1. Acute myeloid leukemia (AML)
Justyna Rybka
Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation
Wroclaw Medical University
Klinika Hematologii, Nowotworów Krwi
i Transplantacji Szpiku

2. AML is a heterogeneous haematological malignancy of the myeloid blood cells1
Lineage affected in AML
AML causes clonal expansion of blast cells
Acute myeloid leukaemia (AML), also known as acute myelogenous leukaemia, is a cancer of the myeloid blood cells, typically characterised by the rapid growth of abnormal white blood cells (WBCs) that accumulate in the BM and other tissues. This accumulation of abnormal blast cells interferes with the production of normal blood cells and blood cellular components, thereby resulting in the clinical presentation of the disease.
Any myeloid neoplasm with ≥20% blasts in the peripheral blood (PB) or BM may be considered:
AML when it occurs de novo
evolution to AML when it occurs in the setting of a previously diagnosed myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasm (MPN)
blast transformation in the setting of a previously diagnosed MPN.
Reference
Vardiman JW, et al. Blood 2009;114:937–51
Any myeloid neoplasm with ≥20% blasts in the PB or BM may be considered an AML2
1. NCCN clinical practice guidelines in oncology. Acute myeloid leukaemia. Version Available at NCCN.org
2. Vardiman JW, et al. Blood 2009;114:937–51
AML = acute myeloid leukaemia
BM = bone marrow; PB = peripheral blood

3. Several risk factors are associated with mutations in AML1
De novo* (large proportion)
Genetic disorders e.g. Down’s syndrome
Somatic mutations
Physical and chemical exposures e.g. Benzene, cigarettes
Leukemogenic risk factors (small proportion)
The development of AML has been associated with several risk factors, e.g.:
Children with Down’s syndrome have a 10–20-fold increase in the likelihood of developing leukaemia.1
Therapeutic radiation has been found to increase the risk of AML.2
Alkylating agents have been reported to increase the incidence of AML.3
Specific risk factors include:4
Genetic disorders: Down’s syndrome, Klinefelter syndrome, Patau syndrome, ataxia telangiectasia, Shwachman syndrome, Kostmann syndrome, neurofibromatosis, Fanconi anaemia and Li-Fraumeni syndrome.
Physical and chemical exposure: benzene, drug-specific exposure, e.g. pipobroman, pesticides, cigarette smoking, embalming fluids and herbicides.
Radiation exposure: non-therapeutic and therapeutic radiation.
Chemotherapy: alkylating agents, topoisomerase-II inhibitors, anthracyclines and taxanes.
Generally, however, leukaemogenic risk factors account for only a small proportion of observed cases of AML.5
The vast majority of AML cases arise de novo with no specific exposure to leukaemogenic risk factors.4
References
1. Fong CT, et al. Cancer Genet Cytogenet 1987;28:55–76
2. Kossman SE & Weiss MA. Cancer 2000;88:620–4
3. Le Beau MM, et al. J Clin Oncol 1986;4:325–45
4. Deschler B & Lübbert M. Cancer 2006;107:2099–107
5. Sandler DP & Collman GW. Am J Epidemiol 1987;126:1017–32
Radiation exposure
Chemotherapy
*No clinical history of prior MDS, MPD, or exposure to leukaemogenic therapies or agents2
MDS = myelodysplastic syndrome; MPD = myeloproliferative disorder
1. Deschler B & Lübbert M. Cancer 2006;107:2099–107
2. Cheson BD, et al. J Clin Oncol 2003;21:4642–9

