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.

Outcomes of Autologous Stem Cell Transplantation as a Consolidative Strategy for the Treatment of Primary and Isolated Secondary Central Nervous System Diffuse Large B Cell Lymphomas.

INTRODUCTION: Standard consolidation for primary diffuse large B cell lymphoma (DLBCL) of the central nervous system (CNS) (PCNSL) is not established. This single center, retrospective observational study aims to define the outcomes of consolidative high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in patients with PCNSL and isolated secondary CNS DLBCL (SCNSL) and evaluate the prognostic factors. PATIENTS AND METHODS: All consecutive patients performed an HDC/ASCT for PCNSL or isolated SCNSLs between October 2012 and February 2022 were identified. Primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Among 35 patients included, 28 had PCNSL and 7 had isolated SCNSL. Median age was 51 (16-78). Males constituted 48.6%. Median follow-up after HDC/ASCT was 42.0 months. MATRIX (51.4%) and TEAM (80.0%) were the most frequent regimens of induction and conditioning, respectively. OS and PFS 1- and 2-year after HDC/ASCT were 68.0%, 57.0%, 58.0%, 48.0%, respectively. Increasing age, poor performance and comorbidities were associated with lower OS and PFS and higher non-relapse mortality (NRM). Complete response (CR) 1 at HDC/ACST was independently associated with higher OS and PFS [hazard ratio (HR): 4.67 and 6.99, respectively]. CONCLUSION: In patients < 60 years consolidative HDC/ASCT yields promising OS and PFS. Patients ≥ 60 years may less likely benefit from consolidative HDC/ASCT and should be studied further in trials of novel agents, lower doses of consolidative radiotherapy and dose-adjusted conditioning regimens. Not only age, but also comorbidities, clinical performance and response to induction correlate with outcomes. Patients with isolated SCNSL may achieve similar outcomes.

Gemcitabine, Cisplatin, and Dexamethasone as a Salvage and Mobilization Chemotherapy Before Autologous Stem Cell Transplantation is Effective and Safe Outpatient Regimen in Relapsed and Refractory Hodgkin Lymphoma Patients.

BACKGROUND: Second line salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the current standard treatment for eligible patients with relapsed and refractory (R/R) Hodgkin lymphoma (HL). Several salvage regimens have been used before ASCT. However the optimal salvage regimen is still unclear. We report outcome of patients with R/R HL treated with gemcitabine, cisplatin, and dexamethasone (GDP) regimen before ASCT in this retrospective study aiming at evaluating efficacy, stem cell mobilization activity and safety of GDP in a real-life setting. PATIENTS AND METHODS: Forty-five patients with R/R HL who were treated with GDP as salvage and mobilization regimen before ASCT were analyzed retrospectively. Peripheral blood stem cells (PBSC) were collected after GDP. All patients underwent ASCT after 2 cycles of GDP. RESULTS: Thirty-six (80%) patients achieved overall response including 24 (53.3%) complete response (CR). PBSC collections were adequate in all patients with a median number of 11.01 × 106/kg CD34+ cells. The most common grade 3/4 hematological adverse events were thrombocytopenia (31.1%) and neutropenia (22.2%). There were no febrile neutropenic episodes. Grade 3 or 4 renal, hepatic, or cardiac toxicity was not observed. The 4 year progression-free survival and overall survival for patients receiving GDP followed by ASCT were 72% and 92%, respectively. CONCLUSION: Our results suggest that GDP is a viable therapeutic option before ASCT with high response rate, favorable toxicity profile and excellent mobilization potential. Applicability of GDP on an outpatient setting also provides advantage over other effective salvage regimens.

Endoscopic evaluation of acute intestinal graft-versus-host disease after allogeneic hematopoietic cell transplantation.

