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The treatment of chronic lymphocytic leukemia (CLL) currently relies on the use of chemo-immunotherapy, Bruton’s tyrosine kinase inhibitors, or BCL2 inhibitors alone or combined with an anti-CD20 monoclonal antibody. However, the availability of multiple choices for the first-line setting and a lack of direct head-to-head comparisons pose a challenge for treatment selection. To overcome these limitations, we performed a systematic review and a network meta-analysis on published randomized clinical trials performed in the first-line treatment setting of CLL. For each study, we retrieved data on progression-free survival (according to del17/P53 and IGHV status), overall response rate, complete response, and incidence of most frequent grade 3–4 adverse event. We identified nine clinical trials encompassing 11 different treatments, with a total of 5288 CLL patients evaluated. We systematically performed separated network meta-analyses (NMA) to evaluate the efficacy/safety of each regimen in the conditions previously described to obtain the surface under the cumulative ranking curve (SUCRA) score, which was subsequently used to build separated ranking charts. Interestingly, the combination of obinutuzumab with acalabrutinib reached the top of the chart in each sub-analysis performed, with the exception of the del17/P53mut setting, where it was almost on par with the aCD20 mAbs/ibrutinib combination (SUCRA aCD20-ibrutinib and O-acala: 93.5% and 91%, respectively) and of the safety evaluation, where monotherapies (acalabrutinib in particular) gave better results. Finally, considering that NMA and SUCRA work for single endpoints only, we performed a principal component analysis to recapitulate in a cartesian plane the SUCRA profiles of each schedule according to the results obtained in each sub-analysis, confirming again the superiority of aCD20/BTKi or BCL2i combinations in a first-line setting. Overall, here we demonstrated that: (1) a chemotherapy-free regimen, such as the combination of aCD20 with a BTKi or BCL2i, should be the preferred treatment choice despite biological/molecular characteristics (preferred regimen O-acala); (2) there is less and less room for chemotherapy in the first line treatment of CLL.

Background: Multiple myeloma is a complex pathology which represents about 10 % of all hematological neo-plasms. It can often present changes in the hemorheological profile and, in relation to this last topic, our aim is to evaluate the hemorheological profile in a group of multiple myeloma patients, with reference to erythrocyte deformability. Methods: We have examined the profile of the erythrocyte deformability in multiple myeloma enrolling 29 pa-tients; this profile, expressed as elongation index at several shear stress, has been obtained using the diffracto-metric method. Results: By comparing normal controls and MM patients, a significant decrease in erythrocyte deformability, especially at low shear stresses, but we did not observe any significant differences about this profile subdividing the whole group of MM patients according to the degree of bone marrow plasma cell infiltration, to the red blood cell distribution width and to the serum values of LDH. Conclusions: In this paper we have taken in consideration all the hypothesis for a possible explanation of the behaviour of this a reduced erythrocyte deformability in multiple myeloma. Erythrocyte deformability interferes with the physiological release of oxygen to tissues, with several clinical implications.

Background: Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal expansion of plasma cells that can release monoclonal immunoglobulins (monoclonal component) or part of theme. Since 2001, the k and λ serum free light chains (sFLC) evaluation and their ratio (rFLC) have made up the laboratory analysis more sensitive and precise in MM patients. The role of rFLC has been widely studied and discussed and now it is validated in the literature. Instead, the value of free light chains difference (dFLC), especially in MM is less known yet. The aim of this study is to evaluate the relationship between the dFLC and the kidney damage parameters in patients with MM, in comparison with the rFLC value. Methods: We conducted a retrospective population-based study on 58 MM patients and we individuated two groups obtained considering the measures of dFLC and rFLC in relation to abnormal and normal values of some renal function markers, such us Bence-Jones proteinuria (BJ), albuminuria, proteinuria and serum creatinine. The Mann-Whitney test was used to test the difference between two independent samples. Results: We observed a significant greater mean score of dFLC in patients with abnormal levels of BJ (2322.91>297.47, p=0.0001), albuminuria (2650.61>671.37, p=0.0016) and proteinuria (2327.19>593.14, p= 0.0025), while there was no significant difference for serum creatinine (1636.18

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.

