Polatuzumab vedotin, rituximab, and bendamustine combination in relapsed or refractory diffuse large B-cell lymphoma: a real-world data from Turkey.

Polatuzumab vedotin (Pola) with bendamustine and rituximab (BR) is a promising option for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We analyzed the data of 71 R/R DLBCL patients who had been treated with Pola-BR in the named patient program from March 2018 to April 2021 from 32 centers in Turkey. All patients received up to six cycles of Pola 1.8 mg/kg, rituximab 375 mg/m2 on day 1, and bendamustine 90 mg/m2 on days 1-2 of each cycle. Median age at Pola-BR initiation was 55 (19-84). The overall response rate was 47.9%, including 32.4% CR rate when a median of 3 cycles was applied. With a median follow-up of 5 months, the median OS was 5 months. Grade 3-4 neutropenia and thrombocytopenia were the most common hematological toxicities. The real-world data from our cohort showed the Pola-BR is an effective option with a manageable toxicity profile.

International Forum: The Turkish perspective on apheresis activity: The Turkish apheresis registry report.

Therapeutic apheresis is an extracorporeal treatment that selectively removes abnormal cells or harmful substances in the blood that are associated with or cause certain diseases. During the last decades the application of therapeutic apheresis has expanded to a broad spectrum of hematological and non-hematological diseases due to various studies on the clinical efficacy of this procedure. In this context there are more than 30 centers performing therapeutic apheresis and registered in the apheresis database in Turkey. Herein, we, The Turkish Apheresis Registry, aimed to analyze some key articles published so far from Turkey regarding the use of apheresis for various indications.

Does waterpipe smoking increase the risk of Helicobacter pylori infection?

Background: In this study, we aimed to evaluate whether waterpipe smoking can be associated with the transmission of Helicobacter pylori infection or not. Materials and Methods: Between March 2018 and April 2019, 445 patients aged over 18 years old who were admitted to outpatient clinics with dyspeptic complaints were recruited for the study. Patients are divided into two groups - Group 1 is H. pylori-positive patients and Group 2 is negative. Waterpipe smoking, smoking, age, gender, and educational status were compared among groups. Results: Two hundred and sixty-one women (58%) and 184 men (42%), totally 445 patients, tested for H. pylori infection. Seventy-nine of 261 (30%) women and 60 of 184 (32%) men had H. pylori positive. One hundred and sixty-two of 445 (36%) patients were smoking cigarette and 66 of 445 (14%) patients were using waterpipe tobacco. Waterpipe smoking individuals were found to be associated with the H. pylori positivity (P < 0.001); whereas, age, gender, educational level, and smoking were not found to be statistically significant (all P > 0.05). In binary logistic regression analysis, waterpipe tobacco smoking was found to be the only independent predictor of H. pylori infection (P < 0.001, odds ratio = 5.51, confidence interval: 3.158-9.617). Conclusion: Waterpipe smoking seems to be an important risk factor for H. pylori infection and may be one of the reasons of high prevalence of H. pylori infection.

Efficacy and safety of plasmapheresis in symptomatic hyperviscosity and cast nephropathy: A Multicenter Experience in Turkey.

BACKGROUND AND OBJECTIVES: Cast nephropathy (CN) and hyperviscosity (HV), which we encounter in plasma cell diseases, are serious clinical manifestations that increase mortality and morbidity if not managed well in the early period. Therapeutic plasma exchange (TPE) procedures based on the removal of patient plasma is a frequently preferred treatment modality. TPE is recommended at varying levels of evidence for the treatment of CN and HV in plasma cell disorders. MATERIAL AND METHODS: A total of 61 patients, 50 with multipl myeloma (MM) and 10 with Waldenström macroglobulinemia (WM), who underwent TPE for CN and HV, were included in our multicenter, and retrospective study. RESULTS: A statistically significant decrease was found in all disease-related biochemical markers, which were measured 1 week after the application of TPE added to standard medical treatment (IgG; p < 0.001, IgM; p = 0.004, IgA; p = 0.14, kappa light chain; p < 0.001, lambda light chain; p < 0.001, ß-2 microglobulin; p < 0.001, total protein; p < 0.001, albumin; p < 0.001, LDH; p = 0.02, creatine; p < 0.001, hemoglobin; p = 0.010). Clinically, all 11 patients who underwent TPE for HV responded. While a partial response (PR: 80 %) was obtained in 40 of 50 MM patients with CN, no response was obtained in 10 patients (non-response: 20 %). CONCLUSION: In conclusion, it was observed that TPE reduced all biochemical markers related to HV and CN, while making a significant contribution to clinical improvement. We believe that adding TPE to the standard treatment in this patient group will reduce mortality and morbidity in the early period and have a positive effect on survival in the long term.