BACKGROUND/AIMS: Acute graft-versus-host disease (GVHD) is a common complication of haematopoietic cell transplantation (HCT), with the gastrointestinal tract (GIT) as one of the main target organs. There is a lack of consensus regarding the site in GIT with the highest sensitivity for biopsy. The present study aimed to determine the endoscopic and histological findings in acute GVHD. MATERIALS AND METHODS: The data of 111 patients who had received allogeneic HCT were retrospectively reviewed. RESULTS: Allogeneic HCT was performed in 111 patients, of whom 27 (24.3%) had developed acute GVHD. Nineteen of the 111 patients with intestinal symptoms were evaluated for intestinal involvement, and 17 were diagnosed with acute intestinal GVHD. Upper endoscopic findings had a sensitivity of 64.7%, a specificity of 50%, a positive predictive value of 91.6% and a negative predictive value of 14.2%. The diagnostic accuracy of upper endoscopy was 63.1%. Lower endoscopic findings had a sensitivity of 40% and a specificity of 0%. The diagnostic accuracy of upper endoscopy with duodenal biopsy and sigmoidoscopy was 94.1%. CONCLUSION: Endoscopic findings are nonspecific in acute intestinal GVHD. There is little agreement between endoscopic findings and histopathology; thus, biopsies are essential. In patients with intestinal symptoms after HCT, upper endoscopy with duodenal biopsy and sigmoidoscopy has an acceptable diagnostic yield for intestinal involvement.

Health-care associated bacteremia in geriatric cancer patients with febrile neutropenia.

OBJECTIVE: The aim of this study was to determine the epidemiology, clinical manifestations, and outcome of health-care associated bacteremia in geriatric cancer patients with febrile neutropenia. MATERIALS AND METHODS: We retrospectively evaluated cancer patients with febrile neutropenia aged ≥60years with culture proven health-care associated bacteremia between January 2005 and December 2011. The date of the first positive blood culture was regarded as the date of bacteremia onset. Primary outcome was the infection related mortality, defined as the death within 14days of bacteremia onset. RESULTS: The two most common pathogens responsible for bacteremia were Staphylococcus epidermidis (36.1%) and Escherichia coli (31.5%), with high rates of methicillin resistance and extended-spectrum ß-lactamase (ESBL) production, respectively. There were no statistically significant differences in infection related mortality rate according to the type of malignancy (p=0.776). By the univariate analysis, factors associated with 14day mortality among febrile neutropenic episodes were prolonged neutropenia (p=0.024), persistent fever (p=0.001), hospitalization in ICU (p<0.001) and the initial clinical presentations including respiratory failure (p<0.001), hepatic failure (p=0.013), hematological failure (p<0.001), neurological failure (p<0.001), severe sepsis (p<0.001), and septic shock (p=0.036). Multivariate analysis showed that persistent fever was an independent factor associated with infection related mortality (odds ratio, 18.0; 95% confidence interval, 5.2-62.6; p<0.001). CONCLUSIONS: The only independent risk factor for mortality was persistent fever. Although the most frequently isolated pathogens were S. epidermidis and E. coli, high rates of methicillin resistance and ESBL production were found respectively.

Plasma concentrations of angiopoietin-1, angiopoietin-2 and Tie-2 in colon cancer.

BACKGROUND/AIM: despite the rapidly accumulating histopathological data reporting differences in the expression of members of the angiopoietin family on the surface of various normal and tumour cells, data for these growth factors in plasma from cancer patients, including colon cancer, are scarce. The aims of the present study were to measure the plasma concentrations of Ang-1, Ang-2 and Tie-2 in colon cancer patients, and to assess the correlation between the concentrations of these factors and the stage of the tumor. PATIENTS AND METHODS: the study cohort included 36 patients (18 male, 18 female) with colon cancer (mean age 52.6 ± 15.0), and 36 sex- and age-matched, healthy controls who were free of inflammatory, neoplastic, atherosclerotic and connective tissue disease, recruited from hospital staff and attendees at hospital for check-up. Concentrations of Ang-1, Ang-2 and Tie-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: concentrations of Ang-2 (median 3,188.0 pg/mL, min: 1,070.5-max: 5,765.5) and Tie-2 (median 22 ng/mL, min:12-max:46) were significantly higher in patients with colon cancer, while concentrations of Ang-1 were not statistically different between the groups. Furthermore, concentrations of Ang-2 (median 4,292.0 pg/mL, min: 3,090.0-max: 5,765.5) were found to be significantly higher in stage III patients compared to stage II patients, whereas no difference was found between the concentrations of Ang-1 and Tie-2 in different colon cancer stages. CONCLUSION: plasma concentrations of Ang-1, Ang-2 and Tie-2 may be valuable, additional, tumor markers in colon cancer that should be tested in further trials.

