Acute myeloid leukemia (aml)

Acute myeloid leukemia (AML) is a malignant disease that starts from immature precursors of red blood cells, platelets and some white blood cells. AML is the most common form of acute leukemia in adults. Thanks to the intensive research work of the last decades, the treatment options and healing chances have improved significantly. Therefore, the diagnosis of AML should not lead to hopelessness. A previously incurable disease has become curable in many cases!

Acute myeloid leukemia (AML) is a malignant disease of the hematopoietic system (blood cancer) in which an early precursor of a myeloid cell degenerates and multiplies uncontrollably. Myeloid cells include red blood cells, platelets and part of the white blood cells. In healthy people, the multiplication and renewal of blood cells is strictly regulated. In AML, this process is out of control:
Due to the changes in the genetic material, the affected cell begins to divide and multiply unchecked, but without developing into normal, functional blood cells. The resulting cells are called myeloid blasts designates. They spread rapidly in the bone marrow, where they interfere with the formation of healthy blood cells. Through the blood, the blasts can eventually be distributed throughout the body, affecting and damaging other organs.

Causes and frequency

Acute myeloid leukemia is not a hereditary disease and, like other forms of cancer, is neither contagious nor can it be transmitted to other people. AML is caused by malignant genetic changes in the bone marrow that are acquired during a person’s lifetime. Risk factors for this are ionizing radiation and certain chemical substances. Also, some drugs that are themselves used to treat cancer can, in rare cases, trigger so-called secondary AML years later. Patients with various diseases of the blood or bone marrow (z.B. With myelodysplastic syndrome) or genetic conditions such as Down syndrome also have an increased risk of developing AML. In the vast majority of cases, however, it remains completely unclear what has triggered the disease.

Acute myeloid leukemia is one of the most common forms of leukemia in the world, with 3.5 new diagnoses per 100 patients per year.000 inhabitants a rare disease, but the most frequent form of acute leukemia in Germany. Men are affected slightly more often than women. Unlike ALL, which occurs predominantly in children, AML is a disease of the elderly – about half of patients are over 70 years of age.

Symptoms

The symptoms of AML usually develop within a few weeks. They are caused on the one hand by a lack of normal blood cells and on the other hand by the infestation of organs with myeloid blasts.

very common symptoms

anemia (anemia, reduction of red blood cells) leads to pallor, fatigue, exhaustion, reduced performance, shortness of breath, general weakness and malaise
Fever and/or increased Susceptibility to infection by a reduction of the white blood cells (leukopenia)
abdominal pain and Loss of appetite By enlargement (organ infestation) of the spleen and/or liver
Increase in leukocytes (leukocytosis) due to overproduction of lymphoid blasts

common symptoms

Decrease in platelets (thrombocytopenia) caused by the overproduction of lymphocytic blasts Bleeding (small pinpoint bleeding on the skin (petechiae), bruises, nosebleeds, prolonged bleeding z.B. after a visit to the dentist or after injuries, prolonged menstrual bleeding in females, rarely also cerebral hemorrhages)
lymph node swellings on the neck, in the armpits or in the groin
joint and bone pain due to the spread of blasts into the bone

rare symptoms

Involvement of the brain, spinal cord or meninges with neurological changes such as headaches, visual disturbances, vomiting or nerve paralysis
Skin changes and chloromas (deposits of blasts z.B. in the skin or bone marrow)
Shortness of breath

Some patients have hardly any symptoms and the leukemia is discovered by chance during a routine blood test.

All the symptoms described also occur in the context of other, comparatively harmless diseases and in most cases have nothing to do with leukemia. However, if symptoms persist, it is advisable to have the cause clarified by a physician. If acute myeloid leukemia is actually present, therapy must be started as soon as possible.

Diagnosis of AML

If leukemia is suspected, extensive examinations of the blood and bone marrow are necessary first to confirm the diagnosis and then to determine the type of leukemia. In addition, the extent of the disease is determined with the help of so-called imaging procedures.

