Eleonora Arboscello

Adenosine in the treatment of supraventricular tachycardia: 5 years of experience (2002-2006).

We report a retrospective analysis of 5 years of adenosine use in our emergency department (2002-2006). We treated 454 patients with an intravenous bolus of adenosine. The cohort was made up of 40.7% men and 59.3% women, with mean age of 47.32 years, mean heart rate of 162.48 beats per minute. Among them, 73% responded immediately to the 6-mg dose, 15% responded after the second 12-mg dose, and 11% responded to a further 12-mg dose, whereas 11% were unresponsive. We observed minor side effects in a high percentage of patients (ie, chest tightness 83%, flushing 39.4%, sense of impending death 7%). Only 1 major adverse effect was recorded, that is, administering 12 mg of adenosine induced a marked acceleration in the ventricular rate of a patient with an undiagnosed atrial flutter, caused by induction of atrioventricular conduction (1:1). Our results confirm that when patients are appropriately selected, adenosine is probably the best available drug to treat paroxysmal supraventricular tachycardias, especially in emergency situations.

Dexamethazone-induced acute tumor lysis syndrome in a T-cell malignant lymphoma.

We report a case of steroid-induced acute tumor lysis syndrome and review the literature. A 60-year-old woman was started on steroid therapy for dyspnea due to bilateral pleural effusion and a large mass involving the anterior mediastinum. The final diagnosis was precursor T-lymphoblastic lymphoma-leukemia. Following steroid therapy, the patient developed acute renal failure and laboratory evidence of metabolic changes induced by massive cytolysis. She received vigorous hydration, diuretic and allopurinol therapy, and haemodialysis. Her diuresis, renal function and laboratory data returned to normal within 2 weeks. A review of the medical literature on T-cell lymphoma revealed only one similar case of steroid-induced acute tumor lysis syndrome, a life-threatening metabolic emergency. This risk should be kept into account in the management of patients with lymphoproliferative disorders.

Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion.

Ponatinib (Iclusig, ARIAD Pharmaceuticals-Incyte Co.) is a third-generation structure-guided tyrosine kinase inhibitor that is approved for treatment of Philadelphia chromosome-positive leukaemias resistant or intolerant to other inhibitors. The clinical use of ponatinib is complicated by the possible development of cardiovascular events, primarily hypertension and arterial or venous thrombotic events. The US Food and Drug Administration and the European Medicine Agency recommend that the cardiovascular profile of patients candidate for ponatinib should be carefully evaluated. For patients deemed to carry a high risk of cardiovascular events, other life-saving therapeutic options should be considered. When alternative options are not available, treatment with ponatinib is indicated but requires that haematologists and cardiologists collaborate and identify modalities of surveillance and risk mitigation in the best interest of the patient. This article reports on the expert opinion provided by a panel of Italian haematologists, cardiologists and clinical pharmacologists. It summarises suggestions that may help to improve the therapeutic index of ponatinib, primarily in the settings of chronic-phase chronic myeloid leukaemia.

Cardiovascular adverse events complicating the administration of rituximab: report of two cases.

Rituximab is a murine/human chimeric monoclonal antibody directed against the CD20 antigen. It is widely used in combination with polychemotherapy regimens for the treatment of hematological disorders. There is no evidence of direct cardiotoxicity of the drug but a few cases of cardiovascular adverse events have been reported in the literature. We report on two patients affected by stage IV non-Hodgkin lymphoma with bone marrow infiltration and peripheral blood involvement who experienced cardiovascular accidents temporally related to rituximab infusion. In both cases the monoclonal antibody was administered in association with a polychemotherapy regimen but administration was postponed several days later in order to avoid severe cytokine release syndrome because of the high tumor burden. The first case concerns an episode of atrial fibrillation in a patient with a diagnosis of small B-cell lymphoma. The episode happened immediately after rituximab infusion. In the second case there was an episode of chest pain associated with fever and chills during rituximab infusion in a patient with a diagnosis of mantle cell lymphoma. In both cases we noticed an unusual correlation between symptom recurrence and the speed of rituximab infusion. Both patients presented several cardiovascular risk factors but preliminary cardiac function assessment excluded signs of heart dysfunction. The pathogenesis of cardiovascular events during rituximab infusion remains unclear. A key role might be played by cytokine release from B cells as a consequence of rituximab activity. Moreover, pre-existing silent cardiac damage could be co-responsible for the clinical manifestations we reported. We consider our clinical experience relevant because it raises an issue of good clinical practice: despite rituximabs good tolerability profile, patients with cardiovascular risk factors should undergo accurate cardiac assessment so that silent heart disease can be detected. If the suspicion of cardiac damage is high, more extensive cardiac assessment is recommended.

