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As chronic lymphocytic leukemia (CLL) has a variable disease course, novel prognostic markers and risk assessment models are being developed in order to identify high-risk patients who may need early treatment. The two tumor necrosis factor family proteins BAFF and APRIL and their receptors BAFF-R, TACI and BCMA are considered to play a critical role in the survival of normal B cells. In order to highlight the pathophysiological role of this complicated biological network, we aimed to analyze the potential prognostic effects of BAFF, APRIL, TACI and BCMA in CLL patients. We investigated the prognostic impact of serum BCMA, TACI, BAFF and APRIL levels in 129 newly diagnosed CLL patients [median age: 64 (39-88) years; male/female: 85/44]. Serum BAFF, TACI and BCMA levels were significantly lower in the patient group compared to the control group (p \ 0.001), while serum APRIL level did not differ significantly between two groups (p [ 0.05). Serum BCMA [(p = 0.029; r = 0.208)] and TACI levels [(p = 0.011; r = 0.241)] were positively correlated with serum free light chain ratio. Serum BAFF [(p = 0.008; r =-0.236)] and BCMA [(p = 0.042; r =-0.183)] levels were negatively correlated with Rai stage. Overall survival (OS) was relatively better in patients with low serum BAFF levels [60 (1-187) months vs 39.5 (0-256) months; p = 0.063]. Probability of OS was higher in patients with low BAFF levels when compared to patients with normal levels, without statistical significance (53.6% vs 23.6%; p [ 0.05). Large prospective studies are needed to validate the prognostic role of this essential biological pathway in CLL.

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 çellfree DNA seem to be associated with transplant-related morbidities and may be considered an adverse prognostic factor for allogeneic hematopoietic stem cell transplant recipients.

Objectives: T-cell immunoglobulin and mucin domain-containing protein-3 (TIM-3) is considered as a negative regulator of T-cell driven immune response. This study is planned to investigate the prognostic role of pre-transplant soluble TIM-3 (sTIM-3) levels in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: Pre-transplant serum sTIM-3 levels were measured in 177 allo-HSCT recipients [median age: 36(16-66) years; male/female: 111/66]. Results: Pre-transplant sTIM-3 levels were significantly higher in acute myeloid leukemia (AML) patients compared to acute lymphoblastic leukemia (ALL) patients (p = 0.01). Pre-transplant sTIM-3 levels were significantly lower in patients with abnormal cytogenetics (p = 0.017). Pre-transplant sTIM-3 levels were significantly higher in patients who developed viral hemorrhagic cystitis (p = 0.034). A positive correlation was demonstrated between sTIM-3 levels and acute graft versus host disease (GvHD) grade (p = 0.013; r = 0.299). Overall survival (OS) was not statistically different between low-and high-TIM-3 groups (% 35.2 vs %20.4; p > 0.05). Primary diagnosis (p = 0.042), sinusoidal obstruction syndrome (p < 0.001), acute GvHD (p = 0.001), chronic GvHD (p = 0.009) and post-transplant relapse (p = 0.003) represented significant impact on OS. Discussion: Increased sTIM-3 levels in AML patients seem to be compatible with the previous reports. The inhibitor role of TIM-3 in cellular immune response may be a possible explanation for the association of sTIM-3 with viral infections and GvHD. However, the main challenge remains to be the ambiguous association of pre-transplant sTIM-3 levels and post-transplant complications, as allo-HSCT recipients are expected to represent donor genetic features in the post-transplant setting. Conclusion: Further studies are warranted to clarify the particular role of sTIM-3 in the allo-HSCT setting.

Objective: Paraoxonase-1 (PON1) is an HDL-associated enzyme implicated in the pathogenesis of atherosclerosis by protecting lipoproteins against peroxidation. PON1 has two genetic polymorphisms both due to amino acid substitution, one involving glutamine and arginine at position 192 and the other leucineand methionine at position 55. Our study aimed to compare the effect of PON192 polymorphism and PON1 activity in patients with type 2 diabetes mellitus (T2DM) and non-diabetic controls. Material and Methods: 50 patients with T2DM and 30 non-diabetic controls were included in this study. The PON192 polymorphism was studied by polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). Paraoxonase activity was measured by spectrophotometric method. Results: The frequencies of the QQ, QR and RR genotypes were found as 36.5 and 14% in type 2 diabetes patients and 26.67, 46.66, 26.67% in control subjects, respectively. The paraoxonase activity was detected at lower levels in diabetics (102.0 ±38.9) than in control subjects (158.1±63.7). PON1192 RR homozygotes had significantly higher PON activity than QR and QQ genotypes among control and type 2 diabetes patients (p<0.005). Conclusion:In comparing the activities of three genotypes of the control and type 2 diabetic groups; all activities were found significantly lower in diabetics. In conclusion, we suggested that paraoxonase activities are affected by PON1 genetic variability in patients with type 2 diabetes mellitus and controls.