334O - Additional chromosomal abnormalities in chronic myeloid leukemia: Lest we forget

Date 19 December 2016
Event ESMO Asia 2016 Congress
Session Haematological malignancies
Topics Leukaemia
Pathology/Molecular Biology
Presenter Madhav Danthala
Citation Annals of Oncology (2016) 27 (suppl_9): ix104-ix111. 10.1093/annonc/mdw586
Authors M. Danthala
  • Medical Oncology, Nizam's Institute of Medical Sciences, 500033 - Hyderabad/IN

Abstract

Background

Clonal cytogenetic evolution with additional cytogenetic aberrations (ACAs) in chronic myeloid leukemia (CML) are associated with adverse prognosis and decreased response to tyrosine kinase inhibitor therapy (TKI). The presence of ACAs at the time of diagnosis is now considered a criteria for accelerated phase. However, the differential prognostic impact of individual ACAs is unknown, and a formal classification system incorporating this information is lacking.

Methods

In a retrospective analysis, we included data from 1,367 patients with CML treated with frontline Imatinib mesylate at a single institution between 2008 and 2014. The aim of the study was to stratify risk based on assumed prognostic impact of individual ACAs and determine their impact on survival endpoints.

Results

ACAs were present in 92 of 1,367 patients (6.7%) at the time of diagnosis or progression. The common ACAs were trisomy 8 in 32 (2.3%) patients, additional Ph in 17(1.2%) patients, increased ploidy in 11(0.8%) patients, trisomy 19 and monosomy 7 in 9(0.6%) patients each, lack of Y chromosome and hypoploidy in 5(0.3%) patients each and 29 minor route (all other) ACAs. Variant Ph chromosome seen in 9(0.6%) patients was not considered an ACA. Survival outcomes were analysed based on stratification into group 1 including those without ACAs, group 2 including trisomy 8, -Y, an additional Ph chromosome, trisomy 19 and increased ploidy, group 3 including -7, i(17)(q10), 3q rearrangements, presence of 2 or more ACAs and hypoploidy, and group 4 with minor route ACAs. The overall survival was significantly better in group 1 in comparison with group 2, group 4 and group 3 respectively (Log-rank Mantel-Cox Χ2=7.96, p = 0.04).

Conclusions

In an era where molecular monitoring takes precedence over all others in CML, cytogenetic monitoring is mandatory and must not be overlooked. A risk stratification system based on prognostic relevance of individual ACAs may be a useful guide to prognosticate and guide treatment of CML at diagnosis and clonal evolution, instead of the overtly simplified categorization of ACAs as major and minor route abnormalities.

Clinical trial indentification

not applicable

Legal entity responsible for the study

Nizam\'s Institute of Medical Sciences Ethics Committee

Funding

Nizam\'s Institute of Medical Sciences

Disclosure

All authors have declared no conflicts of interest.