Real-world data on the effectiveness and safety of Ixazomib-Lenalidomide-Dexamethasone therapy in relapsed/refractory multiple myeloma patients: a multicenter experience in Turkey.

A multicenter, retrospective, observational study was conducted to explore effectiveness and safety of ixazomib plus lenalidomide with dexamethasone (IRd) in relapsed/refractory multiple myeloma (RRMM) patients following at least ≥ two lines of therapy. Patients' treatment responses, overall response rate, progression-free survival rate, and adverse events were recorded. Mean age of 54 patients was 66.5 ± 9.1 years. There were 20 patients (37.0%) with progression. Median progression-free survival was 13 months in patients who received a median of three therapy lines in a 7.5-month follow-up period. Overall response rate was 38.5%. Of 54 patients, 19 (40.4%) had at least one adverse event, and nine (19.1%) had an adverse event of at least grade 3 or more. Of 72 adverse events observed in 47 patients, 68% were grade 1 or 2. Treatment was not stopped in any patient due to adverse events. IRd combination therapy was effective and safe in heavily treated RRMM patients.

Clinical use of CAR T-cells in treating acute lymphoblastic leukemia.

Chimeric antigen receptor (CAR) T-cell therapy has transformed the treatment landscape for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). However CAR T-cell therapy of R/R T-ALL has unique challenges, such as the lack of specific tumor antigens, cell fratricide and T cell aplasia, in comparison with that of R/R B-ALL. Despite promising therapeutic outcomes in R/R B-ALL, application of this therapy is limited by high relapse rates and immunological toxicities. Recent studies suggest patients who underwent allogeneic hematopoietic stem cell transplantation post-CAR T-cell therapy would achieve durable remission and better survival, but this remains controversial. Herein, I briefly review published data on the clinical use of CAR T-cells in treating ALL.

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.

The course of COVID-19 in patients with hematological malignancies and risk factors affecting mortality: A cross-sectional study.

Objective: This study aimed to determine the clinical outcomes and risk factors affecting mortality in patients with COVID-19 following hematological malignancy (HM). Methods: Patients diagnosed with HM and hospitalized for COVID-19 were included in this retrospective study. The age, demographic and clinical characteristics, prognosis and treatment of surviving and non-surviving patients were compared. Results: A total of 49 patients were included in this study, 17 (34.6%) of whom died within 28 days of being diagnosed with COVID-19. Older age (p = 0.001), diabetes (p = 0.001), chronic obstructive pulmonary disease (p = 0.002), secondary infection (p < 0.001) and secondary bacterial infection (p = 0.005) were statistically significantly higher in non-survivors. The remission status of HM was higher in surviving patients (p < 0.001). In multivariate regression analysis, age (OR: 1.102, p = 0.035) and secondary infection (OR: 16.677, p = 0.024) were risk factors increasing mortality, the remission status of HM (OR: 0.093, p = 0.047) was a protective factor from mortality. Conclusion: The older age, the remission status of HM and secondary infection due to COVID-19 were determined as prognostic factors predicting mortality in HM patients with following COVID-19.

Retrospective analysis on efficacy of convalescent plasma in acute respiratory distress syndrome due to COVID-19

ABSTRACT BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing global health threat. However, currently, no standard therapy has been approved for the disease. OBJECTIVES: To evaluate the clinical effectiveness of convalescent plasma (CP) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN AND SETTING: Retrospective study conducted at Kayseri City Education and Research Hospital, Kayseri, Turkey. METHODS: The case group consisted of adult patients (> 18 years) with ARDS due to COVID-19 who received CP in combination with antiviral and supportive treatment. These patients were compared with others who only received antiviral and supportive treatment. RESULTS: During the study period, a total of 30 patients with ARDS due to COVID-19 were included. Eleven patients (36%) received CP in combination with antiviral and supportive treatment, whereas nineteen patients (64%) in the control group only received antiviral and supportive treatment. On admission, the median age, demographic and clinical data and initial laboratory test results were similar between the groups (P > 0.05). On the 14th day of treatment, the laboratory values remained similar between the groups (P > 0.05). The mortality rates were not significantly different between the groups. CONCLUSION: CP treatment did not affect mortality or lead to clinical improvement for COVID-19 patients with ARDS.

The Real-World Experience With Single Agent Ibrutinib in Relapsed/Refractory CLL.

