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.

Clinical Characteristics and Outcomes of COVID-19 in Turkish Patients with Hematological Malignancies

Objective: Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey. Materials and Methods: In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection. Results: Forty four patients were asymptomatic at diagnosis of SARS-CoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixty-nine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use. Conclusion: Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.

Could Antinuclear Antibody Positivity Be a Factor Affecting Treatment Response in Immune Thrombocytopenia Patients on Eltrombopag?

Objective: Eltrombopag remains a prominent option in the treatment of steroid-dependent or steroid-refractory immune thrombocytopenia (ITP) patients. Unfortunately, not all patients respond to eltrombopag. Antinuclear antibody (ANA) positivity can be seen at rates of up to 30% in ITP patients. Despite being widely used, more markers to predict the response to eltrombopag are still needed. In the present study, we aimed to show the association between ANA positivity and eltrombopag response in ITP patients. Materials and Methods: Patients who were diagnosed with ITP in the Trakya University Faculty of Medicine's Department of Hematology and who underwent eltrombopag treatment due to their resistance to steroids and other treatments were included in our study. ANA measurement was performed by indirect fluorescent antibody method and titers of 1:160 and above were considered positive. ANA measurements were made before starting eltrombopag. Results: Forty-five patients were included in our study, 33 being women and 12 men. The mean age of the patients was 45.73 years. There were 14 patients with ANA positivity and 31 patients were found to be ANA-negative. Response rates were higher in ANA-negative patients compared to ANA-positive patients in the 1st and 6th months of eltrombopag treatment (p<0.05). Conclusion: ANA positivity in ITP may indicate unresponsiveness to eltrombopag treatment, a finding that should be further supported by prospective studies involving more patients.

Sarcopenia in Hodgkin's lymphoma evaluated with 18-FDG PET/CT, focus on age, performance, and treatment.

Sarcopenia is defined as a progressive and generalized muscle disorder associated with certain physiological and pathological conditions. We aimed to evaluate the prevalence of sarcopenia in patients with HL using 18-fluoro deoxyglucose (FDG) PET/CT, which would provide a data of muscle mass with the CT compartment and also data of muscle metabolism with the 18-FDG compartment of the imaging modality. Fifty-nine patients diagnosed with HL were included in the study. PET/CT images before and after treatment were evaluated with regard to lumbar muscle mass and metabolism. Mean lumbar muscle evaluation with CT before treatment was 92, 40 HU, and after treatment was 89, 41 HU. Mean metabolic tumor volume (MTV) evaluated with FDG PET before treatment was 4, 13 mm3 while after treatment was 4, 10 mm3. The lumbar muscle mass in terms of HU which was evaluated with CT was observed to be decreased after treatment. Likewise, the metabolic evaluation was observed to be also decreased after treatment. Despite the decline in muscle mass after treatment in the whole group, this decline was particularly observed in the better initial performance group. In patients with BMI > 32, there was a significant decline in muscle mass. Abdominal nodal involvement was related with poorer muscle mass and quality. In HL care, particular attention should be given to patients who are younger and with better physical condition in terms of preserving the muscle reserves and preventing sarcopenia.

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.

The Incidence of Venous Thromboembolism and Impact on Survival in Hodgkin Lymphoma.

BACKGROUND: Thrombosis increase the acute and long-term morbidity and mortality in malignancy patients. We analyzed venous thromboembolism (VTE) in patients with Hodgkin lymphoma, the impact of VTE on survival, predisposing factors for VTE, and predicting value of Khorana and ThroLy score models. PATIENTS AND METHODS: We included 150 adult patients with Hodgkin lymphoma between January 2010 and 2018 at our university hospital. RESULTS: VTE was observed in 31 patients (20.7%). The types of VTE were 18 upper and 3 lower extremity deep vein thrombosis and 10 pulmonary embolism (1 with lower extremity deep vein thrombosis). Twenty-nine patients developed VTE during the treatment with a median time of episode as 5 months. In logistic regression analysis, a body mass index of >32 kg/m2, high fibrinogen levels, initial thrombocytosis and leukocytosis, splenic and extranodal involvement, presence of a central venous line, advanced stage, line of treatment status of thromboprophylaxis, VTE timing, and better Eastern Cooperative Oncology Group performance scores were observed to be related with VTE. Kaplan Meier survival analysis showed a negative impact of VTE on survival. Khorana and ThroLy risk assessment models were found predictive for VTE (P = .000 and P = .003, respectively), although only ThroLy score was associated with the survival. CONCLUSION: Thromboprophylaxis and precautions for VTE in patients with Hodgkin lymphoma according to validated risk assessment models can improve prognosis and quality of life owing to the impact of VTE on survival in the study.