Extracorporeal photopheresis in steroid-refractory chronic graft-versus-host disease: A retrospective multicenter study.

BACKGROUND AND OBJECTIVES: Extracorporeal photopheresis (ECP) is a treatment strategy in steroid-refractory chronic graft-versus-host disease (cGvHD). In this study, we aimed to share our multicenter experience using ECP in our steroid-refractory cGvHD patients. MATERIALS AND METHODS: In this multicenter observational retrospective study with the participation of four Turkish transplant centers, 100 patients with the diagnosis of steroid-refractory cGvHD who underwent ECP were analyzed. All ECP procedures were performed with the off-line system. RESULTS: Severe cGvHD was observed in 77 % of the patients. 50 % of the patients had more than 1 organ involvement. The overall response rate in cGvHD was 58 %, and the complete response (CR) rate was 35 %. The skin was the most involved organ, with a response rate of 61.2 % (CR rate 30.6 %) in cGvHD. At a median 13 months (1-261) follow-up, overall survival (OS) was 41 % (n = 41) and the mortality rate was 59 % (n = 59). Median overall survival (OS) was 2 months for non-responders and 91 months for responders (p < 0.001). Significant OS differences were observed for patients responding to ECP in cGvHD (HR = 4.1, p = 0.001) patients. CONCLUSIONS: ECP is a good therapeutic alternative and could be used earlier in patients with steroid-resistant cGvHD.

Extracorporeal photopheresis in the treatment of acute graft-versus-host disease: A multicenter experience.

BACKGROUND AND OBJECTIVES: Extracorporeal photopheresis (ECP) is one of the second-line treatment strategies in steroid-refractory acute graft-versus-host disease (aGvHD). We aimed to share our multicenter experience using ECP in our steroid-refractory aGvHD patients. MATERIALS AND METHODS: A retrospective observational series of 75 aGvHD patients from 4 transplant centers were analyzed. All ECP procedures were performed with the off-line system. All patients received ECP as second-line therapy. RESULTS: 74.7 % of aGvHD patients were grade 3 or 4. The overall response rate was 42.7 % (32/75) in aGvHD including 17 complete responses (22.7 %). Median follow-up was 6 months (range, 1-68). Median overall survival (OS) was 5 months for non-responders and 68 months for responders (p < 0.001). Twenty-seven (36 %) patients are alive, and 48 (64 %) patients have died. CONCLUSIONS: Early initiated ECP could be an effective treatment alternative in patients with steroid-refractory aGvHD.

Mesenchymal stem cell transfusion: Possible beneficial effects in COVID-19 patients.

SARS-CoV-2 attaches to the angiotensin-converting enzyme 2 (ACE-2) receptor on human cells. The virus causes hypercytokinemia, capillary leak, pulmonary edema, acute respiratory distress syndrome, acute cardiac injury, and leads to death. Mesenchymal stem cells (MSCs) are ACE-2 negative cells; therefore, can escape from SARS-CoV-2. MSCs prevent hypercytokinemia and help the resolution of the pulmonary edema and other damages occurred during the course of COVID-19. In addition, MSCs enhance the regeneration of the lung and other tissues affected by SARS-CoV-2. The case series reported beneficial effect of MSCs in COVID-19 treatment. However, there are some concerns about the safety of MSCs, particularly referring to the increased risk of disseminated intravascular coagulation, and thromboembolism due to the expression of TF/CD142. Prospective, randomized, large scale studies are needed to reveal the optimum dose, administration way, time, efficacy, and safety of MSCs in the COVID-19 treatment.

A multicenter retrospective analysis on therapeutic plasma exchange in immune thrombocytopenic purpura.

