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.

A COVID-19 mystery: multisystem inflammatory syndrome in adults (MIS-A) associated with splenic rupture.

Severe inflammation and one or more extrapulmonary organ dysfunctions have been observed in those who had recently developed COVID-19, except for a macrophage activation syndrome-like picture. A 50-year-old female patient was admitted to the emergency department with fever and a history of COVID-19 infection. More than one area of hemophagocytosis was found in the bone marrow aspiration. The HLH-2004 protocol was started with neurological involvement and she underwent splenectomy due to massive intra-abdominal bleeding secondary to splenic laceration on the 3rd day. Multiple microthrombosis and infarcts were observed in the splenectomy specimen. At the 4th week of the treatment, she was discharged with oral agents. Splenic microthrombosis and splenic rupture due to "multisystem inflammatory syndrome in adults" are the most important findings of this report.

Lateral flow assay (LFA) in the diagnosis of COVID-19-associated pulmonary aspergillosis (CAPA): a single-center experience.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is seen during coronavirus-2019 (COVID-19), has been reported in different incidences, and is defined as COVID-19-associated pulmonary aspergillosis (CAPA). Detection of galactomannan antigen is an important diagnostic step in diagnosing IPA. Enzyme-linked immunoassay (ELISA) is the most frequently used method, and lateral flow assay (LFA) is increasingly used with high sensitivity and specificity for rapid diagnosis. The present study aimed to compare the sensitivity of LFA and ELISA in the diagnosis of CAPA in COVID-19 patients followed in our hospital's ICU for pandemic (ICU-P). METHODS: This study included patients with a diagnosis of COVID-19 cases confirmed by polymerase chain reaction and were followed up in ICU-P between August 2021 and February 2022 with acute respiratory failure. The diagnosis of CAPA was based on the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology 2020 (ECMM/ ISHAM) guideline. Galactomannan levels were determined using LFA and ELISA in serum samples taken simultaneously from the patients. RESULTS: Out of the 174 patients followed in the ICU-P, 56 did not meet any criteria for CAPA and were excluded from the analysis. The rate of patients diagnosed with proven CAPA was 5.7% (10 patients). A statistically significant result was obtained with LFA for the cut-off value of 0.5 ODI in the diagnosis of CAPA (p < 0.001). The same significant statistical relationship was found for the cut-off value of 1.0 ODI for the ELISA (p < 0.01). The sensitivity of LFA was 80% (95% CI: 0.55-1.05, p < 0.05), specificity 94% (95% CI: 0.89-0.98, p < 0.05); PPV 53% (95% CI: 0.28-0.79, p > 0.05) and NPV was 98% (95% CI: 0.95-1.01, p < 0.05). The risk of death was 1.66 (HR: 1.66, 95% CI: 1.02-2.86, p < 0.05) times higher in patients with an LFA result of ≥ 0.5 ODI than those with < 0.5 (p < 0.05). CONCLUSIONS: It is reckoned that LFA can be used in future clinical practice, particularly given its effectiveness in patients with hematological malignancies and accuracy in diagnosing CAPA.

Beta Thalassemia Minor: Patients Are Not Tired but Depressed and Anxious.

OBJECTIVE: We aimed to investigate whether the severity of fatigue and the incidences of depression and anxiety of patients with beta thalassemia minor (BTm) are different from healthy individuals using the Fatigue Severity Scale (FSS) and Hospital Anxiety and Depression Scale (HADS). SUBJECTS AND METHODS: BTm patients who were followed at the University of Health Sciences Istanbul Training and Research Hospital Hematology Clinic between 2016 and 2017 and who had normal biochemical parameters, thyroid function tests and C-reactive protein levels, and did not use any medications, consume alcohol or tobacco, have any chronic diseases or sleep disturbances were included in the study. Healthy control subjects who were matched with age, sex, marital status, educational status, and body mass index (BMI) were also included for comparison. RESULTS: Thirty-nine BTm patients and 25 healthy controls were included in the study. The BTm and the control groups were comparable in terms of gender, age, BMI, educational status and marital status (p = 0.368, 0.755, 0.851, 0.785, and 0.709, respectively). FSS score was ≥4 in 23 (59.0%) BTm subjects and in 15 (60%) control subjects (p = 1.0). HADS anxiety score was ≥10 in 20 (51.3%) BTm subjects and in 5 (20.0%) control subjects (p = 0.018), and HADS depression score was ≥7 in 20 (51.3%) BTm subjects and in 6 (24.0%) healthy control subjects (p = 0.039).There was no correlation of hemoglobin with FSS score (p = 0.526, r = -0.105), HADS anxiety score (p = 0.703, r = -0.063), or HADS depression score (p = 0.718, r = -0.06) in the BTm group. CONCLUSION: We found that both depression and anxiety were higher in BTm patients than in healthy individuals, but this difference was not feasible for fatigue.

