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Assessment of host-related factors is a crucial aspect in the comprehensive management of cancer patients. A distinct nutritional disturbance linked to cancer has been recognized to be associated with negative outcomes. However, compared to solid tumors, only a limited number of studies have looked specifically at nutritional issues in the field of lymphoma. The aim of this review is to integrate the current knowledge on interactions between malnutrition and lymphoma and address most relevant and pertinent questions. We first provide a literature review on the mutual biological relationship between malnutrition and lymphoma. Next, we explore the overlap between malnutrition, sarcopenia, cachexia and frailty in lymphoma studies. In addition, we summarize the clinical assessment scales used to measure malnutrition in lymphoma subjects. Furthermore, we address the problem of nutritional interventions aimed at patients who are candidates for treatment for lymphoma. Malnutrition can arise as a consequence of lymphoma disease and can in turn promote lymphomagenesis, negatively affect the response to therapy and favor adverse event to treatment. There is increasing evidence that malnutrition, sarcopenia and cachexia in lymphoma are intimately inter-related and are a hallmark of frailty. A variety of different tools are recorded with the apparent ability to describe nutritional status and to impact prognosis in lymphoma patients. Finally, a network of prognostic host- and disease-related factors is proposed where malnutrition can interact with each other in complex ways.

Myeloproliferative neoplasms (MPN) are traditionally regarded as a disease of older adults, though a not negligible fraction of cases occurs at a younger age, including women of childbearing potential. MPN in younger patients, indeed, offer several challenges for the clinical hematologist, that goes from difficulties in reaching a timely and accurate diagnosis to a peculiar thrombotic risk, with a relatively high incidence of thromboses in unusual sites (as the splanchnic veins or the cerebral ones). Moreover, the issue of pregnancy is recently gaining more attention as maternal age is rising and molecular screening are widely implemented, leading to a better recognition of these cases, both before and during pregnancy. In the present work we aim at discussing four clinical topic that we identified as areas of uncertainty or true unmet medical needs in the management of younger patients with MPN, with a particular focus on the topic of pregnancy. For each of these topics, we critically reviewed the available evidence that support treatment decisions, though acknowledging that recommendations in this field are mostly based on expert opinion or derived from guidelines of other clinical conditions that share with MPN a high vascular risk, as antiphospholipid syndrome. Taking into consideration both the lack of evidence-based data and the clinical heterogeneity of MPN, we support an individualized strategy of counseling and management for both young patients and for expectant mother with MPN.

B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune system a critical target for new therapies. In the current therapeutic scenario enriched by chemo-free regimens, it is important to establish the effect of various drugs on the disease, as well as on the restoration of immune functions. In fact, treatment of B-cell lymphoma with passive immunotherapy that targets tumor cells or targets the tumor microenvironment, together with adoptive immunotherapy, is becoming more frequent. The aim of this review is to report relevant data on the evolution of the immune system during and after treatment with targeted therapy of B-cell lymphomas.

The treatment scenario for newly-diagnosed transplant-ineligible multiple myeloma patients (NEMM) is quickly evolving. Currently, combinations of proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD) +/- the monoclonal antibody Daratumumab are used for first-line treatment, even if head-to-head comparisons are lacking. To compare efficacy and safety of these regimens, we performed a network meta-analysis (NMA) of 27 phase 2/3 randomized trials including a total of 12935 patients and 23 different schedules. Four efficacy/outcome and one safety indicators were extracted and integrated to obtain (for each treatment) the surface under the cumulative ranking-curve (SUCRA), a metric used to build a ranking chart. With a mean SUCRA of 83.8 and 80.08 respectively, VMP+Daratumumab (DrVMP) and Rd+Daratumumab (DrRd) reached the top of the chart. However, SUCRA is designed to work for single outcomes. To overcome this limitation, we undertook a dimensionality reduction approach through a principal component analysis, that unbiasedly grouped the 23 regimens into 3 different subgroups. On the bases of our results, we demonstrated that first line treatment for NEMM should be based on DrRd (most active, but continuous treatment), DrVMP (quite "fixed-time" treatment), or, alternatively, VRD and that, surprisingly, melphalan as well as Rd doublets still deserve a role in this setting. This article is protected by copyright. All rights reserved.