Purpose Insufficient knowledge of primary immune thrombocytopenia purpura (ITP) in the elderly, together with a lack of clinical trial data, has resulted in wide variation in treatments. Here, we present a study focused on clinical characteristics of ITP in older subjects at diagnosis integrated with the subsequent course of the disease and treatment history. Methods In a retrospective monoinstitutional study, we evaluated >65-year-old patients with primary ITP. Clinical characteristics at the time of diagnosis were described and analyzed. We aimed to delineate whether subsequent lines of therapy influenced the number of relapses. In addition to initial regimens, we reported subsequent treatments and the impact on relapse trends. Results A total of 50 patients (56% males, mean age 78 years) were included. With regard to clinical variables at diagnosis, statistical significance was found for Eastern Cooperative Oncology Group performance status 1 (46% of patients, p

Background/Aims: Cardiovascular risk factors are not considered in the current scores for evaluation of the thrombotic risk in myeloproliferative neoplasms, and in polycythemia vera (PV) in particular. Cytoreduction is currently not indicated in low-risk patients with PV, despite the absence or presence of cardiovascular risk factors. Our purpose is to highlight how cardiovascular risk factors in patients with PV increase the thrombotic risk both in low- and high-risk patients. Methods: We collected and analyzed data from 165 consecutive patients with a diagnosis of PV followed at our institution and compared the frequency of thrombosis in subgroups of patients distinguished by the presence or absence of cardiovascular risk factors. The statistic tools used to obtain the results were the χ2 and the Kruskal-Wallis test for frequencies, and the Kaplan-Meyer method as well as the log-rank test for analysis of survival data. Results: The major result obtained is that the frequency of thrombotic events in our population is strictly linked with the cardiovascular risk, and it increases with the number of risk factors. Moreover, survival significantly worsens with the number of cardiovascular risk factors, despite the classical PV risk stratification. Conclusion: It should be useful to design perspective studies to determine the real influence of cardiovascular risk factors on the thrombotic risk for patients with PV and on survival in order to evaluate the opportunity to develop new specific therapeutic recommendations.

The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in the 8% of multiple myeloma patients, and it may be caused by artero-venous shunts, enhanced angiogenesis, glutamminolysis, hyperammonemia and hemorheological alterations with increase in plasma viscosity. The high output heart failure in multiple myeloma is associated with significant morbidity and mortality, emphasizing the need for a multidisciplinary approach.

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.

Essential thrombocythemia is chronic myeloproliferative neoplasia, as defined by WHO in 2016, with the best prognosis. A small percentage of ET cases can be considered Familial ET. In this report we describe 6 cases of Familial ET, evaluating the heterogeneity of the mutational state and the clinical presentation.

BACKGROUND: in this study, with a re-evaluation of the hemorheological determinants previously described in MGUS subjects and in MM patients, we have detected the calculated whole blood viscosity, according whether to the hematocrit and total plasma protein concentration (de Simone formula) or to the haematocrit and plasma fibrinogen level (Merrill formula), and a marker of the erythrocyte aggregation (albumin/fibrinogen level). METHODS: data were expressed as means±standard deviation. Student’s t test for unpaired data was used to compare MGUS subjects and MM patients. The correlation coefficient between mean erythrocyte aggregation (MEA) and hematocrit (Ht) was evaluated in MGUS, MM and MGUS + MM groups using the Spearman test. RESULTS: the comparison between MGUS and MM shows that the measured blood viscosity and calculated blood viscosity based on hematocrit and total plasma protein, but not which estimated in relation to the hematocrit and plasma fibrinogen, differentiate the two groups. A difference between the two groups also regards the measured erythrocyte aggregation and its surrogate marker. In addition, the measured plasma viscosity at low shear rate (0.51 s–1) and, in particular, the ratio between plasma viscosity at low (0.51 s–1) and high (450 s–1) shear rates distinguish MGUS and MM. CONCLUSIONS: calculated blood viscosity (de Simone formula and other formulas) and the surrogate marker of erythrocyte aggregation disclose an alike trend with the corresponding hemorheological determinants obtained by using their direct measurement.