The impact of transfusion burden and comorbidities on the prognosis of patients with myelodysplastic syndromes.

PURPOSE: Early comorbidity detection has been reported to be associated with treatment-related outcomes in several diseases. Two main goals of the present study were to investigate both the impact of comorbidities and transfusion frequencies on the survival and quality of life of patients with myelodysplastic syndromes (MDS). METHODS: One hundred and four MDS patients with a median International Prognostic Scoring System (IPSS) score of 0.5 (range: 0-3) were included in the study. Almost half of the patients had more than one comorbidity. RESULTS: Median short form health surveys (SF)-36 mental and physical scores were 42.1 (range: 20.6-66.1) and 38.7 (range: 18-59.7), respectively. Mean scores of the Eastern Cooperative Oncology Group (ECOG) performance scales at diagnosis and during recruitment were 1.0 (1.4 ± 1.0) and 2.0 (1.8 ± 1.1), respectively. The mean Charlson Comorbidity Index (CCI) score was 1.0 (1.4 ± 1.5). In the model that was constructed using variables with a p value < 0.100 in the univariate analysis, factors that predicted death were refractory anemia with excess blasts (RAEB) and ECOG scores at recruitment. When ECOG was removed from the model, RAEB and CCI at diagnosis moved to the forefront as mortality predictors. CONCLUSION: This study demonstrated that both CCI and ECOG performance status had an impact on survival in MDS patients who had low IPSS scores. ECOG stood out as a better and more practical predictor of survival than CCI, especially after considering its (ECOG) ease of use.

Rethinking the usefulness of bone marrow biopsy on treatment decision in CLL patients at diagnosis.

We aimed to investigate the role of bone marrow infiltration pattern (BMIP) and bone marrow reticulin fibrosis (BMRF) in determining treatment demand in patients with diagnosis of chronic lymphocytic leukemia (CLL). We retrospectively evaluated the data of 65 patients, who were followed with the diagnosis of CLL at Istanbul Training and Research Hospital, Department of Hematology, between July 2007 and June 2016. The median age of the patients was 64 years (range, 32-83). Twenty-three (35.4%) patients were female, and 42 (64.6%) were male. Early/mild grade BMRF was observed in 46 (70.8%) patients and advanced grade BMRF in 19 (29.2%) patients. Eleven (23.9%) of 46 patients with early/mild grade BMRF and 10 (52.9%) of 19 patients with advanced grade BMRF required treatment during follow-up (p = 0.04). According to the BMIP, 14 (21.5%) patients had diffuse and 51 (78.5%) patients had non-diffuse BMIP. Eleven (78.6%) of 14 patients with diffuse BMIP and 10 (19.6%) of 51 patients with non-diffuse BMIP required treatment during follow-up (p < 0.001). In univariate analysis, both advanced grade BMRF and diffuse BMIP had an impact on occurrence of treatment demand (p = 0.028, HR = 3.535 vs. p < 0.01 HR = 15.033). Multivariate analysis also revealed diffuse BMIP to be effective (p < 0.001, HR 13.089), while advanced grade BMRF failed to significantly influence treatment demand (p = 0.140, HR 2.664). In conclusion, in the light of our findings, it is reasonable to consider that bone marrow biopsy at the time of diagnosis might provide a preliminary information about treatment demand in patients with CLL.

