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 outcome of COVID-19 in patients with hematological malignancy.

In this study, we aim to report the outcomes for COVID-19 in patients with hematological malignancy in Turkey. Data from laboratory-confirmed 188 897 COVID-19 patients diagnosed between 11 March 2020 and 22 June 2020 included in the Republic of Turkey, Ministry of Health database were analyzed retrospectively. All COVID-19 patients with hematological malignancy (n = 740) were included in the study and an age, sex, and comorbidity-matched cohort of COVID-19 patients without cancer (n = 740) at a 1:1 ratio was used for comparison. Non-Hodgkin lymphoma (30.1%), myelodysplastic syndrome (19.7%), myeloproliferative neoplasm (15.7%) were the most common hematological malignancies. The rates of severe and critical disease were significantly higher in patients with hematological malignancy compared with patients without cancer (P = .001). The rates of hospital and intensive care unit (ICU) admission were higher in patients with hematological malignancy compared with the patients without cancer (P = .023, P = .001, respectively). The length of hospital stay and ICU stay was similar between groups (P = .7, P = .3, retrospectively). The rate of mechanical ventilation (MV) support was higher in patients with hematological malignancy compared with the control group (P = .001). The case fatality rate was 13.8% in patients with hematological malignancy, and it was 6.8% in the control group (P = .001). This study reveals that there is an increased risk of COVID-19-related serious events (ICU admission, MV support, or death) in patients with hematological malignancy compared with COVID-19 patients without cancer and confirms the high vulnerability of patients with hematological malignancy in the current pandemic.

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.

Convalescent plasma therapy in patients with COVID-19.

INTRODUCTION: Passive antibody therapy has been used to immunize vulnerable people against infectious agents. In this study, we aim to investigate the efficacy of convalescent plasma (CP) in the treatment of severe and critically ill patients diagnosed with COVID-19. METHOD: The data of severe or critically ill COVID-19 patients who received anti-SARS-CoV-2 antibody-containing CP along with the antiviral treatment (n = 888) and an age-gender, comorbidity, and other COVID-19 treatments matched severe or critically ill COVID-19 patients at 1:1 ratio (n = 888) were analyzed retrospectively. RESULTS: Duration in the intensive care unit (ICU), the rate of mechanical ventilation (MV) support and vasopressor support were lower in CP group compared with the control group (p = 0.001, p = 0.02, p = 0.001, respectively). The case fatality rate (CFR) was 24.7 % in the CP group, and it was 27.7 % in the control group. Administration of CP 20 days after the COVID-19 diagnosis or COVID-19 related symptoms were associated with a higher rate of MV support compared with the first 3 interval groups (≤5 days, 6-10 days, 11-15 days) (p=0.001). CONCLUSION: CP therapy seems to be effective for a better course of COVID-19 in severe and critically ill patients.

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.

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.

Outcome of COVID-19 in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitors.

INTRODUCTION: In this study, we aim to report the outcome of COVID-19 in chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitor (TKI). METHOD: The data of 16 laboratory-confirmed COVID-19 patients with CML receiving TKI and age, gender, and comorbid disease matched COVID-19 patients without cancer at a 3/1 ratio (n = 48), diagnosed between March 11, 2020 and May 22, 2020 and included in the Republic of Turkey, Ministry of Health database, were analyzed retrospectively. RESULTS: The rates of intensive care unit (ICU) admission, and mechanical ventilation (MV) support were lower in CML patients compared to the control group, however, these differences did not achieve statistical significance (p = 0.1, and p = 0.2, respectively). The length of hospital stay was shorter in CML patients compared with the control group; however, it was not statistically significant (p = 0.8). The case fatality rate (CFR) in COVID-19 patients with CML was 6.3%, and it was 12.8% in the control group. Although the CFR in CML patients with COVID-19 was lower compared to the control group, this difference did not achieve statistical significance (p = 0.5). When CML patients were divided into 3 groups according to the TKI, no significant difference was observed regarding the rate of ICU admission, MV support, CFR, the length of stay in both hospital and ICU (all p > 0.05). CONCLUSION: This study highlights that large scale prospective and randomized studies should be conducted in order to investigate the role of TKIs in the treatment of COVID-19.

Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG).

Autologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real-world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma.

Can Pseudothrombocytopenia be recognised at first look?

Our aim was to determine the laboratory parameters that distinguish pseudothrombocytopenia from true thrombocytopenia. A total of 107 patients who were referred to the adult hematology outpatient clinic with thrombocytopenia and subsequently diagnosed with acute myeloid leukaemia, immune thrombocytopenia and pseudothrombocytopenia were included in our study. Hemogram parameters on admission, platelet value in the control hemogram and peripheral smear findings were recorded. Forty three (40.2%) males and 64 (59.8%) females, were included in our study. There were 25 patients in the leukaemia group, 39 in the immune thrombocytopenia group and 43 in the pseudothrombocytopenia group. Control platelet value and red cell distribution width/platelet ratio were found to be statistically significantly different between the 3 groups. Receiver operating characteristic analysis based on platelet values showed that platelet value ≤ 38,000/µL (86% sensitivity, 78.1% specificity, P < .001), difference between 2 consecutively measured platelet levels ≤ 11. 000/µL (79.1% sensitivity, 79.7% specificity, P < .001), red cell distribution width/platelet ratio ≥ 0.413 (90.7% sensitivity, 78.1% specificity, P < .001) were found to be in favor of true thrombocytopenia. In the differentiation of pseudothrombocytopenia and true thrombocytopenia, the difference between the hemogram parameters at the time of admission and the platelet count in the control blood count may be guiding. This result may reduce patient and physician anxiety and prevent patient referral.

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.

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.

COVID-19 in hematopoietic cell transplant recipients.

In this study, we aim to report the outcome of COVID-19 in hematopoietic cell transplant (HCT) recipients. HCT recipients (n = 32) with hematological disease and hospitalized for COVID-19 were included in the study. A cohort of age and comorbid disease-matched hospitalized COVID-19 patients with hematological malignancy but not underwent HCT (n = 465), and another cohort of age and comorbid disease-matched hospitalized COVID-19 patients without cancer (n = 497) were also included in the study for comparison. Case fatality rate (CFR) was 5.6% in patients without cancer, 11.8 in patients with hematological malignancy and 15.6% in HCT recipients. The CFR in HCT recipients who were not receiving immunosuppressive agents at the time of COVID-19 diagnosis was 11.5%, whereas it was 33% in HCT recipients who were receiving an immunosuppressive agent at the time of COVID-19 diagnosis. In conclusion, our study reveals that for the current pandemic, HCT recipients, especially those receiving immunosuppressive drugs, constitute a special population of cancer patients.

Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data

Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients. Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed. Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5). Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.

Triple or quadruple tetracycline-based therapies versus standard triple treatment for Helicobacter pylori treatment.

BACKGROUND: Our aim was to compare lansoprazole-tetracycline-metranidazole (LTM) as first-line treatment with the classical lansoprazole-amoxicillin-clarithromycin (LAC) and bismuth-containing quadruple treatments. PATIENTS AND METHODS: This prospective, single-center, randomized study included 464 consecutive Helicobacter pylori-positive patients with dyspeptic symptoms. A total of 415 patients completed the study. The patients were allocated into 4 study groups using random sampling numbers as follows-LAC group: lansoprazole 30 mg twice daily, amoxicillin 1000 mg twice daily, and clarithromycin 500 mg twice daily for 14 days; BLTM group: bismuth subcitrate 300 mg 4 times a day, lansoprazole 30 mg twice daily, tetracycline 500 mg 4 times a day, and metronidazole 500 mg twice daily for 10 days; RBLTM group: ranitidine bismuth citrate 400 mg twice daily, lansoprazole 30 mg twice daily, tetracycline 500 mg 4 times a day, and metronidazole 500 mg twice daily for 10 days; and LTM group: lansoprazole 30 mg twice daily, tetracycline 500 mg 4 times a day, and metronidazole 500 mg twice daily for 10 days. RESULTS: The per protocol H. pylori eradication rate in LAC, BLTM, RBLTM, and LTM groups were 37 of 104 (35.6%), 56 of 102 (54.9%), 67 of 104 (64.4%), and 63 of 105 (60%), respectively. The intention-to-treat eradication rate was 37 of 113 (32.7%) in LAC, 56 of 119 (47.1%) in BLTM, 67 of 117 (57.3%) in RBLTM, and 63 of 115 (54.8%) in LTM group. The BLTM, RBLTM, and LTM treatment groups achieved a significantly better eradication rate than the LAC treatment group (P < 0.001). There was not any significant statistical difference between the groups of BLTM, RBLTM, and LTM. CONCLUSION: LTM treatment group achieved a significantly better eradication rate than the LAC treatment group. The success ratio of LTM therapy is comparable with quadruple bismuth-based treatments.

