Childhood acute myeloid leukaemia

The information provided on pretend to support, not replace, the relationship between patients/visitors of this website and their doctor.

Dr. Albert Català. Pediatrician specialising in hematology at the Hospital Sant Joan de Déu, Barcelona


Production of blood cells (or hematopoiesis)

Hematopoiesis is the process of formation, development and maturation of blood cells. After birth, the bone marrow becomes principally responsible for hematopoiesis during the entire person's life.

All hematopoietic cells originate from stem cells, which produce others that differentiate into the various cells that make up the hematopoietic system. The first great differentiation is into lymphoid and myeloid cells, both of which have their particular functions.

What is childhood acute myeloid leukaemia and whom does it affect?

Acute leukaemias are a group of cancer diseases characterised by the malignant transformation and uncontrolled production of immature hematopoietic cells of the lymphoid line (acute lymphoblastic leukaemia, ALL) or myeloid line (acute myeloblastic leukaemia, AML).

With acute myeloid leukaemia, the cells of the myeloid line (myeloblasts) proliferate abnormally and progressively invade the bone marrow, interfering with the normal production of blood cells, leading to bone marrow failure and the infiltration of extramedullary tissues.

Acute leukaemias are the most frequent cancers during childhood and account for 32% of the cancers during this period (under 15 years of age). The lymphoid form is the most frequent and AML accounts for 20% of the leukaemias diagnosed during this stage of life. The annual incidence of AML during childhood is 8 cases per million children under the age of 15. (US Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program). 

AML during childhood is most frequent before the age of two. Its incidence declines during school years and then increases progressively with age after adolescence.

The specific causes of most cases of childhood AML are not known. Only in a very small percentage of cases (around 5%), do acute childhood leukaemias develop in patients with an underlying genetic disorder that predisposes them to leukaemia such as, for example, Down syndrome or inherited bone marrow failure syndromes (Fanconi anemia and dyskeratosis congenita, amongst others).

Types of acute myeloid leukaemia

The two most commonly used methods for classifying AML are the French-American-British (FAB) system, based on the leukaemia cell's microscopic characteristics and its expression of certain proteins (immunophenotype), and the new World Health Organization (WHO) system, which incorporates genetic and molecular information about the leukaemia cell and clinical information of prognostic interest.

In our country the most commonly used method is the FAB classification.



Childhood %














Undifferentiated AML

AML with minimal maturation

AML with maturation

Acute promyelocytic leukemia

Acute myelomonocytic leukemia

Acute myelomonocytic leukemia with eosinophilia

Acute monocytic leukemia


Acute erythroid leukemia


Acute megakaryoblastic leukemia














The WHO classification, updated in 2016, takes into account genetic and molecular aspects of the leukaemia cells. The most common cytogenetic alterations in AML are translocations; the attachment of a fragment of a chromosome to another chromosome (indicated as t). For example: t(8;21), a fragment of chromosome 8 has become attached to a part of chromosome 21; or, within the same chromosome, t(16;16). Chromosome inversions may also be observed when a segment of a chromosome changes direction within the same chromosome (this is indicated as inv).

The translocations and inversions detected in cytogenetic studies generate the rearrangement of the genes located in the affected regions of the chromosome. These are indicated by the names of the genes involved, so in the case of t(8;21) it will generate a rearrangement of the genes RUNX1 and RUNX1T1. Cytogenetic alterations have proved to be a very important prognostic factor and are used is most treatment protocols to determine their intensity.

In recent years, mutations have been described in one or various genes of the leukaemia cells of most patients. Some of them have proved to be of prognostic importance and of relevance when determining the intensity of treatment. Thus, the WHO's recent classification includes the mutations in NPM1 and CEBPA, which are associated with a more favourable prognosis.

Most childhood cases are classified within the AML group with recurrent genetic alterations or non-specific AML.

WHO classification of AML and related neoplasias

AML with recurrent genetic abnormalities

AML with t(8;21); RUNX1-RUNX1T1

AML with inv(16) o t(16;16); CBF-MYH11

AML with t(15;17); PML-RARA

AML with t(9;11); MLLT3-KMT2A

AML with t(6;9); DEK-NUP214

AML with inv(3) o t(3;3);GATA2, MECOM

AML (megakaryoblastic) with t(1;22); RBM15-MKL1

AML with NPM1 mutation

AML with CEBPA biallelic mutation

Provisional entities:


AML with RUNX1 mutation

AML with myelodysplasia-related changes

Therapy-related AML

AML not otherwise specified (NOS)

AML with minimal differentiation

AML without maturation

AML with maturation

Acute myelomonocytic leukaemia

Monoblastic/monocytic leukaemia

Erythroid leukaemia

Acute megakaryoblastic leukaemia

Acute basophilic leukaemia

Panmyelosis with acute myelofibrosis

Myeloid sarcoma

Myeloid proliferations related to Down syndrome

Transient Abnormal Myelopoiesis

Myeloid leukaemia associated with Down syndrome

Acute leukaemias of ambiguous lineage


Symptoms and diagnosis

The clinical presentation of AML is variable and, in general, the symptoms diagnosed are due to the infiltration of the bone marrow, and other organs, by leukaemia cells. Although its initial presentation may be insidious, childhood AML is usually acute, with less than three months between the onset of symptoms and diagnosis.

