Nivolumab for relapsed or refractory Hodgkin lymphoma: real-life experience.

BACKGROUND: Reed-Sternberg cells of classical Hodgkin's lymphoma (cHL) are characterized by genetic alterations at the 9p24.1 locus, leading to over-expression of programmed death-ligand 1 and 2. In a phase 1b study, nivolumab, a PD-1-blocking antibody, produced a high response in patients with relapsed or refractory cHL, with an acceptable safety profile. PATIENTS AND METHODS: We present a retrospective analysis of 82 patients (median age: 30 years; range: 18-75) with relapsed/refractory HL treated with nivolumab in a named patient program from 24 centers throughout Turkey. The median follow-up was 7 months, and the patients had a median of 5 (2-11) previous lines of therapy. Fifty-seven (70%) and 63 (77%) had been treated by stem-cell transplantation and brentuximab vedotin, respectively. RESULTS: Among 75 patients evaluated after 12 weeks of nivolumab treatment, the objective response rate was 64%, with 16 complete responses (CR; 22%); after 16 weeks, it was 60%, with 16 (26%) patients achieving CR. Twenty patients underwent subsequent transplantation. Among 11 patients receiving allogeneic stem-cell transplantation, 5 had CR at the time of transplantation and are currently alive with ongoing response. At the time of analysis, 41 patients remained on nivolumab treatment. Among the patients who discontinued nivolumab, the main reason was disease progression (n = 19). The safety profile was acceptable, with only four patients requiring cessation of nivolumab due to serious adverse events (autoimmune encephalitis, pulmonary adverse event, and two cases of graft-versus-host disease aggravation). The 6-month overall and progression-free survival rates were 91.2% (95% confidence interval: 0.83-0.96) and 77.3% (0.66-0.85), respectively. Ten patients died during the follow-up; one of these was judged to be treatment-related. CONCLUSIONS: Nivolumab represents a novel option for patients with cHL refractory to brentuximab vedotin, and may serve as a bridge to transplantation; however, it may be associated with increased toxicity.

Biological screening of some Turkish medicinal plant extracts for antimicrobial and toxicity activities.

Screening of antibacterial activity and toxicity of 22 aqueous plant extracts from 17 Turkish plants was conducted. Antibacterial activity was performed with six bacteria including Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Streptococcus pyogenes, Staphylococcus aureus and Staphylococcus epidermidis. Extracts of Tussilago farfara leaves, Helichyrsum plicatum flowers, Solanum dulcamara aerial parts and Urtica dioica leaves gave the best inhibitory activity against S. pyogenes, S. aureus and S. epidermidis. Of the 22 plant extracts, 20 extracts displayed toxicity (LC50 was <1000 mg L(-1)) in the brine shrimp bioassay. For radish seed bioassay, two different determinations (root length and seed germination) were performed with a comparison between two concentrations (50,000 mg L(-1) and 10,000 mg L(-1)). At low concentration (10,000 mg L(-1)), S. dulcamara aerial parts and Primula vulgaris leaf extracts were observed to inhibit the root length more than the other plant extracts. Also, the most inhibitive plant extract for seed germination was obtained with S. dulcamara aerial parts.

Prognostic factors and treatment of patients with advanced synovial sarcoma: A single-center experience.

BACKGROUND: Synovial sarcoma (SS) is a malignant mesenchymal tumor, which comprises 5%-10% of all the sarcomas. There is insufficient information on prognostic factors and salvage treatments of advanced SS. In this study, we aimed to further clarify the clinicopathological features, prognostic factors, and treatment modalities in advanced SS. MATERIALS AND METHODS: A total of 45 SS patients followed up between 2001 and 2015 at our cancer institute, Department of Medical Oncology, were retrospectively evaluated. Eleven patients were initially metastatic, and remaining patients developed metastasis or became inoperable due to locally advanced disease. Overall survival was evaluated by Kaplan-Meier analysis. RESULTS: The median age of patients was 37 (17-70) years and 60% (n = 26) of them were female. SS was most commonly localized in the lower extremity and abdomen-pelvis (29% and 29%, respectively). Median follow-up time was 33 (6-175) months. Patients were treated with a median of two (1-5) line chemotherapies at metastatic stage. Ifosfamide plus adriamycin (IMA) (49%, n = 22) and cisplatin-etoposide (13%, n = 6) were the most often used chemotherapy regimen as first line in metastatic stage. Partial response was obtained in 32% of the patients treated with IMA chemotherapy. Furthermore, median progression-free survival was 6 (1-123) months. Median survival of metastatic stage at diagnosis or in follow-up was 21 months (14-27) and 21 (12-29) months (P = 0.53), respectively. Most metastatic locations were lung (75%) and bone. Factors influencing survival at metastatic stage were evaluated; statistically significant longer survival was observed in patients with lung metastasis, primary tumor size smaller than 10 cm, patients who underwent surgery for the metastasis, and development-to-metastasis period longer than 12 months. CONCLUSION: Median survival of patients in metastatic stage SS was 21 months. Lung was the most common metastatic site.

