Expanded Proliferation Centers (PC) Identify a Histological Subtype of Chronic Lymphocytic Leukemia (“Accelerated” CLL) with Adverse Clinical Outcome
E Gine, N Villamor, A Lopez-Guillermo, M Camos, D Martinez, J Esteve, X Calvo, P Abrisqueta, C Rozman, E Montserrat, E Campo, F Bosch, A Martinez. Hospital Clinic, IDIBAPS, UB, Barcelona, Spain; Hospital Clinic, Barcelona, Spain; Hospital Sant Joan de Deu, Barcelona, Spain
Background: Proliferation in CLL occurs in the PCs of the lymphoid tissues, where the microenvironment regulates CLL cell cycle and survival. The PC is composed by clusters of larger cells and mostly CD4+ T-cells with expression of THF related antigens. CLL cells in PCs differed from the small lymphocytic component in the expresion of several genes: survivin, bcl-2, IRF-8, IRF-4 CD20, CD23, CD27 and Ki-67 expression. Disease progression is associated with increased tumor burden with no significant changes in gene expression when the peripheral blood component is analyzed. The role of PC in the evolution of the disease is poorly understood.
Design: Here we analyze the role of PC in tissue biopsies obtained from 100 CLL patients diagnosed between 1990 and 2008. The size of PC delineated by p27 negative immunostaining and the proliferation rate assessed by mitosis count and Ki-67 staining were recorded and correlated with the main clinical features and the survival from the time of biopsy.
Results: CLL diagnosis was established in 78 cases and DLBCL transformation (RS) in 22 cases. Upon variables selection by statistics tests, CLL cases with prominent PCs (broader than 20x field) (p=0.001), >2.4 mitosis/PC (p=0.019), or >30% Ki-67/PC (p=0.0024) were considered “accelerated” CLL (n= 23). The biopsy was performed to rule out RS in 73% of cases. The time from diagnosis to tissue biopsy was longer in RS than in CLL (68.8 vs. 45.4 months, respectively, p=0.001). “Accelerated” CLL displayed high beta-2-microglobulin, elevated ZAP-70 and unmutated IgVH more frequently than “non-accelerated” CLL. Median survival of “accelerated” CLL from the time of biopsy was 34 months, whereas it was of 75 months (HR 2.2, 95%CI HR 1.21-3.86; p=0.008) for “non-accelerated” CLL. RS patients (n=22) had a median survival of 4 months. Notably, only one patient with an “accelerated” CLL transformed into RS after 5 years.
Conclusions: The presence of prominent PCs and/or an increased PC proliferation identifies a previously unrecognized group of patients with poor survival (“accelerated” CLL)despite that do not seem to transform into RS. Whether these patients require specific therapeutic approaches warrants investigation.
Monday, March 22, 2010 1:00 PM
Poster Session II # 157, Monday Afternoon