PB1896 ATYPICAL CHRONIC LYMPHOCYTIC LEUKEMIA HAS A WORSE PROGNOSIS THAN CLL AND SHOWS DIFFERENT CLINICAL AND LABORATORY FEATURES FROM B‐CELL PROLYMPHOCYTIC LEUKEMIA
Authors: Ahn A. , Kim M.‐S. , Park C.‐J. , Seo E.‐J. , Jang S. , Cho Y.‐U. , Ji M. , Choi Y.M. , Lee K.‐H. , Lee J.‐H. , Lee J.‐H. , Yoon D.H. , Suh C.W. 
Published: June 2019

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 β2‐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 statistically significant difference (P = 0.043) (Figure1).

Summary/Conclusion:

CLL, aCLL, and B‐PLL showed different clinical, immunophenotypic, and cytogenetic characteristics. aCLL has a worse prognosis than CLL; therefore, it is important to distinguish aCLL from CLL and B‐PLL.

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