4. Incidence of AML increases with age
Males
Females
Incidence rate per 100,000 inhabitants
According to current SEER statistics, the median age of diagnosis of AML is ~66 years, with 54% of patients diagnosed at ≥65 years of age. As such, there is a prevalence of AML in older patients and as the global population continues to age, the incidence of AML is likely to rise further.1
Data shown includes incidence of acute lymphoblastic leukaemia, chronic lymphocytic leukaemia, AML and chronic myeloid leukaemia (CML) in the UK between 2008 and
References
1. SEER National Cancer Statistics. Available at: seer.cancer.gov/faststats
2. Cancer Research UK. Leukaemia incidence statistics. Available at:
AML is predominantly a disease of older patients with a slight prevalence in males; the majority of cases occur in patients ≥65 years of age
1. Cancer Research UK. Leukaemia incidence statistics. Available at: cancer-info/cancerstats/types/leukaemia/incidence/uk-leukaemia-incidence-statistics

5. Common symptoms of AML Haematological symptoms
Headache
Anaemia → fatigue
Haematological symptoms
Non-haematological symptoms
Neutropenia → infections
Leukostasis (rare)
Thrombocytopenia → bleeding
Loss of appetite
Fever
Dyspnoea
Hepatomegaly or splenomegaly
Skin rash
American Cancer Society. Available at: acute-myeloid--myelogenous--signs-symptoms

6. Diagnostic work-up for suspected AML
Purpose
Techniques
Histological staining
Assessment of blasts
BM and PB morphology
Morphological assessment
Assessment of lineage
Flow cytometric and/or IHC assessment of blasts
Immunophenotyping
Assessment of cytogenetics and mutational analysis
The aim of the clinical work-up of any patient with suspected AML is:
To define heritable and acquired factors that may have contributed to disease.
To determine patient-specific factors, e.g. presence of comorbidities that may preclude patients from specific treatments.
Of note, additional techniques may also be undertaken at time of diagnosis, e.g. test for eligibility of allogeneic transplant; however, these are not required to make a diagnosis.
Reference
Vardiman JW, et al. Blood 2009;114:937–51
Conventional karyotyping, FISH, RT-PCR, SNP-A
Genetic risk assessment
Diagnosis
FISH = fluorescence in-situ hybridisation; IHC = immunohistochemistry RT-PCR = reverse transcriptase polymerase chain reaction SNP-A = single-nucleotide polymorphism array
Vardiman JW, et al. Blood 2009;114:937–51

7. Morphological assessment is essential in the diagnostic work-up of AML1,2
myeloblasts
monoblasts
Sample collection (PB and BM aspirate;* both required)
Included in blast count
BM smear (1:1000) (Wright–Giemsa stain)
promonoblasts +
(≥200 leukocytes on any blood sample; ≥500 nucleated cells on any BM sample)
Blood and marrow smears are morphologically examined using a Wright-Giemsa stain (≥200 leukocytes on any blood sample; ≥500 nucleated cells on any BM sample).1
Myeloblasts, monoblasts, promonocytes and megakaryoblasts are included in the blast count; proerythroblasts are not counted.1,2
In AML with monocytic or myelomonocytic differentiation, monoblasts and promonocytes may be counted as ‘blast equivalents’.1
References
Dohner H, et al. Blood 2010;115:453–74
Vardiman JW, et al. Blood 2009;114:937–51
megakaryoblasts
proerythroblasts
Not included in blast count
PB smear (1:1000) (Wright–Giemsa stain)
*Trephine biopsy may be considered for IHC in some patients if the aspirate is poor quality or in the presence of marrow fibrosis, especially when blasts are CD34+
1. Dohner H, et al. Blood 2010;115:453–74; 2. Vardiman JW, et al. Blood 2009;114:937–51