Gilteritinib (XOSPATA®) in Turkey: Early Access Program Results.

Background And Objectives: Gilteritinib (XOSPATA®, Astellas) is a type I oral FLT3 inhibitor, a tyrosine kinase AXL inhibitor, involved in both c-Kit and FMS-like tyrosine kinase 3 (FLT3) resistance. In the phase 3 ADMIRAL trial, gilteritinib was compared with the standard of care in (R/R) acute myeloid leukemia (AML) patients who harbored any FLT3 mutation and showed superior efficacy with regard to response and survival. Objectives: This research aimed to investigate the real-life efficacy and safety of gilteritinib in FLT3-positive R/R AML patients who were treated as a part of an early access program held in Turkey in April 2020 (NCT03409081). Results: The research included 17 R/R AML patients who had received gilteritinib from seven centers. The overall response rate was 100%. The most common adverse events were anemia and hypokalemia (7 patients, 41.2%). Grade 4 thrombocytopenia was observed in one patient only (5.9%), leading to permanent treatment discontinuation. Patients with peripheral edema had a 10.47 (95% CI: 1.64-66.82) times higher risk of death than those without peripheral edema (p<0.05). Conclusion: This research showed that patients with febrile neutropenia and peripheral edema were at a high risk of death when compared to patients without febrile neutropenia and peripheral edema.

Charlson Comorbidity Index (CCI) in Diffuse Large B-cell Lymphoma: A New Approach in a Multicenter Study.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of adult lymphomas. The incidence of DLBCL increases with age and has a fairly rapid fatal course without treatment. Patients often have difficulty tolerating standard chemotherapy regimens due to their comorbidities. Charlson Comorbidity Index (CCI), which is calculated by considering 19 different comorbidities, was developed in 1987 and is widely used for mortality prediction in cancer patients. Literature data on CCI and hematological malignancies are limited. Main aim in this study is to evaluate the effectiveness of CCI and compare to the International Prognostic Index (IPI) scoring system in the DLBCL patient group. Methods: A total of 170 patients diagnosed with DLBCL between 1.1.2002- 1.12.2020 were included in the study. Statistical analyzes were performed among patients whose IPI and CCI scores were recorded by considering baseline data. Results: The median age of patients was 58 (range: 17-84). Thirty-five (20.6%) patients had stage III and 76 (44.7%) had stage IV disease. When the CCI, IPI and ECOG scores were compared with the mortality status of the patients as a reference, AUCs were resulted as 0.628 (95% CI: 0.506-0.749), 0.563 (95% CI: 0.484-0.639) and 0.672 (95% CI: 0.596-0.743), respectively. There was no significant difference between the ROC curves of CCI, IPI and ECOG scores. Patients with a CCI score of ≥ 4 had shorter OS comperad to those with a score of < 4. Conclusion: Rather than claiming that CCI is superior to IPI, ECOG or another scoring system in a single-center patient population, it should be stated that CCI is also an effective scoring system in patients diagnosed with DLBCL. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01567-5.

Premarital hemoglobinopathy screening in Kayseri: a city in Middle Anatolia region of Turkey.

OBJECTIVE: The aim of the present study was to report the frequency of ß-thalassemia trait and other hemoglobinopathies in Kayseri province, which is located in Middle Anatolia of Turkey, as part of the premarital screening program. METHODS: The study included subjects admitted to Family Planning Center for premarital screening test between January 2009 and March 2010. Blood samples of the couples were obtained during admission to the marriage office. Complete blood counts and hemoglobin (Hb) variant analysis were performed with automatic counter and capillary electrophoresis. RESULTS: A total of 10,261 people were screened. The prevalence of patients with the ß-thalassemia trait was 1.71% (175/10261). Moreover, HbD Punjab and HbO Arab were the most common Hb variants after ß-thalassemia trait with the frequencies of 0.36% and 0.09%, respectively. Only 2 HbS were detected in 15 months of screening time. In 2 couples both partners were found to be carriers of ß-thalassemia trait, and both partners of 1 couple to be carrier of HbD. CONCLUSIONS: Kayseri is not a high-risk region according to Mediterranean parts of Turkey, but the city takes migrations apart from neighbor cities, migrations from East and South provinces because of its geographic and industrial situation. For that reason detecting carrier couples with premarital screening program is an effective way of controlling thalassemia major.

