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Commentary on: ‘Age, not therapy intensity, determines outcomes of adults with acute myeloid leukemia’

Leukemia volume 30, pages 1636–1637 (2016)Cite this article

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In this reanalysis of a series of large German acute myeloid leukemia (AML) trials with similar designs, Dr Buchner et al.1 focus on subsets of older patients in an attempt to demonstrate whether planned dose intensity has an effect on survival and other outcomes, independent of patient age. They make the reasonable assumption that medical and biological factors would be similar in ‘younger older’ patients aged ⩾57–<60 years and ‘older older’ individuals aged >60–<63 years, and, in fact, the demographic data from these two groups were very similar. In a unique feature of the study design, the implications of which will be discussed further below, all patients were randomized at the time of study entry to different approaches to dose and schedule of therapy with the plan to analyze the results using the principle of intent to treat (ITT).

Obviously, distinctions at dichotomous age cutoffs do not make sense biologically, cannot be used to provide recommendations for individual patients and in this case, given the median age of 65–70 years at time of AML diagnosis, likely do not apply to the larger population of what I have termed ‘olderly’ patients. Nonetheless, in these protocols that treated AML patients of all ages, this cutoff could be informative, if indeed there were major differences in the therapy planned for these two groups. The younger group was to receive two sequential courses of induction therapy independent of post treatment marrow findings, with a randomization to either thioguanine, cytarabine, daunorubicin (TAD) or high dose cytarabine, mitoxantrone (HAM) as their initial course followed by a second course of HAM. Patients in complete remission received another course of TAD and were randomized to either 2 years of maintenance chemotherapy or autologous stem cell transplantation. Older patients were randomized to TAD or HAM with a second course of HAM if a marrow showed residual leukemia, followed by TAD if in complete remission (CR), and then maintenance chemotherapy. The so-called ‘high-dose’ cytarabine was a feature of the HAM regimen, with six doses of 3 g/m2 in the younger group compared with lower doses of 1 g/m2 in the older patients.

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References

  • Buchner T, Krug UO, Gale RP, Heinecke A, Sauerland C, Haferlach C et al. Age, not therapy-intensity, determines outcomes of adults with acute myeloid leukaemia. Leukemia 2016.

  • Burnett AK, Russell NH, Hills RK, Hunter AE, Kjeldsen L, Yin J et al. Optimization of chemotherapy for younger patients with acute myeloid leukemia: results of the medical research council AML15 trial. J Clin Oncol 2013; 31: 3360–3368.

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  1. Department of Medicine and Oncology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit, MI, USA

    C A Schiffer

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  1. C A Schiffer
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Schiffer, C. Commentary on: ‘Age, not therapy intensity, determines outcomes of adults with acute myeloid leukemia’. Leukemia 30, 1636–1637 (2016). https://doi.org/10.1038/leu.2016.141

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