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Summary: Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79–4.91; p

Background: Acute myeloid leukaemia(AML) is a disease of the haematopoietic stem cells. Beta-catenin, a key element of the Wnt signalling, which is particularly active in various cancers. Our aim of this study was to determine beta-catenin gene expression levels in AML patients. Then, it is planned to compare the genes between AML grouped according to beta-catenin gene expression levels by DNA microarray. When the gene group identified in this way is combined with the genes in the control group, the aim is to determine the genes that are associated with beta-catenin in AML. Methods: In this study, beta-catenin gene expression levels were determined in 19 AML patients and 3 controls by qRT-PCR. Transcriptome analysis was performed on AML grouped according to beta-catenin expression levels. Differentially expressed genes(DEGs) were identified and investigated with using DAVID, GO, KEGG and STRING. Results: The transcriptome profiles of our AML samples showed different molecular signature profiles according on their beta-catenin levels(high-low). A total of 20 genes have been identified as hub genes. Among these, TTK, HJURP, KIF14 and BTF3, RPL17, RSL1D1 were found to be associated with poor survival and suggested to be associated with beta-catenin in AML. Furthermore, for the first time in our study, the ELOV6 gene, which is the most highly up-regulated gene in human AML samples, was correlated with a poor prognosis via beta-catenin high levels. Conclusion: It is suggested that the identification of beta-catenin-related gene profiles in AML may help to select new therapeutic targets for the treatment of AML.

Objective: The discovery of imatinib was a milestone for chronic myeloid leukemia (CML). As the life expectancy of CML patients has approached that of the general population, research has shifted towards improving quality of life and economic considerations. After 2010, it was shown that some patients could maintain molecular response even after discontinuing imatinib. This national multicenter prospective cohort study aimed to observe the long-term consequences of discontinuing imatinib therapy in adult chronicphase CML patients. Materials and Methods: We enrolled 41 CML patients from 4 different centers in this non-randomized single-arm trial. Molecular responses of all patients were re-evaluated using real-time polymerase chain reaction at a single center. The median follow-up time after imatinib discontinuation was 48 months (minimum-maximum: 6-81 months). Results: The rate of molecular relapse-free survival at 48 months was 33.2% (confidence interval: 48.2-18.2). Twenty-seven of 41 patients lost their major molecular response, treatment was started again, and deep molecular response was re-achieved with imatinib in all cases. There was no significant relationship between molecular relapse and clinical factors such as duration of treatment or molecular response status. Discontinuing imatinib resulted in savings of approximately 4,392,000 Turkish lira or 245,150 US dollars. Conclusion: Tyrosine kinase inhibitor discontinuation with close molecular monitoring is a safe option and provides important national economic benefits for chronic phase CML patients. This approach should be considered for all eligible patients. This is the first tyrosine kinase inhibitor discontinuation study from Türkiye.

Objective: Patients with solid malignancies are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection than the healthy population. The outcome of SARS-CoV-2 infection in highly immunosuppressed populations, such as in patients with hematological malignancies, is a point of interest. We aimed to analyze the symptoms, complications, intensive care unit admissions, and mortality rates of patients with hematological malignancies infected with SARS-CoV-2 in Turkey. Materials and Methods: In this multicenter study, we included 340 adult and pediatric patients diagnosed with SARS-CoV-2 from March to November 2020. Diagnosis and status of primary disease, treatment schedules for hematological malignancies, time from last treatment, life expectancy related to the hematological disease, and comorbidities were recorded, together with data regarding symptoms, treatment, and outcome of SARS-CoV-2 infection. Results: Forty four patients were asymptomatic at diagnosis of SARSCoV- 2 infection. Among symptomatic patients, fever, cough, and dyspnea were observed in 62.6%, 48.8%, and 41.8%, respectively. Sixtynine (20%) patients had mild SARS-CoV-2 disease, whereas moderate, severe, and critical disease was reported in 101 (29%), 71 (20%), and 55 (16%) patients, respectively. Of the entire cohort, 251 (73.8%) patients were hospitalized for SARS-CoV-2. Mortality related to SARS-CoV-2 infection was 26.5% in the entire cohort; this comprised 4.4% of those patients with mild disease, 12.4% of those with moderate disease, and 83% of those with severe or critical disease. Active hematological disease, lower life expectancy related to primary hematological disease, neutropenia at diagnosis of SARS-CoV-2, ICU admission, and first-line therapy used for coronavirus disease-2019 treatment were found to be related to higher mortality rates. Treatments with hydroxychloroquine alone or in combination with azithromycin were associated with a higher rate of mortality in comparison to favipiravir use. Conclusion: Patients with hematological malignancy infected with SARS-CoV-2 have an increased risk of severe disease and mortality.

Background: Cell-free DNA, which may be considered as “liquid” biopsy, may serve as a diagnostic and prognostic marker not only in hematological malignancies but in solid tumors as well. Aims: To investigate the prognostic role of pre-transplant cell-free DNA levels in allogeneic hematopoietic stem cell transplant recipients. Study Design: Retrospective cohort study. Methods: A total of 177 allogeneic hematopoietic stem cell transplant recipients [median age: 36 (16-66) years; male/female: 111/66] with an initial diagnosis of acute leukemia were included in the study. Cell-free DNA was extracted from pre-transplant serum samples by using the MagNA Pure Compact Nucleic Acid Isolation Kit I with the MagNA Pure Compact instrument (Roche Diagnostics, Penzberg, Germany). Results: A positive correlation was demonstrated between cell-free DNA and age (p=0.018; r=0.177). Pre-transplant cell-free DNA levels were lower in bcr-abl (+) patients (p=0.001), while an adverse correlation was indicated between cell-free DNA and bcr-abl levels (p=0.001; r=−0.531). Acute lymphoblastic leukemia patients with bcr-abl positivity (p=0.001) or abnormal cytogenetics (p=0.038) represented significantly lower pre-transplant cell-free DNA levels. Cell-free DNA levels were lower in patients who developed sinusoidal obstruction syndrome (p=0.035). In terms of long-term complications, acute myeloid leukemia patients who experienced post-transplant relapse had significantly lower pre-transplant cell-free DNA levels (p=0.024). Overall survival was not statistically different between high- and low- cell-free DNA groups (45.2% vs 22.5; p=0.821). Conclusion: In general, low serum levels of pre-transplant çell-free DNA seem to be associated with transplant-related morbidities and may be considered an adverse prognostic factor for allogeneic hematopoietic stem cell transplant recipients.