Doxorubicin effect on myocardial metabolism as a prerequisite for subsequent development of cardiac toxicity: A translational18F-FDG PET/CT observation

The present translational study aimed to verify whether serial 18F-FDG PET/CT predicts doxorubicin cardiotoxicity. Methods: Fifteen athymic mice were treated intravenously with saline (n = 5) or with 5 or 7.5 mg of doxorubicin per kilogram (n = 5 each) and underwent dynamic small-animal PET beforehand and afterward to estimate left ventricular (LV) metabolic rate of glucose (MRGlu). Thereafter, we retrospectively identified 69 patients who had been successfully treated with a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine for Hodgkin disease (HD) and had undergone 4 consecutive 18F-FDG PET/CT scans. Volumes of interest were drawn on LV myocardium to quantify mean SUV. All patients were subsequently interviewed by telephone (median follow-up, 30 mo); 36 of them agreed to undergo electrocardiography and transthoracic echocardiography. Results: In mice, LV MRGlu was 17.9 ± 4.4 nmol × min−1 × g−1 at baseline. Doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9 ± 9 nmol × min−1 × g−1, P < 0.05 vs. controls) and high-dose subgroups (37.2 ± 7.8 nmol × min−1 × g−1, P < 0.01 vs. controls, P < 0.05 vs. standard-dose). In HD patients, LV SUV showed a progressive increase during doxorubicin treatment that persisted at follow-up. New-onset cardiac abnormalities appeared in 11 of 36 patients (31%). In these subjects, pretherapy LV SUV was markedly lower with respect to the remaining patients (1.53 ± 0.9 vs. 3.34 ± 2.54, respectively, P < 0.01). Multivariate analysis confirmed the predictive value of baseline LV SUV for subsequent cardiac abnormalities. Conclusion: Doxorubicin dose-dependently increases LV MRGlu, particularly in the presence of low baseline 18F-FDG uptake. These results imply that low myocardial 18F-FDG uptake before the initiation of doxorubicin chemotherapy in HD patients may predict the development of chemotherapy-induced cardiotoxicity, suggesting that prospective clinical trials are warranted to test this hypothesis.

Hepatosplenic T-cell lymphoma with aberrant expression of serum β-HCG: a case report

Background Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of hematologic malignancies frequently presenting at advanced stage of diagnosis. Methods We report a case of PTCL with an uncommon and aggressive onset with disseminated intravascular coagulation (DIC). Results Laboratory findings revealed an aberrant expression of β subunit of human chorionic gonadotropin (β-HCG). Other than for determination of pregnancy, β-HCG is regularly found as a tumor marker in germ cell tumors with trophoblastic differentiation and its aberrant expression has been reported in the literature in other neoplastic conditions only in the context of case reports. Conclusions In hematologic malignancies, β-HCG expression has been described only in sporadic cases. Awareness of this feature could avoid diagnostic delay in such an aggressive disease.

Abiraterone acetate and prednisone in the pre- and post-docetaxel setting for metastatic castration-resistant prostate cancer: A mono-institutional experience focused on cardiovascular events and their impact on clinical outcomes

Background: The aim of this work was to to evaluate the incidence and risk factors of adverse events (AEs), focusing on cardiovascular events (CVEs) and hypokalemia, in patients treated with abiraterone acetate (AA) and prednisone (PDN) outside clinical trials, and their association with survival outcomes. Methods: This was a retrospective cohort study of 105 patients treated from 2011 to 2016. Incidence of AEs was descriptively summarized in the whole cohort and by subgroup (pre- versus post-docetaxel). Multivariable Cox proportional hazards models assessed factors associated with progression-free survival (PFS) and overall survival (OS). Results: Overall, median PFS and OS were 14.9 and 24.6 months, respectively. Prostate-specific antigen (PSA) ⩾ 10 ng/ml (p = 0.007), Gleason Score >7 (p = 0.008), Eastern Cooperative Oncology Group (ECOG) performance status (PS)1–2 (p = 0.002), duration of androgen deprivation therapy (ADT) ⩽ 43.2 months (p = 0.01), and body mass index (BMI) > 25 (p = 0.03) were associated with worse PFS; presence of pain (p = 0.01), ECOG PS1–2 (p = 0.004), duration of ADT ⩽ 43.2 (p = 0.05), and BMI > 25 (p = 0.042) were associated with worse OS. Incidence of CVEs was as follows: hypertension 17.1%, fluid retention 4.8%, cardiac disorders 8.6%. 16.2% of patients developed hypokalemia. Age ⩾ 75 years was associated with higher probability of cardiac disorders (p = 0.001) and fluid retention (p = 0.03). CVEs did not impact on PFS or OS. Hypokalemia was associated with better median OS (p = 0.036). Similar associations were observed after stratification by subgroup. Conclusions: Median PFS and OS estimates and incidence of CVEs and hypokalemia in our series are consistent with those of pivotal trials of AA plus PDN, confirming the efficacy and safety of this regimen also in the real-world setting. Elderly patients have higher odds of developing/worsening CVEs. However, regardless of age, CVEs were not associated with worse outcomes. Treatment-related hypokalemia seemed to be associated with longer OS, albeit this finding needs confirmation within larger, prospective series.

