Abstract
Abstract 1669
Acute myeloid leukemia (AML) with normal karyotype (NK) comprises of 40–50% in overall AML population, presenting diverse and heterogeneous clinical behavior and prognosis. Recent study by Tiu et al (JCO 2009, 27(31); 5219-26) presented that new lesions detected by genome-wide single nucleotide polymorphism arrays (SNP-A) based karyotyping represent worse prognosis in 140 AML patients including 50 patients with AML-NK. The current study investigated diagnostic and prognostic role of SNP-A based karyotying in 100 patients with AML-NK treated with homogeneous treatment protocol.
A total of 100 patients with AML-NK confirmed by cytogenetic analysis and FISH analysis included in this study. All of the patients were diagnosed as AML-NK between 1998 and 2009 and received idarubicin plus cytarabine 3+7 induction chemotherapy at 4 hospitals in Korea. Genome-Wide Human SNP 6.0 Array (Affymetrix, CA, USA) was performed using DNAs derived from marrow samples taken at the time of diagnosis. Genotyping Console version 3.1 software was used for SNP-A karyotyping analysis.
In overall patients, complete remission (CR) rate was 89%, and the 2-years' rate of EFS and OS was 56.6±5.6% and 63.2±5.5%, respectively. The median duration of EFS and OS was 32.7 months and 76.6 months. Ninty-six clonal aberrations (CAs) were identified in 34 patients (34%) which were not detected by metaphase cytogenetics which were normal karyotype. These CAs included 44 losses at 17q, 17p, 7q, 11p, 1p, 5q, 6q, 7p, and 19p; 23 gains at chromosome 8, 9p, 15q, 17p, 17q, 21q, and 22q; and 29 uniparental disomies (UPDs) at 13q, 11p, 11q, 19q, 21q and 22q.
When analyzed the CR rate according to the presence of CAs, no association was noted between the group with and without CAs (91% vs 87%; p=0.6). With respect to EFS, the group with CAs showed worse 2-years' EFS rate than those without CAs (39.0±9.5% vs 64.9±6.6%; p=0.05). As regards to OS, the group with CAs showed worse 2-years' EFS rate than those without CAs (40.7±9.6% vs 73.7±6.4%; p=0.01).
Multivariate analyses showed that the CAs detected by SNP-A karyotyping has unfavorable prognostic value for EFS (hazard ratio [HR] = 3.29; 95% CI, 1.70 to 6.37; P<0 .001) and OS (HR = 4.06; 95% CI, 1.93 to 8.56; P<0.001) together with other significant prognostic factors (age above 60 years and WBC counts over 100×109/L at presentation).
Our data showed that 1) Ninty six CAs were detected in one third of patients with AML-NK, and that 2) CAs represent unfavorable prognostic factor, thus requiring further sophisticated treatment strategy including allogeneic stem cell transplantation and novel therapy.
Overall and event free survival by the presence of clonal aberrations (CAs) detected by SNP-array karyotyping (dot: group without CAs/line: group with CAs)
No relevant conflicts of interest to declare.
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