Evaluation of Second Primary Cancer Risk Among Chronic Lymphocytic Leukemia Patients: Multicenter Study.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) have an increased risk of developing second primary cancers (SPC). The aim of this study is to determine the frequency of SPC in CLL patients and determine the relationship between these cancers and their treatment status, cytogenetic factors, and other risk factors. METHODS: The study was designed as multicenter and retroprospective. The sample comprised 553 subjects with a CLL diagnosis. Data collection commenced in August 2016, and completed at May 2021. RESULTS: Fifty one of 553 patients followed for CLL, had a history of SPC. SPC development rate was 9.2%. Epithelial tumors were mostly observed. According to the incidence skin, lymphoma, renal, breast, lung, gastrointestinal system, thyroid, malignant melanoma, prostate, Kaposi's sarcoma, neuroendocrine tumor, ovarian, larynx and salivary gland cancers were detected respectively. The 13q deletion was the most common genetic abnormality in those who developed SPC, and the frequency of 13q deletion was found to be increased statistically significant in those with malignancy, compared to those who did not. CONCLUSION: In CLL patients with SPC, the age of diagnosis, 13q and CD38 positivity, and treatment rates with fludarabine and monoclonal antibodies were found to be higher. Also, we determined that SPC frequency increased independently from hemogram values (except hemoglobin values), ß2 microglobulin level on admission, number of treatment lines, and genetic mutations other than 13q, in CLL patients. In addition, the mortality rate was higher in CLL patients with SPC and they were prone to be in advanced stages at the time of diagnosis.

Treatment options in primary mediastinal B cell lymphoma patients, retrospective multicentric analysis; a Turkish oncology group study.

Introduction and Aim: Primary mediastinal B-cell lymphomas (PMBL) are aggressive B- cell lymphomas. Although the initial treatment models vary in PMBL, appropriate treatment methods are not known. We aim to show real-life data on health outcomes in adult patients with PMBL who received various type of chemoimmunotherapies in Turkey. Method: We analyzed the data of 61 patients who received treatments for PMBL from 2010 to 2020. The overall response rate (ORR), overall survival (OS) and progression-free survival (PFS) of the patients were evaluated. Results: 61 patients were observed in this study. The mean age of the study group was 38.4 ± 13.5 years. From among them, 49.2% of the patients were female (n = 30). For first-line therapy, 33 of them had received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen (54%). Twenty-five patients had received rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-EPOCH-R) regimen. The ORR was 77%. The median OS and PFS were as follows: 25 months (95% CI: 20.4-29.4) and 13 months (95% CI: 8.6-17.3), respectively. The OS and PFS at 12 months were 91.3% and 50%, respectively. The OS and PFS at five years were 64.9% and 36.7%, respectively. Median follow-up time period was 20 months (IQR 8.5-38.5). Conclusion: R-CHOP and DA-EPOCH-R showed good results in PMBL. These remain one of the best determined systemic treatment options for first-line therapy. Also, the treatment was associated with good efficacy and tolerability.

The Effect of Platelet and Mean Platelet Volume Levels on Standard-dose Methylprednisolone Treatment Response in Primary Immune Thrombocytopenia.

