Background: Chronic lymphocytic leukemia (CLL) is a neoplasm composed of monomorphic small mature B cells that coexpress CD5 and CD23. The finding of ≥55% prolymphocytes defines B-cell prolymphocytic leukemia (B-PLL), and cases with 15-55% of the prolymphocytes called atypical CLL (aCLL, previously called CLL/PL). Aims: The aim of this study was evaluation of the clinical and prognostic significance of aCLL. Methods: We reviewed the medical records, peripheral blood, and bone marrow findings of 121 patients with untreated CLL (n = 101), aCLL (n = 9), and B-PLL (n = 11) between January 1995 and June 2018. CLL and aCLL patients were classified as Binet stage A (<3 areas of lymphadenopathy, hemoglobin >10 g/dL, platelets >100k/mL), B (≥3 areas of lymphadenopathy, hemoglobin >10 g/dL, platelets >100 k/mL), or C (hemoglobin <10 g/dL or platelets <100k/mL). All patients underwent immunohistochemistry and/or flow cytometric immunophenotyping, among them; 107 patients underwent karyotyping, and 15 patients underwent fluorescent in situ hybridization.
Results:The median age at diagnosis was 63.5 (range 25-85) years, 68.0 (40-77) years, and 66.0 (29-78) years and the ratio of males to females was 2.0, 2.0, and 1.8 in CLL, aCLL, and B-PLL, respectively. Lymphadenopathy was more common in CLL (42%, 42/101) and aCLL (56%, 5/9) than in B-PLL (0%), whereas splenomegaly was more in B-PLL (100%) than CLL (25%, 25/101) and aCLL (33%, 3/9). (P = 0.683 and 0.010, respectively). aCLL showed more severe anemia, elevated lactate dehydrogenase, and b2-microglobulin than CLL and B-PLL (P = 0.001, 0.027, and 0.037, respectively). Binet stage A and B were more in CLL (51% and 26%) than in aCLL (30% and 0%), whereas Binet stage C was more in aCLL (70%) than CLL (23%). (P = 0.013). Patients with B-PLL had an atypical immunophenotype with high frequencies of CD5 or CD23 negativity, FMC7 positivity, and strong CD22 positivity (P = 0.672, 0.440, 0.004, and <0.001, respectively). Especially in this study, patients with aCLL showed higher frequencies of FMC7 positivity and strong CD22 positivity than CLL in Western study (P = 0.032 and <0.001, respectively). In B-PLL, normal karyotype was less common and complex karyotype was more common than CLL and aCLL (P = 0.028). In the CLL group, cytogenetic abnormalities were observed in 35% of patients (33/94). The descending order of frequency was trisomy 12 (11%, 10/94), 13q deletion (10%, 9/94), complex karyotype (7%, 7/94), 11q deletion (5%, 5/94), 14q deletion (2%, 2/94), and 17p deletion (1%, 1/94). In the aCLL group, cytogenetic abnormalities were present in 50% of patients (4/8), including 3 cases of trisomy 12, 2 cases of 14q deletion, 1 case of 13q deletion, 11q deletion, 17q deletion and complex karyotype. In the B-PLL group, cytogenetic abnormalities were observed in 80% of patients (8/10), of whom 4 had complex karyotypes. The overall survival rate at 10 years were 65.6%, 22.2%, and 46.3 % in patient with CLL, aCLL, and B-PLL, respectively (P = 0.155). However, only OS of CLL and aCLL showed ...