Serum albumin and ferritin levels: a practical indicator of prognosis in acute myeloid leukemia over 50 years of age?

BACKGROUND: Low albumin and high ferritin levels have negative effects on survival in acute myeloid leukemia (AML). In this study, the aim is to determine the role of these factors on survival in patients over 50 years of age with AML. METHODS: Eighty patients followed up between January 2014 and July 2019 were included in the study. Patients were categorised into three subgroups: The favorable, intermediate and high-risk groups. RESULTS: The overall survival of the favorable group was found to be longer in a statistically significant way. CONCLUSION: In this study, it has been shown that serum albumin and ferritin values are useful and simple laboratory values to show prognosis in AML over 50 years of age.

Secondary Immunodeficiency Frequency in Patients with Chronic Lymphocytic Leukemia: The Relationship with Stage and Treatment.

Background: Chronic lymphocytic leukemia (CLL) is one of the most common hematological malignancies. In patients with CLL, serum immunoglobulin levels decrease over time due to both the disease itself and the chemo-immunotherapeutic agents used. It was aimed to reveal the relationship between hypogammaglobulinemia and disease stage, and chemo-immunotherapies. Materials and Methods: Data were obtained by retrospectively examining 74 patients who were followed-up between 2008-2019. The relationship between all parameters (demographic characteristics, RAI stages or therapy subtypes) and serum IgG levels was analyzed. Results: Thirty-two of 74 patients received a therapy. Twenty-two patients were on combined therapy with rituximab or only rituximab and 10 were treated with chemotherapeutic agents only. The frequency of hypogammaglobulinemia was 5.4% at the diagnosis, this rate was 55% in patients receiving a therapy. Hypogammaglobulinemia was higher in advanced stages. In patients with rituximab, higher levels of IgG decrease were observed. Conclusion: Serum IgG level was significantly lower in patients with advanced-stage, received chemotherapy, especially rituximab. In addition to basal IgG, immunoglobulin levels should be checked during treatment, and follow-up period. Early replacement intravenous immunoglobulins will be important to reduce severe infection attacks due to secondary immunodeficiency.

A new approach in acute myeloid leukemia (AML): Samatya-predicting score.

We aimed to examine the efficiency for prediction of prognosis and response in non-APL AML cases of the "Samatya-predicting score". A total of 213 patients diagnosed between January 2010-December 2020 were examined. Of the 158 patients included in the study, the median value of risk score was determined as 2,5. The sensitivity for mortality was 88% and the specificity was 42%. In terms of being non-responder to induction therapy, the sensitivity was 90,1%, the specificity was 25,3%. OS was shorter in those with high risk scores. This study makes an important contribution to the literature in terms of creating a different perspective to predict prognosis in AML.

Iron overload during the treatment of acute leukemia: pretransplant transfusion experience.

BACKGROUND: Recent studies have shown the increased risk of mortality in cases with acute leukemia and iron overload. We aimed to determine the status of iron overload in patients with acute leukemia. MATERIALS & METHODS: Patients diagnosed with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) between January 2015 and December 2019 were included in the study. RESULTS: At 6 months, there were statistically more patients with serum ferritin >1000 in the AML group compared to the ALL group (p = 0,011). CONCLUSION: Iron overload occurs earlier in patients with AML; the difference disappears after 6 months of treatment. It is the correct point to emphasize that iron overload is an important factor of pretransplant morbidity, especially in AML cases.

A new FLT3 inhibitor with two cases: the gilteritinib experience.