Objective: Standard-dose methyl-prednisolone (methyl-Pd) is generally preferred as the first-line treatment in immune thrombocytopenia (ITP) unless there is an urgent indication to increase the platelet value. A significant proportion of patients (around 40%) does not benefit from this treatment. This study investigated whether pretreatment platelet level and other hemogram indices in patients with ITP patients can be used to predict early response to standard-dose methyl-Pd treatment. Methods: Patients who received first-line standard-dose methyl- Pd therapy with the diagnosis of primary ITP were included. Patients were categorized as complete responder (CR), responder (R), and non-responder (NR) according to the response status obtained within the first 14 days of treatment. The hemogram indices of the CR, R, and NR groups measured at the start of the treatment were compared retrospectively. Results: One hundred forty four patients with ITP were included in the study. The number of patients with NR, R, and CR were 47 (33%), 40 (28%), and 57 (39%), respectively. The mean platelet level of the NR group was lower than responders (R and CR groups) (p=0.002 and p=0.049, respectively). The mean platelet volume (MPV) levels of the NR group were statistically lower than that of the CR group (p=0.018). If MPV ≥10 fL and platelet >12,000/mm³, the probability of an early response with methyl-Pd is higher [sensitivity =98.1% (95% confidence interval (CI) =89.7-99.9%), specificity =45% (95% CI =23.1-68.5%), positive predictive value =82.3% (95% CI =75.7-87.4%), negative predictive value =90% (95% CI =54.9-98.5%)]. Conclusions: Patients with ITP with low platelet and MPV levels were less responsive to standard-dose methyl-Pd treatment. It may be more appropriate to apply more effective treatments to these patients other than standard-dose methyl-Pd alone.

Comparison of maintenance regimens in Acute Promyelocytic Leukemia patients.

Maintenance therapy in APL is still a standard especially in high-risk patients treated with chemotherapy+ATRA combination whereas the role of the maintenance therapy in low-risk patients is controversial. This study aims to compare the efficacy and toxicity of ATRA monotherapy and ATRA+MTX+ 6-MP combination as the maintenance treatment for 2 years in APL patients who achieved molecular complete response after induction and consolidation with ATRA+chemotherapy. A total of 71 patients from 4 different centers were included in this study. After a median follow-up of 54 months (5-180 months), the 5-year RFS was 89 % in the ATRA monotherapy arm, the 5-year RFS was 78.5 % in the combined treatment arm (p = 0.643, HR:1.3, 95 % CI: 0.35-5.3). Hematological toxicity in all grades and Grade III/IV hematological toxicity was observed significantly more in the combined treatment arm than in the ATRA monotherapy arm (All grades: 76.9 % vs 18.9 %, p < 0.001; Grade III/IV: 20.5 % vs. 3.1 %, p = 0.035). Hepatotoxicity at all levels was significantly higher in the combined treatment arm than in the ATRA monotherapy arm (61.5 % vs 25 %, p = 0.002). Our study concluded that two years of ATRA monotherapy and combined maintenance therapy, both of which were found to be similar in terms of disease control and long term survival, ATRA Monotherapy could be a safer maintenance treatment option since both hematological and non-hematological toxicities were observed less often in the ATRA monotherapy arm.

Effect of Blood Groups on Clinical Presentations and Treatment Outcomes in Immune Thrombotic Thrombocytopenic Purpura Patients with Severe ADAMTS13 Deficiency: A Multi-Center Experience.

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy caused by accumulation of ultra-large von Willebrand factor (vWF) due to the significantly reduced activity ADAMTS13. Limited studies have been published examining the blood group as an epidemiological factor that can contribute to development of TTP. It has been suggested that due to low vWF levels, the distribution of the "O" blood group among TTP patients may be lower than anticipated compared to the blood group distribution rates in the normal population. The aim of this study was to explore the relationship between blood groups and the clinical outcome of immune TTP (iTTP). Methods: Thirty patients with iTTP with severe ADAMTS13 deficiency were enrolled. Data collection commenced in January 2011 and was completed by June 2020. It was analyzed whether there was a difference between the blood groups in terms of frequency of iTTP, response to treatment, frequency of relapse, and clinical and laboratory results. Results and Conclusions: The distribution of group "A" among patients with iTTP was higher than expected. Although not statistically significant, patients with blood group "O" required more TPE for the treatment and relapse rate was statistically higher than other blood groups. Mortality rate in all patients was 6.7%. Although blood group "A" is a risk factor for iTTP, the frequency of relapse is higher in the blood group "O."

Do we need to evaluate patients with spontaneous subconjunctival haemorrhage for bleeding disorders?