Background: Transarterial chemoembolization is the most widely used palliative treat-ment for unresectable hepatocellular carcinoma; however, arterioportal shunt represents a contraindi-cation to this treatment. Objective: The study aims to assess the feasibility of balloon-occluded radiofrequency ablation in the transitory resolution of an extensive arterioportal shunt in patients with advanced hepatocellular carci-noma as a bridge to safe and effective transarterial chemoembolization. Methods: 12 consecutive patients advanced multinodular unilobar unresectable hepatocellular carci-noma with a target lesion larger than 5 cm (mean diameter 7.7 ± 1.4 cm), not suitable to transarterial chemoembolization due to extensive arterioportal shunt, were recruited. Balloon-occluded radiofre-quency ablation of the hepatic area surrounding the shunt during occlusion of the artery supplying the shunt was performed, followed by lobar conventional chemoembolization. Intra/periprocedural complications were evaluated. Technical success was defined by the result of radiofrequency abla-tion in terms of immediate disappearance, reduction, or persistence of the shunt. Local efficacy of chemoembolization was evaluated at 1-month computed tomography according to m-RECIST crite-ria. Results: Technical success was achieved in all patients. No major complications were observed. 1-month follow-up showed a mean necrotic diameter of 6.3 cm (range: 3.8-8.7 cm), with an acceptable procedural result and persistence of the shunt. An overall response rate was obtained in all patients, with 25% complete response and 75% partial response. Conclusion: Balloon-occluded radiofrequency ablation of an arterioportal shunt in patients with ad-vanced hepatocellular carcinoma can temporarily reduce shunting, allowing to perform safe and ther-apeutically useful chemoembolization, with satisfactory control of tumor growth.

Background: Though tyrosine kinase inhibitors managed to reach outstanding responses in the treatment of Chronic Myeloid Leukemia, resistance is still a challenging point, occurring in approximately 10–20% of the cases, due to several mechanisms. STAT5 expression has been strictly linked to resistance and disease progression and may thus represent a significant target to overcome resistance to TKI in CML. The aim of the study is to explore the in vitro antineoplastic role of the STAT5 inhibitor Pimozide in association with 2nd and 3rd generation inhibitors on chronic myeloid leukemia cells. Methods: The cytotoxic effect was evaluated by the Trypan blue dye exclusion test. K562 cell lines were exposed to pimozide alone and in association with ponatinib and dasatinib at different concentrations to explore the drugs association effect and the in vitro cytotoxic concentrations. Conclusions: Pimozide showed a synergic effect when associated with ponatinib and dasatinib in survival inhibition of K562 cell lines. This results are of note and pave the way for a possible in vivo associations.

In the last four decades the name of Gramsci has spread well beyond the boundaries of Italian political theory and Marxist thought where it was originally confined, reaching disciplinary fields as diverse as literary criticism, sociology, communication studies, anthropology, international relations, history, and linguistics, and countries as far from Italy as Korea, India, and South Africa. Why this success and still before how this success has been possible? What social conditions had to be fulfilled to have Gramsci recognized as such a key author in so many intellectual fields and regions of the world? Making use of an exceptional data set, i.e. the Gramscian Bibliography created and managed by the “Gramsci institute” in Rome, which encompasses more than 19 thousands items (books, journal articles, conference proceedings about Gramsci, as well as the whole Gramscian production including translations and different editions), our research aims at tracing the global diffusion of Gramsci’s work in Italy and out of it since the 1940s, identifying patterns, trajectories, timing, agents, and modes of its reception in different national contexts and languages. Focusing on both translations of Gramscian texts and critical writings on and about Gramsci, the chapter will provide quantitative data about the global circulation of a thought whose international success has been certainly favored by Marxist internationalism and the Italian geopolitical location after WWII, but also hampered by the original language and the textual genres (private letters and personal notebooks written while in prison) in which it was embedded, as well as the strong national focus and disarming fragmentation of its content. We suggest that all these seemingly negative conditions exerted indeed a positive effect on the reception process, allowing for highly selective (and idiosyncratic) local appropriations, flexibility in publishing strategies, and the building of context-specific consecration strategies.

