We evaluated the prognostic role of the largest distance between two lesions (Dmax), defined by positron emission tomography (PET) in a retrospective cohort of newly diagnosed classical Hodgkin Lymphoma (cHL) patients. We also explored the molecular bases underlying Dmax through a gene expression analysis of diagnostic biopsies. We included patients diagnosed with cHL from 2007 to 2020, initially treated with ABVD, with available baseline PET for review, and with at least two FDG avid lesions. Patients with available RNA from diagnostic biopsy were eligible for gene expression analysis. Dmax was deduced from the three‐dimensional coordinates of the baseline metabolic tumor volume (MTV) and its effect on progression free survival (PFS) was evaluated. Gene expression profiles were correlated with Dmax and analyzed using CIBERSORTx algorithm to perform deconvolution. The study was conducted on 155 eligible cHL patients. Using its median value of 20 cm, Dmax was the only variable independently associated with PFS (HR = 2.70, 95% CI 1.1–6.63, pValue = 0.03) in multivariate analysis of PFS for all patients and for those with early complete metabolic response (iPET‐). Among patients with iPET‐low Dmax was associated with a 4‐year PFS of 90% (95% CI 82.0–98.9) significantly better compared to high Dmax (4‐year PFS 72.4%, 95% CI 61.9–84.6). From the analysis of gene expression profiles differences in Dmax were mostly associated with variations in the expression of microenvironmental components. In conclusion our results support tumor dissemination measured through Dmax as novel prognostic factor for cHL patients treated with ABVD.

Since the end of February 2020, Italy is facing an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the clinical picture associated with the infection has been named COVID-19. The COVID-19 patients may develop multiple organ dysfunction with signs of endothelial derangement. Vascular damage has been proposed as a relevant mechanism that can perpetuate the activation of complement system, and might therefore enhance the inflammatory stimulus. Recently post-mortem analysis in a series of patients with COVID-19 by Varga et al. 1 demonstrated endothelial cell involvement in different

IgM monoclonal gammopathies of undetermined significance (IgM MGUS) are associated with a risk of progression to Waldenstr€ om macroglobulinaemia (WM) or other lymphoproliferative disorders (LPD) of 1-2% per year. We analysed 176 consecutive patients with IgM MGUS to evaluate risk factors for progression. With a median follow-up of 83 months (1214 person-years), 15 patients (8Á5%) progressed to WM (n = 14) or marginal zone lymphoma (n = 1). The rate of progression was 1Á32% per year (95% confidence interval [CI] 0Á80-2Á20). The serum monoclonal protein concentration and the MYD88 mutation were independent risk factors for progression (Hazard ratio [HR] 23Á3, 95% CI 2Á0-273Á3, P = 0Á012 and HR 24Á4, 95% CI 2Á2-275Á3, P = 0Á010, respectively). The cumulative incidence of progression, while considering death as a competing event, was 11Á6% at 5 years and 38Á0% at 10 years in MYD88-mutated patients with a serum monoclonal protein of 10 g/l or higher, as compared with 0% at 5 years and 1Á1% at 10 years for patients with none or one risk factor. This risk-stratification model is able to identify a subset of patients with IgM MGUS at high risk of progression to WM or LPD who deserve a lifelong follow-up.Keywords: monoclonal gammopathy of undetermined significance, Waldenstr€ om macroglobulinaemia, MYD88 mutation, risk of progression, follow-up.Monoclonal gammopathies of undetermined significance (MGUS) represent a common condition in the general population with a reported prevalence of 3% above the age of 50 years, and 5% above 70 years (Kyle et al, 2006). Although MGUS are considered benign conditions with a low rate of transformation to multiple myeloma (MM) or lymphoproliferative disorders (LPD), the risk continues indefinitely and therefore patients with MGUS are usually followed lifelong. The size and type of the M protein, and the free light chain (FLC) ratio are helpful in identifying patients who are at a higher risk of progression. In a risk-stratification model proposed by Rajkumar et al (2005), risk factors were a serum monoclonal (M) protein >15 g/l, IgA or IgM isotype, and an abnormal serum FLC ratio. The risk of progression at 20 years was 5% when none of the risk factors were present, 21% with one risk factor, 37% with two risk factors and 58% when all the three risk factors were present (Rajkumar et al, 2005).IgM MGUS represent approximately 25% of all MGUS and are characterized by a higher risk and a different pattern of progression as compared with IgG or IgA MGUS, with Waldenstr€ om macroglobulinaemia (WM) being the most frequent evolution. In a recent study on 1384 patients with a median follow-up of 34Á1 years, the risk of progression among patients with IgM MGUS was 2% per year in the first

Hairy cell leukemia (HCL) is a rare lymphoproliferative disease with an excellent prognosis after treatment with cladribine (2CDA), although relapse may occur during follow-up. The aim of the study is to review the efficacy, safety, long-term remission rate, and overall survival (OS) in those patients who received 2CDA as first-line treatment. We retrospectively reviewed data of HCL patients treated with 2CDA between March 1991 and May 2019 at 18 Italian Hematological centers: 513 patients were evaluable for study purpose. The median age was 54 years (range 24–88) and ECOG was 0 in 84.9% of cases. A total of 330 (64.3%) patients received 2CDA intravenously and 183 (35.7%) subcutaneously. ORR was 91.8%: CR was obtained in 335 patients (65.3%), PR in 96 (18.7%), and hematological response in 40 (7.8%) patients; in 42 (8.2%) no response was observed. Hemoglobin value (p = 0.044), frequency of circulating hairy cells (p = 0.039), recovery of absolute neutrophil count (p = 0.006), and normalization of spleen (p ≤ 0.001) were associated with CR compared to PR in univariable analysis. At a median follow-up of 6.83 years (range 0.04–28.52), the median time to relapse was 12.2 years. A significant difference in duration of response was identified between patients that obtained a CR and PR (19.4 years versus 4.8 years, p < 0.0001). Non-hematological grade 3 or higher early toxicity was reported in 103 (20.1%) patients. Median OS was not reached: 95.3%, 92.4%, and 81.8% of patients were estimated to be alive at 5, 10, and 15 years, respectively. Forty-nine patients died (9.5%), following an infection in 14 cases (2.7%), natural causes in 14 (2.7%), cardiovascular events in 13 (2.5%), a second neoplasm in 6 (1.2%), and progression of HCL in 2 cases (0.4%). Following treatment of HCL with 2CDA, 80% of patients are estimated to be alive 15 years after diagnosis.