Acute myeloid
leukemia (AML)

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Diagnostics

Method:
Anticoagulant:
Recommendation:

Method:

Cytomorphology
Anticoagulant:

EDTA
Recommendation:

obligatory

Method:

Immunophenotyping
Anticoagulant:

EDTA or Heparin
Recommendation:

obligatory

Method:

Chromosome analysis
Anticoagulant:

Heparin
Recommendation:

obligatory

Method:

FISH
Anticoagulant:

EDTA or Heparin
Recommendation:

facultative

Method:

Molecular genetics
Anticoagulant:

EDTA or Heparin
Recommendation:

obligatory

Classification
Diagnostics
MRD
Prognosis
Therapy
Recommendation

Acute myeloid leukemias (AML) are a heterogeneous group of diseases. AML can either develop de novo, after previous cytotoxic and/or radiotherapy (t-AML), or secondarily from a pre-existing myeloproliferative disease or MDS (s-AML). The incidence of AML is 2.5 - 3.0 / 100,000 inhabitants per year. The median age is 65 years. In children under the age of 15, AML accounts for only about 15-20% of acute leukemias.

Classification of AML

The new AML WHO Classification 2017 divides AML into specific AML subgroups, first according to the patient's medical history (de novo, t-AML, s-AML) and then taking into account a large number of recurrent, balanced cytogenetic abnormalities (see Table 1). Overall, this means that 80% - 90% of patients with AML can now be classified by cytogenetic and/or molecular genetic markers.

AML WHO Classification 2017
(Arber DA et al. 2016, Swerdlow et al. 2017)

Acute myeloid leukemia (AML) and related neoplasms

AML with recurrent genetic abnormalities

AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
Acute promyelocytic leukaemia (APL) with PML-RARA
AML with t(9;11)(p21.3;q23.3); KMT2A-MLLT3
AML with t(6;9)(p23;q34.1); DEK-NUP214
AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM
AML (megakaryoblastic) with t(1;22)(p13.3;q13.3); RBM15-MKL1
AML with BCR-ABL1 (provisional entity)
AML with mutated NPM1
AML with biallelic mutation of CEBPA
AML with mutated RUNX1 (provisional entity)

AML with myelodysplasia-related changes

Therapy-related myeloid neoplasm

AML, not otherwise classified (NOS)

AML with minimal differentiation
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monoblastic and monocyte leukemia
Pure erythroid leukemia
Acute megakaryoblastic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis

Myeloid sarcoma

Myeloid proliferation associated with Down syndrome

Transient abnormal myelopoiesis (TAM)
Myeloid leukemia associated with Down syndrome

According to the WHO classification, a blast percentage of at least 20% in peripheral blood or bone marrow is required for the diagnosis of AML. In AML with t(8;21)(q22;q22.1), RUNX1-RUNX1T1 or inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 and acute promyelocytic leukemia (APL) with PML-RARA, the disease is classified as acute leukemia even if the blast count is below 20%.

≥20%

blasts in blood or bone marrow define a AML

(Onkopedia guidelines AML)

AML - Diagnostics

The cytomorphology together with the cytochemistry (myeloperoxidase and esterase) belong to the standard diagnostics. It serves to secure the diagnosis and is also required for classification according to WHO. Cytomorphologic remission assessment is still a gold standard for follow-up examinations under therapy.

Acute myeloid leukemia (AML) is often first diagnosed on the basis of cytomorphology and cytochemistry. The only exceptions are AML with minimal differentiation and acute megakaryoblast leukemia, which can only be diagnosed reliably by immunophenotyping. This is one of the reasons why immunophenotyping is always part of the routine diagnosis of AML. In addition, typical immunophenotypes are available for some genetic abnormalities occurring in AML. However, these correlations are not complete and therefore only have a guiding role in diagnostics.

In acute promyelocytic leukemia (APL), a characteristic finding in the scatter plot is shown in association with infiltration by atypical promyelocytes. In addition, HLA-DR and CD34 are usually not expressed. However, these findings can also be found in some other AML cases (e.g. AML with NPM1 mutation and normal karyotype). AML with maturation and t(8;21)(q22;q22)/RUNX1-RUNX1T1 is typically associated with aberrant coexpression of CD19 and CD56. This constellation is not specific to a particular AML subtype too. The same is true for the immunophenotype of myelo-monocytic AML with abnormal eosinophils, where one can specifically find a positivity for CD2 as well as an asynchronous coexpression of CD15 and CD34.