ABO blood group and risk of pancreatic cancer in a Turkish population in Western Blacksea region.

BACKGROUND: We aimed to investigate the relationship between blood groups and pancreatic cancer in a Turkish population in Western Blacksea region. METHODS: This is a retrospective study. Zonguldak Karaelmas University outpatient oncology clinic records were screened for the period between 2004 and 2011. RESULTS: The median age of patients were 56 (± 16) and 132 of 633 study population had pancreatic cancer. Pancreatic cancer patients had significantly higher rates of blood group A compared to controls (OR 1.8, 95%CI, p 0.005). Rates of blood group AB was significantly lower than the control group (OR 0.37, 95% CI, p 0.04). The median survival (IR) time in subjects having the blood groups A, B, AB and O were 7.0 (1-28), 7.0 (2-38), 10 (2-36) and 9.0 (2-48) months respectively; the blood group 0 had significantly higher overall survival (OS) compared to the non-0 groups (p 0.04). CONCLUSIONS: Pancreatic cancer patients had more common blood group A in our population. Moreover, blood group AB appeared to be a protective factor against pancreatic cancer in our population. Blood group 0 had a significantly longer survival compared to non-0, regardless of prognostic factors.

Plasma concentrations of Ang-1, Ang-2 and Tie-2 in gastric cancer.

BACKGROUND/AIM: Ang-1 and Ang-2 have both been identified as ligands for Tie-2, a receptor expressed on endothelial cells (EC). They play critical roles in angiogenesis, in concert with VEGF. Ang-1-binding to Tie-2 maintains and stabilizes mature vessels by promoting interactions between EC and the surrounding extra-cellular matrix. However, Ang-2 shows context-dependent, proangiogenic and antiangiogenic activities. Despite the rapidly accumulating histopathological data reporting differences in the expression of members of the Ang family on the surface of various normal and tumour cells, data for these growth factors in plasma from cancer patients, including gastric cancer, remain scarce. The aims of the present study were to measure the plasma concentrations of Ang-1, Ang-2 and Tie-2 in gastric cancer patients, and to assess the correlation between the concentrations of these factors and the stage of the tumor. PATIENTS AND METHODS: The study cohort consisted of 50 patients (33 male, 17 female) with gastric cancer, ranging in age from 38 to 74 years (mean age 55.3±12.4), and 50 sex- and age-matched, healthy controls. Determinations of Ang-1, Ang-2 and Tie-2 were performed using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: Concentrations of Ang-2 and Tie-2 were significantly higher in patients with gastric cancer than controls, while concentrations of Ang-1 were not statistically different between the groups. Concentrations of Ang-1, Ang-2 and Tie-2 were not statistically significantly different in gastric cancer patients with different stages of disease. CONCLUSION: Ang-2 and Tie-2 plasma concentrations might be useful, additional tumor markers in gastric cancer.

Effects of pegylated interferon α on fibrinolytic parameters in patients with chronic hepatitis C.

Interferon (IFN) interacts with endothelial cells and modulates the functions of these cells. In our study, we aimed to determine the effects of treatment with pegylated IFN-α (peg-IFN-α) on fibrinolytic parameters in patients with chronic hepatitis C. Fifteen patients with chronic hepatitis C were treated with peg-IFN-α once per week plus daily oral ribavirin. Euglobulin lysis time (ELT), plasma levels of D-dimer, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI) were determined before treatment, 2 weeks, 1 month, and 3 months after the initiation of the treatment. Plasma levels of t-PA increased significantly 1 month and 3 months after the treatment (P < .05). The PAI-1 and TAFI levels in 2 weeks, 1 month and 3 months after treatment were not statistically different as compared with pretreatment levels (P > .05) No significant difference in plasma D-dimer levels was observed during peg-IFN-α treatment (P > .05). There was a significant decrease in ELT 1 month and 3 months after the treatment (P < .05). Our results indicated that treatment with peg-IFN-α may be associated with enhanced fibrinolysis.