Autologous Hematopoietic Stem Cell Transplantation (auto-HSCT) has become a therapeutic option for first-line consolidation in Acute Myeloid Leukemia (AML) patients with favorable and intermediate risk features. A total of 101 AML patients in first complete remission, who were not eligible for allogeneic HSCT, were randomized to receive intensive cytarabine-based chemotherapy or to undergo auto-HSCT. The probability of LFS was significantly better in auto-HSCT recipients compared to chemotherapy arm (43% vs 4.8%, p=0.008). At the end of 915 (30-4470) days of followup, the probability of overall survival was better in auto-HSCT group compared to chemotherapy, without statistical significance (79.2% vs 38.8%, p=0.054). Multivariate analysis revealed a significant predictive impact of cytogenetic risk status on OS (p=0.002, HR: 2.824, 95% CI: 1.445- 5.521). Auto-HSCT is considered as an effective consolidation approach in favorable and intermadiate risk AML patients.

Objective: Non-responsiveness to hepatitis B virus (HBV) vaccines is not rare in hemato-oncological patients due to disease-associated or treatment-induced immune suppression. Although different strategies have been employed to improve the response rates, to date there is not an approved schedule for HBV immunization in patients with hematological malignancies. We designed a prospective randomized study to evaluate the efficacy of 3 different induction regimens for HBV vaccination. Materials and Methods: In the standard-dose (SD) group, total vaccine dose delivered was 40 μg and patients were vaccinated with 20 μg at weeks 0 and 4. In the high-dose dose-intensive (HDDI) group, total vaccine dose delivered was 80 μg and patients were vaccinated with 40 μg at weeks 0 and 4. In the high-dose time-intensive (HDTI) group, total vaccine dose delivered was 80 μg and patients were vaccinated with 20 μg at weeks 0, 2, 4, and 6. Results: In a cohort of 114 patients, 38.6% responded to HBV vaccination. The response rate in the SD arm, HDDI arm, and HDTI arm was 26.2%, 29.7%, and 44.4%, respectively (p>0.05). Age was the only variable identified as having a negative impact on response. Conclusion: Short of achieving statistical significance, a higher response rate was observed in the HDTI arm. Therefore, this study supports a high-dose, time-intensive HBV vaccine induction regimen in patients with hematological malignancies who are not on chemotherapy.

INTRODUCTION: To investigate the influence of chemotherapy (CT) on HBsAb titer in patients receiving CT due to hematological malignancy. METHODS: The data of 75 patients who received CT with the diagnosis of various hematological malignancies and who had serum HBsAb levels measured prior to and after the cessation of CT were evaluated retrospectively. RESULTS: The median age of the patients was 52 years (range: 16-78) with 49 (65%) males and 26 (35%) females. Median HBsAb titer decreased significantly after CT compared to the pre-CT median HBsAb titer [68 (range: 0-1000) vs. 100 (range: 6.2-1000)] (p=0.001). In subgroup analysis, median HBsAb titer decreased significantly after CT in acute leukemia patients [110 (range: 6.2-1000) vs. 67.8 (range: 0-1000)] (p=0.003) and in patients receiving intensive CT [97.2 (range: 6.2-1000) vs. 71 (range: 0-1000)] (p=0.036). The decrease in median HBsAb titer was significant in male patients (p

OBJECTIVE: Monoclonal B lymphocytosis (MBL) is considered to be a precursor state for chronic lymphocytic leukemia (CLL). This study was planned to evaluate the MBL prevalence in first-degree relatives of CLL patients in Turkey, which is considered to be an ethnic and geographic bridge between the Eastern and Western worlds. METHODS: A total of 136 volunteers [median age: 40 (17-77) years; male/female: 60/76] from 61 families were included. Flow cytometry analysis by 4-colour staining was used for MBL diagnosis. RESULTS: MBL was demonstrated in 17 cases (12.5%). A total of 14 cases (10.3%) were classified as CLL-like MBL, while 3 (2.2%) exhibited a non-CLL-like phenotype. The prevalence of MBL was 12.72% in subjects aged less than 40 years, 12.28% in subjects between 40 and 60 years, and 40% in subjects over 60 years, without statistical significance (p>0.05). A total of 115 cases were evaluated for intermarriage, which was observed in 19 cases (16.5%). The prevalence of MBL did not differ based on intermarriage status (p>0.05). CONCLUSION: The current report is the first MBL prevalence study in a Eurasian population that demonstrates a similar distribution pattern of MBL in Anatolian CLL kindreds. Further efforts should be made to refine our understanding of the natural history and clinical outcomes of MBL.

neurotrophiccytokines epidermal growth factor (EGF) and interleukin-6 (IL-6) plays a role in the pathogenesisof cobalamin (Cbl) deficiency-induced neuropathy. The aim of this study was to evaluate autonomicnervous system dysfunction and to look for any relationship between autonomic nervous systemdisturbances and serum cytokine levels (TNF-