AML with minimal differentiation shows no myeloperoxidase (MPO) positivity (<3%) in cytochemistry, therefore this diagnosis cannot be made morphologically alone. Immunophenotyping differentiates AML from ALL and detects the expression of CD13, CD33 and CD117 and other myeloid antigens. At the same time lymphatic antigens are not expressed or the lymphatic score is not sufficient for the diagnosis of a biphenotypic acute leukemia. In about half of the cases, despite the cytochemical negativity for myeloperoxidase, an expression of MPO can be detected by flow cytometry and thus the diagnosis of AML can be made.

Acute megakaryoblast leukemia is also cytochemically negative for MPO and esterase. Due to the frequently existing myelofibrosis, a cytological evaluation is difficult. In immunophenotyping, the expression of CD41 or CD61 can be detected.

Immunophenotyping plays an important and increasing role in the determination of MRD (Schuurhuis et al. 2018). Together with molecular genetics (see below), it provides the decisive parameters for therapy stratification. Depending on the expression of certain markers, the sensitivity is 10^-4 to 10^-5.

The classical chromosome analysis to determine the karyotype of leukemia cells is now part of the standard diagnostic procedure for every AML patient. The karyotype and the numerous characteristic chromosomal abnormalities are used for classification according to WHO, but also represent the most important independent prognostic parameters. For some genetically defined subtypes of AML, therapeutic consequences can be drawn from the chromosomal analysis findings. About 50-75% of adult patients and 75-85% of children with AML show clonal chromosomal alterations. While the incidence of different chromosomal abnormalities depends on age, the prognostic significance of a cytogenetic alteration is largely independent of the patient's age.

FISH is a fast method for the detection of specific abnormalities

The FISH analysis serves as an important addition to the classical chromosome analysis and answers specific questions, e.g. the detection of the translocation t(15;17)(q24;q21) (with a rearrangement of the genes PML and RARA) in suspected cases of acute promyelocyte leukemia. It is a fast and reliable method, with which a PML-RARA rearrangement can be detected after only 3 hours. Other genetic abnormalities frequently occurring in AML, such as t(8;21)(q22;q22), inv(16)(p13q22) and rearrangements of the KMT2A gene, are relevant for the classification of AML within the WHO classification. They can also be detected by FISH. Frequent unbalanced changes, such as deletions of the long arm of chromosome 5 or 7 or monosomes (-7) or trisomies (+8, +11, +13, +21) can also be detected by FISH. With the help of a manageable set of FISH probes, even a large proportion of AML cases with complex aberrant karyotype can be correctly classified.

24-color FISH for complex karyotypes

The so-called "chromosome painting" with 1-3 or 24 colours (24-colour-FISH) on metaphase chromosomes is performed in addition to the classical chromosome analysis, if the karyotype cannot be clearly clarified by chromosome analysis using the classical banding technique. This is often the case with complex aberrant karyotypes.

Detection of minimal residual disease with FISH

The FISH method can also be used in the course of AML after therapy to detect residual disease. It is more sensitive and specific than cytomorphology, but less sensitive than PCR and immunophenotyping.

For the detection of molecular mutations a variety of detection techniques are available. For example, conventional reverse transcription (RT) PCR (fusion genes), gene scan analysis (NPM1, FLT3-ITD), melting curve analysis (FLT3-TKD, NPM1, RAS, KIT D816) and real-time PCR (KMT2A-PTD, fusion genes, EVI1 expression). If a mutation is detected using these techniques, sequencing can be used for precise characterization. In the following, these molecular markers open up new target structures for the PCR-based detection of minimal residual disease (MRD). Today, so-called Next-Generation-Sequencing (NGS) is often used to sequence a large number of genes (e.g. 75) in one gene panel and in one step in order to keep examination times short and to obtain a comprehensive picture of the molecular landscape of the respective AML with diagnostic, prognostic and increasingly also therapeutic significance.

Common reciprocal chromosome rearrangements (fusion genes)

Reciprocal chromosomal rearrangements are present in about 25% of all AML. The molecular correlates or fusion genes of most reciprocal rearrangements, which can also be detected cytogenetically, are known. The most frequent reciprocal translocations t(15;17)(q24;q21), t(8;21)(q22;q22), and inv(16)(p13q22)/t(16;16)(p13;q22) lead to the formation of the fusion genes PML-RARA, RUNX1-RUNX1T1 and CBFB-MYH11 at the molecular level. Rearrangements of the KMT2A gene are found in about 5% of all AML, with more than 50 different translocation partners described. In addition, numerous other rare rearrangements can be detected, which often affect less than 1% of all cases, but in individual cases represent useful target structures for diagnosis. For fusion genes, quantification at the time of diagnosis is useful, since this measurement value serves as a starting point for future follow-ups (MRD).

