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. 2023 Jun 19;13(1):93.
doi: 10.1038/s41408-023-00850-6.

Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Jacobien R Hilberink  1 , Isabelle A van Zeventer  1 , Dana A Chitu  2 , Thomas Pabst  3 , Saskia K Klein  1   4 , Georg Stussi  5 , Laimonas Griskevicius  6 , Peter J M Valk  7 , Jacqueline Cloos  8 , Arjan A van de Loosdrecht  8 , Dimitri Breems  9 , Danielle van Lammeren-Venema  10 , Rinske Boersma  11 , Mojca Jongen-Lavrencic  7 , Martin Fehr  12 , Mels Hoogendoorn  13 , Markus G Manz  14 , Maaike Söhne  15 , Rien van Marwijk Kooy  16 , Dries Deeren  17 , Marjolein W M van der Poel  18 , Marie Cecile Legdeur  19 , Lidwine Tick  20 , Yves Chalandon  21 , Emanuele Ammatuna  1 , Sabine Blum  22 , Bob Löwenberg  7 , Gert J Ossenkoppele  8 ; Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON); Swiss Group for Clinical Cancer Research (SAKK); Gerwin Huls  23
Collaborators, Affiliations

Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Jacobien R Hilberink et al. Blood Cancer J. .

Abstract

Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery < 9 and 17% ADL index < 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule. None of the patient-related variables showed a significant association with OS. Multivariable analysis revealed that age > 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Flow diagram of patient cohort.
One-hundred-forty-four patient were included in the Hovon135 study, for the current analysis 115 patient were included.
Fig. 2
Fig. 2. Kaplan-Meier estimates for overall survival stratified by patient-related variables.
A OS stratified by SPPB score. B OS stratified by ADL score. C OS stratified by HCT-CI. D OS stratified by ECOG performance score. E OS stratified by ELN 2017 risk groups. F OS stratified by diagnosis. G OS stratified by sex. H OS stratified by age.
Fig. 3
Fig. 3. Mutational spectrum stratified by age group.
A Forest plot indicating the OR and 95% CIs for the association between recurrently mutated genes and age > 76 years, and a pyramid plot displaying the proportion of patients and absolute numbers with a mutation in the recurrently mutated genes per age group. B Boxplot with the distribution of the highest VAF per individual stratified by age group. C Violin plot showing the distribution of the number of mutations per individual stratified by age group.
Fig. 4
Fig. 4. Mutational spectrum stratified by sex.
A Forest plot indicating the OR and 95% CIs for the association between recurrently mutated genes and male sex, and a pyramid plot displaying the proportion of patients and absolute numbers with a mutation in the recurrently mutated genes for male and female patients. B Boxplot with the distribution of the highest VAF per individual in female and male patients. C Violin plot showing the distribution of the number of mutations per individual in female and male patients.
See this image and copyright information in PMC

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