BSH2022 Poster presented at: RESULTS s INTRODUCTION METHOD CONCLUSIONS REFERENCES ACKNOWLEDGEMENT CONTACT INFORMATION Chronic lymphocytic leukemia (CLL) is a disease of aging adults and it is characterized by the accumulation and proliferation of clonal B cells in the blood, marrow, and lymph nodes [1]. CLL is a heterogeneous disease where some patients have stable clinical course and receiving no treatment with survival rates similar to that of a normal population, whereas others have aggressive course of the disease [2]. CLL management focus on stratification of patients according to the clinical staging that enables physicians to decide the best therapeutic strategies and can help predict a patient's prognosis [3,4]. CD38 is a single chain type II transmembrane glycoprotein that is expressed by a variety of hematological cells in activation and differentiation dependent manner. In CLL patients, the elevated expression of CD38 is associated with several adverse prognostic factors such as advanced disease stage, higher incidence of lymphadenopathy, hepatomegaly, high-risk cytogenetic [5]. Moreover, CD38 mutation demonstrated to be associated with higher CD38 expression [6]. This study aims at detecting the frequency of CD38 gene polymorphism (rs1800561) in Sudanese CLL patients and its impact on hematological parameters and clinical staging. This cross-sectional study conducted in the hematology clinic of Radiation and Isotope Center at Khartoum (RICK) from July 2021 to December 2021. A total of 62 patients (42 males, 20 females; with median ages of 62 years) diagnosed with CLL based on blood film picture and flowcytometric immunophenotyping were included in this study. Demographic characteristics and clinical data, were collected using designed interview based questionnaires and patient’s records. Detection of rs1800561 was performed using Amplification Refractory Mutation System PCR (ARMS-PCR). Hematological parameters, including: Leukocytes count, lymphocytes count, platelets count and haemoglobin levels were assessed using the Sysmex analyzer. Non-normally distributed continuous variables are presented as medians. Continuous variables were analyzed using a Kruskal-Wallis test. The clinical-staging of the patients was performed using Rai classification systems. The Rai staging system classifies CLL into 5 stages based on the lymphocytosis > 15 × 109/L and whether or not the patient has lymph nodes enlarged, and enlarged liver or spleen, anemia (Hb level < 11 g/dL); or thrombocytopenia ( platelet count <100 × 10 9 /L) [3]. Table 1 summarizes the Rai stages. The modified Rai classification system classifies CLL into three separate risk groups; patients who are in the Stage 0 defined as having low risk disease, patients who are in the Stage I and II defined as having intermediate risk disease and patients who are in the Stage III and IV defined as having high risk disease [7]. In CLL patients the CD38 mutation had a significant association with younger age. The homozygous genotype is significantly associated with a higher lymphocyte count, higher platelets count. In addition, more than 50% of patients with homozygous CD38 polymorphism are having high risk disease as they were in advance clinical stage (III and IV). CD38 gene polymorphism rs1800561 was detected in 52/62(83.9%) patients, 15 of whom (24.2% of total) were homozygous and 37 patients (59.7% of total) were heterozygous. The wild genotype detected in 10 patients (16.1%). The median age was significantly higher in patients with wild type CD38 genotype than those with homozygous or heterozygous CD38 mutation (69 years vs 59 years and 62 years, P = 0.004). There was a significant difference in leukocytes count between the three groups of patients (P = 0.022). The median of the absolute lymphocyte count was significantly higher in patients with homozygous CD38 mutation (80 x10 9 /L) compared to those with heterozygous CD38 mutation (31x10 9 /L) and wild