AIM OF THE STUDY: Subconjunctival haemorrage (SCH) is a frequent bleeding manifestation and a common cause of visits to the primary care. Trauma in young patients and vascular damage such as hypertension in the elderly are the most common causes of SCH and the prevalence of haematological diseases is <1%. We aimed to evaluate the prevalence of congenital or acquired bleeding disorders in patients with once or recurrent SCH. METHODS USED TO CONDUCT THE STUDY: It is a retrospective study and included fifty-two patients with SCH whose aetiologic factor was not detected. Haemostatic tests were studied in 52 patients (25 male and 27 females). All patients included were evaluated for congenital or acquired bleeding disorder and SCH with once and those with two or more were compared for the laboratory results. RESULTS OF THE STUDY: Type I von Willebrand disease (vWD) was diagnosed in one patient with recurrent SCH and one patient with single SCH (3.8%). The prevalence of patients with type 1 vWD in the study was not statistically significant when compared with the frequency of vWD in the normal population. Fibrinogen level was found to be statistically higher in patients who had SCH once than those who had recurrent SCH. However, fibrinogen level was in normal range in all patients. CONCLUSIONS DRAWN FROM THE STUDY AND CLINICAL IMPLICATIONS: There was no increase in the incidence of congenital or acquired bleeding disorder in SCH compared with normal population. Fort this reason, it was thought there was no need for evaluation for bleeding disorders in spontaneous SCH.

Effects of sleeve gastrectomy on neutrophil-lymphocyte ratio.

OBJECTIVES: Obesity and related diseases have become one of the most important health problems in the modern age. In addition to its clinical use in the treatment of obesity, bariatric surgery reduces obesity-induced inflammation. Neutrophil-lymphocyte ratio (NLR) is a cheap and easily attainable inflammatory marker. The purpose of this study is to show the effect of bariatric surgery on NLR at preoperative and postoperative 3rd, 6th, and 12th months after SG. METHODS: 298 patients, who underwent sleeve gastrectomy (SG) in general surgery clinic between 2015 and 2017, were included in the study. We excluded the patients younger than 18 years old, and did not have any inflammatory, infectious, hematological, and comorbide diseases such as diabetes mellitus, cardiovascular diseases, ischemic heart disease, hypertension, renal insufficiency, cancer, and respiratory problems like asthma, obstructive sleep apnea syndrome. We evaluated the levels of NLR at preoperative and postoperative 3rd, 6th, and 12th months visits. RESULTS: There were a total of 298 adult patients (age: mean 38.6, minimum 18, maximum 69 years old). Of whom 247 were female (82.9%) and 51 were male (17.1%). We found that NLR levels decreased significantly at 3rd, 6th, and 12th month visits after SG (p<0.001). CONCLUSIONS: We concluded that NLR levels decrease after surgery in a proportional reduction in adipose tissue. The decrease in NLR levels may also be associated with the protective effects of sleeve gastrectomy against low-grade inflammation-related diseases.

MATRA-A: A study on massive transfusion.

BACKGROUND: We use massive transfusion in various clinical conditions and it is associated with high mortality. Although some massive transfusion protocols improve patient outcomes, the clinical circumstances requiring it are not well defined. METHODS: MATRA-A is a multicenter retrospective study. Six University and Training Research Hospitals in Ankara participated in the study. We collected clinical data on patients (>18 years) who received massive transfusions (≥10 units/24 h) from 2017 through 2019. RESULTS: Overall, 167 (0·27% of transfused patients) received a massive transfusion of 2586 units of red blood cells (1·5% of total RBCs transfused). The median interquartile range values for RBCs, fresh frozen plasma (FFP) and platelets were 13 (11-176), 16 (9-33) and 4 (0-11), respectively. Surgical patients received 90% of massive transfusions. The most common clinical indications for massive transfusion were cardiovascular diseases (42·6%), trauma (20·3%) and malignancies (11%). FFP: RBC: Platelets ratio was 1·9:1:0·5. The overall and trauma-related mortality rates were 57·4% and 61·8%, respectively. The hospital mortality rates of trauma patients that received high vs. low ratio (FFP: RBCs > 1:1·5 vs. ≤1:1·5) transfusions were 47·6% and 86·6% and the difference was statistically significant (P = 0·03). CONCLUSION: Cardiovascular diseases and trauma occasion are the most common causes of massive transfusion. It is infrequent in clinical settings and is associated with high mortality rates. Additionally, in massively transfused trauma patients, a high FFP:RBCs ratio seems to be associated with increased survival. Focused prospective studies are required to define the areas that need improvement on a national scale.