If the family doctor/internist finds indications of acute leukemia on the basis of the medical history and physical examinations, he will first examine the blood. If this confirms the suspicion of leukemia because z.B. If immature cells are found in the blood and anemia or thrombocytopenia is present, the diagnosis must also be confirmed by analysis of the bone marrow. Such examination is performed at a specialized hospital by a specialist in blood and cancer diseases (hematologist/oncologist). Bone marrow is removed from the hip bone or sternum with a syringe under local anesthesia (bone marrow puncture). This short, outpatient procedure can be somewhat uncomfortable for the patient, as it takes a few minutes for the bone marrow to enter the syringe.

The subsequent laboratory examinations of the bone marrow include the biological properties, external cell characteristics and genetic changes of the affected cells. In addition to the type of leukemia, the analysis can also be used to determine the exact subtype of the disease. Because subtypes of acute myeloid leukemia differ markedly in their disease course, prognosis, and response to various therapies, detailed examination of the bone marrow is critical to developing an appropriate plan for treatment.

If AML is diagnosed, additional examinations are necessary, depending on the individual case, in order to be able to exclude the infestation of other organs of the body with blasts. This includes chest x-rays, computerized tomography, and ultrasound of the abdomen and heart. In exceptional cases, a sample is taken from the spinal fluid (lumbar puncture) to determine whether there is leukemia in the brain.

In the further course after the start of therapy, bone marrow punctures and other control examinations are always necessary. Thus z.B. check by MRD diagnostics whether the leukemia has completely regressed (remission).

Classification of AML

Acute myeloid leukemia is not a single disease, but rather a group of different subtypes that can be distinguished from one another based on their biological characteristics, external cellular features, and genetic alterations. The assignment to a certain subtype plays an important role for the therapy decision, since the different subtypes differ in terms of the course of the disease and the chances of recovery (prognosis) and are differently sensitive to chemotherapy. Basically, a distinction is made between primary and secondary AML: If the AML occurs independently and without previous bone marrow or cancer, it is called primary or de novo AML. Secondary AML develops from another bone marrow disease (z.B. a myelodysplastic syndrome) or arises as a result of earlier chemotherapy or radiation therapy. Since secondary AML is usually associated with multiple genetic alterations, it has a worse prognosis than primary AML.

The classification of AML is nowadays mostly based on the WHO classification. This combines the older FAB classification, in which blasts are divided into eight subgroups (M0-M7) according to their external, microscopically visible features, with genetic features of leukemic cells. The external characteristics as well as the underlying genetic alterations can be determined using comparative laboratory tests such as microscopy, cytochemistry, immunophenotyping, molecular genetics, cytogenetics or in situ hybridization.

Acute promyelocytic leukemia (APL)

Acute promyelocytic leukemia (APL) is a rare subtype of AML that is diagnosed in about 5% of AML patients. A particular genetic alteration called a translocation t(15;17) can be detected in this disease. It leads to the formation of the defective protein PML-RARA, which is causally involved in the development of the disease. APL plays a special role with regard to the course of the disease, prognosis and treatment. The disease occurs mainly in younger patients and is associated with a good prognosis: Combining chemotherapy with all-trans retinoic acid (ATRA), which stimulates leukemia cells to mature, more than 75% of patients can be cured today. However, treatment in a specialized leukemia center is a prerequisite, because APL often causes blood clotting disorders and is therefore associated with a high rate of bleeding complications.

Treatment of acute myeloid leukemia

AML is a serious disease that, if left untreated, can lead to death within a few weeks. Therefore, it is extremely important that therapy is started immediately after diagnosis. The most important part of treatment is chemotherapy with adjunctive therapy to treat the side effects. Bone marrow transplantation may be added to this in individual cases. Radiation therapy plays a minor role in AML. All components of the therapy serve to kill the leukemia cells everywhere in the body as completely as possible, so that the bone marrow can resume its original function – blood formation.