INTRODUCTION: In acute myeloid leukemia (AML), a heterogeneous group of leukemias, there are various factors to determine prognosis. Among these prognostic factors, cytogenetic results are increasing in importance day by day. FLT3 mutations are among the most common molecular abnormalities in AML, patients with recurrent or refractory (R/R) AML with this mutation have a low response rate to salvage therapy. Gilteritinib has activity against FLT3, ALK and AXL. This article shall present two cases, for which Gilteritinib was used, a new FLT3 inhibitor, and the results of the treatment. Case 1: A 52-year-old female patient presented to the emergency clinic with weakness and fever. In initial biochemical analysis, leukocyte was 104000/mm3. Peripheral smear contained diffuse myeloid blastoid cells, peripheral blood flow cytometry also supported the AML M0-1 phenotype. The bone marrow biopsy aspiration performed on the 14th day of induction "3+7" treatment, contained diffuse blastic infiltrate and supported refractory disease. In addition to the FLAG-IDA salvage regimen, 120 mg/day Gilteritinib was also started. Bone marrow aspiration performed on the 28th day of salvage therapy was compatible with remission. Case 2: 53 years old male patient with also no comorbidity other than known hypertension. In the initial biochemical analysis of the patient, leukocyte was 156000/mm3, platelet 58000/mm3 and hemoglobin 7.6 g/dl. Peripheral blood flow cytometry supported the AML M5 phenotype, whose peripheral smear showed diffuse monoblastoid cells. On the 14th day of the patient's 3+7 induction treatment, the control bone marrow aspiration showed diffuse blast infiltration and was considered refractory, FLAG-IDA salvage therapy with again 120 mg/day Gilteritinib per oral were started. On the 28th day, control bone marrow aspiration was evaluated as remission. DISCUSSION AND CONCLUSION: Unlike other FLT 3 inhibitors, Gilteritinib has been shown to be a highly effective agent in R/R AML with FLT3 mutations. Being the first data to be reported from Turkey, we think it would be quite guiding the titular.

A rare extramedullary involvement in myeloma: lung parenchyma and association with unfavorable chromosomal abnormalities.

Although pulmonary complications developing secondary to lung infections and involvement in ribs occur frequently in multiple myeloma (MM), involvement of the lung parenchyma is quite rare. In clinical studies, the involvement of lung parenchyma has been found to be associated with unfavorable prognosis. Here, a MM case in whom involvement of lung parenchyma was accompanied by unfavorable prognostic cytogenetic markers is presented. A 62-year-old male presented with complaint of cough, and heterogeneous hypodense mass was detected in thorax computerized tomography. The patient underwent bronchoscopic biopsy. Pathological examination revealed diffuse plasma cell infiltration staining with kappa immunohistochemically. In bone marrow biopsy, plasma cell infiltration was observed. In conventional cytogenetic examination, hypodiploidy was established. In cytogenetic examination carried out with fluorescence in situ hybridization, deletion (13q) was determined. In conclusion, in patients diagnosed with MM and presenting with pulmonary mass lesion, lung involvement associated with plasma cell infiltration should also be considered in the differential diagnosis. As overall survival is low in these cases, more aggressive treatment approaches such as high-dose treatment should be immediately considered.

Evaluation of risk factors for thrombophilia in patients with cerebral venous thrombosis.

OBJECTIVE: The increased risk for thrombosis is known as hypercoagulability or thrombophilia. In our study, we aimed to compare the frequency of the identified defects for thrombophilia in patients with central venous thrombosis and under the age of 50 years, with the findings in the current literature. METHODS: Forty-three patients (16-50 years old) were retrospectively evaluated. Thrombophilia investigation included determinations of protein C, protein S, antithrombin, and activated protein C resistance, factor V Leiden (FVL), prothrombin 20210A (PT 20210) and methylene tetrahydrofolate reductase (MTHFR) C677T mutations, antiphospholipid antibodies (APA), factor VIII levels, and homocysteine levels. RESULTS: We detected a single thrombophilic defect in 67.4%, two defects in 27.9% and three defects in 4.7% of our patients. The most common thrombophilic defect was mutation in the MTHFR gene (41.8%), and this was followed by the FVL mutation (34.9%). CONCLUSION: Since the prevalence of individual thrombophilic defects varies in each population, ethnic group and geographical location, screening for thrombophilic defects in patients presenting with cerebral venous thrombosis should primarily investigate the most frequent thrombophilia risk factors.