8. Immunophenotyping is used to determine lineage involvement in suspected AML
Flow cytometry
IHC
Confirms cells as blasts using specific antigenic markers e.g. CD34, CD117
Cell sorting allows lineage assessment
Method of choice for immunophenotyping of haematological neoplasms1
Confirms cells as blasts via staining of antigenic markers
Staining patterns can allow differentiation of lineage
Less effective than flow cytometry; however, may be useful when flow cytometry is unavailable2
Normal
AML
Immunophenotyping using either flow cytometry or immunohistochemistry (IHC) is mandatory for diagnosing AML with minimal differentiation, i.e. AML without morphological or cytogenetic evidence of myeloid differentiation.
Antibody-conjugated stains commonly used for IHC when assessing patients with suspected AML include:
1) myeloperoxidase (MPO)
2) Sudan black B (SBB)
3) non-specific esterase (NSE)
Detection of MPO (if present in 3% of blasts) indicates myeloid differentiation. However, its absence does not exclude a myeloid lineage as early myeloblasts and monoblasts may lack MPO.
SBB staining parallels MPO but is less specific.
NSE stains show diffuse cytoplasmic activity in monoblasts (usually 80% positive) and monocytes (usually 20% positive).
Reference
Dohner H, et al. Blood 2010;115:453–74
Negative IHC staining of bone marrow (MPO stain)
Positive IHC staining of bone marrow (MPO stain)
Myeloid blast population
1. Craig & Koon. Blood 2008;111:3941– Manaloor EJ, et al. Am J Clin Pathol 2000;113:814–22

9. Other techniques for the genetic assessment of patients with suspected AML1
RT-PCR2
FISH3
SNP-A karyotyping4
Mutational studies of NPM1, CEBPA, and FLT-3 are recommended for all cytogenetically normal patients with AML.
Mutated JAK2 should be analysed in patients with BCR-ABL-1-negative MPN.
Mutational analysis of other prognostic genetic markers (e.g. KIT, NRAS, PTNP11 etc.) should be undertaken as clinically indicated.
Reference
Vardiman JW, et al. Blood 2009;114:937–51
Can play a supplementary role to conventional karyotyping when chromosome morphology is poor quality
May play a supplementary role in detecting gene rearrangements when conventional karyotyping fails
SNP-A can detect microdeletions and regions of uniparental disomy that are undetectable by conventional karyotyping
1. Dohner H, et al. Blood 2010;115:453– Mrózek K, et al. J Clin Oncol 2001;19:2482– Frohling S, et al. J Clin Oncol 2002;20:2480–5 4. Raghavan M, et al. Cancer Res 2005;65:375–8

10. Conventional karyotyping is integral to the evaluation of patients with suspected AML1
Normal healthy karyotype
AML t(16;21)(p11;q22) karyotype
Conventional karyotyping allows analysis of cytogenetics via assessment of specific banding patterns on patient chromosomes
A minimum of 20 metaphase cells is considered obligatory to establish a diagnosis1
PB or BM cells may be used for the identification of an abnormal karyotype.
Reference
Dohner H, et al. Blood 2010;115:453–74
Owing to the high prevalence of chromosomal abnormalities in patients with AML,2,3 cytogenetic evaluation should be considered mandatory at diagnosis
1. Dohner H, et al. Blood 2010;115:453– Mrózek K, et al. Blood Rev 2004;18:115– Grimwade D. Best Pract Clin Haematol Res 2001;14:497–529

11. The French–American–British classification was originally used to classify AML
Description
Blast count
M0 – minimally differentiated
≥30% blasts <3% blasts MPO+, SBB+
M1 – without maturation
<10% maturing myeloids (promyelocyte and beyond)
M2 – with maturation
≥30% blasts ≥10% maturing myeloids
M3 – promyelocytic
≥30% neoplastic promyelocytes and blasts
M4 – myelomonocytic
≥30% blast equivalents (myeloblasts, monoblasts, promonocytes)
M5 M5a – monoblastic (>80% monoblasts) M5b – monocytic (<80% monoblasts)
≥80% NSE+ monocytic elements
<20% MPO+, SBB+ myeloid elements
M6 – erythroid
M6a – erythroleukaemia
M6b – pure erythroid leukaemia
≥50% erythroid elements
≥30% of nonerythroid elements are myeloid blasts
≥80% immature erythroid elements
M7 – megakaryocytic
≥30% blasts ≥50% blasts should be of megakaryocytic lineage
Following a diagnosis of AML, the disease should be classified.
The French–American–British (FAB) classification essentially follows branches of myeloid development, and as a result relies predominantly on staining and morphology to guide a diagnosis. Moreover, the classification assigns a cut-off of 30% blasts to define AML.
Notably, the FAB classification was the standard of choice for ~30 years, until the publication of a newer system by the World Health organisation (WHO).
Reference
Bennett JM, et al. Br J Haematol 1982;51:189–99
FAB = French–American–British; MPO = myeloperoxidase; SBB = Sudan black B; NSE = nonspecific esterase
Bennett JM, et al. Br J Haematol 1982;51:189–99