Fusion genes detectable by RT-PCR:

RUNX1-RUNX1T1
CBFB-MYH11
PML-RARA
KMT2A-Fusionen
CALM-AF10
CHIC2-ETV6
NUP98-HOXA9
DEK-NUP214
MYST3-CREBBP
BCR-ABL1

Table 1: Rearrangements with the associated fusion genes in AML

Cytogentics	Fusion gene	Frequency
Cytogentics	Fusion gene	Children	Adults
t(8;21)(q22;q22)	RUNX1-RUNX1T1	10-15%	8-12%
inv(16)(p13q22)	CBFB-MYH11	6-12%	8-12%
t(15;17)(q24;q21)	PML-RARA	8-15%	8-10%
t(6;11)(q27;q23)	KMT2A-MLLT4 (KMT2A-AF6)	2-5%	< 1%
t(9;11)(p21;q23)	KMT2A-MLLT3 (KMT2A-AF9)	8-10%	1-2%
t(10;11)(p12;q23)	KMT2A-MLLT10 (KMT2A-AF10)	< 1%	1-2%
t(11;19)(q23;p13)	KMT2A-MLLT1 (KMT2A-ENL)	< 1%	< 1%
t(11;19)(q23;p13)	KMT2A-ELL	< 1%	< 1%
t(3;21)(q26;q22)	RUNX1-EVI1	1%	< 1%
t(6;9)(p23;q34)	DEK-NUP214	1-2%	< 1%
t(8;16)(p11;p13)	KAT6A-CREBBP	< 1%	< 1%
t(1;22)(p13;q13)	RBM15-MKL1	2%	-
t(7;11)(p15;p15)	NUP98-HOXA9	-	< 1%
t(10;11)(p13;q14)	CALM-AF10	-	< 1%
t(16;21)(p11;q22)	FUS-ERG	-	< 1%

Molecular mutations common in NPM1 and FLT3-ITD and RUNX1

Mutations in the nucleophosmin (NPM1) gene are found in approximately 35% of all AML cases and 55% of cases with a normal karyotype. The transcription factor RUNX1 is mutated in 15-30% of AML cases. Mutations in the transcription factor CEBPA have been described in 7-15% of AML cases with normal karyotype. In the WHO classification of 2017, both the NPM1 and the biallelic CEBPA mutation were introduced as a separate AML entity. Internal tandem duplications (ITDs) of the FMS-like tyrosine kinase 3 gene (FLT3-ITD) occur in 25% of younger adults with cytogenetically normal AML. Studies have shown that the ratio of mutation load to wild type plays a prognostic role. Patients with a ratio ≥0.5 show a less favourable prognosis as well as a higher recurrence rate and are also more likely to benefit from a stem cell transplant (Schlenk et al. 2014, Döhner et al. 2017).

Table 2: Molecular mutations in AML

Mutation	Most common subtypes	Total frequency	Prognosis
NPM1	normale-karyotype (55%)	30%	favourable, if FLT3-ITD is not mutated
FLT3-ITD	normale-karyotype (40%)	25%	adverse
FLT3-TKD	all AML	6-7%	depending on additional abnormality
KMT2A-PTD	normale-karyotype (11%) trisomy 11 (20-50%)	6.5%	adverse
CEBPA	normale-karyotype (7%)	4%	favourable, only if biallelic
KITD816	t(8;21) (12%)	1.5%	adverse
KITexon8	inv(16) (10%)	< 1%	adverse, may TKI possible
NRAS	inv(16) (45%) inv(3)/t(3;3) (40%)	10%	intermediate
KRAS	inv(16); t(8;21) (5-20%) (in children)	< 1%	prognostic significance unclear
RUNX1	AML minimally differentiated (22%) trisomy 21 (30%)	15%	adverse
IDH1/2	normale-karyotype (30%)	15-20%	depending on the type of mutation, specifically treatable
TET2	-	15-25%	not yet clearly defined
DNMT3A	normale-karyotype (35%)	20%	adverse

