The evaluation of risk factors leading to early deaths in patients with acute promyelocytic leukemia: a retrospective study.

Acute promyelocytic leukemia (APL) differs from other forms of acute myeloid leukemia (AML), including coagulopathy, hemorrhage, disseminated intravascular coagulation (DIC), and treatment success with all-trans retinoic acid (ATRA). Despite ATRA, early deaths (ED) are still common in APL. Here, we evaluated factors associated with ED and applicability of scoring systems used to diagnose DIC. Ninety-one APL patients (55 females, 36 males, and median age 40 years) were included. ED was defined as deaths attributable to any cause between day of diagnosis and following 30th day. DIC was assessed based on DIC scoring system released by the International Society of Thrombosis and Hemostasis (ISTH) and Chinese Diagnostic Scoring System (CDSS). Patients' median follow-up time was 49.2 months, and ED developed in 14 (15.4% of) cases. Patients succumbing to ED had higher levels of the Eastern Cooperative Oncology Group Performance Status (ECOG PS), lactate dehydrogenase (LDH), and ISTH DIC, and lower fibrinogen levels (p <0.05). In multivariate Cox regression analysis, age >55 and ECOG PS ≥2 rates were revealed to be associated with ED. Based on ISTH and CDSS scores, DIC was reported in 47.3 and 58.2% of the patients, respectively. Despite advances in APL, ED is still a major obstacle. Besides the prompt recognition and correction of coagulopathy, those at high ED risk are recommended to be detected rapidly. Implementation of local treatment plans and creating awareness should be achieved in hematological centers. Common utilization of ATRA and arsenic trioxide (ATO) may be beneficial to overcome ED and coagulopathy in APL patients.

Evaluation of Sarcopenia with F-18 FDG PET/CT and relation with disease outcomes in patients with multiple myeloma.

INTRODUCTION: Multiple myeloma (MM) is a potentially incurable haematological malignancy with devastating manifestations including lytic bone lesions leading to fractures and renal insufficiency. As a disease of patients with a mean age of 66 years, both the disease and the continuous efforts of treatments lead to frailty and devastation. From this stand point, we aimed to evaluate the development of muscle loss in MM patients and also with a new method of sarcopenia evaluation, F-18 FDG PET/CT. While used for bone disease routinely, this method brings a fresh perspective of metabolic quantitation of alteration of muscles which may be regarded as muscle quality. MATERIALS AND METHODS: Data and images of 105 patients with MM both before and after treatment were evaluated in a retrospective manner. RESULTS: Both female and male patients were observed to be effected after MM treatment in terms of lumbar and femoral muscle evaluations with CT. Metabolic evaluations confirmed a loss of quality in muscles in terms of metabolic volume and total lesion glycolysis. CONCLUSION: Sarcopenia should be evaluated in every patient and regarded as a treatment target. FDG PET/CT is an easy and handy tool to assess muscle mass and quality as well as MM disease status.

Polypharmacy and potentially inappropriate medication use in older patients with multiple myeloma, related to fall risk and autonomous neuropathy.

PURPOSE: Multiple myeloma is a chronic, uncurable hematological cancer with the involvement of multiple organ systems. As a disease affecting older patients, the treatment of multiple myeloma should be based on individual patient characteristics. Polypharmacy is an increasing problem in the care of older patients and in patients with multiple myeloma, polypharmacy is almost inevitable. We aimed to evaluate the applicability of polypharmacy definitions and the relation of polypharmacy with disease outcomes in patients with multiple myeloma. METHODS: Eighty patients older than 65 years and diagnosed with multiple myeloma were retrospectively enrolled. Patient files, prescriptions, evaluations for polypharmacy were determined according to Beers and START/STOPP criteria. Outcomes were recorded from files in terms of fractures, autonomous neuropathy, and renal functions. RESULTS: Polypharmacy with ≥4 drugs was observed in 65 patients while polypharmacy with ≥5 drugs was observed in 51 patients. Autonomous neuropathy, polypharmacy with more than four or five medications, and use of multiple medications in the same category were related with poor ECOG performance status in women, while prolonged use of benzodiazepines and central nervous system (CNS) affecting drugs and inappropriate polypharmacy were more frequent in men with poor ECOG performance status. The majority of patients aged 75-84 years were observed to use inappropriate polypharmacy. Autonomous neuropathy and fall risk were observed to be significantly related with inappropriate polypharmacy. CONCLUSIONS: Drugs affecting balance and perception should be reconsidered in patients with multiple myeloma.