12. In 2008, WHO revised their classification in line with up-to-date scientific and clinical information
Description
Blast count
AML with recurrent genetic abnormalities
AML with t(8;21)(q22;q22); RUNX1-RUNX1T1
AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22), CBFβ/MYH11
Acute promyelocytic leukemia with t(15;17)(q22;q12), PML/RARA
AML with t(9;11)(p22;q23); MLLT3-MLL AML with t(6;9)(p23;q34); DEK-NUP214 AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1 AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1 Provisional entities: AML with mutated NPM1 or CEBPA
Any Any Any ≥20% in PB or BM ≥20% in PB or BM ≥20% in PB or BM ≥20% in PB or BM Not specified
AML with myelodysplasia-related changes
≥20% in PB or BM
Therapy-related myeloid neoplasms
≥20% in PB or BM
AML, not otherwise specified AML, minimally differentiated AML without maturation AML with maturation Acute myelomonocytic leukaemia Acute monoblastic/acute monocytic leukaemia Acute erythroid leukaemia Pure erythroid leukaemia / erythroleukaemia, erythroid/myeloid Acute megakaryoblastic leukaemia
Acute basophilic leukaemia Acute panmyelosis with myelofibrosis
≥20% in PB or BM ≥20% in PB or BM ≥20% in PB or BM ≥20% in PB or BM ≥20% in PB or BM ≥20% in PB or BM ≥20% in PB or BM ≥20% in PB or BM ≥20% in PB or BM
In 2008, a revised version of the WHO classification was published. The aim of the revision was to include up-to-date scientific and clinical information and refine the classification criteria in line with the changes that had occurred since 2001.
Significant changes from the 2001 classification are described below:1
1. AML with recurrent genetic abnormalities
a) As in the 2001 WHO classification, AML with t(8;21)(q22;q22), inv(16)(p13.1q22) or t(16;16)(p13.1;q22), and acute promyelocytic leukaemia (APL) with t(15;17)(q22;q12) are considered as acute leukaemia regardless of blast count in the PB or BM, but in contrast to the previous edition, for AML with t(9;11)(p22;q23) or other 11q23 abnormalities, as well as for all other subgroups (except the rare instance of some cases of erythroleukaemia), blasts of 20% or more of WBCs in PB or of all nucleated BM cells are required for the diagnosis of AML.
b) In APL with t(15;17)(q22;q12); PML-RARA, variant RARA translocations with other partner genes are recognised separately; not all have typical APL features and some have all-trans retinoic acid (ATRA) resistance.
c) The former category, AML with 11q23 (MLL) abnormalities, has been redefined to focus on AML with t(9;11)(p22;q23);MLLT3-MLL. Translocations of MLL other than that involving MLLT3 should be specified in the diagnosis. Other abnormalities of MLL, such as partial tandem duplication of MLL, should not be placed in this category.
d) Three new cytogenetically defined entities have been added: (1) AML with t(6;9)(p23;q34); DEK-NUP214, (2) AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1; and (3) AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1.
e) Two provisional entities have been added: AML with mutated NPM1 and AML with mutated CEBPA. Although not included as a distinct or provisional entity, examination for mutations of FLT3 is strongly recommended in all cases of cytogenetically normal AML.
2. AML with myelodysplasia-related changes
a) The name was changed and expanded from ‘AML with multilineage dysplasia’ to ‘AML with myelodysplasia-related changes’.
b) Cases of AML are assigned to this category if (1) they have a history of MDS or MDS/MPN and have evolved to AML, (2) they have a myelodysplasia-related cytogenetic abnormality or (3) at least 50% of cells in two or more myeloid lineages are dysplastic.
3. Therapy-related myeloid neoplasms
Cases are no longer subcategorised as ‘alkylating agent related’ or ‘topoisomerase II-inhibitor related’.
4. AML, NOS
a) Some cases previously assigned to the subcategory of AML, not otherwise specified (NOS), as acute erythroid leukaemia or acute megakaryoblastic leukaemia may be reclassified as AML with myelodysplasia-related changes.
b) Cases previously categorised as AML, NOS, acute megakaryoblastic leukaemia should be placed in the appropriate genetic category if they are associated with inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1, or AML (megakaryoblastic) with t(1;22)(p13;q13); RBM15-MKL1. Down’s syndrome-related cases are now excluded from this category.
Reference
Vardiman JW, et al. Blood 2009;114:937–51
*red text denotes amendments from the 2001 WHO classification
Vardiman JW, et al. Blood 2009;114:937–51