Concepts of Double Hit and Triple Hit Disease in Multiple Myeloma, Entity and Prognostic Significance.

Risk assessment in newly diagnosed multiple myeloma patients (NDMM) is the first and the most crucial determinant of treatment. With the utilization of FISH analysis as a part of routine practice, high risk Multiple Myeloma (MM) is defined as having at least one of the mutations related with poor prognosis including; t(4;14) t(14;16), t(14;20), del 17p, p53 mutation, gain 1q and del 1p. M-Smart MM risk stratification guideline by Mayo Clinic has proposed a concept similar to high grade lymphomas. Having two of the high risk genetic abnormalities were defined as double hit MM and having any three as triple hit MM. Based on these definitions which may bring a much more clinically relatable understanding in MM prognosis, we aimed to assess our database regarding these two concepts and their probable significance in terms of outcome and prognosis. We retrospectively evaluated 159 newly diagnosed multiple myeloma patients and their clinical course. Among these patients; twenty-four patients have one high risk determinant and also seven and two patients were classified as double hit MM and triple hit MM respectively. Overall survival (OS) of the patients with double hit MM was 6 months, 32.0 months for patients with single high risk abnormality and 57.0 months for patients with no high risk abnormality. Univariate analysis showed that Double Hit and Triple Hit MM is a predictive of low OS. Hazard Ratio of patients with one high risk abnormality was 1.42, double-hit MM patients was 5.55, and triple-hit MM patients was 7.3. Despite the development of novel drugs and their effects of prolonging survival, the treatment has not been individualized. Understanding the biology of each patient as a unique process will be the success of the treatment. As it is known that some MM patients harbor high risk genetic abnormalities according to FISH analysis, we can continue the argument that some patients bring an even higher risk and that can be defined as double or triple hit MM.

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.

Late onset left ventricular dysfunction and cardiomyopathy induced with ibrutinib.

INTRODUCTION: Ibrutinib, an oral inhibitor of Bruton's tyrosine kinase, has altered the treatment perspective of chronic lymphocytic leukemia and showed modest activity against several types of non-Hodgkin's lymphomas. According to phase studies and real-world data, reported serious adverse effects included atrial fibrillation, diarrhea, and bleeding diathesis. However, heart failure was not reported to be a probable adverse effect linked with ibrutinib. CASE REPORT: In this paper, we present a 66-year-old female chronic lymphocytic leukemia patient who developed significant and symptomatic left ventricular dysfunction at the 13th month of ibrutinib treatment. MANAGEMENT AND OUTCOME: Following cessation of ibrutinib, ejection fraction and clinical findings of the left ventricular dysfunction alleviated. DISCUSSION: Although the use of ibrutinib is generally well tolerated, cardiac functions should be monitored occasionally in all patients.

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.

The epidemiology of dermatomyositis in northwestern Thrace region in Turkey: epidemiology of dermatomyositis in Turkey.

Dermatomyositis (DM) is a rare disease that may affect the skeletal muscles and the skin. Literature data on its incidence and prevalence are limited. There are no data on its incidence or prevalence in Turkey. Patients diagnosed with DM at the Trakya University Medical Faculty, Department of Rheumatology from November 2004 to November 2014 were reviewed retrospectively. Patients' clinical and demographic features, laboratory data, treatment modalities, follow-up durations, disease courses, outcomes, and complications were evaluated. Our study included 23 patients with DM; 14 were females and 9 were males (female/male: 1.55). Over the course of the study, the annual incidence of DM was 3.7 per million (95% CI 0-18.8) person years, and the overall prevalence was 32.2 per million (95% CI 18.1-46.3). Incidence in women was higher (4.6/1,000,000 person years) compared to men (2.9/1,000,000 person years). The frequencies of most common findings were as follows: heliotrope rash (82.6%), Gottron papules (87%), proximal myopathy (78.3%), and facial erythema (60.9%). In our hospital-based study, the frequency of DM was lower than those reported in North America; however, they were similar to European countries.