INTRODUCTION/BACKGROUND: The emergence of novel agents targeting the B-cell receptor pathway and BCL-2 has significantly changed the therapeutic landscape of CLL. We evaluated the safety and efficacy of single-agent ibrutinib in relapsed/refractory CLL in real-world settings. PATIENTS/METHODS: A total of 200 relapsed/refractory CLL patients with a median age of 68 were included in this retrospective, multicenter, non-interventional study. Data of the study were captured from the patient charts of the participating centers. RESULTS: The median for lines of previous chemotherapy was 2 (1-6); 62 (31.8%) patients had del17p and/or p53 mutations (del17p+/p53mut). Of the study group, 146 (75%) patients achieved at least PR, while 16 (8.7%) patients discontinued ibrutinib due to TEA. The most common drug-related adverse events were neutropenia (n: 31; 17.4%) and thrombocytopenia (n: 40; 22.3%), which were ≥ grade 3 in 9 (5%) and 5 (3.9%) patients, respectively. Pneumonia (n: 42; 23.7%) was the most common nonhematologic TEA. Atrial fibrillation (n: 5; 2.8%) and bleeding (n: 11; 6.3%) were relatively rare during the study period. Within a median follow-up period of 17 (1-74) months, 42 (21%) patients died. The estimated median OS of the study cohort was 52 months. Only the response to ibrutinib (CR/PR vs. SD/PD) was significantly associated with OS. CONCLUSION: Our results indicate good safety and efficacy for single-agent ibrutinib in R/R CLL in daily practice.

Brentuximab vedotin and bendamustine: an effective salvage therapy for relapsed or refractory Hodgkin lymphoma patients.

The prognosis is poor for relapsed or refractory (R/R) classical Hodgkin Lymphoma (cHL) patients. The brentuximab vedotin (Bv) and bendamustine (B) combination has been used as a preferable salvage regimen in R/R cHL patient trials. We retrospectively evaluated response rates, toxicities, and the survival in R/R cHL patients treated with the BvB combination. In a multi-centre real-life study, 61 R/R HL patients received intravenous doses of 1.8 mg/kg Bv on the first day plus 90 mg/m2 B on the first and second days of a 21-day cycle as a second-line or beyond-salvage regimen. Patients' median age at BvB initiation was 33 (range: 18-76 years). BvB was given as median third-line treatment for a median of four cycles (range: 2-11). The overall and complete response rates were 82% and 68.9%, respectively. After BvB initiation, the median follow-up was 14 months, and one- and two-year overall survival rates were 85% and 72%, respectively. Grade 3/4 toxicities included neutropenia (24.6%), lymphopenia (40%), thrombocytopenia (13%), anaemia (13%), infusion reactions (8.2%), neuropathy (6.5%), and others. The BvB combination could be given as salvage regimen aiming a bridge to autologous stem cell transplant (ASCT), in patients relapse after ASCT or to transplant-ineligible patients with manageable toxicity profiles.

Retrospective analysis on efficacy of convalescent plasma in acute respiratory distress syndrome due to COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an ongoing global health threat. However, currently, no standard therapy has been approved for the disease. OBJECTIVES: To evaluate the clinical effectiveness of convalescent plasma (CP) in patients with acute respiratory distress syndrome (ARDS) due to COVID-19. DESIGN AND SETTING: Retrospective study conducted at Kayseri City Education and Research Hospital, Kayseri, Turkey. METHODS: The case group consisted of adult patients (> 18 years) with ARDS due to COVID-19 who received CP in combination with antiviral and supportive treatment. These patients were compared with others who only received antiviral and supportive treatment. RESULTS: During the study period, a total of 30 patients with ARDS due to COVID-19 were included. Eleven patients (36%) received CP in combination with antiviral and supportive treatment, whereas nineteen patients (64%) in the control group only received antiviral and supportive treatment. On admission, the median age, demographic and clinical data and initial laboratory test results were similar between the groups (P > 0.05). On the 14th day of treatment, the laboratory values remained similar between the groups (P > 0.05). The mortality rates were not significantly different between the groups. CONCLUSION: CP treatment did not affect mortality or lead to clinical improvement for COVID-19 patients with ARDS.

Patients with hematologic cancers are more vulnerable to COVID-19 compared to patients with solid cancers.