13. Molecular abnormalities
Cytogenetics
Patients with AML can be divided into prognostic subgroups based on cytogenetics
Risk status
Cytogenetics
Molecular abnormalities
Favourable risk
t(8;21)(q22;q22)
inv(16)(p13.q22), t(16;16) (p13.q22)
t(15;17)
Normal cytogenetics with NPM1 mutation or CEBPA mutation in absence of FLT3-ITD
Intermediate risk
Normal cytogenetics +8
t(3;5)4
t(9;11)(p22q23)
Other non-defined
c-KIT mutation with: t(8;21)(q22;q22), or inv(16)(p13.q22), t(16;16) (p13.q22)
Poor risk
Complex karyotype (>3 abnormalities)
MK+
-5, 5q-
-7, 7q-
Any 11q23 abnormality other than t(9;11)
Inv(3)(q21q26.2), t(3;3)(q21q26.2)
t(6;9), t(9;22)
Any 17p abnormality
High EVI1 expression (with or without 3q26 cytogenetic lesion)
Normal cytogenetics with FLT3-ITD in the absence of NPM1 mutation
Cytogenetics remain the most important disease-related prognostic factor in AML, and are well-characterised as favourable risk, intermediate risk and adverse risk. These risk groups are based upon presenting cytogenetics and genetic lesions.1
Table is adapted from2, 3.
References
Foran JM. Hematology Am Soc Hematol Educ Program 2010;2010:47‒55
Dohner H, et al. Blood 2010;115:453–74
Byrd JC, et al. Blood 2002;100:4325–36
Foran JM. Hematology Am Soc Hematol Educ Program 2010;2010:47‒55