Background: Despite recent improvements in survival due to advances in treatment, the quality of life of patients with lymphoma may be compromised by the long-term complications of chemotherapy and steroid therapy. Among these, a potentially relevant problem is bone loss and the development of fragility fractures.Aim: To provide further evidence of clinical or subclinical skeletal complications in correlation with biological variables and markers of bone disease in patients with complete response to therapy.Method: A cross-sectional observational study was conducted on subjects diagnosed with lymphoma with subsequent antineoplastic treatment, disease status after therapy defined as complete response disease for at least a year now. We performed: blood chemistry tests, imaging techniques (DEXA) and screening tools for the assessment of functional status and quality of life (SARC-F and mini-OQLQ).Results: Approximately 50% of the patients had osteoporosis. We found hypovitaminosis D and high PTH levels in most of the patients. We also found a high prevalence of vertebral fractures in 65.5% of cases. In the majority of patients, we found hypovitaminosis D and high levels of PTH. Furthermore, a statistically significant association between high PTH levels and previous lymphoma treatment. Finally, the Mini Osteoporosis Quality of Life questionnaire demonstrated a loss of quality of life as a consequence of the change in bone status.Conclusions: Patient treatment design for personalized chemotherapy would be desirable to reduce late effects on bone. Also, early prevention programs need to be applied before starting treatment. The most benefited subpopulations could be not only elderly but also young patients.

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.

Thrombosis and neoplasms are strictly linked, and the diagnosis of a malignancy is a relevant risk factor for venous thromboembolism (VTE). In particular, between gammopathies, the VTE risk is known to be increased in both monoclonal gammopathy of uncertain significance and in multiple myeloma, with a 3- and 9-fold increase respectively, when compared to the general population. The risk appears to be further increased in patients treated with immunomodulating drugs, such as thalidomide, especially when in combination with dexamethasone or conventional cytotoxic chemotherapies, and lenalidomide. In 2008 the International Myeloma Working Group put out thrombosis prophylaxis recommendations for myeloma patients treated with IMiDs. Current recommendations for thromboprophylaxis suggest the use of low-dose acetylsalicylic acid in patients with low risk for thrombosis and therapeutic dose anticoagulation with LMWH or warfarin for high-risk patients. However, these recommendations have been frequently not followed in the clinical practice, due to various reasons that involve the patients' will, the level of evidence of the recommendations and some selection biases in the studies that were taken as basis for writing down the indications. The new direct oral anticoagulants have been preliminarily evaluated for the prophylaxis of thrombotic events in IMiDs-treated myelomas, being promising, even if more expensive. Currently, the most reliable tool for a correct thrombotic risk stratification appears to be the complete clinical and anamnestic evaluation of the myeloma patients added to a strong physician awareness of the evidences that the literature contains until now.

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.

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.

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.

The complement system is an essential component of the innate immune defence that, if overly activated, may damage organs and tissues. For this reason, there is a fine complement regulatory system. The complement modulation system includes two proteins with important regulatory activity, CD55 or decay accelerating factor (DAF) and CD59 or membrane inhibitor of reactive lysis (MIRL). The paroxysmal nocturnal hemoglobinuria (PNH) is a clonal and non-neoplastic disease characterized by intravascular haemolysis, occurrence of thrombosis and bone marrow failure. In clinical practice, in opposition to PNH, a variety of pathological conditions have been observed with an acquired and non-genetic deficiency of the regulatory proteins CD55 and CD59. This abnormal, non-clonal, reduced expression of complement regulatory proteins configures what we may define as PNH-like phenotype. Similarly to PNH, even in the PNH-like phenotype diseases there has been a greater exposure to the mediated complement cellular lysis and, a likely increased risk of thromboembolic events. Therefore, the knowledge of the potential roles of the complement system becomes necessary for a deeper understanding of several pathological conditions and for an improved clinical management of the patients.