Next-Generation-Sequencing (NGS) identified new molecular markers

The introduction of new sequencing techniques ("next-generation-sequencing", NGS) has facilitated the expansion of the spectrum of molecular markers. Mutations in the TET2 gene ("TET oncogene family member 2") on chromosome 4q24 were detected in 15-25% of all AML cases. They are also detectable in numerous other myeloid entities such as MDS. Whether or not this has an influence on the prognosis is the subject of current studies. Mutations of the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes have been detected in up to 20% of all AML patients. Specific drugs are available for these patients. In addition, de novo AML mutations in the ASXL1 (additional sex-comb like 1) gene, which is located on chromosome section 20q11, have been identified in about 10% of all patients. Very rare are mutations in the "Casitas B-cell lymphoma" (CBL) gene located on chromosome 11q23 (< 2% of all AML cases).

AML: MRD (Measurable Residual Disease)

The determination of Measurable Residual Disease (formerly known as minimal residual disease) opens up new possibilities for certain AML subgroups in terms of prognosis and classification with regard to response to therapy. The search for suitable parameters is often difficult. The diversity of clones can be high, and preleukemic clones and subclones exist side by side. Over time, the composition of the clones may change, especially under the selection pressure of the therapy. Nevertheless, it has been shown very well that certain markers are suitable for prognostic assessment.

The determination of the mutation load of the marker NPM1 by means of quantitative polymerase chain reaction (qPCR) can, for example, be used very well to assess the risk of recurrence and give an indication as to which patient should be given an allogeneic stem cell transplantation or not due to MRD negativity. Patients with wild-type NPM1 and intermediate risk benefit from an MRD determination after induction therapy by flow cytometry, which also allows a prognosis of the risk of relapse. The determination of the transcription level of fusion proteins such as RUNX1-RUNX1T1 at specific points in time during therapy also allows an assessment of the risk of relapse. MRD negativity is a very favourable parameter for survival and a low risk of relapse (Freeman et al. 2019, Rücker et al. 2019, Schuurhuis et al. 2018).

Prognosis of AML

Karyotype and molecular genetic changes most important prognostic parameters

In addition to age, leukocyte count and general condition, the karyotype and molecular genetic changes are important prognostic parameters and have a major influence on the therapy strategy. Several studies have shown that especially patients with normal karyotype benefit from additional molecular genetic information regarding therapy choice and prognosis assessment (Döhner et al. 2010, 2015, 2017). Modern genetic prognosis systems combine molecular mutations and cytogenetics (Grimwade et al. 2016, Döhner et al. 2017).

The cytogenetic abnormalities and molecular genetic changes with prognostic relevance defined so far are listed in Tables 3 and 4.

Table 3: Risk distribution with independent prognostic relevance in younger AML patients (16 - 60 years)

(according to Grimwade et al. 2016)

Risk category	Genetic abnormality
Favourable	t(15;17)(q24;q21) / PML-RARA t(8;21)(q22;q22) / RUNX1-RUNX1T1 inv(16)(p13q22) / t(16;16)(p13;q22) / CBFB-MYH11 Mutated NPM1 (no FLT3-ITD and no mutated DNMT3A) Biallelic mutated CEBPA
Intermediate	aberrations, which are not classified as favourable or adverse
Adverse*	abn(3q) except t(3;5)(q21~25;q31~35)/ NPM1-MLF1) inv(3)(q21q26) / t(3;3)(q21;q26) / GATA2/EVI1 add(5q) / del(5q), -5 t(5;11)(q35;p15.1) / NUP98-NSD1 t(6;9)(p23;q34) / DEK-NUP214 add(7q) / del(7q), -7 t(11q23) except t(9;11)(p21~22;q23) and t(11;19)(q23;p13) t(9;22)(q34;q11) / BCR-ABL1 -17 / abn(17p) / mutated TP53 complex karyotype (≥ 4 independent abnormalities ) mutated ASXL1, mutated DNMT3A, mutated RUNX1 FLT3-ITD, KMT2A-PTD

*only if none of the cyto- and molecular genetic abnormalities classified as favourable are present

Table 4: Risk classification according to ELN recommendation

(Döhner et al. 2017)