Determination of serum imatinib and its' metabolite in patients chronic myeloid leukemia.

INTRODUCTION: Imatinib has favorable pharmacokinetic properties, but primary and secondary resistance mechanisms may cause a decrease in clinical response over time. There is a positive correlation between serum imatinib concentrations and treatment response. Our aim was to develop a method for the measurement of imatinib and its' active metabolite N-desmethyl imatinib. METHODS: Serum imatinib and N-desmethyl imatinib levels were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and validation studies were carried out according to CLSI (The Clinical & Laboratory Standards Institute) protocols. Serum samples were collected from 40 patients with chronic myeloid leukemia (CML) and analyzed with LC-MS/MS and ultra high-performance liquid chromatography (UHPLC) methods. RESULTS: The linearity range and correlation coefficient were 12.2-12,500 ng/mL and 0.9987 for LC-MS/MS method, respectively. Limit of quantitation was determined as 24.4 ng/mL. The retention times of imatinib and N-desmethyl imatinib were 1.66 and 1.60 min, respectively. There was no statistically significant difference between the results of both methods. DISCUSSION: This LC-MS/MS method is cost-effective and has adavantages such as using low serum volumes, requiring simple pretreatment steps (only protein precipitation) and reduced turnaround times for analysis.

Evaluation of bone mineral density (BMD) and indicators of bone turnover in patients with hemophilia.

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, calcium, and free testosterone levels were significantly lower (p < 0.001, p = 0.011, p < 0.001, respectively), while PTH, PINP, and activated partial thromboplastin time (aPTT) levels were significantly higher (p < 0.014, p = 0.043, p < 0.001, respectively), in hemophilic patients compared to controls. There was no significant difference between the two groups in NLR, PLR, phosphorus, thyroid-stimulating hormone, and uNTX level. The reduction of bone mass in hemophilic patients may be evaluated using the markers of bone formation and resorption, enabling early detection and timely treatment.

Paraoxonase and arylesterase activities in adults with vitamin B12 deficiency.

OBJECTIVE: The purpose of this study was to investigate paraoxonase (PON) and arylesterase (ARES) enzyme activity in adults with vitamin B12 deficiency, and specific changes in the activities of these enzymes following vitamin B12 treatment. METHODS: A total of 46 patients with vitamin B12 deficiency (aged 18-82 years) and 45 healthy volunteer controls (aged 19-64 years) participated in this study. Venous blood samples were collected, and serum vitamin B12, homocysteine (HCY), methylmalonic acid, PON1, and ARES levels were measured. RESULTS: Paired comparison showed that pre- and post-treatment values for PON and ARES were similar between patients and controls (both P > 0.05). There was no statistically significant relationship between patients' pre-/post-treatment PON or HCY levels and serum vitamin B12 levels, compared with those of the control group (P > 0.05). DISCUSSION: The results of the present study do not support the hypothesis that the antioxidant enzymes PON and ARES have an underlying role in vitamin B12 deficiency and related hyperhomocysteinemia. Our findings suggest that PON and ARES do not play a role in the systemic effects of vitamin B12 deficiency.