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm in which clonal proliferation of hematopoietic stem cells and bone marrow fibrosis coexist.1 Patients may eventually die due to leukemic progression, which occurs in up to 20% of cases, or because of cardiovascular comorbidities or cytopenia, which causes susceptibility to infections and bleeding.2 Myelofibrosis diagnosis relies upon the evaluation of several clinical and laboratory criteria suggested by the World Health Organization (WHO) in 2016.3 The major mutations leading to myelofibrosis usually occur in the JAK2, CALR, and MPL genes. However, in almost 10% of the cases, none of the above-mentioned mutations can be detected (so-called ‘triple-negative patients’). Rarely, a number of several different mutations in genes such as LNK, CBL, TET2, ASXL1, IDH, IKZF1, EZH2, DNMT3A, TP53, SF3B1, SRSF2, and U2AF1 may occur.4,5 In the phase III studies, COMFORT-I and COMFORT-II, ruxolitinib, a JAK 1/2 inhibitor, has been demonstrated to reduce both splenomegaly and symptom burden in patients with international prognostic scoring system (IPSS) intermediate-2 and high-risk myelofibrosis, compared with placebo.6–8 In these trials, therapy discontinuation, for whichever reason (including noncompliance to study procedures), was as high as 55%. Furthermore, in the COMFORT-II trial, ruxolitinib discontinuation was due to adverse events in 24/146 (16.4%) patients in the ruxolitinib arm (R), 5/73 (6.8%) patients in the ‘best-available treatment’ arm, and 6/45 (13.3%) patients in the ruxolitinib after best-available treatment arm. In particular, hematologic toxicity in the ruxolitinib arm was 4.6% (1% anemia and 3.6% thrombocytopenia). Other reasons for therapy discontinuation were consent withdrawn, protocol deviation, noncompliance with either study medication or study procedures, unsatisfactory therapeutic effect, stem cell transplant, meeting protocol-defined imaging discontinuation criteria, investigator decision, important comorbidities/lung cancer), unspecified safety event, and modest spleen response. Recently, ruxolitinib has also been suggested for the treatment of patients who have polycythemia vera, which is resistant to or intolerant of hydroxyurea.9 We report our initial experience with a patient affected by PMF, retreated with ruxolitinib after a 3-month suspension of therapy due to clinical decision.

Background When acute aortic syndromes (AASs) are suspected, pretest clinical probability assessment and d ‐dimer (DD) testing are diagnostic options allowing standardized care. Guidelines suggest use of a 12‐item/3‐category score (aortic dissection detection) and a DD cutoff of 500 ng/mL. However, a simplified assessment tool and a more specific DD cutoff could be advantageous. Methods and Results In a prospective derivation cohort (n=1848), 6 items identified by logistic regression (thoracic aortic aneurysm, severe pain, sudden pain, pulse deficit, neurologic deficit, hypotension), composed a simplified score (AORTAs) assigning 2 points to hypotension and 1 to the other items. AORTAs≤1 and ≥2 defined low and high clinical probability, respectively. Age‐adjusted DD was calculated as years/age × 10 ng/mL (minimum 500). The AORTAs score and AORTAs≤1/age‐adjusted DD rule were validated in 2 patient cohorts: a high‐prevalence retrospective cohort (n=1035; 22% AASs) and a low‐prevalence prospective cohort (n=447; 11% AASs) subjected to 30‐day follow‐up. The AUC of the AORTAs score was 0.729 versus 0.697 of the aortic dissection detection score ( P =0.005). AORTAs score assessment reclassified 16.6% to 25.1% of patients, with significant net reclassification improvement of 10.3% to 32.7% for AASs and −8.6 to −17% for alternative diagnoses. In both cohorts, AORTAs≥2 had superior sensitivity and slightly lower specificity than aortic dissection detection ≥2. In the prospective validation cohort, AORTAs≤1/age‐adjusted DD had a sensitivity of 100%, a specificity of 48.6%, and an efficiency of 43.3%. Conclusions AORTAs is a simplified score with increased sensitivity, improved AAS classification, and minor trade‐off in specificity, amenable to integration with age‐adjusted DD for diagnostic rule‐out.

