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COVID-19 pandemia is a major health emergency causing hundreds of deaths worldwide. The high reported morbidity has been related to hypoxia and inflammation leading to endothelial dysfunction and aberrant coagulation in small and large vessels. This review addresses some of the pathways leading to endothelial derangement, such as complement, HIF-1α, and ABL tyrosine kinases. This review also highlights potential targets for prevention and therapy of COVID-19-related organ damage and discusses the role of marketed drugs, such as eculizumab and imatinib, as suitable candidates for clinical trials.

This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development. Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations. Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea. Ruxolitinib is recommended as first-line approach for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease; in case of intermediate-1 disease, ruxolitinib is recommended in highly symptomatic splenomegaly. Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score. Allogeneic stem cell transplantation is also recommended for transplant-eligible MF patients with intermediate-1 risk score who present with either refractory, transfusion-dependent anemia, blasts in peripheral blood > 2%, adverse cytogenetics, or high-risk mutations. In these situations, the transplant procedure should be performed in a controlled setting.

We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82–1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15–4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00–14.01), ruxolitinib (OR = 3.87, 95% CI 1.18–12.75), and for drug combination (OR = 3.47, 95% CI 1.55–7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.

Background: Pre-exposure passive immune prophylaxis (PrEP) might contribute to improve hematologic malignancy (HM) outcomes; however, there are currently no specific guidelines to inform patient selection. Methods: A literature review and a Delphi consensus process were used to identify COVID-19 risk factors, critical COVID-19 outcomes, and efficacy of PrEP against SARS-CoV-2 in HMs. An analytic hierarchy process was used to assign a priority score to candidate outcomes and to determine the PrEP indications. For these decisions, the experts assumed adequate compliance with anti-COVID-19 vaccination and acknowledged the effectiveness of PrEP in reducing SARS-CoV-2-related mortality and hospital admissions. Results: Based on the literature review, the expert panel identified 80 risk categories among patients with HM and prioritized eight clinical outcomes related to SARS-CoV-2 PrEP. The highest mean priority scores were observed for HM-related mortality (7.0), intensive care unit admission (6.7), and delays in anti-HM treatment (6.6). Based on such a framework, the experts deemed that if there was a variant-specific PrEP promptly available, it would be considered mandatory for all candidates receiving allogeneic hematopoietic cell transplantation, CAR-T therapy, or bispecific antibodies, regardless of local viral epidemiology. During epidemiological waves, variant-specific PrEP would also be recommended for patients with HMs at high risk of unfavorable COVID-19 clinical outcomes. Conclusions: This study identified PrEP indications for patients with HM receiving appropriate active immunization against COVID-19.

Understanding antibody-based SARS-CoV-2 immunity in hematologic malignancy (HM) patients following infection is crucial to inform vaccination strategies for this highly vulnerable population. This cross-sectional study documents the anti-SARS-CoV-2 humoral response and serum neutralizing activity in 189 HM patients recovering from a PCR-confirmed infection. The overall seroconversion rate was 85.7%, with the lowest values in patients with lymphoid malignancies or undergoing chemotherapy. Therapy-naive patients in the “watch and wait” status were more likely to seroconvert and display increased anti-s IgG titers. Enhanced serum neutralizing activity was observed in the following SARS-CoV-2-infected HM patient groups: (i) males; (ii) severe COVID-19; and (iii) “watch and wait” or “complete/partial response”. The geometric mean (GeoMean) ID50 neutralization titers in patients analyzed before or after 6 months post-infection were 299.1 and 306.3, respectively, indicating that >50% of the patients in either group had a neutralization titer sufficient to provide 50% protection from symptomatic COVID-19. Altogether, our findings suggest that therapy-naive HM patients mount a far more robust immune response to SARS-CoV-2 infection vs. patients receiving anti-cancer treatment, raising the important question as to whether HM patients should be vaccinated before therapy and/or receive vaccine formats capable of better recapitulating the natural infection.

