Pertuzumab, trastuzumab and taxane-based treatment for visceral organ metastatic, trastuzumab-naïve breast cancer: real-life practice outcomes.

PURPOSE: In this study, we aimed to describe the real-life practice outcomes of pertuzumab-trastuzumab-taxane (PTT) combination in visceral organ metastatic, trastuzumab-naive breast cancer (BC) patients. METHODS: This study was conducted by Turkish Oncology Group and included 317 patients' data from 36 centers. RESULTS: Median age was 51 (22-82). Median PFS was 28.5 months, while median OS was 40.3 months. Patients with brain metastases (n: 13, 4.1%) had worse PFS (16.8 m vs. 28.5 m; p = 0.002) and OS (26.7 m vs. 40.3 m; p = 0.009). Patients older than 65 years of age (n: 42, 13.2%) had significantly lower OS results (19.8 m vs. 40.3 m; p = 0.01). Two hundred sixty-eight patients (86.7%) received docetaxel while 37 patients (11.7%) received paclitaxel. PFS and OS were similar between taxane groups. In eight patients (2.5%), 5-40% ejection fraction decrement from baseline was detected without any clinical sign of heart failure. CONCLUSIONS: Our RLP trial included only visceral metastatic, trastuzumab-naïve BC patients including cases with brain involvement who received PTT combination in the first-line treatment. Regardless of negative prognostic characteristics, our results are in parallel with pivotal trial. Further strategies for brain metastasis should be developed to improve outcomes despite encouraging results with PTT treatment. Taxane selection can be personalized and endocrine maintenance may further improve outcomes after taxanes were discontinued. To our knowledge, this is the largest scale real-life clinical practice study of pertuzumab-trastuzumab-taxane therapy to date.

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.

A Very Rare Case -  Hairy Cell Leukemia in Patient with Sarcoidosis.

Although the coexistence of hairy cell leukemia with sarcoidosis has been reported in a few cases in the literature, in our case the patient had been diagnosed and followed about 10 years with sarcoidosis and massive splenomegaly. It has been demonstrated that T helper 1 cells exist in organs influenced by sarcoidosis. These cells produce IL-2 and IFN-γ and induce a nonspecific inflammatory response and granuloma formation. Also these cytokines may play a role in the development of hairy cell leukemia.Key words: hairy cell leukemia -  sarcoidosis - massive splenomegaly.

Brentuximab vedotin for relapsed or refractory Hodgkin lymphoma: experience in Turkey.

Current treatment modalities can cure up to 70-80 % of patients with classical Hodgkin lymphoma. Approximately, 20-30 % of patients require further treatment options. Brentuximab vedotin has been approved for the treatment of relapsed and refractory Hodgkin lymphoma. In the present study, we report the experience with brentuximab vedotin as single agent in 58 patients with relapsed or refractory Hodgkin lymphoma. The objective response rate was 63.5 % with 13 complete responders (26.5 %) among 49 patients evaluated at the early phase of treatment (2-5 cycles). Upon treatment prolongation (≥6 cycles), 37 patients achieved a final objective response rate of 32.4 % with 21.6 % of complete and 10.8 % of partial response. Overall survival at 12 months was 70.6 %, and progression-free survival at 12 months was 32.8 %. Median overall survival could not be reached and median progression-free survival was 7 months. While the median duration of response was 9 months in the whole cohort, it was 11.5 months in the complete responders. Complete response rates in patients treated with >3 chemotherapy regimens before brentuximab vedotin were significantly lower (p = 0.016). Fourteen patients were subsequently transplanted. In conclusion, brentuximab vedotin provided a bridge to transplantation in approximately one quarter of the patients. The declining response rates during the course of treatment suggest that transplantation should be implemented early during brentuximab vedotin treatment.