Risk category	Genetic abnormality
Favourable	t(8;21)(q22;q22); RUNX1-RUNX1T1 ^{inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11 mutated NPM1 without FLT3-ITD or with}FLT3-ITD^low Biallelic mutated CEBPA
Intermediate	Mutated NPM1 and FLT3-ITD^high Wild-type NPM1 without FLT3-ITD bzw. FLT3-ITD^low (without adverse-risk genetic lesions) t(9;11)(p21.3;q23.3); MLLT3-KMT2A cytogenetic abnormalities not classified as favorable or adverse
Poor*	t(6;9)(p23;q34.1); DEK-NUP214 t(v;11q23.3); KMT2A rearranged t(9;22)(q34.1;q11.2); BCR-ABL1 inv(3)(q21.3q26.2) oder t(3;3)(q21.3;q26.2); GATA2-MECOM (EVI1) -5 or del(5q); -7; -17/abn(17p) Complex karyotype (≥ 3 unrelated abnormalities)* Monosomal karyotype (one single monosomy (excluding loss of X or Y) in association with at least 1 additional monosomy or structural chromosome abnormality)^# Wild-type NPM1 and FLT3-ITD^high Mutated RUNX1 Mutated ASXL1 Mutated TP53

three or more unrelated chromosome abnormalities in the absence of 1 of the WHO-designated recurring
^# excluding core-binding-factor (CBF) AML

AML - Therapy

For a long time, all AML subtypes were treated with the same standard therapy 7+3 or similar protocols, which were specifically designed for fit patients with a biological age below 75 years. A fast start and intensive treatment was considered important, which consisted of induction therapy with the aim of complete remission (CR) and post-remission therapy to maintain CR. Allogeneic transplantation played a major role in this process. The response to therapy was very much determined by the genetic background of AML. For the first time, it was possible to introduce a specific therapy for acute promyelocytic leukemia with all-trans-retinoic acid (ATRA) (later also in combination with arsenic), which was specifically oriented on the genetics of AML. In recent years, the spectrum of targeted therapies has expanded for several other AML subgroups, relapsed patients and especially patients who did not seem suitable for intensive therapy due to comorbidities. The most accurate genetic characterization of AML is essential for the use of targeted therapies.
For clinically stable patients at the time of the initial diagnosis delay in the start of therapy due to the genetic analyses, which can take several days, does not lead to a worse response but rather to an improved long-term prognosis through the use of adapted therapies.

Today, according to the Onkopedia guidelines (status: 10/2019), patients with

CD33-positive Core Binding Factor AML (CBF-AML) and with CD33-positive NPM1 mutation in FLT3wt
FLT3 mutation
AML-MRC and patients with therapy-associated AML (t-AML) at FLT3wt
CD33-positive intermediary risk-AML in FLT3wt

can be treated with an alternative induction scheme.

The B-cell lymphoma (BCL-2) inhibitor Venetoclax, in combination with hypomethylating agent (HMA) therapy, showed very good success in older patients with NPM1 mutant AML, who otherwise have a comparatively adverse prognosis compared to younger patients. Studies with a small cohort of older de novo AML patients with an intermediate or adverse risk profile after ELN also showed that venetoclax in combination with decitabine or azacidine is a very good alternative to standard therapy. CR rates of between 54% and 67% were shown, with a response being achieved as early as 1 to 2 cycles, mortality was only 3 to 6% and survival was significantly prolonged (DiNardo et al. 2019).

FLT3 inhibitors represent a new therapeutic option for patients with mutated FLT3. FLT3 inhibitors of class I (midostaurine) or II (gilteritinib, quizartinib) are used as first-line therapy as well as in recurrence. The FLT3 inhibitor midostaurine, together with conventional chemotherapy, has a positive effect on all risk groups grouped by ELN (Döhner et al. 2020). Studies have shown that second-generation FLT3 inhibitors in combination with the 7+3 regimen in refractory patients lead to improved CR rates (48% vs. 27%), longer survival (6.2 months vs. 4.7 months) and a higher probability of receiving a stem cell transplant. So far it is questionable whether these inhibitors also have a positive effect in maintenance therapy, although initial study results suggest that they do (DiNardo et al. 2020).

Older patients who do not respond to HMA in first-line therapy have had an adverse prognosis. This prognosis has been improved by the introduction of IDH antagonists (IDH1-ivosidenib and IDH2-enasidinib) for AML patients with IDH mutation. Response rates of 29% to 34% and a median survival of 9 months demonstrate the potency of these drugs. Of the patients who responded to an IDH antagonist, 50% were still alive after 18 months. In addition, 21% of the patients achieved deep remission of IDH1 (DiNardo et al. 2020).

