Acute Myeloid Leukemia (AML)

Acute myeloid leukemia develops when immature myeloid precursor cells in the bone marrow go through genetic changes. These changes block normal maturation and growth control. Normally, stem cells and precursor cells mature step by step into functioning blood cells. These include granulocytes, monocytes, red blood cells, and platelets. In AML, a mutation or chromosomal change can occur in a single precursor cell. The cell then remains in an early, immature stage and multiplies without control. The resulting myeloblasts gradually displace normal blood formation in the bone marrow. This leads to too few healthy red blood cells, too few functioning white blood cells, and too few platelets. As a result, anemia, increased susceptibility to infections, and a tendency to bleed can occur.

The underlying genetic changes mainly affect genes that control cell growth, cell differentiation, and DNA repair. Growth signals may become permanently active, while maturation signals are blocked. In most cases, AML does not result from a single change. It usually develops through the interaction of several mutations. This process can take years before AML appears. It is not always possible to explain exactly why AML developed. However, several well-documented risk factors can increase the likelihood of genetic damage.

Age is an important factor. AML mainly occurs in older adults. With increasing age, spontaneous DNA damage becomes more common. The body may no longer repair this damage well enough. Clonal hematopoiesis also becomes more common with age. This means that certain mutations appear in blood-forming cells. These mutations can form the basis for later AML.

Classic external risk factors include higher exposure to ionizing radiation and certain chemical substances. These include benzene and long-term exposure to organic solvents. They can damage the DNA of stem cells and increase the likelihood of leukemia.

Therapy-related AML is also well documented. It can occur after chemotherapy or radiation therapy used to treat another cancer. Alkylating agents and topoisomerase II inhibitors are especially relevant. They can promote AML years after treatment because they may damage healthy bone marrow cells as well as tumor cells. In these cases, doctors often find characteristic chromosomal changes. These changes are typical of therapy-related leukemias.

There are also inherited genetic syndromes that clearly increase the risk of AML. These include Down syndrome, Fanconi anemia, Li-Fraumeni syndrome, and certain familial bone marrow disorders. In these conditions, DNA repair or cell growth regulation is already disturbed. This makes leukemia-related mutations more likely to develop and spread.

Another risk factor is a previous blood disorder. These include myelodysplastic syndromes, myeloproliferative neoplasms, and certain aplastic or chronic bone marrow disorders. A secondary AML can develop from these earlier conditions when further mutations occur. These forms often differ in prognosis and response to treatment.

The symptoms of acute myeloid leukemia mainly occur because leukemic blasts increasingly crowd out normal blood formation in the bone marrow. As a result, the body gradually has fewer healthy red blood cells, functioning white blood cells, and platelets. At first, the symptoms are often unspecific. They can easily be mistaken for exhaustion or infections. Typical signs include:

• increasing tiredness
• reduced performance
• paleness
• shortness of breath during mild exertion or palpitations

At the same time, the immune defense is weakened. This happens because the existing white blood cells do not work properly:

• frequent or unusually severe infections
• recurring fever
• colds that last longer than usual
• frequent pneumonia
• inflammation of the skin and mucous membranes

Another important group of symptoms is linked to a tendency to bleed. A lack of platelets can lead to spontaneous bruising, tiny pinpoint skin bleeding, nosebleeds, or bleeding gums. In more severe cases, stronger bleeding can occur. This may affect the gastrointestinal tract or happen after even minor injuries.

Symptoms can also occur when leukemic cells infiltrate other organs. For example, bone pain or back pain can occur because of increased cell production in the bone marrow. The spleen or liver may also become enlarged. This can cause pressure or a feeling of fullness in the upper abdomen. In some cases, lymph nodes may swell. Skin changes can also occur when leukemic cells settle outside the bone marrow.

Warning signs that should be watched carefully include:

• rapidly increasing exhaustion
• unexplained weight loss
• persistent fever without a clear cause
• frequent infections
• unusual bleeding or increased bruising without a clear cause

A combination of several of these symptoms over several weeks can be an important warning sign. It may suggest that blood formation in the bone marrow is disturbed. This should be checked by a doctor.

