Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population‐based series of acute myeloid leukaemia

Abstract

Unsuccessful cytogenetics (UC) in patients with acute myeloid leukaemia (AML) treated on different SWOG trials was recently reported to be associated with increased age and dismal outcome. To ascertain whether this holds true also in unselected patients with AML, we retrieved all cytogenetic reports in cases from the population-based Swedish AML Registry. Between 1997 and 2006, 1737 patients below 80 yr of age without myelosarcoma or acute promyelocytic leukaemia received intensive treatment. The frequencies of UC and unperformed cytogenetics (UPC) were 2.1% and 20%, respectively. The early death rates differed between the cytogenetic subgroups (P = 0.006) with the highest rates in patients with UC (14%) and UPC (12%) followed by high-risk (HR) AML, intermediate risk (IR) and standard risk (SR) cases successfully karyotyped (8.6%, 5.9%, and 5.8%, respectively). The complete remission rate was lower in UC and UPC and HR compared with the other risk groups (P < 0.001). The overall five-year survival rates were 25% for UC and 22% for UPC, whereas the corresponding frequencies for SR, IR and HR AML patients without UC and UPC were 64%, 31% and 15%, respectively. In conclusion, lack of cytogenetic data translates into a poor prognosis.

Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge

“…New technologies such as whole genome sequencing (WGS) could replace such workflows in the future, as suggested in a recent cost/effect comparative adult AML study [ 156 ]. However, a very high rate of unsuccessful karyotypes was observed in this study (especially if we include karyotypes with no abnormalities and fewer than 20 metaphases analyzed), much higher than the 4% pediatric and adult AML rate observed in the French report of quality indicators (C. Lefebvre and B. Gaillard for the GFCH, manuscript in preparation), the 2–7% rate reported in adult AML [ 130 , 155 ], or the 3–7% range reported in pediatric AML [ 22 , 157 ]. Furthermore, FISH analyses directed by karyotype results, as suggested in our proposed workflow, such as CBFB-MYH11 fusion probe in cases with 16q22 breakpoint or KMT2A break-apart probe in cases with non-informative karyotypes were not applied (but rather applied after WGS), thus limiting the value of this comparative study.…”

Incidence, Survival, and Risk Factors for Adults with Acute Myeloid Leukemia Not Otherwise Specified and Acute Myeloid Leukemia with Recurrent Genetic Abnormalities: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Database, 2001–2013

“…We were not able to determine if records that lacked a WHO classification contained cytogenetic data; however, the possibility exists that some of these patients would have been assigned to one of the categories of AML-RGA and perhaps benefited from a more targeted therapy. In a recent study of the population-based Swedish AML registry, Lazarevic et al [23] discovered not only that 20% of patients did not undergo cytogenetic analysis, but also that these patients had a greater rate of early death than did patients with high-risk AML, lower 5-year survival rates than did standard- and intermediate-risk patients, and lower remission rates.…”

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid

“…Both the karyotype and molecular genetic abnormalities are important prognostic factors for AML relapse [ 1 ]. Furthermore, several studies have demonstrated that the biological characteristics of the overall AML cell population (i.e., both the leukemic stem cells and the more mature cell population) are associated with relapse risk and survival, and these included mRNA gene expression profiles, noncoding RNA profiles, epigenetic and metabolic regulation [ 26 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. Moreover, no morphological signs of residual bone marrow disease 14 days after the start of induction treatment and complete remission were achieved after one induction cycle, which are also favorable prognostic factors with regard to the risk of later AML relapse, and both of these criteria refer to the chemosensitivity of the overall AML cell population.…”