Polycythemia vera and essential thrombocythemia of intermediate-age: A real-life, multicenter analysis of first-line treatment approach.

BACKGROUND: The treatment of patients with polycythemia vera (PV) and essential thrombocythemia (ET) is conducted according to well-defined risk stratification systems. We hypothesized that adherence to the guidelines, namely the decision to refrain from introducing cytoreduction in non-high-risk patients, is particularly difficult in patients diagnosed when they are between 40 and 59 years of age (intermediate-age group). OBJECTIVES: To evaluate the group of intermediate-age PV and ET patients, focusing on a first-line treatment approach adapted at diagnosis. MATERIAL AND METHODS: The study group consisted of 308 PV and ET patients recruited from 6 Polish Adult Leukemia Group (PALG) Centers. Patients were analyzed with respect to disease phenotype, risk group, treatment approach, cardiovascular (CV) risk factors, and occurrence of bleeding or thrombosis. RESULTS: Overall, 74% of patients in the study group were started on cytoreduction at diagnosis, including 70% of the low-risk PV patients and 85-89% of the non-high-risk ET patients. Factors influencing the decision to start the treatment included higher hemoglobin (Hb) concentration (in PV) as well as higher platelet (PLT) count, and the presence of CV risk factors (in ET). Introducing cytoreduction at diagnosis had no impact on thrombotic events. Patients harboring CV risk factors experienced a higher incidence of complications both at diagnosis and follow-up, independently of the treatment strategy. CONCLUSIONS: We underline the low adherence to recommendations in the treatment of intermediate-age PV and ET patients. Moreover, we emphasize the importance of CV risk factors and stress their impact on disease phenotype in this patient population.

Effectiveness of antazoline versus amiodarone, flecainide and propafenone in restoring sinus rhythm at the emergency department.

PURPOSE: Little is known about the effectiveness of pharmacological cardioversion (PCV) with antazoline in comparison to flecainide. The aim of this study was to compare the effectiveness of antazoline in restoring sinus rhythm (SR) versus amiodarone, flecainide and propafenone in a group of emergency department (ED) patients. MATERIALS/METHODS: This was a single-centre retrospective analysis of patient records from an ED in a large hospital in Poland. We analysed a total of 1878 patient records, divided based on the anti-arrhythmic drug (AAD) administered during PCV: antazoline (n â€‹= â€‹1080), antazoline â€‹+ â€‹ß-blocker (n â€‹= â€‹479), amiodarone (n â€‹= â€‹129), flecainide (n â€‹= â€‹102), propafenone (n â€‹= â€‹88). Of the patients, 63.5 â€‹% were female (median 65 years, [19-100]). RESULTS: The percentage of successful PCV was significantly higher in the antazoline group (84.3 â€‹%) than in the antazoline â€‹+ â€‹ß-blocker (75.8 â€‹%, p â€‹= â€‹0.0001), propafenone (75.6 â€‹%, p â€‹= â€‹0.0364) and amiodarone (68.8 â€‹%, p â€‹< â€‹0.0001) groups. Post-hoc analysis revealed that patients who received PCV with antazoline, antazoline â€‹+ â€‹ß-blocker, flecainide and propafenone had significantly shorter time to SR than those who received amiodarone (p â€‹< â€‹0.0001). Univariate regression analysis revealed that patients who underwent PCV with antazoline were almost twice as likely to return to SR compared to the other groups (p â€‹< â€‹0.0001, OR 1.81, 95 â€‹% CI 1.44-2.27). CONCLUSIONS: This is the first study comparing the effectiveness of antazoline in PCV versus flecainide in addition to the previously studied amiodarone and propafenone. Our results indicate that antazoline is more effective in restoring SR than amiodarone, flecainide and propafenone. In addition, antazoline restored SR significantly faster than amiodarone or propafenone.

Illness Perception and the Severity of Depression and Anxiety Symptoms in Patients with Multimorbidity: Observational Cohort Studies.