Background There is now great interest in using digital health tools to monitor patients' health status in real-world practice. Such tools often include electronic-patient-reported outcome (ePRO) systems in which symptoms questions are included into online interfaces for patient self-reporting, with real-time alerts triggered to the treating physician if severe symptoms or problems are reported. However, there is little information about the clinical utility and user perceptions of these systems, and this is particularly true in the area of hematology. Objectives This study investigates physicians' perceptions of usability and clinical utility of using remote ePROs in routine practice of patients with hematologic malignancies and explored implications in the delivery of patient care. Patients and Methods Remote ePROs are being gathered since December 2020 by the ALLIANCE Digital Health Platform, whose details of the development process have been previously described (Efficace F. et al., JMIR Res Protoc. 2021 Jun 1;10:e25271). Adult patients diagnosed with any hematologic malignancy are eligible to enter the platform, after having provided written informed consent. Aspects related to health-related quality of life (HRQoL), symptoms and medication adherence are assessed via validated PRO measures. The platform allows for real-time graphical presentation to physicians of individual patient symptoms and HRQoL outcomes. Based on a pre-defined algorithm, which includes the presence of clinically important problems and symptoms, the platform triggers automated alerts to the treating haematologists and medical staff. The definition of clinically important problems and symptoms is based on previously defined evidence-based thresholds (Giesinger J. et al., J Clin Epidemiol. 2020 Feb;118:1-8). We asked treating haematologists a feedback about their experience in using the platform, by an ad hoc web-survey consisting of 27 items covering several domains, including: usability and benefits, current use, evaluation of patient health-status, symptoms and adverse events, as well as physician-patient communication. We summarized characteristics of enrolled patients and treating haematologists by proportions, mean, median and range. We also used logistic regression analysis to check the possible association of characteristics of haematologists with survey results. Results Of the 201 patients invited to participate between December 2020 and June 2021 (cut-off date for current analysis), 180 (90%) accepted to enter the ALLIANCE platform, currently activated in 19 centers. The median age of patients was 57 years (range 21-91) and 58% were males. The majority were diagnosed with chronic myeloid leukemia (n=32, 18%) and multiple myeloma (n=31, 17%) and were in stable disease (n=89, 49%). Twenty-three hematologists (44% males) with a median age of 42 years (range 31-63) and an average 17 years (range 5-34) of experience in clinical practice, completed the survey. The majority of physicians (78%) accessed the platform at least once per month (of whom 39% at least once per week), regardless the alerts sent by the system about patients' clinically relevant problems. The frequency of access on a regular basis was also independent of physician sex (p=0.393) and years of experience in clinical practice (p=0.404). Overall, 57% of hematologists discussed often or very often ePROs with their patients, while 83% and 61% deemed this information helpful to better identify symptomatic adverse events (AEs) of grade 1-2 or of grade 3-4, respectively (see figure). Also, 87% and 91% of hematologists found ePROs useful to improve physician-patient communication and the accuracy of documentation of symptomatic AEs (regardless of severity), respectively. Physicians' responses to selected items of the survey are reported in the figure. Conclusions: Current findings support the clinical utility, from the perspective of the treating physician, of integrating ePROs into routine cancer care of patients with hematologic malignancies. Figure 1 Figure 1. Disclosures Efficace: Takeda: Consultancy; Janssen: Consultancy; Abbvie: Consultancy, Other: Grants (to Institution); Amgen: Consultancy, Other: Grants (to Institution). Breccia: Bristol Myers Squibb/Celgene: Honoraria; Pfizer: Honoraria; Abbvie: Honoraria; Incyte: Honoraria; Novartis: Honoraria. Fazio: Janseen: Honoraria. Petrucci: Karyopharm: Honoraria, Other: Advisory Board; GSK: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board. Rigacci: Merck: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tafuri: Roche: Research Funding; Celgene: Research Funding; Novartis: Research Funding. Siragusa: Novartis, CSL, Behring, Amgen, Novonoridsk, SOBI, Bayer: Consultancy, Honoraria, Speakers Bureau. Patriarca: Incyte: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Argenix: Honoraria. Luppi: Abbvie: Honoraria; Novartis: Honoraria; Sanofi: Honoraria; MSD: Honoraria; Gilead Science: Honoraria, Other: Travel grant; Daiichi-Sankyo: Honoraria; Jazz Pharma: Honoraria. Vignetti: Novartis: Honoraria; Incyte: Honoraria; Amgen: Consultancy, Honoraria.