Genetic Diagnosis of Hereditary Hemorrhagic Telangiectasia: Four Novel Pathogenic Variations in Turkish Patients

Aims: Hereditary hemorrhagic telangiectasia is an autosomal dominant disorder characterized by telangiectasia, epistaxis, and vascular malformations. Pathogenic mutations were found in ENG, AVCRL1, SMAD4, and GDF genes. In this study, we present our database of patients with hereditary hemorrhagic telangiectasia regarding the phenotype-genotype relations and discuss two novel ENG gene pathogenic variations in two unrelated families. Methods: Next Generation Sequencing analysis was performed on the peripheral blood of nine patients with hereditary hemorrhagic telangiectasia in four unrelated families. All patients were diagnosed with hereditary hemorrhagic telangiectasia according to the Curaçao criteria. Data on treatment and screenings of visceral involvement were recorded from files. Results: We have found a pathogenic variation in either the ENG or ACVRL1 gene in each family. Two novel pathogenic variations in the ENG gene, including NM_000118.3 (ENG): c.416delC (p.P139fs*24) and NM_000118.3(ENG): c.1139dupT (p.Leu380PhefsTer16), were found in the same family. The NM_000020.2(ACVRL1): c.1298C>T (p.Pro433Leu) pathogenic variation in the ACVRL1 gene in our first family and a novel heterozygous likely pathogenic NM_000020.2(ACVRL1): c.95T>C (p.Val32Ala) variation was found in our second family. Seven of the nine patients were treated with thalidomide for controlling bleeding episodes. All patients responded to thalidomide. In one patient, the response to thalidomide was lost and switched to bevacizumab. Conclusion: In HHT certain type of mutations correlates with disease phenotypes and with next generation sequencing method, new pathogenic variations can be revealed which might help managing HHT patients.

Thalidomide for the Management of Bleeding Episodes in Patients with Hereditary Hemorrhagic Telangiectasia: Effects on Epistaxis Severity Score and Quality of Life

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominantly inherited disorder characterized by bleeding episodes. These episodes tend to happen spontaneously and reduce the quality of life. Patients are often unresponsive to local measures. With the pathophysiological role of angiogenesis in HHT, antiangiogenic drugs including thalidomide are used to control bleeding episodes. In our study, we evaluated 6 patients with HHT, calculating their Epistaxis Severity Score (ESS) and performing a quality of life assessment with the 36-Item Short Form Health Survey Questionnaire (SF-36), and we studied the alterations of these evaluations with thalidomide treatment. Three patients were male and three were female. Mean age was 60.50 years. No side effects were observed during the treatment period. Improvements of certain SF-36 dimensions including physical functioning, physical component summary, and mental component summary and of the ESS were observed after treatment. Thalidomide may be effective to control bleeding episodes with a reasonable tolerance profile in patients with HHT.

A biomarker and therapeutical target in immune thrombocytopenia: TNF receptor-associated factor 6.

BACKGROUND: Immune thrombocytopenia (ITP) is an acquired disease characterized by various pathogenetic mechanisms. We aimed to evaluate the value of TRAF6 as a biomarker of pathogenesis in ITP. METHODS: 85 newly diagnosed ITP patients and 85 controls were included. RESULTS: In the patient group, mean TRAF6 level was 2348 pg/ml and in the control group, TRAF6 level was 25.57 pg/ml. In corticosteroid-responding patients, TRAF6 levels were lower than nonresponding patients. DISCUSSION: TRAF6 levels were observed to be higher than healthy controls, which suggest a solid relation with ITP pathogenesis. The observation that in patients who present with high TRAF6 levels, there was a significant corticosteroid refractoriness and responsiveness.

A case of refractory chronic lymphocytic leukaemia with an unusual course.