Oxidative stress status and plasma trace elements in patients with asthma or allergic rhinitis

Introduction: This study was conducted to evaluate the oxidant/antioxidant balance (oxidative stress status) and plasma essential trace element levels in patients with bronchial asthma or allergic rhinitis. Methods: A total of 94 individuals consisting of 19 allergic asthmatics; 17 non-allergic asthmatics; 22 patients with allergic rhinitis; and 36 healthy control people were enrolled into this study. Superoxide dismutase (CuZnSOD) and glutathione peroxidase (GSH-Px) activity as antioxidant defence mechanism parameters, along with malondialdehyde (MDA) as a marker of lipid peroxidation, were determined in erythrocytes of patient groups and controls. Plasma copperand zinc levels were also determined in all groups. Results: CuZnSOD activity was significantly lower in all groups of patients (p<0.001 for allergic asthmatics, p=0.008 for allergic rhinitis patients, and p<0.001 for non-allergic asthmatics) when compared to those of controls. Erythrocyte GSH-Px enzyme activity was not different when compared to that of the control group. Similarly, the patient groups had no difference from those of the controls with respect to erythrocyte MDA levels. While plasma Cu levels in all asthmatic patients were not different from those of the controls, allergic rhinitis patients had significantly elevated (p<0.001) Cu levels compared to those of the controls. No statistically significant difference was established between patient groups and controls with respect to plasma zinc levels. Conclusion: While defective CuZnSOD activity observed in all patients groups was expected to cause an increase in lipid peroxidation indicated by high MDA levels in these patients groups, the fact that MDA levels were not different from those of controls in all patient groups indicates that other components of anti-oxidant defence system preserve their functions in these patients. On the other hand, statistically significant difference between all patients groups and controls with respect to trace elements was only observed in allergic rhinitis patients who had higher levels of Cu than those of controls (AU)

Oxidative stress status in patients with chronic idiopathic urticaria

Aim: The controversial data related to oxidative stress status in patients with chronic idiopathic urticaria (CIU) have been reported. Therefore, the present study was aimed to contribute to this debate by determining oxidative stress markers along with some trace element levels inpatients with CIU. Methods: Twenty-five patients with CIU (10 males, 15 females) and 36 healthy controls were enrolled into the study. Erythrocyte lipid peroxidation status, scavenger enzyme activities and trace element levels were determined. Results: While erythrocyte MDA levels, erythrocyte GSH- Px activities and erythrocyte Zn levels showed no differences between the patient and control groups, a statistically significant decrease and increase were observed in erythrocyte CuZn-SOD activities and Cu levels, respectively, in the CIU patients when compared to those of the controls (p < 0.001 for both of them). Conclusion: In conclusion, an oxidative burden which can be relieved by some preserved antioxidant mechanisms seems to be present in patients with CIU even if they are clinically stable and it may probably have a role in the pathogenesis (AU)

Oxidative stress status and plasma trace elements in patients with asthma or allergic rhinitis.

INTRODUCTION: This study was conducted to evaluate the oxidant/antioxidant balance (oxidative stress status) and plasma essential trace element levels in patients with bronchial asthma or allergic rhinitis. METHODS: A total of 94 individuals consisting of 19 allergic asthmatics; 17 non-allergic asthmatics; 22 patients with allergic rhinitis; and 36 healthy control people were enrolled into this study. Superoxide dismutase (CuZnSOD) and glutathione peroxidase (GSH-Px) activity as antioxidant defence mechanism parameters, along with malondialdehyde (MDA) as a marker of lipid peroxidation, were determined in erythrocytes of patient groups and controls. Plasma copper and zinc levels were also determined in all groups. RESULTS: CuZnSOD activity was significantly lower in all groups of patients (p<0.001 for allergic asthmatics, p=0.008 for allergic rhinitis patients, and p<0.001 for non-allergic asthmatics) when compared to those of controls. Erythrocyte GSH-Px enzyme activity was not different when compared to that of the control group. Similarly, the patient groups had no difference from those of the controls with respect to erythrocyte MDA levels. While plasma Cu levels in all asthmatic patients were not different from those of the controls, allergic rhinitis patients had significantly elevated (p<0.001) Cu levels compared to those of the controls. No statistically significant difference was established between patient groups and controls with respect to plasma zinc levels. CONCLUSION: While defective CuZnSOD activity observed in all patients groups was expected to cause an increase in lipid peroxidation indicated by high MDA levels in these patients groups, the fact that MDA levels were not different from those of controls in all patient groups indicates that other components of anti-oxidant defence system preserve their functions in these patients. On the other hand, statistically significant difference between all patients groups and controls with respect to trace elements was only observed in allergic rhinitis patients who had higher levels of Cu than those of controls.

