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Yikilmaz, Senturk A.1; Avcı, D. N.2; Bakanay, Mine S.1; Akinci, S.2; Falay, M.2; Ozet, G.1; Dilek, I.1

doi: 10.1097/01.HS9.0000566048.83902.ed
Publication Only: Chronic lymphocytic leukemia and related disorders - Biology & translational research

1Hematology, Yıldırım Beyazıt University

2Hematology, Bilkent City Hospital, Ankara, Turkey

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B-cell chronic lymphocytic leukemia (CLL) is the most common haematological malignancy in advanced age. The clinical course of the disease is highly variable, therefore there is a need to investigate the various prognostic factors. The transmembrane receptor tyrosine kinase-like orphan receptor 1 (ROR1) is upragulated in chronic lymphocytic leukemia (CLL) cells. ROR1 has a special expression on CLL as a diagnostic marker.

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The aim of this study was to compare the relationship between expression of ROR on CLL cells and clinical / laboratory features of CLL patients.

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Between February 2010 and June 2018, 30 cases diagnosed with CLL were analyzed. CLL cases were divided into 2 different groups as high (HrROR1) or low (LrROR1) ROR1 expression according to flow cytometric analysis at initial diagnosis. Clinical and laboratory findings of 2 groups were compared during the mean follow-up period of 19 months. Statistical analyzes were performed using chi-square test using SPSS version 16.0 (SPSS Inc., Chicago, IL, USA). A value of less than 0.05 was considered significant. Receiver operating characteristic (ROC) curves were formulated to estimate a cut-off of ROR 1 for advanced stage disease. A two- sided p value < 0,05 was considered statistically significant.

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The clinical and laboratory data of 30 CLL patients with a median age of 60 (37-83) years and with Female/Male ratio of 16/14 were evaluated. Mean follow-up time was 38.5 (SD ± 34.1) months. One patient (3.3%) died during follow-up. The number of cases with RAI stage 0-1, stage 2, stage 3-4 was 14 (46.7%), 11 (36.6%) and 5 (16.7%). The CD 38 positivity of the patients was 10% with flow cytometry analysis. ROC were used to obtain cut-off levels of ROR1 positivity for RAI stage (early versus intermediate+high). We established a cut-off level of 60% for ROR1 percentage in these subjects for intermediate + high RAI stage (p: 0.032). The calculated cut-off levels had the highest sensitivity compared to the other cut-off levels. The ROC area for percentage of ROR1 was 0,73 with a cutoff value of 60% of ROR1 positivity. The sensitivity and specificity was 92.9% and 62.5%, respectively (figure 1). The count of high rate of ROR1(HrROR1) positivity patients were 20 (66.7%) cases. The clinical and laboratory findings of HrROR1 patients and LrROR1 positivity patients were compared each other (Shown in Table 3). HrROR 1 positivity was associated with presence of splenomegaly (p = 0.011), presence of anemia (p = 0.002) and high beta 2 microglobulin value ≥3 mg/dL and the need for first line treatment (p = 0.029). In 5 out of the 12 patients who had anemia at the initial diagnosis, anemia was related with involvement of CLL. When 7 patients whose anemia is not associated with CLL disease involvement were excluded, HrROR 1 positivity was still associated with the presence of anemia (p = 0.046). All patients in need of first line treatment were in the patient group with HrROR1 positivity.



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In our CLL patients, higher rate of ROR1(HrROR1) positivity is related to presence of splenomegaly, presence of anemia, beta 2 microglobulin value ≥3 mg/dL, having RAI Stage 2/3/4 disese and need for first line treatment.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.