The impact of tetraploidy/near-tetraploidy karyotype in AML

Tetraploidy or Near Tetraploidy (T/NT), a complex karyotype with numerical or structural abnormality, is a rare cytogenetic abnormality in Acute Myeloid Leukemia (AML). AML patients with T/NT karyotype are usually grouped in the high-risk cytogenetic AML category. The clinical significance and prognostic impact of T/NT karyotype in AML is unclear, thus the rationale for this study.

Lanshan Huang from the University of Texas MD Anderson Cancer Center (MDACC), Houston, Texas, and colleagues published data from their study in Leukemia Research. The article was originally published ahead of print on 2^nd December 2016.

In this study, the authors analyzed the cytogenetics, pathology, and survival outcomes of 38 AML patients (median age = 65 years; men = 26 and women = 12) with T/NT karyotype from the MDACC database between the years of 2000 to 2015.  

The key results are:

• The Bone Marrow (BM) of patients (n = 38) with T/NT karyotype had large blasts with prominent nucleoli (n = 30)
• Large blast features included cytoplasmic vacuoles (n = 16), cytoplasmic inclusions (n = 14), irregular contours (n = 14), and nuclear budding (n = 8)
• 29% (n = 11) of patients had T/NT karyotype with <3 additional chromosomal abnormalities (non-complex), 71% (n = 27) of patients had T/NT karyotype with ≥3 additional chromosome abnormalities (complex), and 55% (n = 21) of patients had pseudodiploid/triploid clones
• After detection of T/NT karyotype, patients were treated with chemotherapy (n = 32) and allogenic Stem Cell Transplantation (allo-SCT) (n = 10)
• At median follow-up of 6.2 months, 12% (n = 5) of patients were alive in Complete Remission (CR), 32 patients died from SCT associated complications, and 1 patient had persistent AML
• Median Overall Survival (OS) in male and female patients were 7.8 and 3.5 months respectively; P = 0.021
• Median OS in patients with complex T/NT karyotype (n = 27) was significantly worse than patients with non-complex T/NT karyotype (n = 11); 3.4 and 10.7 months respectively; P = 0.0287
• Complex T/NT karyotype was associated with poor prognosis; HR = 2.879, P = 0.0037

In summary, T/NT karyotype is characterized by distinctive morphological features and it is associated with poor outcomes in AML patients. Additionally, patients with non-complex T/NT karyotype convey an intermediate risk and they have a better prognosis compared to patients with complex T/NT karyotype.

The author concluded by suggesting that complex T/NT karyotype should be distinguished from non-complex T/NT karyotype in order to provide more prognostic information for AML patients.  

Abstract

A tetraploid/near tetraploid (T/NT) karyotype is a rare finding in acute myeloid leukemia (AML). Here we report 38 AML patients with a T/NT karyotype, including 26 men and 12 women with a median age of 65 years. T/NT karyotype was detected at initial diagnosis of AML in 16 patients, and acquired during the course of disease in 22 patients. All patients showed large blasts with frequent prominent nucleoli, cytoplasmic vacuoles and/or inclusions, nuclear irregularity and/or budding. Eleven patients had a non-complex and 27 had a complex T/NT karyotype; 21 patients also had pseudodiploid and/or triploid clones. After T/NT karyotype detection, 32 patients received chemotherapy and 10 also received stem cell transplant. After a median of 6.2 months follow-up, 32 patients died of disease or complications, 5 were alive with complete remission, and 1 alive with persistent AML. Median overall survival (OS) was 5 months. Patients with a non-complex T/NT karyotype had a significantly superior OS compared to those with a complex T/NT karyotype (10.7 vs. 3.4 months, p=0.0280). We conclude that T/NT karyotype in AML is often associated with distinctive morphologic features and conveys generally poor outcomes. Distinction of complex versus non-complex T/NT karyotype provides further prognostic information.