14. The most commonly mutated genes in patients with AML
Genetic mutations
The most commonly mutated genes in patients with AML
Genetic mutation
Incidence
Clinical impact
NPM1
25–30% of AML; 45–64% of CN-AML; approx. 40% with FLT3-ITD; 10–15% with FLT3-TKD; 35–40% with del(9q) outside of a CK; approx. 15% with trisomy 8; higher prevalence in females
Predicts for achievement of CR and favourable RFS and OS, when present without FLT3-ITD
CEBPA
10–18% in CN-AML; approx. 40% in del(9q) outside of a CK
Higher CR rate and favourable RFS and OS
FLT3-ITD
Approx. 20% of AML; 28–34% of CN-AML
Inferior outcome
FLT3-TKD
5–10% of AML; 11–14% of CN-AML
Trials underway to determine clinical significance
MLL-PTD
5–11% of CN-AML, and ≤90% of AML with trisomy 11
In initial studies: shorter CR duration, inferior RFS and EFS, but not OS
NRAS
9–14% of CN-AML, ≤40% in CBF-AML
May predict sensitivity to cytarabine
WT1
10–13% of CN-AML
Most studies: negative prognostic impact
Poor prognosis with post-remission high-dose cytarabine
WT1 SNP rs16754 associated with inferior outcome in CN-AML
Testing for NPM1, CEBPA, FLT3-ITD mutations is now recommended in clinical practice. The prognostic relevance of other genes remains investigational.
Reference
Marcucci G, et al. J Clin Oncol 2011;29:475–86
CBF-AML = core binding factor acute myeloid leukaemia; EFS = event-free survival
PTD = partial tandem duplication; RFS = relapse-free survival
TD = internal tandem duplication ; TKD = tyrosine kinase domain
Marcucci G, et al. J Clin Oncol 2011;29:475–86

15. ELN system proposed for grouping genetic abnormalities in AML*
Genetic mutations
ELN system proposed for grouping genetic abnormalities in AML*
Genetic group
Subsets
Favourable
t(8;21)(q22;q22);RUNX1-RUNX1T1
inv(16)(p13.1;q22) or t(16;16)(p13.1;q22); CBFB-MYH11
Mutated NPM1 without FLT3-ITD (CN-AML)
Mutated CEBPA (CN-AML)
Intermediate-1
Mutated NPM1 and FLT3-ITD (CN-AML)
Wild-type NPM1 and FLT3-ITD (CN-AML)
Wild-type NPM1 without FLT3-ITD (CN-AML)
Intermediate-2
t(9;11)(q22;q23);MLLT3-MLL
Cytogenetic abnormalities not classified as favourable or adverse
Adverse
inv(3)(q21q26.2) or t(3;3)(q21;q26.2); RPN1-EVI1
t(6;9)(p23;q34); DEK-NUP214
–5 or del(5q); –7; abn(17p); CK†
The European LeukemiaNet proposed a standardised reporting system for cytogenetic and molecular abnormalities in AML that correlate with clinical outcome.
This includes data from cytogenetic analysis and from mutational analyses of NPM1, CEBPA, and FLT3, and will allow for a better comparison of data among studies.
Reference
Dohner H, et al. Blood 2010;115:453–74
Genetic abnormalities can be incorporated into cytogenetic categories to refine risk assessment
*Correlating data from cytogenetic and mutational analyses of NPM1, CEBPA and FLT3 with clinical outcome; n number not specified; †≥3 abnormalities in the absence of t(15;17), t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23), t(6;9), inv(3) or t(3;3); ELN = European LeukemiaNet
Dohner H, et al. Blood 2010;115:453–74

16. Current standard of intensive treatment for patients with AML1
Induction therapy With the aim to eradicate the leukaemic clone
Consolidation therapy With the aim to maintain remission
Standard-dose chemotherapy (1–4 cycles)
Standard dose chemotherapy 7 days of cytarabine + 3 days of anthracycline (7+3)
Ultimate goal: CR*
The current standard of intensive treatment for patients with AML involves:
Induction therapy with the aim to eradicate the leukaemic clone and confer complete response by the patient. The 7+3 regimen is the mainstay for induction therapy and will be explained in detail later.
Consolidation therapy with the aim to maintain remissions. This can involve further chemotherapy, autologous HSCT or allogeneic HSCT.
Reference
Roboz GJ, et al. Curr Opin Oncol 2012;24:711–9
Autologous HSCT
Allogeneic HSCT
*Definition of CR according to the ELN: BM blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease ANC >1.0x109/L; platelets >100x109/L; independent of RBC transfusions2 ANC = absolute neutrophil count
1. Roboz GJ. Curr Opin Oncol 2012;24:711–9
2. Dohner H, et al. Blood 2010;115:453–74