The most common symptoms are the result of anemia caused by a deficiency in red blood cells (fatigue, debility, dizziness, pallor); platelet deficiency (bruises, petechiae, bleeding gums, nosebleeds, bleeding from other foci), and white blood cell deficiency (fever and infections).

Sometimes a growth can be observed of the lymphatic ganglions, the liver or the spleen. Specific symptoms of the infiltration of the central nervous system may also be observed (headaches, vomiting, drowsiness, etc.), skin (disseminated nodules or lumps), mucous membrane (inflammation of the gums), vision (blurred vision, blindness), amongst others.

As well as the basic blood and bone marrow tests that are performed for all leukaemias, cytogenetic tests (to detect specific chromosome anomalies) and molecular diagnoses (to detect specific genetic alterations), are also performed since they are of fundamental importance for categorising and classifying the disease. Certain genetic and molecular alterations are associated with a greater or lesser response to therapy, or a greater or lesser risk of relapse.

Studies must also be conducted to determine whether the disease has spread to the central nervous system by performing a lumbar puncture in order to analyse the cerebrospinal fluid it contains.


The prognosis for childhood AML has improved significantly over recent decades. This improvement is the result, in part, of the better classification and stratification of each patient into risk groups, which is to say, according to each individual's risk of relapse. This stratification makes it possible to apply adapted therapeutic strategies whereby more intensive therapies are employed for patients presenting high-risk prognostic factors, and lower-level therapies for those considered to have a low risk of relapse.

The final aim of the treatment is to achieve complete remission from the disease and that this remission be profound (at the molecular level) and permanent.

A distinction is to be drawn between two phases of treatment: induction, and post-remission (or consolidation), therapies. The maintenance phase with low doses of chemotherapy, used in the protocols for acute lymphoblastic leukaemia, have been abandoned in most protocols for AML, being considered to offer no additional benefit, except in the case of the subgroup of acute promyelocytic leukaemia (see below).

Treatment for childhood AML is always based on intensive chemotherapy; the intravenous administration of various cytostatic drugs (chemotherapy) over various courses of treatment. Normally, although this can vary according to the protocol being followed, 1 or 2 induction courses are administered, followed by 2-3 courses of consolidation.

The aim of the induction therapy is to eliminate the leukaemia cells in the blood, and most of the disease present in the bone marrow, thereby returning it to its normal function, something referred to as achieving complete remission. This clinical situation can usually be achieved after the first course of induction therapy, although it is sometimes necessary to administer two more courses of induction therapy to achieve this result. With the protocols currently in use, more than 85% of patients achieve complete remission after the induction therapy phase.

This is followed by post-remission, or consolidation, therapy, the aim of which is to eliminate any residual leukaemia cells (minimal residual disease), that could be responsible for a future relapse.

Chemotherapy specifically targeting the central nervous system directly must also be administered (intrathecal chemotherapy). These drugs are administered by means of lumbar puncture. The use of cranial radiotherapy has been removed from most protocols.

For some patients a transplant of hematopoietic progenitors (HPT) may be indicated as part of the consolidation treatment. Most present-day protocols no longer include autologous bone marrow transplant (from one's self) as part of the consolidation treatment for this disorder, but in cases in which it is indicated, it is recommended that the HPT be from a compatible donor, that is to say, an allogenic transplant, from either a related or a non-related donor.

HPT in cases of childhood AML is a subject that is under constant review. The indications for HTP for patients with AML during the first complete remission (patients who have not presented relapse) are controversial and are not the same in all countries. Generally speaking, this treatment is reserved for cases considered to be of high risk on account of the biological characteristics of the disease, or because of an unsatisfactory response to chemotherapy. Most patients who have suffered a relapse but achieve a second complete remission are candidates for HPT.


The chances for a cure are determined by the patient's characteristics, those of the disease (genetic/molecular alterations), the treatment administered and the patient's response to this treatment. In contrast with adults, when the patient's characteristics, such as advanced age or the co-existence of other disorders, may be of great importance, in the case of children, such factors are not relevant.