type CD38 (11 x10 9 /L) groups (P= 0.022). Patients with homozygous CD38 mutation displayed a significantly higher median of platelets count (208 x10 9 /L) compared to those with heterozygous CD38 mutation (126x10 9 /L) and wild type CD38 (117x10 9 /L) groups (P=0.007). There was no significant difference in Hb levels between the three groups of patients (P=0.60). The clinical data were available for 23 patients only. Using the clinical data and laboratory results, based on Rai staging system, the patients were classified to stage I (3 patients,13.04%), stage II (9 patients ,39.13%), stage III (10 patients.43.47%) and stage VI (1 patients, 4.34%). Figure 1 According to Rai staging classification and their CD38 mutational status it appears that: in stage I (33.3% of patients with wild type CD38 and 66.7% patients with heterozygous CD38), in stage II (11.1% wild type CD38, 11.1% heterozygous CD38 patients and 77.8% homozygous CD38), in stage III (10.0% of patients with wild type CD38 patients, 20.0% with heterozygous CD38 and 70.0% with homozygous CD38) and in stage VI one patient (100%) is homozygous CD38. Figure2 Table1:Demographics and Hematological parameters of the CLL patients according to their CD38 mutational status Variables (Median) CD38 wild type CD38 Mut Heterozygous CD38 Mut Homozygous P value Patients n (%) 10 (16.1%) 37 (59.7%) 15 (24.2%) - Age (years) 69.5 59 62 0.004* Leukocyte (x10 9 /L) 18.9 40.2 83.7 0.022* lymphocyte count (x10 9 /L) 11 31 80 0.022* Platelets (x10 3 /L) 117 126 208 0.007* Haemoglobin (g/dL) 10.6 9.5 11 0.602 Impact of CD38 Gene Polymorphism (rs1800561) on Hematological Parameters and Clinical Staging in Patients with Chronic Lymphocytic Leukemia Maysara Baroud 1 , Hiba Fadl 2,3 , Rayyan Ahmed 4 , Ahmed Habbani 1 and Sahar Elbager 1 1 Faculty of Medical Laboratory Sciences, University of Medical Sciences and Technology (UMST), Khartoum, Sudan 2 Faculty of Medical Laboratory Sciences, Al-Neelain University, Khartoum, Sudan 3 Medical Laboratory Department, Sudanese Medical Research Association (SMRA), Khartoum, Sudan 4 Graduate College, University of Medical Sciences and Technology (UMST), Khartoum, Sudan Rai Stage High levels of lymphocytes Enlarged lymph nodes Enlarged spleen or liver Low levels of Hb Low levels of platelets 0 Yes No No No No I Yes Yes No No No II Yes Yes or no Yes No No III Yes Yes or no Yes or no Yes No IV Yes Yes or no Yes or no Yes or no Yes Dr. Sahar Elbager. saharelbager@gmail .com Haemaology Department Faculty of Medical Laboratory Sciences University of Medical Sciences and Technology (UMST) PO Box 12810. Khartoum, Sudan 1. Ozman C, Montserrat E. Chronic lymphocytic leukemia. N Engl J Med. 1995;333:1052-1057. 2. Kipps TJ, Stevenson FK, Wu CJ, et al. Chronic lymphocytic leukaemia. Nat Rev Dis Primers. 2017;3:16096. 3. Rai KR, Sawitsky A, Cronkite EP, et al. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46(2):219-234. 4. Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48(1):198–206. 5. Basabaeen, A.A., Abdelgader, E.A., et al. Combined analysis of ZAP-70 and CD38 expression in sudanese patients with B-cell chronic lymphocytic leukemia. BMC Res Notes.2019;12:282. 6. Eyada, T.K., Hussein, S.K., Younan, S.A. et al. CD38 Gene polymorphisms and susceptibility to B cell chronic lymphocytic leukemia. Comp Clin Pathol .2012;22:573–57922 7. Rai KR. A critical analysis of staging in CLL. In: Gale RP, Rai KR, eds. Chronic Lymphocytic Leukemia: Recent Progress and Future Directions. New York, NY: Alan R. Liss, Inc; 1987:253-264. Table 1 summarizes the Rai stages. AIM We would like to thank the doctors and patients, involved in this study. The molecular biology laboratory scientific staff at Central Laboratory for their technical and analytical assistance. Figure 2: Rai staging classification of CLL patients according to their CD38 mutational status Figure1: Classification of CLL patients according to the Rai staging system EP-043 Sahar Elbager Lymphoma, CLL