Cryopreservation for the long-term storage of platelets (PLTs) is a useful method to overcome the limits of platelet shortage. This is an in vitro prospective study to evaluate the count, viability, and function of buffy coat-derived pooled platelet concentrates (BC-PLTs), treated with dimethyl sulphoxide (DMSO) and cryopreserved (CRY BC-PLTs) at −80 °C with a modified Valeri method. PLTs were stored in 6% DMSO with a patented kit. Overall, 49 BC-PLTs from 245 healthy volunteer donors were prepared, cryopreserved, and analysed before and after 3, 6, and 9 months of storage. In flow cytometry, a statistically significant reduction in CD 42b (92.7 ± 4.29% at T0 vs. 23.6 ± 27.5% at T3, 16.38 ± 12.54% at T6, and 17.3 ± 9.6% at T9) and PAC-1 (1.9 ± 1.34% at T0 vs. 0.62 ± 0.4% at T3, 0.63 ± 0.83% at T6, and 0.49 ± 0.48% at T9) was observed after storage. CRY BC-PLTs showed a good and stable endogenous thrombin generation potential (nM min): 529.25 ± 98.64 at T0 vs. 533.04 ± 103.15 at T9 months. CRY BC-PLTs showed a good viability in vitro, according to currently accepted criteria for cryopreserved PLTs.

The conventional thrombotic risk stratification in essential thrombocythemia (ET) distinguishes patients in two risk groups based on previous thrombosis and age (< or >60). The IPSET-thrombosis takes into account four risk factors: age greater than 60 years and the presence of CV risk factors, thrombosis history and JAK2 V617F presence. The revised IPSET-thrombosis uses three adverse variables to delineate four risk categories: age greater than 60, thrombosis history, and JAK2 V617F presence. We compared different risk models in the estimation of thrombotic risk in 191 patients with ET and the role of specific driver mutations affecting overall survival, according to thrombotic risk. We also evaluated the mutational status of patients showing history of thrombosis or cardiovascular events versus patients who did not. Finally, we verified whether the thrombotic risk had a significant impact on survival in our ET patients. The data analysis has been performed through the conventional statistics and overall survival estimated by using the Kaplan-Meyer method. Interestingly, either using the traditional system for thrombotic risk or the IPSET-t prognostic score or the current stratification for the thrombotic risk, high-risk patients are always highly represented. This evidence is of note, being the high-risk category indicated for cytoreduction, affecting quality of life, despite the good overall prognosis of patients with ET diagnosis in general. The analysis of overall survival in our patients, according to different models for thrombotic risk, highlighted the poor prognosis of high-risk patients compared with those with a lower thrombotic risk, in particular when using traditional stratification and current stratification. In conclusion, the occurrence of thrombotic or cardiovascular events represents one of the most severe complications at diagnosis or during follow-up of ET despite current recommendations, having a significant impact on morbidity and survival.

