The prognostic significance of monosomal karyotype/ complex karyotype in AML

In adult Acute Myeloid Leukemia (AML) patients, the presence of Monosomal Karyotype (MK) and Complex Karyotype (CK) is associated with adverse prognosis. However, the prognostic value of monosomy 5, monosomy 7 or monosomy 17 is not clearly defined yet in AML, hence the rationale for this study.

In an article published in Leukemia Research, Stephen A Strickland, Vanderbilt-Ingram Cancer Center, Nashville, U.S., and colleagues retrospectively studied the prognostic utility of monosomies including monosomy 5, monosomy 7 and monosomy 17 and karyotype complexity  in patients with MK AML.

In total, 1,592 AML patients who were enrolled between 1990–2008 in four prospective Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network Cancer (ECOG-ACRIN) therapeutic trials were included in this study. Cytogenetic data were evaluable in 1,188 patients. Of these 1,188 patients, MK was identified in 195 patients with 93% (182/195) having karyotype complexity (defined as patients with ≥ 3 clonal abnormalities). 87% (158/182) of MK patients with CK had ≥ 5 clonal abnormalities.

The key results of the study were:

• Median Overall Survival (OS) in patients with or without MK with karyotype complexity ≤ 4 clonal abnormalities; 0.3 vs 1.0 years, HR = 1.98, P < 0.001
• There was no significant difference in the median OS in patients with or without MK with karyotype complexity ≥ 5 clonal abnormalities; 0.5 vs 0.4 years, HR = 1.06, P = 0.82
• The presence of monosomy 5 in MK patients with karyotype complexity ≤ 4 clonal abnormalities significantly associated with poor OS; HR 4.13, P = 0.062
• Median OS in MK patients with karyotype complexity ≤ 4 clonal abnormalities with or without monosomy 17; 0.1 vs 0.4 years, HR 3.11, P = 0.058
• Median OS in MK patients with karyotype complexity ≥ 5 clonal abnormalities with or without monosomy 17; 0.4 vs 0.5 years, HR 1.53, P = 0.01
• The presence of monosomy 7 had no impact on OS in MK patients with karyotype complexity ≤ 4 or ≥ 5 clonal abnormalities

 In summation, the “prognostic utility of MK+ is limited to those with less complex karyotype (complexity ≤ 4)”. Additionally, the presence of monosomy 17 in can “independently predict worse survival” in MK AML patients.

 Abstract

The presence of a monosomal karyotype (MK+) and/or a complex karyotype (CK+) identifies subcategories of AML with poor prognosis. The prognostic significance of the most common monosomies (monosomy 5, monosomy 7, and monosomy 17) within MK+/CK+AML is not well defined. We analyzed data from 1,592 AML patients age 17-93 years enrolled on ECOG-ACRIN therapeutic trials. The majority of MK+ patients (182/195; 93%) were MK+/CK+ with 87% (158/182) having ≥5 clonal abnormalities (CK≥5). MK+ patients with karyotype complexity ≤4 had a median overall survival (OS) of 0.4y compared to 1.0y for MK- with complexity ≤4 (p<0.001), whereas no OS difference was seen in MK+vs. MK- patients with CK≥5 (p=0.82). Monosomy 5 (93%; 50/54) typically occurred within a highly complex karyotype and had no impact on OS (0.4y; p=0.95). Monosomy 7 demonstrated no impact on OS in patients with CK≥5 (p=0.39) or CK≤4 (p=0.44). Monosomy 17 appeared in 43% (68/158) of CK≥5 patients and demonstrated statistically significant worse OS (0.4y) compared to CK≥5 patients without monosomy 17 (0.5y; p=0.012). Our data suggest that the prognostic impact of MK+ is limited to those with less complex karyotypes and that monosomy 17 may independently predict for worse survival in patients with AML.