The effect of leptin gene polymorphisms (LEP rs7799039 and LEPR rs1137101) on febrile neutropenia.

Background and aim: Leptin is mainly produced in adipose tissue and released into systemic circulation. Leptin and its receptor LEPR activate the Janus kinase/signal transducers and activators of transcription signaling cascade and increase cytokine discharge. In our study, we aimed to examine the role of leptin gene (LEP) rs7799039 and LEPR rs1137101 polymorphisms on the susceptibility for febrile neutropenia (FEN) attacks and their relationship with clinical findings during the course of FEN. Methods: This study included pediatric patients with a diagnosis of malignancy who applied to the pediatric emergency department between December 2019 and June 2022 and healthy controls. The genotypes of the LEP rs7799039 and LEPR rs1137101 genes were statistically compared between patients and healthy controls. In addition, the relationship between the genotype distribution of LEP rs7799039 and LEPR rs1137101 polymorphisms and clinical features during the course of FEN was investigated. Results: In the statistical analysis in terms of LEP rs7799039 and LEPR rs1137101 genotype distributions between the patient and healthy groups, there was no significant difference. Patients with the AA genotype of LEPR rs1137101 polymorphism had significantly more commonly a body mass index (BMI) value of <25, and all the patients with the AG/GG genotype had a BMI value of 25 and above. LEP rs7799039 and LEPR rs1137101 genotype distributions were not statistically significant with other clinical features. Conclusions: It was revealed that leptin gene polymorphisms did not have a significant effect during the course of FEN.

Lymphocyte Level at Diagnosis in Hodgkin lymphoma: Could It be an Indicator of the Stage at Initial Diagnosis?

Background: Despite the existence of standard risk classification systems and effective treatment approaches, 34% to 37% of advanced-stage Hodgkin lymphomas (HLs) either relapse or progress. Our goal in our study was to show the relationship between initial lymphocyte count and stage while examining their effects on prognosis. The initial lymphocyte count, which is proven in advanced-stage patients, could be an important factor in terms of showing the prognosis in the early stage. Materials and Methods: Our study included 190 patients diagnosed with HL in our hospital between January 2010 and September 2020. HL subtypes, diagnosis stages, presence of bulky or mediastinal masses, lymphadenopathy areas, and demographic data of patients, such as age and sex. The aim was to obtain a cutoff in the statistical analysis performed to explore the relationship between lymphocyte level and stage, which is the main hypothesis of the study. Results: Of the 190 patients evaluated, 77 were female (40.5%) and 113 were male (59.5%). To obtain a cutoff in terms of lymphocyte level and stage relationship, a value of 2380/mm3 and below was found to be associated with stage 3-4 disease with a sensitivity of 86.44% and a specificity of 33.3% (AUC: 0.613 (0.539-0.682), p<0.007). Conclusion: This result can be improved in combination with conventional imaging methods used for staging purposes. Further studies may shed light on staging and especially the diagnosis of advanced-stage disease with high sensitivity.

How complicated can be a case with immune thrombocytopenic purpura?: postsplenectomy arterial thrombosis.

Arterial thrombus associated with the surgery can be seen in postsplenectomy cases, but there is no clear data in patients diagnosed with immune thrombocytopenic purpura (ITP). A 52-year-old female patient was admitted to the emergency department due to ecchymotic skin changes. Her initial platelet count was 6000/mm 3 ; after two courses of high dose-dexamethasone, intravenous immunoglobulin and rituximab, splenectomy was planned for the patient whose platelet count was again <40 000/mm 3 . She presented to the emergency department with complaints of pain and pallor in the right arm in the second week of follow-up. There was a mural thrombus that caused approximately 50% stenosis in the lumen at the division site in the aortic arch, proximal of the right subclavian artery. The patient's clinic was found to be associated with the presence of an aberrant right subclavian artery and postoperative thrombocytosis/inflammation after elimination other prothrombotic conditions.

Effect of interleukin-2 (IL-2) polymorphisms on multiple myeloma: IL-2RA rs2104286, IL-2 rs2069762 and rs2069763 polymorphisms.