Introduction: Ultrasound (US) assessment of joints is an evolving point of care tool for the detection of early joint arthropathy (Napolitano M, Kessler CM. Hemophilia A and B. Consultative Hemostasis and Thrombosis, Kitchens, 4th edition); population pharmacokinetic (pop-PK) studies are adopted as a useful instrument to set the prophylaxis regimen for patients with hemophilia, they may improve adherence (Nagao A.et al. Thromb Res. 2019 Jan; 173:79-84) and reduce the annual bleeding rate (ABR). Adherence to continuous intravenous administrations of factor VIII or Factor IX products is challenging, thus patients may experience breakthrough bleedings while on prophylaxis. Repeated US examinations of joint status have recently been advocated to attempt to remedy sub-optimal medication adherence (Di Minno A et al., Blood Rev. 2019 Jan;33:106-116). Aim of the current prospective analysis was to evaluate the impact of combined US assessment and pop-PK study on adherence to treatment and health related quality of life in patients with severe hemophilia A(HA) and B (HB) under regular prophylaxis. Material and methods: This prospective observational study was performed at a single tertiary center from January 2017 to June 2019. Research was conducted following the Helsinki Declaration. All patients included in the study provided a written informed consent for study participation. Patients with severe HA and HB routinely underwent, as part of regular 12-months follow-up visits, the following: US joints evaluation of elbows, knees and ankles using the HEAD-US protocol, treatment adherence evaluation by VERITAS-Pro questionnaire, health -related quality of life assessment by the standardized EQ-5D,EQ-VAS and pop-PK study (WAPPS-Hemo, McMaster University) as needed (i.e.in case of changes in life style, planned treatment switch); each patient visualised US and his estimated PK profile during medial encounters. Compliance to the prescribed treatment was also determined by analysis of patient diaries with infusion logs. Statistical analysis was performed using the SPSS software version 25.0 (SPSS Chicago, IL). Statistical tests were 2-sided, with a significance threshold of 0.05. Results: Twenty consecutive males with severe haemophilia were included in the current analysis, 13 with severe HA, 2 with HA with previous inhibitors and 5 HB, with a median age of 30 (range 14- 56) years and a median ABR of 5 (range:0-12). Nine patients were under primary prophylaxis, 8 under secondary prophylaxis and 3 under tertiary prophylaxis, they all self-infused at home. Four patients had one target joint and 3 patients had multiple target joints. For each enrolled subject, HEAD-US score, VERITAS-pro, EQ5D and EQ-VAS score were assessed at enrolment (T0) and at 12 (T12) and 24 (T24) months follow-up visits, respectively. Pop-PK was assessed in 11 patients: in 7 (5 HA,2 HB) it was assessed twice, before and after treatment switch to extended half-life (EHL) products, in 4 it was assessed once to modify prophylaxis treatment schedules for a more active life-style (N=2) or weight changes (N=2). Median ABR was 4 at T12 and 3.8 at T24. Reported breakthrough bleeds at T12 were 14, mainly trauma-related (N= 8) or affecting target joints (N=4), they were not reported at T24 in patients with PK-driven modified schedules (N=4) and in 4 patients under EHL treatments. Mean HEAD-US score at T0 resulted 8 (range:0-16), at T24 it was 6 (range:0-16). Mean Veritas-Pro score values were 42.7 at TO, 40.1 at T12 and 38.7 at T24. At T0, EQ-5D mean utility score was 0.82 (range: 0.68-1), at T24, the mean was 0.87 (range:0.72-1). In detail, at 24 months follow-up, there was a statistically significant (p Conclusion: Several combined measures of haemophilia treatment monitoring, allowing visual assessment of joints status and PK profile estimates by patients have here shown to improve treatment adherence and quality of life in patients with HA and HB, this may be not only related to new available treatments but also to an increased awareness and education of patients. Disclosures Napolitano: BIOFVIIIx: Consultancy; Novonordisk: Consultancy, Speakers Bureau; Shire: Other: Expert Testimony, Speakers Bureau; Kedrion: Other: Expert Testimony, Speakers Bureau; Octapharma: Speakers Bureau; Bayer: Consultancy, Other: Expert Testimony. Di Minno:Novo Nordisk: Speakers Bureau; CSL: Speakers Bureau; Sanofi: Speakers Bureau; Bayer: Consultancy, Honoraria, Speakers Bureau; Kedrion: Speakers Bureau; Pfizer: Speakers Bureau.

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.