Is fibromyalgia frequency increasing in axial spondyloarthritis? Association with fibromyalgia and biological therapies.

Fibromyalgia (FM) is known a common painful syndrome and its frequency is increased in inflammatory rheumatic diseases. We aimed to assess FM frequency in axial spondyloarthritis (AxSpA) patients and age- and sex-matched healthy controls with the 2011 ACR FM criteria. We evaluated the association between receiving biologic disease-modifying antirheumatoid drugs (bDMARD) and presence of FM. 127 patients with Ax-SpA and 73 age- and sex-matched controls were included. Individuals were assessed according to modified 2011 ACR diagnostic criteria for FM. The pain was evaluated by visual analog scale (VAS). Disease activity was assessed by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activation Score (ASDAS). Spinal limitation, quality of life, and functionality were assessed. Drug therapies were noted. AxSpA and control group had similar FM rates. 43 (33.9%) patients in AxSpA group and 22 (30.1%) patients in control group had FM diagnosis (p = 0.589). Age, gender, BMI, and CRP values were similar in the AxSpA patients with and without FM, while global VAS and ASDAS scores were higher in patients with FM. Biologic DMARD use was higher in the AxSpA patients with FM; however, the difference was not statistically significant. In conclusion, FM frequency does not increase in AxSpA patients as compared to healthy controls. FM awareness is one of the key points to determine the appropriate treatment due to the influence on disease activity.

Lower plasma soluble TWEAK concentration in patients with newly diagnosed hypertension.

PURPOSE: To determine circulating levels of the soluble TNF-like weak inducer of apoptosis (sTWEAK)and its association with demographic and biochemical parameters in a young group of patients with newly diagnosed and never treated hypertension. METHODS: A total of 51 patients (mean age 21.7 ±1.4 years, body mass index (BMI) 24.5 ±1.6 kg/m2) with primary untreated hypertension, and 37 age- and BMI-matched healthy controls (mean age 22.5 ± 1.9 years, BMI 24.7 ± 1.5 kg/m2) were studied. Serums TWEAK and plasma asymmetrical dimethyl arginine (ADMA) levels were measured by EIA. RESULTS: In patients and controls, mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) were 149.8±5.65/93.4±3.4 mmHg and 124.2±6.4/78.24±5.5 mmHg, respectively. Serum sTWEAK levels were lower in the patient group (882.6±228.9 µmol/L vs. 1060.2±231.7µmol/L, p=0.001), whereas plasma ADMA levels were higher(0.837±0.34µmol/L vs.0.3176±0.25µmol/L, p < 0.001). sTWEAK serum levels correlated with SBP(r=-0.301; p=0.005) and DBP (r=-0.279; p=0.009). Circulating plasma ADMA levels also correlated with SBP (r=0.734; p < 0.001) and DBP (r=0.733; p < 0.001). CONCLUSION: Young patients with yet untreated primary hypertension have lower circulating serum sTWEAK level compared with healthy controls. Further research for possible associations among serum sTWEAK, endothelial dysfunction and other measures of atherosclerosis may be of benefit in order to better understand the pathophysiology of hypertension and to establish more effective treatment options.

A rare initial manifestation of acute lymphocytic leukemia: bilaterally enlarged kidneys and liver.

A case with early presentation of acute lymphocytic leukemia with bilaterally enlarged kidneys and liver is presented. Both hepatic and renal infiltration with leukemic cells is a rare manifestation of acute lymphocytic leukemia.