Chronic lymphocytic leukaemia (CLL) is a heterogeneous disease with uncertain course. Treatment should be tailored to the patient's disease as well as the prognostic subgroup. With the increased use of rituximab as well as other selective and non-selective immunomodulatory agents, the incidence of infectious complications and second malignancies has also increased. Progressive multifocal leucoencephalopathy (PML) is a complication of rituximab in HIV-negative patients. A 56-year-old male with CLL had been treated and relapsed four times in 6 years. Rituximab was added to the combination after the second relapse and repeated in the third relapse in combination with bendamustine. In the seventh year of diagnosis, relapse of CLL and an ulcerated tumorous lesion was observed in the left index finger, which progressed in 3 months and was later diagnosed as angiosarcoma. The cancer was treated with local radiotherapy and combination chemotherapy. One year after the last rituximab exposure, progressive muscle weakness developed and polyoma JC virus DNA was observed with increased titres in the cerebrospinal fluid, and the patient was diagnosed as having PML. The patient died 2 months later. Our patient had an unusual course of CLL over 8 years, with relapses, complicated with a secondary malignancy and an infectious complication.

The impact of new generic formulations of imatinib mesylate on general quality of life in chronic phase chronic myeloid leukaemia patients.

Treatment with tyrosine kinase inhibitors (TKIs) has dramatically changed the life expectancy of chronic myeloid leukaemia (CML) patients. Although the impact of first-generation TKIs on quality of life (QoL) was shown in CML, the effects of new generic formulations of imatinib mesylate (IM) are unclear. We evaluated differences in QoL under treatment with first- or second-generation TKIs. Fifty-two patients diagnosed with CP-CML completed the European Organization for Research and Treatment of Cancer Quality of Life Questionaire-C30, Hospital Anxiety and Depression Scale, and General Health Questionnaire. General QoL scores were similar between groups. There was a significant difference in the frequency of diarrhoea between IM group and the group using new generic formulations of IM (P = 0.012). General QoL score tended to be higher in patients with disease duration longer than 3 years (P = 0.052). GHQ, anxiety and depression scores correlated positively with symptom scales and negatively with functional subscales.CML patients using new generic formulations of IM reported a higher frequency of diarrhoea than patients using original IM and second-generation TKIs that could result in more drug discontinuation.

Assessment of ventricular and left atrial mechanical functions, atrial electromechanical delay and P wave dispersion in patients with scleroderma.

BACKGROUND: The aim of this study was to investigate ventricular functions and left atrial (LA) mechanical functions, atrial electromechanical coupling, and P wave dispersion in scleroderma patients. METHODS: Twenty-six patients with scleroderma and twenty-four controls were included. Left and right ventricular (LV and RV) functions were evaluated using conventional echocardiography and tissue Doppler imaging (TDI). LA volumes were measured using the biplane area- -length method and LA mechanical function parameters were calculated. Inter-intraatrial electromechanical delays were measured by TDI. P wave dispersion was calculated by 12-lead electrocardiograms. RESULTS: LV myocardial performance indices (MPI) and RV MPI were higher in patients with scleroderma (p = 0.000, p = 0.000, respectively) while LA passive emptying fraction was decreased and LA active emptying fraction was increased (p = 0.051, p = 0.000, respectively). P wave dispersion and inter-intraatrial electromechanical delay were significantly higher in patients with scleroderma (25 [10-60] vs 20 [0-30], p = 0.000, 16.50 [7.28-26.38] vs 9.44 [3.79-15.78] and 11.33 [4.88-16.06] vs 4.00 [0-12.90], p < 0.05, respectively). Interatrial electromechanical delay was negatively correlated with LV E wave, (p = 0.018). LV E wave was demonstrated to be a factor independent of the interatrial electromechanical delay (R² = = 0.270, b = -0.52, p = 0.013). CONCLUSIONS: This study showed that in scleroderma patients, global functions of LV, RV and mechanical functions of LA were impaired, intra-interatrial electromechanical delays were prolonged and P wave dispersion was higher. LV E wave was demonstrated to be a factor that is independent of the interatrial electromechanical delay. Reduced LV E wave may also give additional information on the process of risk stratification of atrial fibrillation.