[An adult case of visceral leishmaniasis in a province of Black-Sea region, Turkey]. / Zonguldak'ta eriskin viseral leysmaniyaz olgusu.

Visceral leishmaniasis (VL) which is a chronic disease caused by the protozoon, Leishmania, occurs widely worldwide and it is widespread in most of the countries in the Mediterranean basin. The infection which is transmitted by a sandfly (Phlebotomus) vector, has a prolonged incubation period and insidious onset. VL generally affects children and may be fatal if not treated. In this report, a 31 years old male patient, who was the first adult VL case from Zonguldak (a province located at western Black-Sea region of Turkey) was presented. He was admitted to the hospital with two-months history of fever, chills, sweating and weight loss. There was no history of travel outside the city nor insect bites, however, he indicated that there would be unnoticed sandfly bites since sandflies were very common in the coal mines he worked. His physical examination revealed body temperatue of 39.2°C and hepatosplenomegaly, while laboratory findings yielded anemia, leucopenia, hypoalbuminemia and hypergamaglobulinemia. Erythrocyte sedimentation rate was 62 mm/h, C-reactive protein was 113 mg/L and liver transaminases were 2 to 5 folds higher than the reference values. The only pathological finding was hepatosplenomegaly in the abdominal ultrasound and computerized tomography. He was further examined to rule out infections with similar signs and symptoms, connective tissue diseases and malignancies and all were found negative. Hypercellular bone marrow were detected in the aspiration material. Bone marrow smears, bone marrow samples inoculated in NNN medium and serum samples of the patient were sent to the reference parasitology laboratory of Refik Saydam National Public Health Agency for evaluation in terms of VL. The diagnosis was confirmed by the detection of Leishmania IgG titer as 1/512 with in-house indirect immunofluorescence antibody test, by positivite rK39 Dipstick (InBios, USA) test and by the observation of Leishmania amastigote forms in the bone marrow smears. Bone marrow culture in NNN medium also revealed positive result by the determination of Leishmania promastigote forms on the 7th day. The treatment was initiated by pentavalent antimony [glucantime 1 x 10 mg/kg/day intramuscular (IM)] however, due to severe adverse effects it has switched to liposomal amphotericin B (3 mg/kg/day). The patient completely recovered without complication. In conclusion VL should be considered in the differential diagnosis of patients, even adults, with persistent fever, hepatosplenomegaly and pancytopenia, in endemic countries such as Turkey.

Piperacillin-tazobactam versus carbapenem therapy with and without amikacin as empirical treatment of febrile neutropenia in cancer patients: results of an open randomized trial at a university hospital.

OBJECTIVE: Empirical beta-lactam monotherapy has become the standard therapy in febrile neutropenia. The aim of this study was to compare the efficacy and safety of piperacillin-tazobactam versus carbapenem therapy with or without amikacin in adult patients with febrile neutropenia. METHODS: In this prospective, open, single-center study, 127 episodes were randomized to receive either piperacillin-tazobactam (4 x 4.5 g IV/day) or carbapenem [meropenem (3 x 1 g IV/day) or imipenem (4 x 500 mg IV/day)] with or without amikacin (1 g IV/day). Doses were adjusted according to renal function. Clinical response was determined during and at completion of therapy. RESULTS: One hundred and twenty episodes were assessable for efficacy (59 piperacillin-tazobactam, 61 carbapenem). Mean duration of treatment was 14.8 +/- 9.6 days in the piperacillin-tazobactam group and 14.7 +/- 8.8 days in the carbapenem group (P > 0.05). Mean days of fever resolution were 5.97 and 4.48 days for piperacillin-tazobactam and carbapenem groups, respectively (P > 0.05). Similar rates of success without modification were found in the piperacillin-tazobactam (87.9%) and in the carbapenem groups (75.4%; P > 0.05). Fungal infection occurrence rates were 30.5 and 18% in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.05). Antibiotic modification rates were 30.5 and 13.1% (P = 0.02) and the addition of glycopeptides to empirical antibiotic regimens rates were 15.3 and 44.3% for piperacillin-tazobactam and carbapenem groups, respectively (P = 0.001). The rude mortality rates were 14% (6/43) and 29.3% (12/41) in piperacillin-tazobactam and carbapenem groups, respectively (P = 0.08). CONCLUSIONS: The effect of empirical regimen of piperacillin-tazobactam regimen is equivalent to carbapenem in adult febrile neutropenic patients.