Immune Thrombocytopenia (ITP) is an autoimmune disease characterized by thrombocytopenia and skin and mucosal bleeding. In patients with an indication for treatment, corticosteroids, intravenous immunoglobulin (IVIg) and anti-D are recommended as the first line, while splenectomy, thrombopoietin receptor agonists or rituximab are recommended second line options. Approximately 10 % of adult patients with ITP fall into the chronic refractory ITP group. Therapeutic plasma exchange (TPE) has generally been tested in patients with refractory ITP, who have failed to respond to conventional treatments, in case of bleeding or prior to surgical interventions. It has been stated that elimination of the antibodies that are held responsible in the pathogenesis of the disease has an effective role in the treatment. In this article, we present the results of 17 patients, who underwent TPE for refractory ITP, together with the literature data.

Apheresis in patients with sepsis: A multicenter retrospective study.

BACKGROUND AND OBJECTIVES: To consider the effectiveness of apheresis, which is a supportive treatment method, in sepsis. MATERIALS AND METHODS: A hundred and eleven adults with sepsis or septic shock were included in this retrospective study. The demographic characteristics of the patients, the focus and source of infection causing sepsis or septic shock, characteristics of the pathogen, Acute Physiological and Chronic Health Assessment (APACHE) II score, routine laboratory values, which apheresis method was used, the characteristics of the replacement fluids used during the apheresis procedure, the number of apheresis procedures, complications related to the apheresis procedure, the follow-up time after the procedure, and mortality were recorded. The primary outcome was 28-day mortality. RESULTS: Sixty-nine (62.2 %) of the patients were male. The mean age of the patients was 47.7 ± 18.6 years. The most common source of sepsis was hospital-acquired (79.3 %), the most common pathogen causing sepsis was gram-negative bacteria (41.4 %), and the most common infection site was the respiratory tract (58.7 %). The median APACHE II score was 19 (13-24). 92 (82.9 %) of the patients had septic shock. Theropeutic plasma exchange (TPE) was performed in 11.7 % of the patients and immunoabsorbtion IA in 88.3 %. The median number of sessions was 3 (3-5). No procedure-related fatal complication was observed in the study. While 28-day mortality was 61.3 % in all patients, when the mortality according to the apheresis procedures was examined, it was 11.3 % and 88.2 % in the patients who underwent TPE and IA, respectively. The most common cause of mortality was multiorgan failure. CONCLUSIONS: Apheresis in sepsis can be considered as a salvage treatment. The indication for apheresis in sepsis is still at the level of patient-based individualized decision in line with the studies done so far, including our study. However, there is a need for a multicenter randomized controlled study with a large number of patients in order to give positive or negative recommendations about its effectiveness.

Extracorporeal blood purification treatment options for COVID-19: The role of immunoadsorption.

The activation of the innate and adaptive immune systems by SARS-CoV-2 causes the release of several inflammatory cytokines, including IL-6. The inflammatory hypercytokinemia causes immunopathological changes in the lungs including vascular leakage, and alveolar edema. As a result of these changes in the lungs, hypoxia and acute respiratory distress syndrome occur in patients with COVID-19. Even though there are clinical trials on the development of therapeutics and vaccines, there are currently no licensed vaccines or therapeutics for COVID-19. Pharmacological approaches have shown poor results in sepsis-like syndromes caused by the hypercytokinemia. Suppressing the cytokine storm is an important way to prevent the organ damage in patients with COVID-19. Extracorporeal blood purification could be proposed as an adjunctive therapy for sepsis, aiming to control the associated dysregulation of the immune system, which is known to protect organ functions. Several extracorporeal blood purification therapies are now available, and most of them target endotoxins and/or the cytokines and aim improving the immune response. For this purpose, plasmapheresis and immunoadsorption may be an important adjunctive treatment option to manage the complications caused by cytokine storm in critically ill patients with COVID-19.

Convalescent plasma therapy in patients with COVID-19.

There are currently no licensed vaccines or therapeutics for COVID-19. Anti-SARS CoV-2 antibody-containing plasmas, obtained from the recovered individuals who had confirmed COVID-19, have been started to be collected using apheresis devices and stored in blood banks in some countries in order to administer to the patients with COVID-19 for reducing the need of intensive care and the mortality rates. Therefore, in this review, we aim to point out some important issues related to convalescent plasma (CP) and its use in COVID-19. CP may be an adjunctive treatment option to the anti-viral therapy. The protective effect of CP may continue for weeks and months. After the assessment of the donor, 200-600 mL plasma can be collected with apheresis devices. The donation interval may vary between countries. Even though limited published studies are not prospective or randomized, until the development of vaccines or therapeutics, CP seems to be a safe and probably effective treatment for critically ill patients with COVID-19. It could also be used for prophylactic purposes but the safety and effectiveness of this approach should be tested in randomized prospective clinical trials.