The diagnosis of acute myeloid leukemia is also made step by step. The aim is to confirm the disease, define the exact subtype, and create a basis for treatment. Diagnosis usually starts with a blood test. This helps doctors check possible differential diagnoses. The blood count often shows typical abnormalities. These include too few red blood cells and platelets, an altered number of white blood cells, and immature precursor cells in the blood. A blood smear is then usually prepared. Under the microscope, doctors may see blasts that suggest acute leukemia.

The final diagnosis and distinction from other forms of leukemia require a bone marrow examination. During this procedure, bone marrow is usually taken from the pelvic bone. It is then examined cytologically and histologically. A clear increase in myeloid blasts is typical of AML. These blasts displace normal bone marrow. Their appearance and staining properties can help identify the specific AML subtype. In addition, immunophenotyping is usually performed using flow cytometry. This test identifies surface and intracellular markers on the blasts. It helps confirm that the cells are myeloid and not part of a lymphatic leukemia.

Today, cytogenetic and molecular genetic tests are also performed. Chromosome analyses can detect typical genetic changes. These changes are important for selecting targeted treatment. Relevant examples include mutations in genes such as NPM1, FLT3, and IDH1/2, as well as certain chromosomal changes. Additional laboratory values can also be checked. They help assess possible organ involvement and organ function. This allows doctors to better estimate disease activity and related complications.

Depending on the clinical situation, imaging may also be used. This can include ultrasound diagnostics, X-rays, or CT scans. These methods can help assess enlargement of the spleen, liver, or lymph nodes. They can also help detect infection sites or organ infiltration.

The treatment of AML is complex, much like the diagnosis. It is always adapted to the individual patient. The main goal is to push back leukemic blasts in the bone marrow and stabilize normal blood formation again. In the long term, treatment aims for cure or at least stable disease control. Because AML can progress quickly, treatment usually begins soon after diagnosis.

Intensive chemotherapy is central to acute myeloid leukemia treatment. It is divided into several phases. During induction therapy, doctors try to achieve complete remission. This means reducing visible leukemia cells in the bone marrow to a level where they can no longer be detected by standard methods. Blood values should also return to normal. A combination of an anthracycline and cytarabine is usually used. If leukemia cells remain, further intensive treatment may be used. This can help reduce the remaining cells and lower the risk of relapse.

In younger and physically fit people, an allogeneic stem cell transplant may be useful. This procedure replaces diseased bone marrow with healthy donor cells. Stem cell transplantation is an intensive treatment. It may offer a chance of long-term disease control or cure in suitable cases.

Targeted therapies are also used more often today. They act on specific signaling pathways that are permanently activated by certain mutations in leukemia cells. These medicines are often combined with chemotherapy. In some cases, they may also be used alone. This is especially relevant for older people or people with other illnesses who cannot receive classic chemotherapy, or can only receive it to a limited extent.

Supportive therapy is another important part of AML treatment. It includes red blood cell and platelet transfusions, treatment and prevention of infections with antibiotics, and control of electrolytes and metabolic problems. It also includes measures against nausea, pain, and exhaustion. These accompanying treatments are very important. They help patients tolerate intensive therapy better and reduce complications.

In addition to conventional medical treatment, complementary medicine may be used as supportive care. Methods such as acupuncture, guided phytotherapy, relaxation methods, exercise, physiotherapy, and nutritional counseling may help relieve symptoms during AML treatment. The aim is to reduce nausea, pain, sleep problems, anxiety, and fatigue. They may also improve quality of life. Studies have shown that acupuncture can have positive effects on nausea, pain perception, nervousness, and well-being. These measures do not replace AML therapy. They can only complement it.

The acute myeloid leukemia prognosis depends on many factors. These include age, general health, other illnesses, genetic changes in the leukemia cells, and early response to treatment. Younger patients with favorable genetic risk profiles often have better chances of long-term remission or cure with modern therapies and, if needed, stem cell transplantation. In older people or people with other illnesses, the goal is often disease control, longer survival, and better quality of life. In some cases, cure may still be possible. Overall, AML treatments have improved in recent years. This is mainly due to the combination of classic chemotherapy, targeted medicines, and improved supportive care and follow-up. The key point is an individual treatment plan. It should consider the patient’s personal situation and include supportive measures for the body and mind.

The information listed contains relevant topics and serves to improve understanding.