Evaluation of 143 cases of immune thrombocytopenic purpura with regards to clinical course and response to treatment.

OBJECTIVE: Immune thrombocytopenic purpura (ITP) is also known as idiopathic thrombocytopenic purpura. Increased platelet destruction and insufficient platelet production are both responsible for its etiopathogenesis. ITP can be diagnosed after excluding other possible causes of thrombocytopenia. MATERIALS AND METHODS: One hundred forty-three cases of chronic ITP that were monitored in a hematology clinic were retrospectively evaluated. All cases received first line treatment of 1 mg/kg/day prednisolone. Corticosteroid nonresponsive (CN) cases and corticosteroid-dependent (CD) cases underwent splenectomies. RESULTS: The rate of CN/CD cases was found to be 53% (n=76). Sixty-six percent of these cases (n=50) underwent splenectomies. The ratio of non-responsive cases to relapse cases after splenectomy (SN/SR) was 30% (n=15). The total number of cases was 41, including those without splenectomy (n=26) and with SY/SR (n=15). Helicobacter pylori (Hp) eradication, immunosuppressive agents and danazol treatments were administered to patients (n=10, n=14 and n=4, respectively). Currently, 13 patients are being monitored without treatment. Fifteen patients who were non-responsive to Hp eradication treatment, immunosuppressive treatment or danazol treatment are still being monitored without any treatment. CONCLUSION: Optimal treatment is not available for splenectomy-resistant cases of ITP. The response rates for Hp eradication treatment, immunosuppressive treatments and anabolic agents are low. Therefore, larger studies with more patients are required using new agents, such as thrombopoietin (TPO) receptor agonists and anti-CD20 monoclonal antibodies.

Natural anticoagulant protein levels in Turkish patients with inflammatory bowel disease.

Thromboembolism is an important cause of morbidity and mortality in patients with inflammatory bowel disease (IBD). The aim of this study was to investigate common thrombophilic markers in patients with IBD and to search for a relation between these predisposing factors and activity of disease. Seventy-four patients with ulcerative colitis, 22 patients with Crohn's disease and 20 healthy volunteers were enrolled into the study. Plasma levels of protein C, protein S, antithrombin III and activated protein C resistance were determined in patients with IBD and healthy controls. Mean values of protein C, protein S and antithrombin III were significantly lower in patients with ulcerative colitis and Crohn's disease compared with the healthy control group. Patients with active ulcerative colitis had lower protein C, protein S and antithrombin III level than patients in remission (P < 0.001, P < 0.001, P < 0.001). Levels of protein C, S and antithrombin III were also decreased in patients with active Crohn's disease compared with those in remission (P < 0.05, P < 0.001, P < 0.05). Differences in all natural anticoagulant levels between patients in remission and healthy individuals in both ulcerative colitis and Crohn's disease groups were not statistically significant (P > 0.05). No significant difference was observed in activated protein C resistance (APCR) between patients with active disease, those in remission and the control group (P > 0.05). Abnormalities in natural anticoagulants are common in patients with IBD during active disease.

The plateled-derived growth factor level (PDGF) in Hodgkin's disease and non-Hodgkin's lymphoma and its relationship disease activation.

The research reported in this paper was designed to study the role of plateled-derived growth factor (PDGF) in Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL). The PDGF levels in 9 patients with HD and 12 NHL and in a control group consisting of 20 people, was measured by ELISA method. The PDGF values in the disease group of 19 patients were raised. The values of PDGF in the control group were 28.977+/-9 pg/ml, but were measured at 147.083+/-54 pg/ml in HD group and 131.487+/-56 pg/ml in NHL group (p < 0.01). The observation of a 5-fold increase in PDGF values in the disease group when compared to the control group suggests that PDGF could itself be considered as a possible factor in the pathogenesis of HD and NHL. In order to support this, there is a need to design additional studies monitoring PDGF in larger number of patients at various stages of the disease.