INTRODUCTION: Many studies have shown a correlation between the patient's engagement in treatment and their perception of the illness. AIM: The aim of this study has been to explore the link between the patient's perception of their illness with anxiety and depression, and to leverage this link to promote health education. MATERIALS AND METHODS: The study was carried out using the following tools: the Hospital Anxiety and Depression Scale and the Illness Perception Questionnaire-Revised. The study participants included N = 143 patients. RESULTS: The participants' age was statistically significantly associated with the expected duration of the illness (p < 0.01), the conviction that the treatment was effective (p < 0.01), and the perception of the severity of the disease symptoms (p < 0.05). The employment status was statistically significantly associated with the illness perception (p < 0.01). Anxiety and depression levels were statistically significantly associated with the perceived impact of the illness on life (p < 0.001) and emotional status (p < 0.001), the perceived control over the illness (p < 0.01), the potential for recovery (p < 0.001), the concern about the illness (p < 0.001), and the impact of the illness on emotional well-being (p < 0.001). CONCLUSIONS: Individuals who perceived a high severity of illness symptoms also assessed that the illness significantly impacted their life and emotional state. The authors demonstrate a strong link of a "negative" perception of the illness with depression and anxiety. A better understanding of the illness predicted a less severe depression and lower anxiety. IMPLICATIONS FOR PRACTICE: The results suggest that the study of illness perception holds significant potential to contribute effectively to educational and psychotherapeutic practices.

Fostamatinib for the treatment of adult persistent and chronic immune thrombocytopenia: Results of two phase 3, randomized, placebo-controlled trials.

Spleen tyrosine kinase (Syk) signaling is central to phagocytosis-based, antibody-mediated platelet destruction in adults with immune thrombocytopenia (ITP). Fostamatinib, an oral Syk inhibitor, produced sustained on-treatment responses in a phase 2 ITP study. In two parallel, phase 3, multicenter, randomized, double-blind, placebo-controlled trials (FIT1 and FIT2), patients with persistent/chronic ITP were randomized 2:1 to fostamatinib (n = 101) or placebo (n = 49) at 100 mg BID for 24 weeks with a dose increase in nonresponders to 150 mg BID after 4 weeks. The primary endpoint was stable response (platelets ≥50 000/µL at ≥4 of 6 biweekly visits, weeks 14-24, without rescue therapy). Baseline median platelet count was 16 000/µL; median duration of ITP was 8.5 years. Stable responses occurred in 18% of patients on fostamatinib vs. 2% on placebo (P = .0003). Overall responses (defined retrospectively as ≥1 platelet count ≥50 000/µL within the first 12 weeks on treatment) occurred in 43% of patients on fostamatinib vs. 14% on placebo (P = .0006). Median time to response was 15 days (on 100 mg bid), and 83% responded within 8 weeks. The most common adverse events were diarrhea (31% on fostamatinib vs. 15% on placebo), hypertension (28% vs. 13%), nausea (19% vs. 8%), dizziness (11% vs. 8%), and ALT increase (11% vs. 0%). Most events were mild or moderate and resolved spontaneously or with medical management (antihypertensive, anti-motility agents). Fostamatinib produced clinically-meaningful responses in ITP patients including those who failed splenectomy, thrombopoietic agents, and/or rituximab. Fostamatinib is a novel ITP treatment option that targets an important mechanism of ITP pathogenesis.

Health-related quality of life and patient-reported outcomes of ofatumumab plus fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide in the COMPLEMENT 2 trial of patients with relapsed CLL.

Chronic lymphocytic leukemia (CLL) is an incurable disease. Quality of life during treatment and periods of subsequent remission is therefore vital. Health-related quality of life (HRQoL) was compared in relapsed CLL during and after treatment with ofatumumab combined with fludarabine and cyclophosphamide versus fludarabine and cyclophosphamide alone. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 v3 and QLQ-CLL16 were used to assess HRQoL in this open-label, phase 3 study. Improvements in prespecified domains of patient-reported outcomes (Global Health Status [GHS]/HRQoL and B symptom scores) were recorded in both treatment arms after three cycles and were sustained after 18 months of follow-up. The two treatment arms were not significantly different at the nominal 0.05 level for GHS/HRQoL (p = .7278) or B symptoms (p = .5968). Small improvements in quality of life were maintained after therapy. The addition of ofatumumab was without any adverse impact on HRQoL (NCT00824265).

