Myelodysplastic syndrome with 10-20% blasts (MDS-EB2) and AML: similar or different entities?


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A Master's thesis.
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Master (thesis) (master)
Myelodysplastic syndrome with 10-20% blasts (MDS-EB2) and AML: similar or different entities?
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Université de Lausanne, Faculté de biologie et médecine
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Myelodysplastic syndromes and acute myeloid leukemia are currently differentiated using a
20% bone marrow (BM) or peripheral blood (PB) blast cutoff. The presence of ³20% blasts
in the BM or PB, based on morphological examination defines AML [1]. However, if the BM
blast percentage is between 10-19% or if the PB blast percentage falls between 5-19%, the
myeloid disorder is classified as MDS-EB2. This method of distinguishing both disorders is
arbitrary, since it is mostly based on blast percentage at presentation. It has been a matter
of discussion whether the classification does a proper job across the board [2]. Patients
presenting with abnormalities consistent with AML but early in the disease progression with
a blast percentage below the 20% threshold are diagnosed with MDS-EB2. The major
question we seek to answer is whether these are two different entities and how different or
similar they are with regards to their clinicopathologic and genetic features, as well as how
their prognosis compare. These different points are not clear, and they do have an impact
on how the disease is managed and which patients can be included in clinical trials. The
access to drugs approved only in the context of AML is limited for patients initially classified
as MDS-EB2, even if they show similar mutations and similar clinical characteristics – new
trials must then be run in this context. For instance, enasidenib, an IDH2 inhibitor is currently
approved for AML patients with an IDH2 mutation but not for MDS patients with the same
mutation. Similarly, ivosidenib – an IDH1 inhibitor is approved only for AML patients with an
IDH1 mutation [3]. In both cases, studies will need to be repeated in MDS patients before
both drugs are eventually approved, thus delaying the access for MDS patients, even though
the mutation is the same.
We try to address whether there are genetic characteristics that are typical of MDS-EB2,
AML or some entities exist and should not be routinely classified but are rather particular
forms of myeloid disorders. We have also tried to assess and compare the outcome of
patients with these malignancies and highlight some prognosis factors.
SMD, MDS-EB2, LMA, AML, hematological malignancies, hemato-oncology, leukemia
Create date
07/09/2020 11:50
Last modification date
04/02/2021 7:26
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