Interleukin-2 (IL-2) is a cytokine secreted from T helper type 1 cells and released after induction of T helper cells with major histocompatibility complexes or antigens presented by antigen presenting cells. IL-2 activity and gene polymorphisms have been studied in both solid and hematological malignancies. In the present study, it was aimed to examine the effects of IL-2RA rs2104286, IL-2 rs2069762 and rs2069763 polymorphisms on multiple myeloma (MM) susceptibility, progression-free survival (PFS) and overall survival (OS). A total of 300 patients diagnosed with MM in our clinic between January 2010 and January 2021, and 170 healthy individuals were included. In addition to the demographic data of the patients, MM subtypes, initial stages, prognostic index scores, laboratory results, treatment preferences, and survival data were recorded. The genotypes of the IL-2RA rs2104286, IL-2 rs2069762 and rs2069763 polymorphisms were statistically compared between patients and healthy controls to reveal their effects on MM susceptibility and survival. In the statistical analysis performed to examine the effect of IL-2RA rs2104286, IL-2 rs2069762 and rs2069763 polymorphisms on disease susceptibility, no significant difference was found between the patient and healthy control groups. Patients with the TG genotype of IL-2 rs2069762 had a significantly shorter median PFS and OS compared to others. Patients with the GG genotype of IL-2 rs2069763 had a significantly shorter median PFS compared to others. Having the TG genotype of IL-2 rs2069762 has been shown to be protective for short PFS and OS. Our study results will be guiding in terms of IL-2 based therapies, the future for MM and MM epigenetics.

Plerixafor in autologous stem cell transplantation: Does it affect engraftment kinetics?

Plerixafor increases stem cell mobilization by reversibly binding to the chemokine receptor CXCR4. In our study, we examined the results of mobilization with plerixafor and granulocyte colony-stimulating factor (G-CSF) and revealed their effects on autologous stem cell transplantation (ASCT) engraftment kinetics. The study included all cases of ASCT performed in the Adult Bone Marrow Transplantation Unit of xxx University between January 2014 and January 2022. It included a total of 300 patients. The total number of CD34 + cells collected was 7.44 ± 4.19 in patients with plerixafor and 9.53 ± 6.09 in patients without plerixafor. The mean neutrophil and platelet engraftment took longer in plerixafor-mobilized patients (neutrophil: 12 ± 4.1 vs. 10.2 ± 2.7 days; platelet: 21.6 ± 13.9 vs. 14.2 ± 5.9 days; p = 0.008 and p = 0.002). The number of febrile neutropenia attacks was significantly higher in plerixafor-mobilized patients (p = 0.04). In the chemo-mobilized patient subgroup, plerixafor-mobilized patients experienced more febrile neutropenia attacks (p = 0.04). The mean time to both neutrophil and platelet engraftment was longer in patients mobilized with plerixafor. In the subgroup of patients with MM, the mean time to platelet engraftment was longer in patients mobilized with plerixafor. Plerixafor and its effect on engraftment kinetics should be evaluated with further studies in a larger population with survival analysis.

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.

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.

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.

The effect of DNA repair gene variants on COVID-19 disease: susceptibility, severity, and clinical course.

Oxidative stress (OS), which leads to DNA damage, plays a role in the pathogenesis of Coronavirus disease 2019 (COVID-19). We aimed to evaluate the role of DNA repair gene variants [X-ray repair cross complementing 4 (XRCC4) rs28360071, rs6869366, and X-ray cross-complementary gene 1 (XRCC1) rs25487] in susceptibility to COVID-19 in a Turkish population. We also evaluated its effect on the clinical course of the disease. A total of 300 subjects, including 200 COVID-19 patients and 100 healthy controls, were included in this study. These variants were genotyped using polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism (RFLP) methods. The patients were divided into three groups: those with a mild or severe infection; those who died or lived at the 28-day follow-up; those who required inpatient treatment or intensive care. There were 87 women (43.5%) and 113 men (56.5%) in the patient group. Hypertension was the most common comorbidity (26%). In the patient group, XRCC4 rs6869366 G/G genotype and G allele frequency were increased compared to controls, while XRCC4 rs6869366 G/T and T/T genotype frequencies were found to be higher in controls compared to patients. For XRCC1 rs25487, the A/A and A/G genotypes were significantly associated with COVID-19 disease. All of the patients hospitalized in the intensive care unit had the XRCC4 rs6869366 G/G genotype. In this study, we evaluated for the first time the impact of DNA repair gene variants on COVID-19 susceptibility. Results suggested that XRCC4 rs6869366 and XRCC1 rs25487 were associated with COVID-19 suspectibility and clinical course.