Oxidative stress status in patients with chronic idiopathic urticaria.

AIM: The controversial data related to oxidative stress status in patients with chronic idiopathic urticaria (CIU) have been reported. Therefore, the present study was aimed to contribute to this debate by determining oxidative stress markers along with some trace element levels in patients with CIU. METHODS: Twenty-five patients with CIU (10 males, 15 females) and 36 healthy controls were enrolled into the study. Erythrocyte lipid peroxidation status, scavenger enzyme activities and trace element levels were determined. RESULTS: While erythrocyte MDA levels, erythrocyte GSH- Px activities and erythrocyte Zn levels showed no differences between the patient and control groups, a statistically significant decrease and increase were observed in erythrocyte CuZn-SOD activities and Cu levels, respectively, in the CIU patients when compared to those of the controls (p < 0.001 for both of them). CONCLUSION: In conclusion, an oxidative burden which can be relieved by some preserved antioxidant mechanisms seems to be present in patients with CIU even if they are clinically stable and it may probably have a role in the pathogenesis.

Comparison of lymphomononuclear cell energy metabolism between healthy, impaired glucose intolerance and type 2 diabetes mellitus patients.

Diabetes mellitus (DM) is a complex disease that affects many systems. The most important cells of the immune system are lymphomononuclear (LMN) cells. Here, we aimed to evaluate the energy metabolism of LMN cells in patients with diabetes and impaired glucose tolerance. We measured LMN cell energy metabolism in patients with type 2 diabetes mellitus, impaired glucose tolerance (IGT) and healthy subjects. Cells were freshly isolated from peripheral blood and the subgroups were determined by flow cytometric method. Lactate production and glycogen utilization were significantly increased in the LMN cells of patients with type 2 DM and IGT when compared with healthy volunteers. No statistical difference was observed between the patients with type 2 DM and IGT. There was a significant correlation between fasting plasma glucose and lactate production in LMN cells. LMN cells changed their energy pathway in a diabetic state and preferred anaerobic glycolysis. Prediabetic range also affected energy metabolism in LMN cells. This abnormal energy production might cause dysfunction in LMN cells and the immune system in diabetic and prediabetic patients. In conclusion, we concluded that impaired glucose metabolism could change energy metabolism.

Detrimental effects of N-acetylcysteine plus desferoxamine combination in an experimental nephrotic syndrome model.

The aim of this study was to evaluate the effects of N-acetylcysteine (NAC) and desferoxamine (DFO) administered alone or in combination together in rats with doxorubicin (DOX)-induced nephrotic syndrome, by monitoring oxidative stress parameters and trace elements in renal tissue and erythrocytes. Fifty-four male Sprague-Dawley rats were included the study. Equal volume of isotonic saline was injected to control rats. After DOX administration, the animals were divided into four experimental groups: (a) rats given only DOX; (b) rats treated with NAC; (c) rats treated with DFO; (d) rats treated with NAC plus DFO. The combination of N-acetylcysteine and DFO has no beneficial effect on reducing proteinuria in experimentally nephrotic rats, although both of these agents ameliorate the condition when administered separately. It seems likely that detrimental effects of NAC plus DFO could be secondary to its effects on erythrocyte selenium levels demonstrated here. Consequently, the results may propose caution to the use of antioxidant therapeutic strategies such as NAC plus DFO against nephropathy.