Most myelofibrosis (MF) drug approvals by Health Authorities are based on 1 or 2 outcome measures such as spleen volume reduction and/or improved quality of life. This 1–2 dimensional approach fails to capture the clinical complexity of MF. A European LeukemiaNet (ELN) task force developed a composite endpoint that allows multiple outcomes to be simultaneously measured. The panel used the Desirability Of Outcome Ranking (DOOR) method to assign 25 outcomes into 4 quartiles based on a multi-dimensional desirability score and build a 5-layer composite outcome named Desirability of Myelofibrosis Outcomes (DEMYO). Outcome operational definitions were tested by Delphi consensus, and correlations with survival were validated by a literature review. The outcomes assigned to the first two quartiles were negatively correlated with leukemia-free survival and survival. DEMYO comprehensively captures relevant MF clinical features and meaningful endpoints. Despite DEMYO requiring validation based on available trial data, it is expected to improve the quality of Health Authority approvals for new drugs for MF.

Purpose Cancer-related fatigue (CRF) is one of the most common symptoms experienced by cancer patients (CPs). The Brief Fatigue Inventory (BFI) is a reliable instrument to assess CRF in CPs. The aim of this study was to evaluate the psychometric properties of the Italian version of the BFI (BFI-I). Methods The BFI-I was developed by using the forward–backward translation approach. The psychometric properties of the BFI-I were assessed in terms of acceptability, internal consistency, and validity. Outpatient CPs filled in BFI-I along with the Medical Outcome Study Quality of Life Short Form 36 (SF36). Demographic and health data were collected. Results The BFI-I had an overall Cronbach alpha for the nine items of 0.94. The inter-item mean correlation was 0.64, and coefficients ranged from 0.47 to 0.81 for the nine items. The results of the factor analysis suggested a 1-factor solution explaining 68 % of the variance, supporting the hypothesis of unidimensionality of the BFI-I. The BFI-I score was compared to SF36 subscales score to evaluate concurrent validity. An expected inverse correlation between the BFI-I and the vitality subscale of the SF36 was observed ( r  = −0.67, 95 % confidence interval −0.73 to −0.59). The correlation with the other subscales of the SF36 ranged between −0.56 and −0.13. Discriminant validity analysis showed the BFI-I mean score significantly increased with increasing Eastern Cooperative Oncology Group values ( p  < 0.001). Conclusions BFI-I is a clinical instrument with satisfactory psychometric properties to assess CRF in Italian CPs.

Health‐related quality of life (HRQoL) of patients with myeloproliferative neoplasms (MPNs) may be impaired across several domains. In this multicenter observational study, we evaluated HRQoL and symptoms in a cohort of MPN patients with validated measures, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire‐Core 30 (EORTC QLQ‐C30), the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN‐SAF TSS), and the Functional Assessment of Chronic Illness Therapy‐Fatigue Scale (FACIT‐Fatigue) questionnaire. The primary objective was to compare the HRQoL profile of patients, by disease subtype, with that of the general population according to the EORTC QLQ‐C30. A total of 572 patients with essential thrombocythemia (ET, n = 228), polycythemia vera (PV, n = 207), and myelofibrosis (MF, n = 137) were assessed. Worse statistically and clinically significant differences were observed for role functioning (ET: ∆ = 8.9, P < 0.001; PV: ∆ = 11, P < 0.001; MF: ∆ = 16.7, P < 0.001) and fatigue (ET: ∆ = 5, P < 0.001; PV: ∆ = 8.3, P < 0.001; MF: ∆ = 11.5, P < 0.001) in all three diagnostic groups. However, patients with MF also reported impairments in other important health domains. Fatigue was the most frequently reported and burdensome symptom, with greater severity correlating with a broader and more complex array of associated symptoms. Our analysis also revealed a substantial underestimation of symptoms by treating hematologists in paired physician–patient reports. Current findings may help to disentangle specific HRQoL limitations and symptomatology experienced by patients with MPNs, and underscore the importance of incorporating patient‐reported outcomes into routine practice to better reflect the patient's perspective of the disease and treatment‐related burden.