The suppressor of cytokine signaling-1 (SOCS1) gene polymorphism and promoter methylation correlate with the course of COVID-19.

The suppressor of the cytokine signaling-1 (SOCS1) gene is a short sequence located on chromosome 16 that functions to induce an appropriate immune response and is an essential physiological regulator of interferon (IFN) signaling. In addition to comparing the global DNA and SOCS1 gene promoter methylation status between our patients with coronavirus disease 2019 (COVID-19) and healthy controls, this study demonstrates the effect of the SOCS1 rs33989964 polymorphism on patients with COVID-19. The study group included 139 patients diagnosed with COVID-19 in our hospital's clinics between June and December 2020, and the control group included 78 healthy individuals. After comparing the initial gene polymorphisms of the patients with the healthy control group, three separate clinical subgroups were formed. The gene polymorphism distribution and the methylation status of SOCS1 were examined in these clinical subgroups. Hypomethylation of the SOCS1 gene was observed in the COVID-19 patient group compared to the healthy control group (p = 0.001). Between the patients divided into two separate clinical subgroups, those with severe and mild infections, the Del/Del genotype of the SOCS1 gene was more common in patients with severe infection than in patients with mild infection (p = 0.018). Patients with the CA/CA and CA/Del genotypes were 0.201 times more likely to have a severe infection (95% CI: 0.057-0.716, p = 0.007). Having a non-Del/Del genotype was a protective factor against severe infection. The effect of the SOCS1 rs33989964 polymorphism and methylation status of the SOCS1 gene throughout the COVID-19 pandemic could be significant contributions to the literature.

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.

AAT: does it have a place in acute leukemia?

Aim: In this study, the authors aimed to investigate the change of AAT, its effect on the response to induction and its effects on the treatment process in acute myeloid leukemia and acute lymphoblastic leukemia patients. Materials & methods: This study included 94 patients who were hospitalized and followed up in Istanbul Training and Research Hospital, Hematology Clinic, between October 2019 and December 2021. Results: Patients with a complete response had higher serum AAT levels than those with a non-complete response (p < 0.05). The mean serum AAT level was found to be significantly higher in patients without Gram-positive growth than in patients with Gram-positive growth. Conclusion: It can be thought that AAT can play a role during the course of acute leukemia management.

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.

Epigenetic and genetic investigation of SOCS-1 gene in patients with multiple myeloma.

Background: The suppressor of cytokine signaling-1 (SOCS-1) functions to induce an appropriate immune response and is an essential physiological regulator of interferon signaling. DNA methylation involves adding a methyl group to the carbon 5 position of cytosine. Besides comparing SOCS-1 gene methylation status between patients with multiple myeloma (MM) and healthy controls, this study also aimed to demonstrate the effect of SOCS-1 gene distribution and the effect of methylation of SOCS-1 on progression-free survival (PFS) and overall survival (OS). Methods: This study included 120 patients diagnosed with MM between January 2018 and 2020 and 80 healthy individuals. The distribution of the SOCS-1 genotypes was statistically compared between MM patients and healthy controls. Additionally, the statistically significant effects of these genotypes on survival were examined. Results: The CA/CA genotype of SOCS-1 was significantly higher in healthy controls (P=0.001), while the Del/Del genotype was significantly higher in patients with MM (P=0.034). The percent methylated reference (PMR) value of the SOCS-1 gene was significantly higher in the healthy controls (median, 43.48; range, 2.76‒247.75; P=0.001). Patients with a PMR value of ≥43.48 were 3.125 times more likely to develop progression than those with a PMR value of ＜43.48. Conclusion: The effects of SOCS-1 polymorphisms on the pathogenesis of.

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.

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.