Abstract
Introduction: Only few studies have prospectively dealt with the prognostic impact on survival of both clinical and laboratory abnormalities in patients with early stage chronic lymphocytic leukemia (CLL) at diagnosis. In our previously published analyses including a prospective cohort of 307 CLL (Oliveira et al, Leuk Lymphoma. 2011; 52:429-35, Oliveira et al, Ann Hematol. 2015; 94:627-32), patients with atypical lymphocyte morphology, 11q deletion, and elevated beta-2 microglobulin had a shorter progression-free survival (PFS) and treatment-free survival (TFS). Abnormal karyotype (AK), 1 or more abnormalities at diagnosis, was not an independent prognostic factor at that time. Complex karyotype (CK), 3 or more abnormalities, despite having been described as an important prognostic marker in retrospective studies, was a rare finding at diagnosis in early stage CLL patients. The aim of this study is to evaluate prognostic factors at diagnosis in patients with early stage CLL for PFS, TFS and also OS, with a longer follow-up.
Patients and methods: 307 patients were prospectively enrolled in the study from 2003 to 2010 in a single center. All clinical and laboratory data were homogeneously collected at diagnosis. Analysis of prognostic factors for survival was performed in 231 patients presenting early stage disease: lymphocytosis without other signs or symptoms of CLL (CLL Rai 0 and monoclonal B lymphocytosis, MBL). Survival curves were plotted using Kaplan-Meier's method and log-rank test was used to identify differences in survival between subgroups. Multivariate analysis was performed with Cox regression model. Variables included in the univariate analysis were: age, gender, LDH, beta-2 microglobulin, lymphocyte morphology, CD38, ZAP-70, deletions of 13q, 11q and 17p, trisomy 12, normal FISH and AK. The significant variables in the univariate analysis were included in the multivariate regression model.
Results: Eighty-one patients had MBL and 150 were diagnosed with CLL Rai 0, 145 (62.8%) patients were male with a median age at diagnosis of 68 years (limits 27-93). One hundred sixteen patients presented a normal karyotype at diagnosis, 54 (23.3%) an AK [7 (3%) of them a CK], in 9 (3.9%) patients no metaphases were obtained for karyotype analysis and in 52 (22.5%) karyotype was not performed. With a median follow-up of 7.8 yrs (range 0.7-13.6), 37 (16%) patients died, 73 (31.6%) presented CLL progression and 60 (26%) required treatment. OS was 84%. AK was an independent prognostic factor for OS (OR 2.2, 95%CI: 1.0-4.6, p=0.038), TFS (OR 2.9, 95%CI: 1.4-6.0, p=0.003), and PFS (OR 2.4, 95%CI: 1.3-4.6, p=0.005). Atypical lymphocyte morphology was also an independent prognostic factor for OS (OR 2.7, 95%CI: 1.3-5.8, p=0.008) and elevated beta-2 microglobulin for PFS (OR 2.1, 95%CI:1.1-3.9, p=0.018).
Conclusions: Abnormal karyotype (not only complex) at diagnosis in early stage CLL (CLL Rai 0 or MBL), is an independent prognostic factor for OS, PFS and TFS.
No relevant conflicts of interest to declare.
