PF380 SINGLE CELL ABNORMALITIES ON CLASSIC G-BANDING ANALYSIS OF CHRONIC LYMPHOCYTIC LEUKEMIA: CLINICOBIOLOGICAL FEATURES AND PROGNOSTIC VALUE
Authors: A. Athanasiadou, M. Gkaitatzi, G. Papaioannou, M. Iskas, O. Asteriou, Z. Lazarou, A. Papalexandri, A. Banti, N. Stavroyianni, A. Anagnostopoulos
Journal: HemaSphere (2019)

Background: Chromosomal abnormalities have a well-accepted clinical and prognostic value in chronic lymphocytic leukemia (CLL). Occasionally, conventional cytogenetics in CLL can detect chromosomal aberrations that do not fulfill clonality criteria. In a previous study we have shown that using two parallel cultures, >2 single cell abnormalities (sc-abs) were detected in 10% of samples. Aims: To characterise the clinicobiological profile and the outcome of patients with >2 sc-abs. Methods: We studied 860 CLL patient samples subjected to classical banding analysis (CBA) by two parallel cultures adding either Phytohemagglutinin and Interleukin 2 (PHA/IL-2) or an immunostimulatory CpG-oligonucleotide DSP30 and IL-2 (CpG/IL-2). Sc-abs were detected in 318/860 (37%) samples. More than 2 sc-abs were revealed in 86 samples (10%). Results: We studied 86 patients bearing >2 sc-abs in CBA. Distribution of the number of sc-abs across samples was as follows: 3 sc-abs were detected in 37 samples, 4 in 18, 5 in 14, 6 in 8, 7 in 4, 8 in 1, 9 in 1, 10 in 1 and 12 in 2 samples. Fifty-four of 86 samples had normal karyotype: amongst these 17 had ≥ 5 sc-abs. The remaining 32 samples had abnormal karyotype: 14 had ≥5 sc-abs (p = 0.43). Overall, 380 sc-abs were detected. All chromosomes participated in these sc-abs. Sixty six samples were checked for 13q deletion: 30 had single, 7 had double and 6 had cells with both single and double del(13q). Seventy eight samples were checked for ATM status: 9 had ATM deletion. Eighty three samples were checked for TP53 deletion and 12 were found positive. Only 2 out of sixty six tested samples showed trisomy 12. Sequence analysis for IGHV mutational status showed 42 IG-unmutated and 44 IG-mutated cases. Clinical data was available in 79 out of 86 cases. Median age of the cohort was 62.7 years (29–86), gender male/female: 59/27. Time from diagnosis to testing ranged between 0–213 months (median: 45); 33/79 patients were in stable disease (subsequently 11 progressed) and 46 were in progression. Thirty five cases underwent CBA before any treatment administration and 44 after treatment. Thirty seven cases had been treated and 18/37 received FCR. Medical history was positive for prior malignancies in 5 patients. Secondary neoplasia developed in 10 patients. In those patients, the median number of sc-abs was 5. The same patient group also carried: 9/14 del(13q), 0/14 trisomy 12, 3/14 del(11q) and 4/15 del(17p). The median follow up since the detection of the sc-abs was 2 years (range 0,4–11,9). Patients received a median of 2 (1–5) treatment lines. Twenty of 79 patients had died with a median OS was 6 (5.6–6.5) years. The median OS of the patients with unmutated or mutated IGHV genes was 2.92 versus 6.07 years (p = 0.0001). The median OS of the patients with ≥5 or 2–3 sc-abs was 2.75 versus 6 years respectively (p = 0.13). Summary/Conclusion: Sc-abs appear to be a common finding in CLL patients regardless of treatment status, alluding to genomic heterogeneity and instability. Sc-abs probably represent an adverse prognostic indicator mainly in patients with either unmutated IGHV genes or ≥5 sc-abs. A higher incidence of secondary malignancies has been observed in this group of patients. Our study reinforces the concept that CBA is of value in accurately defining the prognosis of patients with CLL. Based on our findings, the issue of sc-abs should be systematically addressed in larger patient cohorts with a longer follow up.