17. Allogeneic HSCT can be used for patients with AML and intermediate- or poor-risk cytogenetics
Allogeneic transplant using an HLA-matched sibling donor is an established practice for younger patients with AML.1 However, recent studies have called for transplant eligibility to be determined based on cytogenetics rather than age alone1
Meta-analysis of trials evaluating allo-HSCT versus no allo-HSCT according to cytogenetic risk*2
0.1
0.5
Favours no HSCT
Overall OS benefit in AML-CR1
OS benefit for good-risk AML-CR1
OS benefit for intermediate-risk AML-CR1
OS benefit for poor-risk AML-CR1
p=0.071 1 5 10
Favours HSCT
Hazard ratio of death
1768
188
864
226
N HSCT
3021
359
1635
366
N no HSCT
0.90 (0.82–0.97)
1.07 (0.83–1.38)
0.83 (0.74–0.93)
0.73 (0.59–0.90)
HR (95% CI)
15 Trials
10 Trials
14 Trials
Although allogeneic HSCT is commonly used in younger patients with AML, its use has remained limited in elderly patients or those younger patients with significant comorbidities which deem them unfit for transplant.
In this large meta-analysis, comprising over 6,000 patients in total, the use of allogeneic HSCT was associated with significant reduction in the risk of death. The hazard ratio (95% confidence interval [CI]) for overall survival benefit with allogeneic HSCT was 0.90 (0.82–0.97).
Overall, 16 trials reported overall survival outcomes stratified by cytogenetic risk. Data from these studies indicate significant survival benefits among patients with intermediate- or poor-risk AML, but there was no significant benefit among patients with good-risk AML.
The median patient age in most trials included in this meta-analysis was in the 30s and, while the age eligibility of most individual trials was up to 60 years, the data do not clarify whether older eligible patients obtained an equivalent benefit.
Reference
Koreth J, et al. JAMA 2009;301:2349–61
Significant OS benefit was observed with allo-HSCT compared with no allo-HSCT; benefit could be seen in patients with poor-risk and intermediate-risk karyotypes, but not good-risk AML
*Median age was ~30 years, all trails included patients ≤60 years
CR1 = in first CR
1. Dohner H, et al. Blood 2010;115:453– Koreth J, et al. JAMA 2009;301:2349–61

18. Treatment of AML patients > 60 years old
In elderly patients – worse general condition, co- morbidities, worse cytogenetics results
In patients in good condition, without co- morbidities: induction and consolidation chemotherapy, allo-HSCT with reduce intensity conditioning
Demethylating agents (decytabine, azacytydine) in patients with % blasts cells
Clinical trials with novel agents

19. Supportive care options for patients with AML
During treatment, most AML patients will receive supportive care to protect against periods of very low blood counts
Anti-infectious treatment
Myeloid growth factors
Transfusions
Antibiotics and anti-fungals are used prophylactically to treat bacterial and fungal infections which can occur due to low WBC counts1
Myeloid growth factors can shorten the duration of neutropenia and reduce the incidence and severity of infections2
Transfusion of RBC and/or platelets can be used to correct anaemia and prevent bleeding1
RBC = red blood cells
Dohner H, et al. Blood 2010;115:453–74

20. APL: acute promyelocytic leukemia
5-10% of AML
Pathogenesis: translocation of chromosomes 15 and 17, this causes parts of a gene from each of these chromosomes to join and create a fusion gene called PML/RARA
Symptoms of APL: unexplained bleeding or bruising, abnormalities of clotting system (DIC), persistent tiredness, dizziness, paleness, or shortness of breath
The treatment of acute promyelocytic leukemia (APL) is very different than that of other types of acute leukemia. ATRA plus anthracycline-based chemotherapy for induction and consolidation followed by maintenance ATRA with low-dose chemotherapy is currently the standard of care.
Patients must start treatment quickly after being diagnosed.