Prognostic significance of serum BAFF, APRIL, TACI and BCMA levels in chronic lymphocytic leukemia

B hücreli kronik lenfositik lösemi (B-KLL) çevre kanı ve kemik iliğinde CD5+ B hücrelerin birikimiyle karakterizedir. Klinik seyir oldukça heterojendir. Kronik lenfositik lösemi biyolojisinde apopitoza direncin önemli rol oynadığı bilinmektedir. Erken tedavi gereksinimi olabilecek yüksek riskli hastaların belirlenmesi için yeni prognostik parametrelerin tanımlanmasına gereksinim vardır. Tümör nekroz faktörü ailesinin iki proteini BAFF (TNFSF13B) ve APRIL (TNFSF13) ile reseptörleri BAFF-R (TNFRSF13C), TACI (TNFRSF13B) ve BCMA (TNFRSF17) normal B hücrelerinin sağkalımında kritik rol oynarlar. Bu çalışmada 129 KLL hastasında [yaş: 64(39-88); E/K: 85/44] tanı anında ölçülen serum BAFF, APRIL, TACI ve BCMA düzeylerinin KLL prognozu üzerindeki olası etkilerinin gösterilmesi amaçlandı. BAFF, TACI ve BCMA düzeyleri hasta grubunda kontrol grubuyla karşılaştırıldığında anlamlı düşük tespit edilirken (p0.05). BAFF [(p=0,008; r=-0,236)] ve BCMA düzeyleri [(p=0,042; r=-0,183)] ile Rai evresi arasında negatif korelasyon saptandı. BAFF, BCMA, TACI ve APRIL düzeyleri; κ/λ normal ve anormal olan; LDH düzeyi normal ve yüksek olan; ZAP70 pozitif ve negatif olan hastalar arasında; Rai alt grupları arasında; FISH risk grupları arasında farksız bulundu (p>0,05). TACI düzeyi CD38 (+) olanlarda negatif olanlara göre daha yüksek bulundu [(p=0,06; 0,17(0,1-0,86) vs 0,13(0,1-1,07)]. BAFF düzeyi modifiye Rai evresine göre düşük riskli olanlarda daha yüksek bulundu (p=0,059). Yaş (p=0,002), Rai evresi (p=0,005) ve Modifiye Rai evresi (p=0,051) çok değişkenli analizde sağkalım üzerine etkili faktörlerdi. BAFF, APRIL,TACI ve BCMA düzeylerinin sağkalım üzerine anlamlı etkisi saptanmadı. BAFF, TACI, BCMA ve APRIL'in KLL prognozu üzerine etkisinin belirlenmesi için kapsamlı ve ileriye dönük çalışmalara gereksinim vardır.B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of CD5+ B cells in the peripheral blood and bone marrow. Chronic lymphocytic leukemia has a variable disease course based on certain prognostic parameters. A significant resistance to apoptosis is observed in leukemic cells. Novel prognostic markers and risk assessment models are needed to identify high risk patients who may need early treatment. The two tumour necrosis factor family proteins BAFF (TNFSF13B) and APRIL (TNFSF13) and their receptors [BAFF-R (TNFRSF13C), TACI (TNFRSF13B), BCMA (TNFRSF17)] play a critical role in the survival of normal B cells. We investigated the impact of serum BCMA, TACI, BAFF and APRIL levels on prognosis in 129 newly diagnosed CLL patients [median age: 64(39-88); M/F: 85/44]. Serum BAFF, TACI and BCMA levels were significantly lower in the patient group (p0.05). 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 (κ/λ). Additionally, serum BAFF [(p=0,008; r=- 0,236)] and BCMA [(p=0,042; r=-0,183)] levels were negatively correlated with Rai stage. Serum TACI level was higher in CD38 positive patients [(p=0,06; 0,17(0,1-0,86) vs 0,13(0,1-1,07)]. Serum BAFF levels were higher in low-risk patients based on modified Rai staging system (p=0,059). In multivariate analysis, age (p=0,002), Rai stage (p=0,005) and Modified Rai stage (p=0,051) were shown to have significant impact on overall survival. However, serum BAFF, APRIL, TACI and BCMA levels had no impact on survival in CLL patients. Further large and prospective studies are essential to validate the prognostic role of these particular biomarkers in CLL

Mortality analysis of COVID-19 infection in chronic kidney disease, haemodialysis and renal transplant patients compared with patients without kidney disease: a nationwide analysis from Turkey

Background. Chronic kidney disease (CKD) and immunosuppression, such as in renal transplantation (RT), stand as one of the established potential risk factors for severe coronavirus disease 2019 (COVID-19). Case morbidity and mortality rates for any type of infection have always been much higher in CKD, haemodialysis (HD) and RT patients than in the general population. A large study comparing COVID-19 outcome in moderate to advanced CKD (Stages 3-5), HD and RT patients with a control group of patients is still lacking. Methods. We conducted a multicentre, retrospective, observational study, involving hospitalized adult patients with COVID-19 from 47 centres in Turkey. Patients with CKD Stages 3-5, chronic HD and RT were compared with patients who had COVID-19 but no kidney disease. Demographics, comorbidities, medications, laboratory tests, COVID-19 treatments and outcome [in-hospital mortality and combined in-hospital outcome mortality or admission to the intensive care unit (ICU)] were compared. Results. A total of 1210 patients were included [median age, 61 (quartile 1-quartile 3 48-71) years, female 551 (45.5%)] composed of four groups: Control (n = 450), HD (n = 390), RT (n = 81) and CKD (n = 289). The ICU admission rate was 266/ 1210 (22.0%). A total of 172/1210 (14.2%) patients died. The ICU admission and in-hospital mortality rates in the CKD group [114/289 (39.4%); 95% confidence interval (CI) 33.9-45.2; and 82/289 (28.4%); 95% CI 23.9-34.5)] were significantly higher than the other groups: HD = 99/390 (25.4%; 95% CI 21.3-29.9; P<0.001) and 63/390 (16.2%; 95% CI 13.0-20.4; P<0.001); RT = 17/81 (21.0%; 95% CI 13.2-30.8; P = 0.002) and 9/81 (11.1%; 95% CI 5.7-19.5; P = 0.001); and control = 36/450 (8.0%; 95% CI 5.8-10.8; P<0.001) and 18/450 (4%; 95% CI 2.5-6.2; P<0.001). Adjusted mortality and adjusted combined outcomes in CKD group and HD groups were significantly higher than the control group [hazard ratio (HR) (95% CI) CKD: 2.88 (1.52- 5.44); P = 0.001; 2.44 (1.35-4.40); P = 0.003; HD: 2.32 (1.21- 4.46); P = 0.011; 2.25 (1.23-4.12); P = 0.008), respectively], but these were not significantly different in the RT from in the control group [HR (95% CI) 1.89 (0.76-4.72); P = 0.169; 1.87 (0.81-4.28); P = 0.138, respectively]. Conclusions. Hospitalized COVID-19 patients with CKDs, including Stages 3-5 CKD, HD and RT, have significantly higher mortality than patients without kidney disease. Stages 3-5 CKD patients have an in-hospital mortality rate as much as HD patients, which may be in part because of similar age and comorbidity burden. We were unable to assess if RT patients were or were not at increased risk for in-hospital mortality because of the relatively small sample size of the RT patients in this study