Ruxolitinib side effects include the most frequent hematological toxicity along with a more recently evidenced immunosuppressive activity, interfering both with the innate and adaptive immunity, and several cases of reactivation of latent infections by opportunistic agents in patients in treatment with ruxolitinib have been published in the last years. Several pathophysiological mechanisms may explain an association between ruxolitinib and opportunistic infections. From what we know, the only case of an isolated lymph node TBC reactivation in a ruxolitinib-treated myelofibrosis (MF) patient was reported by Patil et al. in 2016 [Int J Med Sci Public Health. 2017;6(3):1]. Other 10 cases describing TBC reactivations in MF patients assuming ruxolitinib and successfully treated with 4-drug anti-TBC therapy are available in the literature to date. The case we reported describes an isolated lymph nodal TBC reactivation in a patient with the diagnosis of post-essential thrombocythemia-MF during ruxolitinib treatment after a long course of interferon-a (IFN-α2b) assumed for the previous diagnosis of ET. The case we report teaches that lymphadenopathy with or without constitutional symptoms developing during ruxolitinib therapy should be considered as a possible manifestation of a TBC reactivation in patients with a previous positive TBC-exposure test. In these cases, Ziel-Nielsen testing on urine and sputum has to be performed to rule out infectiousness and eventually isolate the patient. Moreover, previous long-time exposition to IFN-α2b may be related with a higher risk for TBC reactivation in these subset of patients. We encourage reevaluation of the cohorts of patients treated with ruxolitinib in previous and current large prospective studies to study the possible correlation between previous exposition to IFN-α2b and TBC reactivation.

The development of viable tissue surrogates requires a vascular network that sustains cell metabolism and tissue development. The coculture of endothelial cells (ECs) and mesenchymal stem cells (MSCs), the two key players involved in blood vessel formation, has been heralded in tissue engineering (TE) as one of the most promising approaches for scaffold vascularization. However, MSCs may exert both proangiogenic and antiangiogenic role. Furthermore, it is unclear which cell type is responsible for the upregulation of angiogenic pathways observed in EC:MSC cocultures. There is disagreement on the proangiogenic action of MSCs, as they have also been shown to negatively affect the formation of capillary networks. To address these issues, we investigated the regulation of key angiogenic pathways in scaffolds hosting different EC:MSC ratios fabricated through extrusion-based bioprinting. Human ECs were cocultured with either rat or human MSCs, and the regulation of fundamental angiogenic and arteriogenic pathways was analyzed through DNA, gene, and protein expression. The use of a hybrid human/rat coculture system facilitated pinpointing each cell type role in the regulation of specific genes and showed that MSCs exert a dose-dependent inhibitory effect on the EC expression of angiogenic factors within the first 24 h. Within a week of coculture, MSCs exert a proangiogenic effect, as corroborated in human/human bioprinted cocultures. Interestingly, juxtacrine signaling promoted secretion of the angiogenic factor vascular endothelial growth factor in direct cocultures (EC and MSC co-encapsulated), while paracrine signaling encouraged secretion of the arteriogenic factor platelet-derived growth factor in indirect cocultures (adjacent bioprinting of EC-laden and MSC-laden scaffolds). Overall, the use of a bioprinted system to elucidate EC:MSC interplay allows rapid leveraging of the data for novel vascular TE applications. Despite the transitory negative effect early in the culture, MSC presence is necessary for the regulation of pathways involved in arteriogenesis. With further validation

Thromboembolic and bleeding events pose a severe risk for patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Many factors can contribute to promoting the thrombotic event due to the interaction between platelets, leukocytes, and endothelium alterations. Moreover, a significant role can be played by cardiovascular risk factors (CV.R) such as cigarette smoking habits, hypertension, diabetes, obesity and dyslipidemia. In this study, we evaluated the impact that CV.R plays on thrombotic risk and survival in patients with PV and ET .

