Abstract
Abstract 4716
Background
Conventional cytogenetic studies by chromosome banding are difficult in chronic lymphocytic leukemia (CLL) because of the low in vitro proliferation or mitotic activity of CLL cells. Interphase Fluorescence in situ hybridization (FISH) has improved the detection of genomic aberrations in CLL. We used this method to identify chromosomal abnormalities in patients with CLL at diagnosis, progression disease, after relapse or treatment failure.
Methods
Mononuclear cells from the blood of 24 Caucasian patients, 12 men and 12 women, age ranged from 39 to 84 years (median, 64) with CLL were analyzed by FISH, for deletions in chromosome bands 11q22.3, 6q23.3, 13q14.3, 17p13.1, and trisomy of chromosome 12. The patients stages were 0A:12; IA:1; IIA: 2; IIB:4; IIIA:1, IIIB:1; IIIC:1; IV:2. The follow up ranged was from 7 to 124 months.
Results
Chromosomal aberrations were detected in 15 of 24 (58.33 percent). The most frequent changes were a 12 trisomy (37.5 percent), a deletion in 11q23.3, (12.5 percent), a deletion in 6q23.3 (8.33 percent), a deletion in 17p13.1 ( 8.33 percent), a deletion in 13q14.3 8.33%. A patient showed four aberrations tri(12), d(17p13.1), d(6q23.3), d(11q23.3), she was resistant to Fludarabine + Cyclophosfamide treatment and Rituximab CHOP and had a survival of 51 months. The other patients with trisomy 12 alone are still alive and the survival were ranged from 7 to 120 month. Trisomy 12 was correlated with enlarged lymph nodes. Two patients undergo Richter transformation one of them with 6q23.3 the other without the aberrations assessed. The patients with deletion 11q23.3 were resistant to standard regimens treatment. Ten patients have stable disease (0A), clinical follow up ranged from 7 to 124 months; three with trisomy 12 the others without the genetic aberrations assesses. Longest survivals (124 month) were found in patients without aberration or with trisomy 12. Patients without aberrations or with trisomy 12 had similar evolution. A female patient, 84 years old state in stage 0A along 13 month with d(17p13.1), and d(11q23.3). Patients with 11q23.3 deletions had the shortest median treatment-free interval (11months), and those with trisomy 12 or deletion 13q14.3 had the longest (124 and 40 months respectively). Patients with 11q23.3 and 6q23.3 deletion had more advanced disease. Two patients died, both of them with 6q23.3, overall survival 51 and 54 months respectively. ZAP 70 and CD38 do not have correlation with presence of the genomic aberration assessed .The present of 11q23.3, 6q23.3, 17p13.1, age, the white-cell count, Rai - Binet stage and the serum lactate dehydrogenase level gave significant prognostic information.
Conclusions
Genomic aberrations are independent prognosis factors of disease progression and survival in Chronic lymphocytic leukemia; establish them properly will be an important goal standard, therefore incorporate FISH assay routinely could give significant prognostic information.
These genetic findings are predictors of outcome treatment regimens and could help to choose the appropriated strategic treatments.
Disclosures:
No relevant conflicts of interest to declare.
In vivo intraclonal and interclonal kinetic heterogeneity in B-cell chronic lymphocytic leukemia
