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Infradiaphragmatic Hodgkin's disease is rare, making up 5-12% of cases in clinical stages I and II; consequently, several questions concerning prognosis and treatment strategy remain to be answered. The aim of this study was to analyze the clinical and prognostic characteristics and outcome of this condition.A series of 282 patients with CS I-II Hodgkin's disease (HD) was investigated. In 31 patients the disease was confined below the diaphragm (BDHD), and in the remaining above the diaphragm (ADHD). The presenting features and outcomes were compared in the two groups.The BDHD group was older (p0.0002), had a higher frequency of males (p0.08) and a different histological subtype group distribution (p0.0001). Stage II BDHD patients had a worse overall survival rate (OS) than stage II ADHD patients (68.8% vs 86.6% at 8 years, p0.01) if age is not considered; patients with more than 40 years of age, in fact, had the same survival rates as those with ADHD. BDHD patients with intra-abdominal disease alone had worse prognostic factors and OS (p = 0.12) than patients with inguinal-femoral nodes.Although BDHD patients present distinct features, they have the same OS and relapse-free survival rate as age-adjusted ADHD patients. According to our experience patients with stage I peripheral BDHD respond well to radiotherapy-based regimens. Those with stage II and or intra-abdominal disease are more challenging; chemotherapy or a combined therapy seem to be more suitable approaches for these patients.

Twenty-four patients with immune thrombocytopenic purpura (ITP) were treated with high doses of intravenous immunoglobulin (Ig). Increase in platelets was observed in all the patients. The maximum value was reached between the seventh and the twelfth day of treatment. The mean number of platelets was 18 x 10(9)/l before the treatment and 150 x 10(9)/l after the treatment. The effect was transient; in fact, a fall in the platelets was observed after 18 days of treatment. Our study confirms that high doses Ig is an effective treatment of ITP, but the high cost and the temporary effect limit its use only in those cases in which other treatments are ineffective or contraindicated.

Several papers authored by international experts have proposed recommendations on the management of BCR-ABL1+ chronic myeloid leukemia (CML). Following these recommendations, survival of CML patients has become very close to normal. The next, ambitious, step is to bring as many patients as possible into a condition of treatment-free remission (TFR). The Gruppo Italiano Malattie EMatologiche dell’Adulto (GIMEMA; Italian Group for Hematologic Diseases of the Adult) CML Working Party (WP) has developed a project aimed at selecting the treatment policies that may increase the probability of TFR, taking into account 4 variables: the need for TFR, the tyrosine kinase inhibitors (TKIs), the characteristics of leukemia, and the patient. A Delphi-like method was used to reach a consensus among the representatives of 50 centers of the CML WP. A consensus was reached on the assessment of disease risk (EUTOS Long Term Survival [ELTS] score), on the definition of the most appropriate age boundaries for the choice of first-line treatment, on the choice of the TKI for first-line treatment, and on the definition of the responses that do not require a change of the TKI (BCR-ABL1 ≤10% at 3 months, ≤1% at 6 months, ≤0.1% at 12 months, ≤0.01% at 24 months), and of the responses that require a change of the TKI, when the goal is TFR (BCR-ABL1 >10% at 3 and 6 months, >1% at 12 months, and >0.1% at 24 months). These suggestions may help optimize the treatment strategy for TFR.

Limited information is available on the impact of the COVID-19 pandemic on the management of chronic myeloid leukaemia (CML). The Campus CML network collected retrospective information on 8665 CML patients followed at 46 centres throughout Italy during the pandemic between February 2020 and January 2021. Within this cohort, we recorded 217 SARS-CoV-2-positive patients (2·5%). Most patients (57%) were diagnosed as having SARS-CoV-2 infection during the second peak of the pandemic (September 2020 to January 2021). The majority (35%) was aged between 50 and 65years with a male prevalence (73%). Fifty-six percent of patients presented concomitant comorbidities. The median time from CML diagnosis to SARS-CoV-2 infection was six years (three months to 18years). Twenty-one patients (9·6%) required hospitalization without the need of respiratory assistance, 18 (8·2%) were hospitalized for respiratory assistance, 8 (3·6%) were admitted to an intensive care unit, while 170 (78%) were only quarantined. Twenty-three percent of patients discontinued tyrosine kinase inhibitor (TKI) therapy during the infection. Twelve patients died due to COVID-19 with a mortality rate of 5·5% in the positive cohort and of 0·13% in the whole cohort. We could also document sequelae caused by the SARS-CoV-2 infection and an impact of the pandemic on the overall management of CML patients.

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.

Background: Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest- and first-generation TKIs. Methods: A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3.5 years. Patients were divided in two groups according to the type of treatment. Group A included patients treated with latest-generation TKI (nilotinib, dasatinib, and ponatinib), while group B included patients treated with first-generation TKI (imatinib). Cardiological evaluation included electrocardiogram, echocardiogram with global longitudinal strain of left ventricle (GLS), and carotid ultrasound scan with arterial stiffness measurement (pulse wave velocity, PWV). Adverse cardiovascular events were recorded in both groups. Results: Statistical analysis showed that cardiovascular adverse events (myocardial ischemia, peripheral artery disease, deep vein thrombosis, and pleural effusion) were significantly more frequent in group A than group B (p value = 0.044). Moreover, there was a significant reduction in GLS and PWV in group A when compared to group B (respectively, p = 0.03 and p = 0.004). Conclusions: Our study confirms that imatinib is a relatively safe drug, while it reveals that the latest-generation TKIs may cause a burden of cardiovascular complications. GLS and PWV allow detection of early signs of cardiac and vascular toxicity in oncohematologic patients treated with TKI, and their use is advisable.

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 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.

A reduction in BCR-ABL1/ABL1IS transcript levels to &lt, 10% after 3 months or &lt, 1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (&ge, MR4, 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3- and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values &gt, 10% at 3 months but &lt, 1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS &lt, 10% at 3 months but &gt, 1% at 6 months (event-free survival 68.2% vs. 32.7%, p &lt, 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months &gt, 10% but &lt, 1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS &lt, 1% at 6 months (75% vs. 18.2%, 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values &lt, 1% at 6 months (p &lt, 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points.

Background/Aim: The Philadelphia chromosome is the most frequent cytogenetic abnormality in chronic myelogenous (CML). More than 95% of CML patients are diagnosed with the e13a2 or e14a2 BCR-ABL1 fusion transcripts while, in about 1% of these individuals, the break generates the e1a2 rearrangement. Furthermore, about 5% of CML patients are diagnosed with rare BCR-ABL1 fusion transcripts, such as e19a2, e8a2, e13a3, e14a3, e1a3 and e6a2. However, there is limited evidence concerning the clinical and prognostic implications of these infrequent oncogenic variants for CML patients receiving tyrosine kinase inhibitors (TKIs). Case Report: We describe a novel atypical e12a2 insertion/deletion (Ins/Del) BCR-ABL1 fusion identified in a CML 59-year-old man diagnosed with a common e13a2 BCR-ABL1 isoform. The use of primers recognizing more distant exons from the common BCR-ABL1 breakpoint region correctly identified and monitored in time the atypical e12a2 Ins/Del BCR-ABL1 fusion. Conclusion: Treatment with second- (nilotinib) and third-generation (ponatinib) TKIs was effective in suppressing leukemic clones exhibiting the atypical e12a2 Ins/Del BCR-ABL1.