Are myelodysplastic syndromes underdiagnosed in Poland? A report by the Polish Adult Leukaemia Group.

OBJECTIVES: The epidemiology of myelodysplastic syndromes (MDS) differs among countries. Here, we present the first epidemiological indices determined for Poland. METHODS: Twenty-one haematological centres participated in the study. Patients diagnosed with MDS and acute myeloid leukaemia (AML) with 20-29% blasts were enrolled. Data collection was conducted for strictly predefined period. RESULTS: The overall crude incidence rate for all MDS subtypes was 1.95 (95% CI, 1.81-2.09) per 100 000 person-years: 2.46 (95% CI, 2.24-2.69) for males and 1.47 (95% CI, 1.31-1.65) for females; after excluding AML cases, the indices were as follows: 2.35 (95% CI, 2.08-2.66) for males and 1.27 (95% CI, 1.08-1.5) for females. Prevalence rate was 6.2 per 100 000 persons (95% CI, 5.96-6.45), that is 6.86 (95% CI, 6.49-7.24) for males and 5.58 (95% CI, 5.26-5.92) for females. Both incidence and prevalence increased with increasing age. The most frequently diagnosed MDS subtype was refractory cytopenia with multilineage dysplasia (RCMD), responsible for 30.3% of all newly diagnosed MDSs. CONCLUSIONS: RCMD is the most frequent MDS subtype in Poland. Incidence and prevalence indices are lower than those reported for other populations, which probably results from inadequate diagnosis of potential cases of this disease.

Ofatumumab plus fludarabine and cyclophosphamide in relapsed chronic lymphocytic leukemia: results from the COMPLEMENT 2 trial.

In this multicenter, open-label, phase III study, patients with relapsed chronic lymphocytic leukemia (CLL) were randomized (1:1) to receive ofatumumab plus fludarabine and cyclophosphamide (OFA + FC) or FC alone; the primary endpoint being progression-free survival (PFS) assessed by an independent review committee (IRC). Between March 2009 and January 2012, 365 patients were randomized (OFA + FC: n = 183; FC: n = 182). Median IRC-assessed PFS was 28.9 months with OFA + FC versus 18.8 months with FC (hazard ratio = 0.67; 95% confidence interval, 0.51-0.88; p = .0032). Grade ≥3 adverse events (≤60 days after last dose) were reported in 134 (74%) OFA + FC-treated patients compared with 123 (69%) FC-treated patients. Of these, neutropenia was the most common (89 [49%] vs. 64 [36%]). OFA + FC improved PFS with manageable safety for patients with relapsed CLL compared with FC alone, thus providing an alternative treatment option for patients with relapsed CLL. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT00824265).

A phase 2, multicenter study investigating ofatumumab and bendamustine combination in patients with untreated or relapsed CLL.

The purpose of this study is to assess the safety and efficacy of the combination of ofatumumab and bendamustine in patients with previously untreated or relapsed chronic lymphocytic leukemia. Patients received IV ofatumumab (cycle 1: 300 mg day 1 and 1,000 mg day 8; cycles 2-6: 1,000 mg on day 1 every 28 days) and IV bendamustine 90 mg m(-2) (previously untreated) or 70 mg m(-2) (relapsed) on days 1 and 2 of each 28-day cycle, for up to 6 cycles. Forty-four previously untreated and 53 relapsed patients were enrolled. Median age was 62.5 years (previously untreated) and 68 years (relapsed); relapsed patients had received a median of 1 (range 1-11) prior therapy. The investigator-assessed overall response rate was 95% (43% complete response [CR]) for the previously untreated, and 74% (11% CR) for the relapsed patients. The regimen was well tolerated with 89% (previously untreated) and 85% (relapsed patients) receiving all 6 cycles. No unexpected toxicities were reported. Grade 3/4 events occurred in 57% of previously untreated, and 72% of relapsed patients. At ∼29 months' follow-up, the median progression-free survival (PFS) was not reached for the previously untreated population, and the 28-month PFS estimate was 72.3%. The median PFS for the relapsed population was 22.5 months (95% CI: 14.0-27.3 months). The combination of ofatumumab and bendamustine was well tolerated and effective in these previously untreated or relapsed populations. Am. J. Hematol. 91:900-906, 2016. © 2016 Wiley Periodicals, Inc.