Role of flow cytometry in multiple myeloma and the prognostic significance of CD87 (uPAR) expression.

OBJECTIVE: The plasminogen activator system consists of the serine protease urokinase plasminogen activator (uPA), two endogenous inhibitors of PAI-1 (plasminogen activator inhibitor-1) as well as the PAI-2 and uPA receptor (uPAR or CD87). The aim of this study was to determine the significance of flow cytometry and CD87, CD45 and CD56 expressions in the diagnosis, follow-up and prognosis of multiple myeloma (MM). METHODS: Twenty-nine MM patients were included in the study. Bone marrow samples were used for flow cytometry. A panel of CD87, CD45, CD56, CD10, CD19, CD20, CD38, and CD138 was tested by flow cytometry. RESULTS: CD87 was negative in 8 (27.5%) cases, dim positive in 9 (31.1%) and bright positive in 12 (41.4%). CD87 expression was significantly higher in CD45 (-) cases. CONCLUSION: Flow cytometry has a significant role in the diagnosis and prognosis of MM. Further clinical studies including large numbers of patients are needed to determine the prognostic role of CD87 in MM.

The relationship between serum ferritin level and fibrosis and splenomegaly in myelofibrosis.

INTRODUCTION: Myelofibrosis (MF) is a disease in which the grade of bone marrow fibrosis increases in proportion to the degree of extramedullary hematopoiesis and splenomegaly. Associated with increased cytokines and inflammation, anemia deepens and an increase in serum ferritin levels is also expected. There are no studies addressing the relationship between ferritin and splenomegaly or fibrosis. In this study, the relationship between serum ferritin level and splenomegaly and bone marrow fibrosis was examined. MATERIAL AND METHOD: The study was performed retrospectively in 46 MF cases diagnosed between 2012 and 2020. MF was divided into 3 separate subgroups: Primary myelofibrosis, secondary myelofibrosis and myeloproliferative neoplasms (MDS/MPN) with myelodsplastic syndrome. RESULTS: Thirty (28.3%) of cases were PMF, 26 (56.5%) were SMF and 7 (15.2%) were MDS/MPN. There was no relation found between serum ferritin and splenomegaly in none of the cases or subgroup analysis (for PMF p: 0.564, for SMF p: 0.192, for MDS/MPN p: 0.364). There was a statistically significant relationship between serum ferritin and marrow fibrosis within the group of ages 60 years and older (p: 0.016). DISCUSSION AND CONCLUSION: Disruption of hematopoiesis and progressive splenomegaly causes an increase in iron stores associated with an increased need for transfusion. This causes iron-related organ toxicity and bone marrow hematopoiesis disruption, leading to an increase in morbidity. We see that a significant relationship between ferritin and fibrosis has been revealed in the group aged 60 years and older. It is an unprecedented study in the literature in terms of both examining the relationship ferritin and fibrosis or splenomegaly and its results.

A case report: paroxysmal nocturnal hemoglobinuria and systemic lupus erythematosus association.

Paroxysmal nocturnal hemoglobinuria (PNH) is defined by acquired intravascular hemolytic anemia, thrombosis and bone marrow failure with pancytopenia. Systemic lupus erythematosus (SLE) also appears as an autoimmune disease. The coexistence of both is rarely reported. Here we report the case of a 30-year-old female presenting with pancytopenia and diagnosed as SLE, who also had a PNH clone. Bone marrow biopsy did not support hypoplastic anemia. The patient was then followed up with the consideration of the existence of a PNH clone with SLE. She was treated by the rheumatology department and complete blood count improved under immunosuppressive treatment. The coexistence of CD59-CD55 deficiency with autoimmune diseases has been reported. It is an important example in terms of receiving clinical response with SLE-specific treatment.