID-19 was inversely related to mortality. Multivariable analysis recognized 4 easy-to-use factors (age, gender, lymphocyte, and platelet count) that were associated with risk of death, both in the admitted and in the not-admitted cohort (HR 3.79 and 8.85 for the intermediate and high-risk group, respectively). Overall, our study shows that patients should not be deprived of the best available treatment for their underlying disease, and indicates which patients are at higher risk of death. This study was registered with ClinicalTrials.gov, NCT04352556.

Between 1967 and 2017, 361 patients with myeloproliferative neoplasms (MPN), age ≤ 40 years, were seen at our institution, constituting 12% of all MPN patients (n = 3023) seen during the same time period; disease-specific incidences were 12% in polycythemia vera (PV; n = 79), 20% in essential thrombocythemia (ET; n = 219) and 5% in primary myelofibrosis (PMF; n = 63). Compared to their older counterparts, younger patients were more likely to present with low risk disease (P < .001) and display female preponderance in ET (P = .04), lower incidence of arterial events overall (P < .001), and higher incidence of venous thrombosis in PV (P = .01). Younger patients were also more likely to express CALR mutations, in ET and PMF, normal karyotype, in PV and PMF, and lower incidence of high molecular risk mutations in PMF (P significant in all instances). Over median follow-up of 11.3, 13, and 7.1 years for PV, ET, and PMF, leukemic transformations were respectively documented in 4%, 2%, and 10% (P values 0.1-0.9) while incidences of fibrotic progression in PV (22%) and ET (16%) were expectedly higher in young patients, because of their longer survival (P < .001). Median survival in young patients was 37 years for PV, 35 for ET and 20 for PMF; the corresponding values were 22, 22, and 8 years for ages 41-60 years and 10, 11, and 3 years for ages >60 years (P < .001). Young MPN patients comprise a unique disease subset defined by an attenuated-risk cytogenetic and mutational backdrop and conspicuously longer survival compared to their older counterparts, which requires assertion during patient counseling.

Among 1306 patients with primary myelofibrosis (PMF), we sought to identify risk factors that predicted leukemic transformation (LT) in the first 5 years of disease and also over the course of the disease. 149 (11%) LT were documented; patients who subsequently developed LT (n = 149), compared to those who remained in chronic phase disease (n = 1,157), were more likely to be males (p = 0.02) and display higher circulating blasts (p = 0.03), ASXL1 (p = 0.01), SRSF2 (p = 0.001) and IDH1 (p = 0.02) mutations. Logistic regression analysis identified IDH1, ASXL1 and SRSF2 mutations, very high-risk karyotype, age > 70 years, male sex, circulating blasts ≥ 3%, presence of moderate or severe anemia and constitutional symptoms, as predictors of LT in the first 5 years of diagnosis. Time-to-event Cox analysis confirmed LT prediction for IDH1 mutation (HR 4.3), circulating blasts ≥ 3% (HR 3.3), SRSF2 mutation (HR 3.0), age > 70 years (HR 2.1), ASXL1 mutation (HR 2.0) and presence of moderate or severe anemia (HR 1.9). HR-based risk point allocation resulted in a three-tiered LT risk model: high-risk (LT incidence 57%; HR 39.3, 95% CI 10.8–114), intermediate-risk (LT incidence 17%; HR 4.1, 95% CI 2.4–7.3) and low-risk (LT incidence 8%). The current study provides a highly discriminating LT predictive model for PMF.

Infections represent one of the major concerns regarding the utilization of ruxolitinib (RUX) in patients with myelofibrosis. With the aim to investigate epidemiology, outcome and risk factors for infections in RUX-exposed patients, we collected clinical and laboratory data of 446 myelofibrosis patients treated with RUX between June 2011 and November 2016 in 23 European Hematology Centers. After a median RUX exposure of 23.5 months (range, 1-56), 123 patients (28%) experienced 161 infectious events (grades 3-4 32%, fatal 9%), for an incidence rate of 17 cases per 100 pts/y. The rate of infections tended to decrease over time: 14% of patients developed the first infection within 6 months, 5% between 6 and 12 months, 3.7% between 12 and 18 months, 3.4% between 18 and 24 months, and 7.9% thereafter (P < .0001). Respiratory tract infections were more frequently observed (81 events, 50%), and bacteria were the most frequent etiological agents (68.9%). However, also viral (14.9%) and fungal infections (2.5%) were observed. In multivariate analysis, previous infectious event (HR 2.54; 95% CI, 1.51-4.28; P = .0005) and high international prognostic score system category (IPSS) (HR 1.53; 95% CI, 1.07-2.20; P = .021) significantly correlated with higher infectious risk. On the contrary, spleen reduction ≥50% from baseline after 3 months of treatment (P = .02) was associated with better infection-free survival. Taken together, these findings reinforce the concept of disease severity as the most important risk factor for infections, and describe, for the first time, that a positive therapeutic effect in reducing splenomegaly may also reduce subsequent infectious complications.