[Thrombotic thrombocytopenic purpura in a patient with systemic lupus erythematosus--complication of connective tissue disease or overlap syndrome?]. / Zakrzepowa plamica maloplytkowa u chorej na toczen rumieniowaty ukladowy--powiklanie ukladowej choroby tkanki lacznej czy zespól nakladania?

Thrombotic thrombocytopenic purpura (TTP) and systemic lupus erythematosus (SLE) are two separate diseases, whose clinical symptoms maybe similar. The coexistence of these two diseases is very rare. We present the case report of a 29-year-old female patient with simultaneous diagnosis of TTP and SLE. The purpose of this article is to draw attention to the diagnostic difficulties which may result from the co-existence of both diseases.

The knowledge of public access to defibrillation in selected cities in Poland.

INTRODUCTION: The Public Access to Defibrillation (PAD) program was designed to raise the awareness of sudden cardiac death (SCA) pre-hospital management among the community. The goal of the following research was to confirm the final impact of the Polish PAD program on various resident groups that differ by age, training and education level. MATERIAL AND METHODS: The trial total number of participants reached 404 people from three cities divided into two groups. In group one (n = 295) were randomly selected people inside the trial area and in group two (n = 109) we had individuals who were theoretically trained in basic life support (BLS) algorithms, including the use of an automatic external defibrillator (AED). The research method was based on two different questionnaires completed by participants from each group. RESULTS: The greatest knowledge of SCA, as well as the use of AED, and the best practical skills, were possessed by the residents of cities with a population over 100 000, aged between 18 and 30 years, who completed secondary or higher education (31.7%). The group with the smallest knowledge about SCA lived in the country (10.7%). The second group with little knowledge of the subject consisted mostly of individuals with primary education (4.19%) or professional abilities and over 50 years old (2.16%). CONCLUSIONS: There must be some actions taken in order to increase the community awareness concerning automatic defibrillation. Training on AED and the possibility of practical exercise needs to be organized and should be conducted especially among residents of the countryside and people under 30 or over 50 years old.

[A case report of idiopathic thrombocytosis in 27-year-old man treated for myocardial infarction]. / Przypadek nadplytkowosci samoistnej u 27-letniego mezczyzny leczonego z powodu zawalu miessnia sercowego.

We present the case of 27-year-old male, physical training teacher in whom the first clinical sign of idiopathic thrombocytosis was myocardial infarction. The infarct was complicated by heart arrest caused by ventricular fibrillation. Streptolysis (streptokinase) was used in treatment. Thrombocytosis 842 G/l was observed in blood tests at admission. To estimate its cause the bone marrow biopsy and trepanobiopsy of hip bone were performed. Tests were performed to exclude the secondary cause of thrombocytosis. The coronarography did not show relevant stenoses of coronary arteries. The results let diagnose myocardial infarction in a patient with essential thrombocytosis.

[Myelodysplastic syndromes--pathogenesis and treatment]. / Zespoly mielodysplastyczne--patogeneza i leczenie.

The essence of myelodysplastic syndromes is damage of CFU. We can also observe different chromosomes' defects which in consequence cause disorder of differentiation and maturation of hematopoietic cells. The aim of therapy is elimination of damaged CFU, possible only by bone marrow transplant. Patients who can not qualify for a transplant are treated by pharmacologic means. Pharmacological treatment aims to induce differentiation of hematopoietic cells and also to inhibit apoptosis. Since in this disease multiple genetics anomalies are affirmed, in the future gene therapy will play a big role in the treatment.