A Score-Based Approach to 18F-FDG PET Images as a Tool to Describe Metabolic Predictors of Myocardial Doxorubicin Susceptibility

Purpose: To verify the capability of 18F-fluorodeoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT) to identify patients at higher risk of developing doxorubicin (DXR)-induced cardiotoxicity, using a score-based image approach. Methods: 36 patients underwent FDG-PET/CT. These patients had shown full remission after DXR-based chemotherapy for Hodgkin’s disease (DXR dose: 40–50 mg/m2 per cycle), and were retrospectively enrolled. Inclusion criteria implied the presence of both pre- and post-chemotherapy clinical evaluation encompassing electrocardiogram (ECG) and echocardiography. Myocardial metabolism at pre-therapy PET was evaluated according to both standardized uptake value (SUV)- and score-based approaches. The capability of the score-based image assessment to predict the occurrence of cardiac toxicity with respect to SUV measurement was then evaluated. Results: In contrast to the SUV-based approach, the five-point scale method does not linearly stratify the risk of the subsequent development of cardiotoxicity. However, converting the five-points scale to a dichotomic evaluation (low vs. high myocardial metabolism), FDG-PET/CT showed high diagnostic accuracy in the prediction of cardiac toxicity (specificity = 100% and sensitivity = 83.3%). In patients showing high myocardial uptake at baseline, in which the score-based method is not able to definitively exclude the occurrence of cardiac toxicity, myocardial SUV mean quantification is able to further stratify the risk between low and intermediate risk classes. Conclusions: the score-based approach to FDG-PET/CT images is a feasible method for predicting DXR-induced cardiotoxicity. This method might improve the inter-reader and inter-scanner variability, thus allowing the evaluation of FDG-PET/CT images in a multicentral setting.

Iron Overload and Iron-Chelation Therapy in Patients with Myelodysplastyc Syndromes

Transfusion-dependency is an independent prognostic factor for survival in myelodysplastic syndromes (MDS). This negative impact is mainly due to the iron overload (IOL) consequent in large part to chronic transfusion therapy because of its detrimental effects on cardiac, hepatic and endocrine functions. The main tools useful for clinical diagnosis and monitoring of IOL should be serum ferritin, transferrin saturation and magnetic resonance imaging. If correctly evaluated, IOL is frequently observed in lower-risk MDS patients, and is more pronounced in longer surviving individuals. A detrimental role of IOL in MDS patients has been documented in several studies, showing a correlation with a shorter overall survival. Treatment of IOL with iron chelating therapy (ICT) has been shown to prevent at least in part these negative effects. The goal of ICT in MDS patients is to prevent and treat complications of IOL and to improve survival.Introduction Myelodysplastic Syndromes (MDS) are a group of clonal disorders of hematopoietic stem cells, characterized by peripheral blood cytopenias with morphological dysplasia due to ineffective hematopoiesis, with a variable but consistent risk of progression to acute myelogenous leukemia (AML) [1]. MDS are one of the most common hematologic malignancies, with an incidence varying from 3 to 12 cases per 100,000 people per year in the general population, which increase up to 15-50 cases per 100,000 in older patients (>70 years of age); the median age at diagnosis is around 75 years in most of the series [2].

Cisplatin inhibits erythroid committed progenitor (BFU‐E) mobilization in peripheral blood

Abstract: Circulating myeloid (CFU–GM) and erythroid (BFU–E) progenitor levels were evaluated weekly throughout 3 courses of treatment with vinorelbine (VNB) ifosfamide (IFO) and filgrastim (G‐CSF) with or without addition of cisplatin (DDP) in 20 stage IIIB or IV non small‐cell lung cancer patients. In IFO, VNB, DDP‐treated patients, BFU‐E mobilization in peripheral blood following chemotherapy and G‐CSF was completely lacking, in contrast with the patients treated with IFO, VNB plus G–CSF. CFU–GM release, however, was of the same order in the 2 groups of patients. Further investigations are needed to explain why presence of DDP in this chemotherapeutic protocol hinders erythroid progenitor release in peripheral blood.