Previous studies reported that COVID-19 patients with cancer had higher rates of severe events such as intensive care unit (ICU) admission, mechanical ventilation (MV) assistance, and death during the COVID-19 course compared to the general population. However, no randomized study compared the clinical course of COVID-19 in patients with hematologic cancers to patients with solid cancers. Thus, in this study, we intend to reveal the outcome of COVID-19 in hematologic cancer patients and compare their outcomes with COVID-19 patients with solid cancers. The data of 926 laboratory-confirmed COVID-19 patients, including 463 hematologic cancer patients and an age-gender paired cohort of 463 solid cancer patients, were investigated retrospectively. The frequencies of severe and critical disease, hospital and ICU admission, MV assistance were significantly higher in hematologic cancer patients compared with the solid cancer patients (p = 0.001, p = 0.045, p = 0.001, and p = 0.001, respectively). The hospital stay was longer in patients with hematologic cancers (p = 0.001); however, the median ICU stay was 6 days in both groups. The case fatality rate (CFR) was 14.9% in patients with hematologic cancers, and it was 4.8% in patients with solid cancers, and there was a statistically significant difference regarding CFR between groups (p = 0.001). Our study revealed that COVID-19 patients with hematologic cancers have a more aggressive course of COVID-19 and have higher CFR compared to COVID-19 patients with solid cancers and support the increased susceptibility of patients with hematologic cancers during the outbreak.

Prospective registry of adult patients receiving therapeutic plasma exchange with a presumptive diagnosis of thrombotic microangiopathy (TMA): The Turkish hematology research and education group (ThREG)-TMA02 study.

Thrombotic microangiopathy(TMA) is a pathological diagnosis characterized by abnormalities of small vessels leading to microvascular thrombosis of arterioles and capillaries. The current prospective, non-interventional, multicenter (n:18) study aimed to define distribution of different TMA forms in adult Turkish patients who were referred for therapeutic plasma exchange (TPE) for a presumptive diagnosis of TMA. Patients with serum ADAMTS13 activity <5% were diagnosed as acquired thrombotic thrombocytopenic purpura (aTTP). Patients presenting with ADAMTS13 activity 6-10 % / normal renal function and patients with ADAMTS13 activity >10 %, normal renal function and no secondary TMA were treated as unclassified TMA. The study included a total of 97 patients (female: 60; male: 30) with a median age of 48 (18-74). Detailed evaluation at 1 month after hospital admission revealed aTTP, secondary TMA, infection/complement-associated hemolytic uremic syndrome and unclassified TMA in 32 (33 %), 33 (34 %), 26 (27 %) and 6 (6%) patients respectively. As subclassification of various TMAs will dictate specific therapy, proper diagnosis in a timely manner is of utmost clinical significance.

Pralatrexate experience in PTCL: A multicenter retrospective study from Turkey.

PURPOSE: Pralatrexate is a new generation antifolate treatment agent used for the treatment of relapsed or refractory peripheral T-cell lymphomas. This study aims to determine the general characteristics of the patients receiving pralatrexate therapy in Turkey, contributing to the literature on the effectiveness of pralatrexate therapy in peripheral T-cell lymphomas by determining the response levels of such patients to the therapy. The study also attempts to clinically examine the major side effects observed in patients during treatment with pralatrexate. METHODS: The study included patients with peripheral T-cell lymphoma followed up in the hematology units of several hospitals in Turkey. Overall, 20 patients aged 18 and over were included in the study. RESULTS: The median age at the time of diagnosis was 58.5 years. PTCL-NOS (Peripheral T-cell lymphoma, not otherwise specified) subtype was in 40% of patients, making the PTCL-NOS the most common subtype in the study. In general, most patients were diagnosed with disease at an advanced stage. Pralatrexate therapy was given to the patients at a median treatment line of 3.5. Pralatrexate dose reduction was required in only 3 patients (15%). Response to pralatrexate therapy with partial remission (PR) and above was observed in 11 (55%) of the patients. CONCLUSION: Pralatrexate seemed to be a promising novel treatment in relapsed refractory PTCL patients. However, patients receiving pralatrexate should be followed up carefully for skin reactions, mucosal side effects, thrombocytopenia and neutropenia.

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.

Therapeutic plasma exchange for envenomation: Is it reasonable?