It is imperative that treatment for AML be performed at a clinic experienced in the treatment of leukemias – especially AML. The clinic should have access to the latest research and be able to carry out necessary special examinations. You can find out more about choosing the right clinic here. Since treatment is lengthy and stressful, patients and their relatives should be fully informed about the planned procedure. The treating physician will talk in detail with the patient and inform him about all treatment options.

Chemotherapy

In chemotherapy, a patient receives drugs called cytostatics that specifically inhibit the growth of leukemia cells. Since a single drug is usually not sufficient to destroy all blasts, several drugs with different modes of action are combined. They are given as infusions, injections or in the form of tablets. Chemotherapy is divided into several cycles, which are separated from each other by breaks (intervals) in which healthy cells can regenerate. Bone marrow and other affected regions are checked at regular intervals to assess the success of the therapy.

Stem cell transplantation

Another treatment option is stem cell transplantation. The goal of this therapy is to replace the diseased bone marrow with healthy bone marrow. In stem cell transplantation, purified blood stem cells from a matching donor (allogeneic) or, less commonly, from the patient himself (autologous) are administered to the patient by infusion. For a successful therapy, all leukemia cells must be killed first. This is achieved by means of strong chemotherapy and radiation, which destroys not only the blasts but also the healthy cells in the bone marrow. Since this is a stressful and high-risk therapy, the patient must be eligible for stem cell transplantation in terms of general condition and age. Stem cell transplantation is usually performed only when the characteristics of the leukemia cells indicate that there is a high risk of relapse or when chemotherapy has not been sufficiently successful.

Therapy studies

If possible, AML patients should be treated within the framework of therapy studies. The patient is given access to the latest scientific findings and is treated with innovative drugs and according to current treatment strategies. Participation in a study does not mean that the application of the drugs used is experimental. In fact, the goal is to improve AML treatment strategies in the future. The decision as to which study is suitable for a patient must be discussed intensively with the attending physician. Various criteria play a role here z.B. disease characteristics, disease phase, pre-treatment, age and risk factors play a role. However, the final decision to participate in a study is always made by the patient himself. In Germany, numerous clinics participate in the studies of the German study groups for adult AML. The current studies can be found in the German Leukemia Study Register.

Treatment options in the event of a relapse

In the event of a relapse of AML, chemotherapy is first administered again. In late relapses, induction therapy can be repeated to achieve complete destruction of the leukemia cells (remission) again. In case of early relapses or if the disease does not respond to therapy (treatment failure), various options z.B. researched with new drugs within the framework of therapy studies. Here, it is important that the treating physicians are informed about all currently available therapy options. The goal is to achieve a complete remission. Often, if age and general condition permit and if a donor can be found, stem cell transplantation is performed.

Follow-up care

The number of cures for AML has steadily increased over the past few decades. However, regular follow-up examinations are necessary. They include a general physical examination as well as blood and bone marrow checks. The aim is to detect signs of relapse or late effects of the therapy at an early stage. As the time between diagnosis and the end of therapy increases, so do the intervals between examinations. The attending physician also advises on the possibility of a rehabilitation measure (Reha). It is usually funded by health insurance and offers a good transitional option to get back to a "normal" life.

Information brochure of the Leukemia Competence Network

The patient brochure on adult acute myeloid leukemia (AML) in the Competence Network Leukemia was developed in cooperation with the UCT Frankfurt and the Leukemia Aid Rhine-Main g.e.V. newly published. She takes into account the current state of research and explains the treatment options for adult AML. In particular, it contains edited information and interesting facts about adult AML for patients and relatives. Important content includes: Symptoms, diagnosis, treatment options and common questions about AML.

Printed brochures are available from the office of Leukamiehilfe Rhein-Main g.e.V. about [email protected] order.

Created by: Hehn (Information Center) on 25.07.2014, lastchange: 13.12.2017