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Clinical Trial
. 2020 Feb;188(4):528-539.
doi: 10.1111/bjh.16203. Epub 2019 Oct 14.

Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup

Yusuke Hara  1   2   3 , Norio Shiba  2   3   4 , Genki Yamato  1   2   3 , Kentaro Ohki  2   5 , Ken Tabuchi  6 , Manabu Sotomatsu  2 , Daisuke Tomizawa  7 , Akitoshi Kinoshita  8 , Hirokazu Arakawa  1 , Akiko M Saito  3 , Nobutaka Kiyokawa  5 , Akio Tawa  9 , Keizo Horibe  3 , Takashi Taga  10 , Souichi Adachi  11 , Tomohiko Taki  12 , Yasuhide Hayashi  2   3   13
Affiliations
Clinical Trial

Patients aged less than 3 years with acute myeloid leukaemia characterize a molecularly and clinically distinct subgroup

Yusuke Hara et al. Br J Haematol. 2020 Feb.

Abstract

Although infants (age <1 year) with acute myeloid leukaemia (AML) have unique characteristics and are vulnerable to chemotherapy, children aged 1-2 years with AML may have characteristics similar to that of infants. Thus, we analysed 723 paediatric AML patients treated on the Japanese AML99 and AML-05 trials to identify characteristics of younger children. We identified patients aged <3 years (the younger group) as a distinct subgroup. KMT2A-rearrangement (KMT2A-R), CBFA2T3-GLIS2, CBFB-MYH11 and NUP98-KDM5A were frequently found in the younger group. Prognostic analyses revealed poor 5-year overall survival (OS), event-free survival (EFS) and cumulative incidence of relapse (CIR) in patients with CBFA2T3-GLIS2 (42%, 17% and 83%, respectively) and those with NUP98-KDM5A (33%, 17% and 83%, respectively). Additionally, we identified KMT2A-R and CBFB-MYH11 as age-specific prognostic markers. Regarding KMT2A-R, the younger group had significantly better OS, EFS and CIR than the older group (aged 3 to <18 years) (P = 0·023, 0·011 and <0·001, respectively). Conversely, concerning CBFB-MYH11, the younger group had significantly poor EFS and CIR than the older group (each P < 0·001), suggesting that certain molecular markers are linked to different prognoses according to age. Therefore, we characterized patients <3 years as a distinct subgroup of paediatric AML.

Keywords: myeloid leukaemia; paediatric oncology; risk factors.

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