The rate of survival for children with AML has improved notably over recent years, approaching 65%. This improvement has been due to the increased intensity of chemotherapy, the improved classification of patients into risk groups, the implementation of more effective support measures such as better antibiotics, the ease with which blood and platelet transfusion may be sought, help with diet and specialised nursing, as well as a notable improvement in the selection of donors for carrying out HPT

New therapeutic strategies

Over recent years progress has been made in more personalised treatments that take into account the characteristics of each individual and those of the disease (genetic subtype, molecular subtype, etc.). Research in this field is very active and it is not surprising therefore that new drugs have been developed for these diseases. Most of them still do not form part of the established protocols for treatment, but many of them are, nevertheless, in advanced phases of clinical use.

Notable amongst the various lines of development for new drugs are:

New chemotherapeutic drugs. These act in a similar way to existing drugs, but are more effective and/or less toxic. For example, daunorubicin liposomal enables high doses of treatment to be administered, which are consequently very effective, while being of low toxicity for the heart, one of the main drawbacks of drugs in this group.

Targeted therapies. These are drugs that target specific components of the cancer cells and they have less impact on healthy cells. Notable amongst this group are:

— Monoclonal antibodies. These combine an antineoplastic drug with an antibody that recognises the proteins of a cancer cell. The identification of cytogenetic molecular alterations in most of the patients suffering from AML has made it possible to develop new drugs which, through various mechanisms, act on these specific 'molecular targets' and are consequently very selective of cancer cells.

— Immunotherapy. Immunotherapy takes advantage of the immune system itself to act against leukaemia cells. Over recent years it has become one of the main fields of research but currently has little application with regard to AML.

Specific subtypes

Acute promyelocytic leukaemia

One of the leukaemias to have most benefited from a strategy of individualised therapy is acute promyelocytic leukaemia. Over recent decades, thanks to scientific research, there has been a considerable improvement in its treatment and, whereas it was once an AML subtype with a very poor prognosis, it is now a disease that responds very well to treatment. This kind of leukaemia is characterised by translocation between chromosomes 15 and 17 [t(15:17)] that affects the retinoic acid receptor alfa (RARα o RARA) making it highly sensitive to treatment with all-trans retinoic acid (ATRA).

Patients with Down syndrome

Children with Down syndrome have 15 times more risk of developing an acute leukaemia. In the case of AML, the disease usually appears before the age of 5 and the subtype is characteristically acute megakaryoblastic leukaemia (M7, according to the FAB classification) or acute erythroid leukaemia (M6, according to the FAB classification).

This group of patients presents a high sensibility to chemotherapy and that means that the rates of cure are high. One of the main difficulties for achieving a cure is the high level of toxicity of some of the chemotherapy drugs, and a high risk of infection. It has therefore been possible to increase the rate of cure for some groups with adapted treatment protocols.

Up to 10% of children with Down syndrome present a transient proliferation of leukaemia cells during the first months of life. These cells are morphologically indistinguishable from AML. This phenomenon is known as transient myeloproliferative syndrome or transient abnormal myelopoiesis. It usually presents a benign course and spontaneously regresses during the first months of life, although some patients may require treatment with low doses of cytostatics. Subsequent monitoring is important since 20% of these infants develop an AML during the first three years of life.

Juvenile myelomonocytic leukaemia (JMML)

JMML is a childhood leukaemia that appears during the first years of life. It is classified as a myeloproliferative/myelodysplastic syndrome. It is a very rare disease with an incidence of 1.2 cases per million children under the age of 15.

80% of patients with this disease present a mutation in characteristic genes (PTPN11, RAS, NF1 and CBL).

The only treatment that has been shown to increase the chances of survival (up to 50%) is HPT. Chemotherapy before the transplant may be indicated for some patients. Azacytidine, at the clinical trial phase for this disease, has proved to be effective. Certain genetic disorders (Noonan syndrome) have a tendency to present a transient process, similar to JMML, which does not require any treatment.

'My brother has cancer'. Visit this article in our BLOG.

Links of interest concerning medical issues relating to childhood acute myeloid leukaemia

For more quality information about childhood acute myeloid leukaemia you can consult the following websites:


Links of interest about other general issues that may be of interest for patients with childhood acute myeloid leukaemia

There are other resources and links of interest that may be of use to patients with childhood acute myeloid leukaemia:

Help and support

On our website you will also find the testimonies of people who are suffering, or who have suffered, from this disease. We would also like to invite you to follow us on our main social networks (Facebook, Twitter and Instagram) where we often share patients' accounts of overcoming the disease.

You can also check other interesting links here.

If you are resident in Spain, you can also contact us via email so that we can help put you in contact with other families who have overcome this disease.

You will find many other topics of interest about diet, fertility, treatments, etc., on our BLOG 'Unstoppable against leukaemia'.

Webpage updated 12/01/2023 13:27:05