Gemtuzumab ozogamicin (GO) is currently used together with the 7+3 regimen as first-line therapy for low and intermediate risk groups classified as ELN. The positive effect occurs mainly with mutations that affect cell signalling (FLT3-ITD, FLT3-TKD, NRAS) and correlate with high CD33 expression (Fournier et al. 2020).

For patients with secondary AML, therapy-associated AML or AML associated with MDS, Vyxeos (CPX-351) represents a new alternative. It consists of a fixed combination of daunorubicin and cytarabine in an optimal 5:1 ratio for the treatment and a liposomal formulation that leads to improved biological accessibility in the body. A group of patients in the intermediate and adverse risk group benefited in several studies in terms of response rate (58% in CR and 55% MRD<10³), overall survival (5.95 vs. 9.56 months) and survival rate after two years (31% vs. 12%).

AML: Recommendation

AML is defined by ≥20% blasts in peripheral blood and/or bone marrow. This differentiates AML from myelodysplastic syndromes. To confirm the diagnosis the following tests are recommended according to the current oncopedia guidelines for AML.

Diagnostic confirmation in case of suspected AML (Oncopedia-LL AML; 10/2019)

Investigations

Medical history and physical examination
Blood count and differential blood count
Bone marrow cytology and cytochemistry
Bone marrow biopsy (absolutely necessary in case of punctio sicca)
Immunophenotyping
Cytogenetics
FISH (if the cytogenetic analysis is not successful: detection of translocations such as RUNX1-RUNX1T1, CBFB-MYH11, KMT2A and EVI1; or loss of chromosome 5q, 7q or 17p)

Molecular genetics (gene mutations)

NPM1
CEBPA
RUNX1
FLT3 (internal tandem duplications (ITD), mutant wild type ratio)
FLT3-TKD (Codon D853 and I836)
TP53
ASXL1

Molecular genetics (gene fusions)

PML-RARA
CBFB-MYH11
RUNX1-RUNX1T1
BCR-ABL1

Arber et al. The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood 2016;127(20):2391-2405.

DiNardo. et al. How I treat acute myeloid leukemia in the era of new drugs. Blood 2020, 35(2):85-96.

DiNardo et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood 2019, 133(1):7-17.

Döhner et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115(3):453-474.

Döhner et al. Acute Myeloid Leukemia. NEJM 2015;373(12):1136-1152.

Döhner et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 2017;129(4):424-447.

Döhner et al. Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia. Blood 2020,135(5):371-380).

Fournier et al. Mutational profile and benefit of gemtuzumab ozogamicin in acute myeloid leukemia. Blood 2020;135(8):542-546).

Freeman et al. MRD evaluation of AML in clinical practice: are we there yet? Haematology 2019, (1):557-569.

Grimwade et al., Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 2010;116(3):354-365.

Grimwade et al. Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance. Blood 2016;127(1):29-41.

Onkopedia Leitlinie „Akute myeloische Leukämie (AML)“. DGHO Oktober 2019.

Rücker et al. Measurable residual disease monitoring in acute myeloid leukemia with t(8;21)(q22;q22.1): results from the AML Study Group. Blood 2019, 34(19):1608-1618.

Schlenk et al. Differential impact of allelic ratio and insertion site in FLT3-ITD-positive AML with respect to allogeneic transplantation. Blood 2014 (23):3441-9.

Schuurhuis et al. Minimal measurable residual disease in AML a consensus document from the ELN MRD Working Party. Blood 2018; 131(12):1275-1291.

Swerdlow SH et al. WHO classification of tumours of haematopoetic and lymphoid tissue. International Agency of Research on Cancer 2017; 4. überarbeitete Version.

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Acute myeloid leukemia (AML)

Classification of AML

AML WHO Classification 2017(Arber DA et al. 2016, Swerdlow et al. 2017)

≥20%

AML - Diagnostics

AML: MRD (Measurable Residual Disease)

Prognosis of AML

Karyotype and molecular genetic changes most important prognostic parameters

Table 3: Risk distribution with independent prognostic relevance in younger AML patients (16 - 60 years)

Table 4: Risk classification according to ELN recommendation

AML - Therapy

AML: Recommendation

Diagnostic confirmation in case of suspected AML (Oncopedia-LL AML; 10/2019)

Investigations

Molecular genetics (gene mutations)

Molecular genetics (gene fusions)

You may also be interested in

Acute myeloid
leukemia (AML)

AML WHO Classification 2017
(Arber DA et al. 2016, Swerdlow et al. 2017)