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Clinical relevance of failed and missing cytogenetic analysis in acute myeloid leukaemia

Leukemia volume 31, pages 1234–1237 (2017)Cite this article

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Chromosomal and genetic abnormalities are important prognostic factors in acute myeloid leukaemia (AML) and most clinically relevant aberrations are detectable by cytogenetic analysis.1, 2 One limitation of cytogenetics is failure due to a lack of analysable metaphases. Despite this shortcoming, chromosomal analysis remains the gold standard test for identifying abnormalities used to risk-stratify treatment because many abnormalities (for example, those involving large chromosomal regions and a complex karyotype) can only be described in cytogenetic terms. Thus, failure to obtain a cytogenetic result impacts on risk stratification. In support of this suggestion, two recent reports concluded that failed and/or missing cytogenetic results were associated with an adverse prognosis.3, 4 Our view is that assignment of risk on the basis of the absence of information is counterintuitive and potentially problematic. Therefore, we investigated the distribution and prognostic impact of failed and missing cytogenetic results in successive Medical Research Council (MRC) AML trials.

Cytogenetic analysis of pre-treatment bone marrow or peripheral blood samples was performed locally, reviewed and collated by the Leukaemia Research Cytogenetics Group. Results were available from 10 685 patients (1–82 years old) recruited to successive trials (AML12, AML14, AML15 and AML16) between 1995 and 2012.1, 5, 6, 7, 8, 9 At diagnosis, patients recruited to AML14 and AML16 were classified, on the basis of presenting features, as suitable or unsuitable for intensive therapy. All studies were approved by the relevant ethics committees and informed consent was obtained in accordance with the Declaration of Helsinki.

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Acknowledgements

We thank all the patients, clinicians and staff who participated in the Medical Research Council/National Cancer Research Institute AML trials. We are also grateful to the member laboratories of the UK Cancer Cytogenetic Group for providing cytogenetic data and the members of the NCRI AML Working Group for their support. This work was supported by Bloodwise (formerly Leukaemia and Lymphoma Research, UK).

Author contributions

LC, AVM and RKH designed the study; LC, IA, RKH, DM, CJH and AVM analysed and interpreted the data. DG and RKH provided clinical and follow-up data; AKB was the chief investigator on all trials. CJH and AVM provided financial and administrative support. AVM wrote the manuscript with input and approval from all the other authors.

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Authors and Affiliations

  1. Leukaemia Research Cytogenetics Group, Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK

    L Chilton, C J Harrison, D Murdy & A V Moorman

  2. Cardiff University School of Medicine, Cardiff, UK

    I Ashworth

  3. Department of Haematology, Cardiff University School of Medicine, Cardiff, UK

    A K Burnett

  4. Department of Medical and Molecular Genetics, King’s College London, London, UK

    D Grimwade

  5. Centre for Trials Research, Cardiff University, Cardiff, UK

    R K Hills

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  1. L Chilton
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  2. C J Harrison
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  3. I Ashworth
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  4. D Murdy
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  5. A K Burnett
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  6. D Grimwade
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  7. A V Moorman
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  8. R K Hills
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Correspondence to A V Moorman.

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The authors declare no conflict of interest.

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Chilton, L., Harrison, C., Ashworth, I. et al. Clinical relevance of failed and missing cytogenetic analysis in acute myeloid leukaemia. Leukemia 31, 1234–1237 (2017). https://doi.org/10.1038/leu.2017.37

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