Determination of lead and nickel in environmental samples by flame atomic absorption spectrometry after column solid-phase extraction on Ambersorb-572 with EDTA.

Lead and nickel were preconcentrated as their ethylenediaminetetraacedic acid (EDTA) complexes from aqueous sample solutions using a column containing Ambersorb-572 and determined by flame atomic absorption spectrometry (FAAS). pH values, amount of solid phase, elution solution and flow rate of sample solution have been optimized in order to obtain quantitative recovery of the analytes. The effect of interfering ions on the recovery of the analytes has also been investigated. The recoveries of Pb and Ni under the optimum conditions were 99 +/- 2 and 97 +/- 3%, respectively, at 95% confidence level. Seventy-five-fold (using 750 mL of sample solution and 10 mL of eluent) and 50-fold (using 500 mL of sample solution and 10 mL of eluent) preconcentration was obtained for Pb and Ni, respectively. Time of analysis is about 4.5 h (for obtaining enrichment factor of 75). By applying these enrichment factors, the analytical detection limits of Pb and Ni were found as 3.65 and 1.42 ng mL(-1), respectively. The capacity of the sorbent was found as 0.17 and 0.21 mmol g(-1) for Pb and Ni, respectively. The interferences of some cations, such as Mn2+, Co2+, Fe3+, Al3+, Zn2+, Cd2+, Ca2+, Mg2+, K+ and Na+ usually present in water samples were also studied. This procedure was applied to the determination of lead and nickel in parsley, green onion, sea water and waste water samples. The accuracy of the procedure was checked by determining Pb and Ni in standard reference tea leaves sample (GBW-07605). The results demonstrated good agreement with the certified values.

Posterior leukoencephalopathy after combination chemotherapy in a patient with lymphoma.

Posterior leukoencephalopathy syndrome is a recently described syndrome involving mainly parieto-occipital gray/white matter of the brain. It occurs secondary to various clinical entities, like hypertension and immunosuppressive therapy. Few cases after combination chemotherapy have been reported. This study describes a 36-year-old woman with primary refractory T-cell lymphoma, who developed central nervous system toxicity due to treatment with intrathecal methotrexate and intravenous ifosfamide, idarubicine and etoposide given as a salvage regimen. Both clinical features as well as magnetic resonance imaging findings were typical for posterior leukoencephalopathy syndrome. The patient died despite anti-hypertensive therapy and haemodialysis. Central nervous system toxicity related to chemotherapeutics and posterior leukoencephalopathy syndrome are discussed briefly.

Idarubicin for remission induction of acute myeloid leukemia: United Kingdom multicenter experience.

Ninety-eight adult patients with acute myeloid leukemia were given variable remission induction/consolidation regimens containing idarubicin. Sixty-nine (70%) were new cases (median age, 56 years) and 29 (30%) were in relapse (n = 24) or had primary refractory disease (n = 5) (median age, 46 years). Complete remission (CR) rates were 57% (39 of 69 patients) of the newly diagnosed patients, with no difference for those below or above 55 years of age (56% v 59%) or for patients exhibiting white blood cell counts of less or more than 50 x 10(9)/L (52% v 69%; P = .8). Of the 39 patients who achieved CR, 26 (67%, 38% of the total number of patients) remain in CR with a median follow-up of 3 months (range, 0 to 61 months). Forty-two percent of the relapsed cases (10 of 24 patients) and 60% of the primary refractory disease cases (three of five patients) achieved CR. Of these 13 responders, six are alive (three continuing in CR and three relapsed) with a median follow-up of 3 months (range, 1 to 20 months), and seven have died with a median survival of 7 months (range, 0 to 12 months). Of the 52 patients who have achieved CR, 84% did so with one course of treatment and 16% with two courses. The presence of normal cytogenetic analysis or favorable chromosomal aberrations significantly improved overall CR rates. The patients in this study had significantly more unfavorable cytogenetic abnormalities than the historic controls. Reported toxicity was hepatic in 13%, cardiac in 9%, and renal in 7% of all cases. These data suggest a comparable efficacy of idarubicin to other anthracyclines in remission induction of acute myeloid leukemia, with a promising role in relapsed/refractory disease.