The Turkish experience with therapeutic plasma exchange: A national survey.

Therapeutic plasma exchange (TPE) is used to treat more than 60 diseases worldwide and has drawn growing interest. Little is known about the current situation of TPE activity in Turkey, so we developed a survey to obtain information about this timely topic. We collected data on TPE from 28 apheresis units throughout Turkey. We performed a total of 24,912 TPE procedures with 3203 patients over the past decade. Twenty years ago, the majority of procedures were performed for neurological and hematological disorders, and today, most TPE procedures are done for the same reasons. The only historical change has been an increase in TPE procedures in renal conditions. Currently, renal conditions were more frequently an indication for TPE than rheumatic conditions. Fresh frozen plasma was the most frequently used replacement fluid, followed by 5% albumin, used in 57.9% and 34.6% of procedures, respectively. The most frequently used anticoagulants in TPE were ACD-A and heparin/ACD-A, used with 1671 (52.2%) and 1164 (36.4%) patients, respectively. The frequency of adverse events (AEs) was 12.6%. The most common AEs were hypocalcemia-related symptoms, hypotension, and urticaria. We encountered no severe AEs that led to severe morbidity and mortality. Overall, more than two thirds of the patients showed improvement in the underlying disease. Here, we report on a nationwide survey on TPE activity in Turkey. We conclude that there has been a great increase in apheresis science, and the number of TPE procedures conducted in Turkey has increased steadily over time. Finally, we would like to point out that our past experiences and published international guidelines were the most important tools in gaining expertise regarding TPE.

Assessment of the underlying causes of the immune thrombocytopenia: Ten years experience.

OBJECTIVE: Immune thrombocytopenia (ITP) is an immune haematologic disorder causing platelet destruction mediated by anti-platelet antibodies. In this study we aimed to evaluate the clinical and laboratory variables of ITP patients in southeast of Turkey. METHODS: In this retrospective study 167 ITP patients between 2005 and 2015 were evaluated. All patients were screened for immunological parameters including ANA (antinuclear antibodies), anti dsDNA (anti-double-stranded-DNA), ACA(anti-cardiolipin) IgM and IgG, LA (lupus anticoagulants). All patients were screened for Helicobacter pylori, HBsAg (Hepatitis B surface antigen), anti-HCV (hepatitis C virus antibody), and anti-HIV ½ (HIV antibody) and brucellosis.. RESULTS: Among the patients, 50 (29.9%) patients were male, 117 (70.1%) were female. The age range of patients was 18-86 (mean 38.16±14). In 56 patients (33.5%) splenectomy was performed. 36 patients (21.6%) were positive for ANA, 5 (3%) were positive for anti dsDNA, 14 (8.4%) for ACA Ig G, and 14 (8.4%) patients for ACA IgM. LA was tested in 165 patients and 30 (18%) patients were positive for LA. Microbiologic evaluation was as follows: 16 patients (9.6%) were positive for HbsAg, 109 (65.3%) positive for Anti-HBs, 5 positive for anti-HCV (3%), 56 (33.5%) patients were positive for Helicobacter pylori antigen, 5 (2.9%) for Brucella and one patient was positive for anti-HIV ½. CONCLUSIONS: Immune thrombocytopenia patients have to be evaluated according to their demographic characteristics and laboratory results. Secondary causes of ITP were HIV, HCV, Helicobacter pylori, brucellosis, tuberculosis, and autoimmune diseases in our region. Management of ITP patients can change in different regions.

Usefulness of ceruloplasmin testing as a screening methodology for geriatric patients with osteoporosis.

[Purpose] To evaluate serum ceruloplasmin levels in geriatric patients with osteoporosis. [Subjects and Methods] Seventy geriatric patients over 65 years of age were recruited. Patients were divided into two groups: group 1 ('OP', n=35) consisted of patients with osteoporosis, and group 2 (n=35) consisted of patients without osteoporosis. Dual-energy X-ray absorptiometry scanning was used in the measurement of bone mineral density in all cases. Inflammatory parameters, including C-reactive protein, sedimentation rate, and serum ceruloplasmin levels were analyzed in blood samples. [Results] No statistical differences in inflammatory parameters were observed between the two groups, however, serum ceruloplasmin levels were significantly higher in group 1 than in group 2. In Pearson analysis, serum ceruloplasmin levels were not found to be correlated with any biochemical parameters. Receiver operator characteristic curve analysis revealed that serum ceruloplasmin levels were predictive of osteoporosis with 85.7% sensitivity and 85.7% specificity over the level of 830.15. [Conclusion] Our study demonstrated that measurement of serum ceruloplasmin levels may have potential as a screening methodology for geriatric patients with osteoporosis.