BACKGROUND AND OBJECTIVES: The incidence of poisoning due to snakebite and Crimean Congo Hemorrhagic Fever (CCHF), referred to as 'envenomation', varies according to the region, and many deaths occur every year. Therapeutic plasma exchange (TPE) is a method of extracorporeal blood purification that clears toxins and virus load from the circulation. Therefore, its use has been increasing recently in envenomation cases. However, there are a limited number of studies on poisoning due to snakebite and CCHF. In the present study, we share our TPE experience retrospectively in patients diagnosed with poisoning due to snakebite and CCHF between 2010 and 2019. MATERIALS AND METHODS: A total of 26 patiens, including 20 patients with poisoning due to snakebite and 6 CCHF patients were treated with TPE. Demographic data, clinical status, and outcomes of patients were recorded. Routine biochemical and hematologic laboratory parameters were analyzed before and after TPE. TPE was performed by using centrifugation technology via a central venous catheter. Fresh frozen plasma was used as replacement fluid. RESULTS: An average of 3.95 (1-11) apheresis sessions were applied to patients poisoned due to snakebite, and 19 patients (95 %) were discharged in an average of 8.3 (1-17) days without any complications. None of the patients enrolled in the study lost their limbs. Only one patient died due to disseminated intravascular coagulopathy. Six patients with CCHF who received 5 sessions of TPE on average were discharged successfully after an average of 6.5 days. No adverse events or complications were observed in any patient after TPE. CONCLUSIONS: TPE is a good alternative and a reliable method in treating envenomation cases who are refractory to supportive measures. TPE should be performed without delay in cases of poisoning due to snakebite and CCHF.

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.

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.

Therapeutic plasma exchange in non-immune hemolytic anemia associated with henna ingestion: A case report.

Henna is a herb that is used in traditional medicine for medical purposes as well as in the field of cosmetic. It is one of the agents that can trigger hemolytic crisis in G6PD deficient patients but it is considered safe in patients with normal G6PD enzyme. Here we present a case of non-immune hemolytic anemia occurred after ingestion of a homemade solution containing henna powder. Therapeutic plasma exchange was performed daily for 3 subsequent days and the hemoglobin levels and hemolytic markers were improved dramatically. Laboratory test revealed a normal G6PD enzyme level six weeks after recovery. We would like to emphasize the possibility of unexpected adverse effects and undefined ingredients of herbal products. Therapeutic plasma exchange can be a promising treatment option in such cases.

COVID-19 clinical course and blood groups: Turkish population-based study

Background/aim: SARS-CoV-2 enters the cell through the binding of the S glycoprotein on the surface of the virus to the angiotensin- converting enzyme 2 (ACE-2) in the host cells and also SARS-CoV S protein binding to ACE-2 was inhibited by anti-A antibodies. The aim of the study was to investigate the relationship between blood groups and the course of COVID-19 in Turkey. Materials and methods: Laboratory confirmed COVID-19 patients aged 18 and over (n = 39.850) were randomized in age and sex- matched groups according to blood groups. Results: Advanced age, male sex and blood group A were found to be related with increased rate of intensive care unit (ICU) admission (OR = 1.089, 95% CI: 1.085­1.093 for age; OR = 1.963, 95% CI: 1.737­2.218 for male sex; OR = 1.216, 95% CI: 1.023­1.446 for blood group A). When blood group O individuals were compared to non-O individuals, no significant difference was observed regarding the rate of hospital and ICU admission, mechanical ventilation (MV) support, length of hospital and ICU stay, and case fatality rate (CFR). The CFR in patients with blood group A, B, O, and AB were 2.6%, 2.2%, 3.1%, and 2.3%, respectively. There were no significant differences between Rh-negative and positive patients regarding the rate of hospital and ICU admission (p = 0.280 and p = 0.741, respectively), also the rate of MV support and CFR was similar (p = 0.933 and p = 0.417). Conclusion: Our study revealed that ABO and Rh blood groups do not have any impact on the rate of hospital admission, hospital and ICU stay, MV support, and CFR.

Clinical characteristics and therapeutic outcomes of paroxysmal nocturnal hemoglobinuria patients in Turkey: a multicenter experience.

The aim of this study is to collect paroxysmal nocturnal hemoglobinuria (PNH) patient data from hematology centers all over Turkey in order to identify clinical features and management of PNH patients. Patients with PNH were evaluated by a retrospective review of medical records from 19 different institutions around Turkey. Patient demographics, medical history, laboratory findings, and PNH-specific information, including symptoms at the diagnosis, complications, erythrocyte, and granulocyte clone size, treatment, and causes of death were recorded. Sixty patients (28 males, 32 females) were identified. The median age was 33 (range; 17-77) years. Forty-six patients were diagnosed as classic PNH and 14 as secondary PNH. Fatigue and abdominal pain were the most frequent presenting symptoms. After eculizumab became available in Turkey, most of the patients (n = 31/46, 67.4%) were switched to eculizumab. Three patients with classic PNH underwent stem cell transplantation. The median survival time was 42 (range; 7-183 months) months. This study is the first and most comprehensive review of PNH cases in Turkey. It provided us useful information to find out the differences between our patients and literature, which may help us understand the disease.