Orbito-ocular granulocytic sarcoma (OOGS) and acute myeloblastic leukemia (AML) with duplication of Philadelphia chromosome.

A 6-year-old Turkish boy with bilateral orbito-ocular granulocytic sarcoma and AML is described. Cytogenetic studies on peripheral blood disclosed an abnormal hyperdiploid population with a double Ph chromosome. Despite intensive chemotherapy, he achieved only partial remission. Repeated cytogenetic studies on bone marrow during relapse revealed the persistence of double Ph chromosome. The aggressive course and the short survival time of this patient, despite adequate chemo-radiotherapy, may be explained by the presence of the double Ph chromosome.

Tension pneumocephalus after transsphenoidal surgery: case report.

The authors present a patient who underwent transsphenoidal surgery for a pituitary adenoma and afterward developed late, severe rhinorrhea and tension pneumocephalus. The patient was treated conservatively.

Intracerebral hemorrhage and hematoma in Behçet's disease: case report.

The authors describe a patient with Behçet's disease who suffered from intracerebral hemorrhage 2 1/2 years after the initial diagnosis. There is strong evidence that this situation is not merely a coincidence; rather, these two abnormalities have a cause and effect relationship.

Association of von Recklinghausen's neurofibromatosis and aqueduct stenosis.

We present 6 patients with a definite diagnosis of von Recklinghausen's neurofibromatosis. All of them had aqueductal stenosis and hydrocephalus requiring surgical intervention because of clinical signs of increased intracranial pressure confirmed by pressure measurements.

Determination of iron and nickel by flame atomic absorption spectrophotometry after preconcentration on Saccharomyces cerevisiae immobilized sepiolite.

Iron and nickel have been preconcentrated on Saccharomyces cerevisiae immobilized sepiolite and determined by flame atomic absorption spectrophotometry (FAAS). Preconcentration studies were conducted by the column method. Effect of pH, amount of adsorbent, elution solution, flow rate and interfering ions on the recovery of the analytes have been investigated. Recoveries of Fe and Ni were 95+/-1 and 99.5+/-0.1%, respectively, at 95% confidence level. The breakthrough capacities of analytes were also investigated and found to be 0.042 mmol g(-1) for Fe and 0.055 mmol g(-1) for Ni. The proposed method was applied to the determination of iron and nickel in brass (NBS SRM 37e). The detection limit of iron and nickel were found as 0.065 and 0.087 mug ml(-1), respectively. The direct determination of trace metals by flame atomic absorption spectrometry (FAAS) is limited and difficult because of low concentration and/or matrix interferences. The proposed method is excellent for the determination of trace metal in matrixes, such as metal alloys.

Direct determination of bismuth, indium and lead in sea water by Zeeman ETAAS using molybdenum containing chemical modifiers.

Direct determination of Bi, In and Pb in sea water samples has been carried out by ETAAS with Zeeman background correction using molybdenum containing chemical modifiers and tartaric acid as a reducing agent. Maximum pyrolysis temperatures and the effect of mass ratios of the mixed modifier components on analytes have been investigated. Mo+Pd+TA or Mo+Pt+TA mixture was found to be powerful for the determination of 50 mug l(-1) of Bi, In and Pb spiked into synthetic and real sea waters. The accuracy and precision of the determination were thereby enhanced. The recoveries of analytes spiked were 94-103% with Mo+Pd+TA or Mo+Pt+TA and they are only 49-61% without modifier.

Hypereosinophilia and metastatic anaplastic carcinoma of unknown primary.

The differential diagnosis of eosinophilia may sometimes be difficult. Eosinophilia may occur in a diverse array of conditions from parasitic infestations to malignacies. Idiopathic hypereosinophilic syndrome has also been described. A 65-year-old male patient presenting with eosinophilia of obscure etiology is described in the present report. Three years after the diagnosis of eosinophilia, metastatic anaplastic carcinoma of unknown primary was detected. Differential diagnosis is disscussed briefly. It is stressed that patients with hypereosinophilia of unknown etiology must be screened for malignancy regularly during follow up.

A simple technique to open the posterior wall of the third ventricle.