Essential thrombocythemia is a rare hematological malignancy with good overall survival, but moderate to high risk of developing arterial or venous thrombosis lifelong. Different thrombotic risk scores for patients with essential thrombocythemia have been proposed, but only one of them (the IPSET-t scoring system) takes into account the classical cardiovascular risk factors as one of the scoring items. Currently, in clinical practice, the presence of cardiovascular risk factors in patients with diagnosis of ET rarely determines the decision to initiate cytoreductive therapies. In our study, we compared different risk models to estimate the thrombotic risk of 233 ET patients and the role of specific driver mutations and evaluated the impact that conventional cardiovascular risk factors (hypertension, cigarette smoking, diabetes, obesity, and dyslipidaemia) have on thrombotic risk in patients with ET. Perspective studies conducted on a polycentric large cohort of patients should be conducted to estimate the impact of cardiovascular risk factors in determining thrombosis in ET patients, evaluating the opportunity of initiating a cytoreductive therapy in patients with cardiovascular risk factors, even if classified into low to moderate risk groups according to other scoring systems.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of Von Willebrand factor (VWF). Bleeding from the gastrointestinal (GI) tract is not uncommon in VWD and is usually associated with angiodysplasia. We report herein on the management of a patient affected by VWD2B with severe GI bleeding secondary to gastrointestinal stromal tumor (GIST) complicated by deep vein thrombosis (DVT). The current case demonstrated that the hemostatic balance, in RBDs under specific circumstances, can range from a tendency toward a hemorrhagic to normal or prothrombotic state. In these patients, a close collaboration between hematologists and surgeons can guarantee appropriate management in high-risk clinical scenarios.

We simulated the extinction spectra of Ag–Au alloyed nanoparticles produced by pulsed laser ablation in liquid of elemental targets followed by re-irradiation of suitable mixtures of the obtained c...

The Essential Thrombocythemia is a Chronic Philadelphia-negative Myeloproliferative Neoplasm characterized by a survival curve that is only slightly worse than that of age- and sex-adjusted healthy population. The criteria for diagnosis were reviewed in 2016 by WHO. The incidence varies from 0.2 to 2.5:100 000 people per year, with a prevalence of 38 to 57 cases per 100 000 people. The main characteristics of ET are the marked thrombocytosis and the high frequency of thrombosis. The spectrum of symptoms is quite wide, but fatigue results to be the most frequent. Thrombosis is frequently observed, often occurring before or at the time of diagnosis. The classification of thrombotic risk has undergone several revisions. Recently, the revised-IPSET-t has distinguished 4 risk classes, from very low risk to high risk. Driver mutations seem to influence thrombotic risk and prognosis, while the role of sub-driver mutations still remains uncertain. Antiplatelet therapy is recommended in all patients aged ⩾ 60 years and in those with a positive history of thrombosis or with cardiovascular risk factors, while cytoreductive therapy with hydroxyurea or interferon is reserved for high-risk patients.

Splenomegaly is one of the major clinical manifestations of primary myelofibrosis and is common also in other chronic Philadelphia-negative myeloproliferative neoplasms, causing symptoms and signs and affecting quality of life of patients diagnosed with these diseases. We aimed to study the impact that such alteration has on thrombotic risk and on the survival of patients with essential thrombocythemia and patients with Polycythemia Vera (PV). We studied the relationship between splenomegaly (and its grade), thrombosis and survival in 238 patients with et and 165 patients with PV followed at our center between January 1997 and May 2019.

Cardiovascular (CV) adverse events are considered common complications of ponatinib treatment. Recently, it has been demonstrated that ponatinib dose reductions in definite settings can obtain optimal responses and lower ponatinib-related CV events. In this study, we describe the management of 5 patients with chronic myeloid leukemia treated with ponatinib, from second to fourth line of tyrosine kinase inhibitor therapy, carrying high pre-ponatinib CV risk, who obtained optimal molecular response and developed no CV adverse event during follow-up. Among these 5 patients, 2 had diagnosis of ischemic heart disease and underwent percutaneous angioplasty, 2 had type 2 diabetes and arterial hypertension, and 1 had only arterial hypertension. Median follow-up for ponatinib therapy is 1,039 days (34.6 months). Median dosage administered is 30 mg a day. SCORE charts were used to estimate risk of CV death in 10 years and Charlson Comorbidity Index was applied to estimate age-adjusted risk of death related to comorbidities. Strict cardiologic follow-up (complete evaluation every 3 to 6 months) and maximum effort in the control of CV modifiable risk factors are strongly recommended in the management of ponatinib treatment in patients at high risk for CV events and may allow the use of ponatinib in patients belonging to CV risk category.