Does moxifloxacin alter oxidant status in the cornea? An experimental study.

OBJECTIVE: In this experimental study, we investigated the possible effects of intracameral moxifloxacin on oxidative stress parameters and endothelial cell morphology in corneal tissue. METHODS: In total, 30 rats were randomly assigned to three groups of 10 rats: the sham group (Group 1, n = 10); the control group (Group 2), where balanced salt solution (BSS) was administered at a dose of 0.01 cc (n = 10); and the treatment group (Group 3), where moxifloxacin was administered at a dose of 0.05 mg/0.01 cc (n = 10). Total antioxidant status (TAS) and total oxidant status (TOS) in corneal tissue and blood samples were measured and the oxidative stress index (OSI) was calculated. Also, corneal tissue histopathology was evaluated with caspase-3 and caspase-8 staining. Apoptotic activity was also evaluated. RESULTS: In blood samples, TAS, TOS, and OSI levels were not statistically significantly different (all p > 0.05). Compared with the sham and control groups, TOS and OSI levels in cornea tissue were significantly different in the moxifloxacin group (all p < 0.05). However, compared with the control group, no statistically significant difference was found in the sham group (all p > 0.05). Compared with the sham and control groups, apoptotic activity was higher in the moxifloxacin group, in both immunohistochemical staining for caspase-3 and caspase-8. CONCLUSIONS: Intracameral moxifloxacin injection seems to be safe systemically, but it may have toxic effects on corneal tissues, as suggested by oxidative stress parameters and a histopathological evaluation.

Urothelial Carcinoma Concomitant With Malakoplakia In Non-Functioning Nephrolithic Kidneys.

Nephrolithic non-functioning kidney and malakoplakia are major health problems. Kidney function cannot be fulfilled and also this leads to a high risk of development of urothelial neoplasm. We report herein a case of urothelial carcinoma concomitant with malakoplakia in non-functioning nephrolithic kidneys.

Evaluation of oxidative stress parameters and urinary deoxypyridinoline levels in geriatric patients with osteoporosis.

[Purpose] To evaluate the oxidative stress parameters and urinary deoxypyridinoline levels in geriatric patients with osteoporosis. [Subjects and Methods] Eighty geriatric patients aged over 65 years were recruited. Patients were divided into two groups: Group 1 (n=40) consisted of patients with osteoporosis, and Group 2 (n=40) consisted of patients without osteoporosis. Bone mineral density measurements were performed for all patients using DEXA. Oxidative stress parameters were analyzed in blood samples, and deoxypyridinoline levels were analyzed in 24-hour urinary samples. [Results] Compared to Group 2, the total antioxidant status and oxidative stress index levels of Group 1 were not significantly different; however, total oxidant status and 24-hour urinary deoxypyridinoline levels were significantly higher. Pearson correlation coefficients indicated that OSI and urinary deoxypyridinoline levels were not correlated with any biochemical parameters. ROC-curve analysis revealed that urinary deoxypyridinoline levels over 30.80 mg/ml predicted osteoporosis with 67% sensitivity and 68% specificity (area under the curve = 0.734; %95 CI: 0.624-0.844). [Conclusion] Our results indicate that oxidative stress would play a role in the pathogenesis of osteoporosis, and that urinary deoxypyridinoline levels may be a useful screening test for osteoporosis.

Primary localised laryngeal amyloidosis.

Localised amyloidosis of the larynx is uncommon and poorly understood. The precise etiology and pathogenesis are not entirely clear. It usually presents with hoarseness, pain and/or difficulty in breathing. We present the case of a 42-year-old woman with primary localised laryngeal amyloidosis who presented with hoarseness and dyspnoea. Biopsy of the specimen revealed amyloid.There were no signs of any systemic disease in the patient and diagnosis was established histopathologically. She was treated surgically by microlaryngoscopy under general anaesthesia. At 6 months, the patient's voice and breathing had both improved substantially.