Third ventriculostomy is an operating technique which is mostly used in benign adult aqueductal stenosis. The most important stage of this operation is the manipulation of the basal membrane of the third ventricle. A technique which facilitates the opening of the posterior wall of the third ventricle is presented.

Determination of iron, manganese and zinc in water samples by flame atomic absorption spectrophotometry after preconcentration with solid-phase extraction onto Ambersorb 572.

A solid-phase extraction method for the preconcentration of Fe, Mn and Zn on a column containing Ambersorb 572 has been developed, and the determination of Fe, Mn and Zn in water using a flame atomic absorption spectrophotometer (FAAS) has been performed. The optimum preconcentration parameters of the procedure have been determined. The effect of the pH, complexing agent, amount of adsorbent, flow rate, concentration and volume of the elution solution and interfering ions on the recovery of the analytes were investigated. The recoveries of Fe, Mn and Zn were 99 +/- 3%, 98 +/- 3% and 99 +/- 3% at the 95% confidence level, respectively, under the optimum conditions. Fe, Mn and Zn were preconcentrated up to 50, 100, 200, respectively. The limits of detection of Fe, Mn and Zn are 2.5, 0.68 and 0.24 micrograms l-1, respectively. The adsorption capacity of the adsorbent was found to be 10.9, 13.1 and 21.5 mg g-1 for Fe, Mn and Zn, respectively. The method has been applied to the determination of these metal ions in tap-water and river-water samples. The precision and the accuracy of the method is very good. The relative standard deviation and the relative error are lower than 4%.

Use of Escherichia coli immobilized on amberlite XAD-4 as a solid-phase extractor for metal preconcentration and determination by atomic absorption spectrometry.

A sensitive solid-phase extraction technique (SPE) for the enrichment of Fe(III), Co(II), Mn(II) and Cr(III) prior to atomic absorption spectrometric analysis is described. Escherichia coli immobilized on Amberlite XAD-4 was used as a solid-phase extractor. The effects of the pH, amount of solid-phase, eluent type and volume of the sample solution on the recovery of the metal ions were investigated. The effect of diverse ions was also investigated. The recoveries of Fe(III), Co(II), Mn(II) and Cr(III) under the optimum conditions were found to be 99 +/- 2, 99 +/- 3, 98 +/- 2, 98 +/- 3%, respectively, at the 95% confidence level. The detection limits of the metal ions were found as to be 2.4, 3.8, 1.3 and 1.7 ng ml(-1) for Fe(II), Co(II), Mn(II) and Cr(III) respectively, by applying a preconcentration factor of 25. The proposed enrichment method was applied to the determination of analytes in Atatürk Dam water samples, and alloy samples (RSD < 5%). The accuracy of the method was verified on certified alloy samples (NBS SRM 85b and NBS SRM 59a). The analytes were determined with a relative error lower than 5% in water and alloy samples.

Chronic uterine inversion: preservation of the uterus--case report.

Uterine inversion is a rare and dangerous complication of labor. Although it can be reconstructed successfully with prompt intervention in acute stages, surgical interventions are usually mandatory in sub-acute or chronic phases. In this report we present a case of chronic uterine inversion, that was successfully treated with abdominal surgery.

Platelet size has diagnostic predictive value for bone marrow metastasis in patients with solid tumors.

Though not very common, solid tumor involvement of the bone marrow (BM) may have serious consequences. Recent studies have shown that mean platelet volume (MPV) is a good indicator for BM disease in the differential diagnosis of thrombocytopenia. We investigated the significance of MPV in the diagnosis of BM metastasis in patients with solid tumors. Patients with histologically-verified solid tumors for whom BM biopsy specimens were available (n = 121) and healthy controls (n = 62) were included in this retrospective study. A total of 183 individuals were analyzed. Of the patients, 61 had a diagnosis of BM metastasis (Group A), 60 did not have BM metastasis (Group B). Group B and C (healthy controls) constituted the control group without BM metastasis (n = 122). The mean MPV was 7.0 +/- 0.8 fl in patients with BM metastasis and 8.4 fl in the control group (P < 0.001). A cut-off point of <7.4 fl was found to have significant predictive value according to receiver-operating characteristics curve analysis. This cut-off point had 85% positive predictive value and 90% negative predictive value in the diagnosis of BM metastasis (odds ratio: 53; 95% confidence interval: 20-135), and a sensitivity of 82.7% and specificity of 89.6%. MPV can be used as a reliable marker to guide the clinician as to the likely presence or absence of BM metastasis in patients with solid tumors.