17p, 6q Deletion Suggest Poorer Response to Treatment, Survival

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[4958] Genomic Aberrations in Chronic Lymphocytic Leukemia and Small

Lymphocytic Lymphoma by Absolute Lymphocyte Count: Analysis of 1694

Patients. Session Type: Publication Only

Apostolia- Tsimberidou, McLaughlin, O'Brien, Sijin

Wen, G. Wierda, T. Manning, Lynne V. Abruzzo,

Lerner, Mark A. Hess, Hagop M. Kantarjian, Emil J. Freireich,

J. Keating Leukemia, University of Texas M.D. Cancer Center,

Houston, TX, USA; Lymphoma; Biostatistics; Hematopathology

Introduction: Genomic aberrations provide information for the

pathogenesis and clinical outcomes of patients with chronic

lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We

assessed whether genomic aberrations in CLL/SLL differ by absolute

lymphocyte count (ALC) and evaluated their prognostic significance in

our series of patients with CLL/SLL.

Methods: We reviewed the medical records of patients with CLL/SLL who

presented to The University of Texas M. D. Cancer Center

from 1985 to 2005. Patients were assessed by conventional bone marrow

cytogenetics and/or fluorescence in situ hybridization (FISH)

analysis using probes for trisomy 12, ATM, LAMP1, D13S319, and P53

genes.

Results: Cytogenetics and/or FISH analysis was performed in 1694 of

2189 consecutive patients with CLL/SLL. Patients with ALC < 5 x 109/L

had lower rates of genomic aberrations by cytogenetic and/or FISH

analysis than did those with ALC > 5 x 109/L (25% vs. 37%, p=0.02).

Deletion 17p +/- other abnormalities and 6q del +/- other

abnormalities were each associated with shorter survival compared

with other genomic aberrations or normal karyotype (p<0.0001 for both

results).

The survival rates by genomic aberration are shown in the Figure

[insert figure here]. In a multivariate analysis of 23 clinical and

laboratory factors, deletion 17p or 6q +/- other genomic aberrations

(p<0.0001) was the strongest independent predictor of shorter

survival.

In patients who required therapy for CLL/SLL, independent factors

predicting response were hemoglobin levels > 11 g/dL (p<0.0001), age

< 60 years (p=0.005), absence of 17p deletion (p=0.048), and absence

of 6q deletion (p=0.03). In multivariate analysis, pretreatment

parameters that remained independently significant for longer failure-

free survival (FFS) were age < 60 years (p<0.0001), absence of 17p

del +/- other abnormalities (p<0.0001), and hemoglobin levels > 11

g/dL (p=0.018).

Conclusions: Patients with CLL/SLL and ALC < 5 x 109/L had lower

rates of genomic aberrations by cytogenetic and/or FISH analysis

(p=0.02), possibly because of less bone marrow infiltration in the

lower-ALC group. Deletion 17p or 6q, with or without other genomic

aberrations was the strongest independent adverse prognostic factor

for survival in CLL/SLL.