Published Ahead of Print on June 28, 2018, as doi:10.3324/haematol.2018.196691. Copyright 2018 Ferrata Storti Foundation.
Acute myeloid leukemia in very old patients by Vladimir Lj Lazarevic, Anders Bredberg, Fryderyk Lorenz, Emma Ölander, Petar Antunovic, Jörg Cammenga, Lovisa Wennström, Lars Möllgård, Stefan Deneberg, Åsa Derolf, Martin Höglund, and Gunnar Juliusson Haematologica 2018 [Epub ahead of print] Citation: Vladimir Lj Lazarevic, Anders Bredberg, Fryderyk Lorenz, Emma Ölander, Petar Antunovic, Jörg Cammenga, Lovisa Wennström, Lars Möllgård, Stefan Deneberg, Åsa Derolf, Martin Höglund, and Gunnar Juliusson. Acute myeloid leukemia in very old patients. Haematologica. 2018; 103:xxx doi:10.3324/haematol.2018.196691 Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in print on a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process.
Acute myeloid leukemia in very old patients 1
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3
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Vladimir Lj Lazarevic , Anders Bredberg , Fryderyk Lorenz , Emma Öhlander , Petar
5
6
7
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Antunovic , Jörg Cammenga , Lovisa Wennström , Lars Möllgård , Stefan Deneberg , Åsa
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Derolf , Martin Höglund , Gunnar Juliusson
1,10
, for the Swedish AML Registry
1) Dept of Hematology, Skåne University Hospital, Lund, Sweden 2) Dept of Laboratory Medicine, Lund University, Lund, Sweden 3) Dept of Hematology, Norrland University Hospital, Umeå, Sweden 4) Dept of Hematology, Sundsvall Hospital, Sundsvall, Sweden 5) Dept of Hematology, Linköping University Hospital, Linköping, Sweden 6) Dept of Hematology, Linköping University, Linköping, Sweden 7) Dept of Hematology, Sahlgren University Hospital, Gothenburg, Sweden 8) Dept of Hematology, Karolinska University Hospital, Stockholm, Sweden 9) Dept of Hematology, Academic Hospital, Uppsala, Sweden 10) Dept of Hematology, Stem Cell Center, Lund University, Lund, Sweden
Running title: AML in very old
Corresponding author: Gunnar Juliusson, Dept of Hematology, Skåne University Hospital, S-221 85 Lund, Sweden
[email protected] phone +46-707-792304
869 words, 1 Table, 1 Figure, 15 references.
More than half of all Swedish adult patients with acute myeloid leukemia (AML) are 70 years
or older at diagnosis (1,2). The AML incidence is peaking in ages 80-84 years, and is declining
among even older, in accordance with the general cancer incidence by age (3-5). AML
biology according to age has again come into focus due to the concept of age-related clonal
hematopoiesis (6). We have previously shown that most patients up to 80 years tolerate and
benefit from intensive chemotherapy (2), and have had an improved outcome over the last
twenty years (7), whereas patients older than 80 years have a very dismal outcome, with no
improvement over time. However, now new therapies with much less toxicity are available
(8,9), which could potentially be tolerated by the oldest patients, who therefore need to be
better characterized.
We previously reported the karyotypic profile in older patients (10). We now report clinical
and diagnostic features according to age with specific focus on the very old (Table 1), with a
comparison to younger patients. Data from patients diagnosed 1997-2016 was extracted in
March 2017 from the Swedish AML registry (1,2). Laboratory data, body mass index (BMI)
and information on hypomethylating therapy were available from 2007. Data on geriatric
assessment (11) and detailed comorbidity (12) were not available.
There are obvious clinical differences by age. The male to female patient number ratio is
lower in older despite higher male incidence up to age 95 years (1), due to the
corresponding sex ratio in the population. Older patients undergo less diagnostic
procedures, such as morphological subclassification and genetic evaluation, due to the lack
of impact on clinical management in the past. Still, AML subclassification according to
FAB/WHO was performed in a higher proportion of Swedish 90+-year old patients than in all
ages according to SEER (13). Older patients have poorer ECOG performance status at
diagnosis, and fewer receive intensive therapy, and fewer of those who receive intensive
therapy achieve complete remission (CR) (2, Table 1). Older patients are, according to
Swedish guidelines, less likely to receive salvage therapy if not responding to first induction
attempt. Thus, survival is increasingly poor with advancing age (Figure 1).
On the other hand, there were no major clinically distinct differences by age in blood counts
at presentation. Total white blood cell counts and blood absolute blast counts were slightly
higher in patients over 85 years (p=0.03 and p=0.0001, respectively), but lactic
dehydrogenase (LDH) was less elevated in older (p=0.02 by non-parametric statistics). Fewer
older patients were obese (BMI>25, p
