Leukemia: Symptoms, Types

Brief overview

• Symptoms: Fatigue and exhaustion, decreased performance, skin pallor, tendency to bleed and bruise (hematoma), tendency to infection, fever of unknown cause, weight loss, night sweats.
• Common forms: Acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL; actually a form of lymphoma)
• Treatment: Depending on the type and stage of leukemia, treatment options include chemotherapy, tyrosine kinase inhibitors, interferons, monoclonal antibodies, radiation therapy and/or stem cell transplantation.
• Prognosis: Acute leukemia is often curable if detected and treated in time. In chronic leukemia, therapy may prolong survival for many patients. Cure is possible at most through a high-risk stem cell transplant.
• Diagnosis: The physician takes the patient’s medical history and performs physical examinations. In addition, ultrasound examinations, magnetic resonance imaging (MRI), computer tomography (CT), scintigraphy, blood tests, tissue samples (biopsy, bone marrow puncture) and examination of the spinal fluid (lumbar puncture) are performed.
• Prevention: There is little to no prevention of leukemia. However, a healthy lifestyle minimizes the risk of developing the disease. Regular preventive examinations, for example, can clarify unspecific signs in good time.

What is leukemia?

The term leukemia refers to a group of cancers of the blood-forming system – also called “white blood cancer” or “leukosis”. Leukemias occur when white blood cells (leukocytes), which arise in the bone marrow from special stem cells, develop defectively and subsequently multiply uncontrollably.

These defective leukocytes are non-functional and, in the course of the disease, increasingly displace the healthy white and red blood cells (erythrocytes) and the blood platelets (thrombocytes).

The development of blood cells proceeds in stages, with each step initially producing a so-called immature precursor cell. Each of the different types of white blood cells matures from its own precursor cell. Disruption of this cell maturation is possible at each individual stage. Therefore, there are different forms of leukemias or blood cancers. None of the different types of leukemia is contagious.

Leukemia: Frequency

Leukemia: Symptoms

Many affected people wonder how leukemia manifests itself or how blood cancer can be recognized. In some cases, leukemia or blood cancer in adults, whether men or women, suddenly becomes apparent with symptoms and progresses rapidly. Doctors then speak of acute leukemia. In other cases, the blood cancer develops slowly and insidiously. Then it is a chronic leukemia.

Symptoms of acute leukemia

In acute leukemia, symptoms develop relatively quickly. Initial symptoms or first signs in both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) include:

• Decreased performance
• Persistent fever
• Night sweats
• Fatigue
• Weight loss
• Bone and joint pain (especially in children with ALL)

Over time, the body of affected individuals produces increasing amounts of immature, nonfunctional white blood cells that crowd out the healthy blood cells. This causes more signs of leukemia accordingly. If there are too few red blood cells, this leads to anemia. Those affected suffer from, for example:

In the event of an injury, it takes longer than usual for a wound to stop bleeding. In addition, people with leukemia or blood cancer get more bruises (hematomas), which look like bruises after a strong impact and form mainly on the legs, i.e. thighs, shins and ankles – another typical sign of blood cancer.

Blood cancer or leukemia also manifests itself through other symptoms on the skin or through skin changes. In cases of severe platelet deficiency (thrombocytopenia), for example, there are punctiform bleedings in the skin, so-called petechiae, which appear as red spots or dots on the skin. However, these should not be confused with red birthmarks. It is not uncommon for the bleeding into the skin in leukemia to be accompanied by itching of the skin.

Leukemia often weakens the immune system. As a result, patients suffer from persistent infections such as poorly healing inflammations in the oral cavity. The reason for this is that the body has too few functional white blood cells, which in turn serve to fight off infections. The immune system in leukemia is therefore weakened overall.

Other possible leukemia symptoms are:

According to traditional Chinese medicine (TCM), a black tongue indicates an immune deficiency or cancer such as leukemia. However, there is no scientific evidence for this.

As with other cancers, symptoms usually increase and worsen in the final stages of acute leukemia.

Symptoms of chronic leukemia

Chronic leukemia begins insidiously. For the first few months or even years, many patients have no symptoms at all. Some report only general symptoms such as fatigue and decreased performance. However, most of those affected do not initially recognize these as signs of leukemia. That is why they do not go to the doctor. Only at an advanced stage do symptoms develop in chronic leukemia that resemble an acute course.

In chronic myeloid leukemia (CML), a distinction is made between three phases in which the disease becomes increasingly aggressive. This is also reflected in the leukemia signs:

• Chronic phase: Here the number of white blood cells is abnormally increased (leukocytosis) and the spleen is enlarged (splenomegaly). The latter often causes a feeling of pressure in the left upper abdomen. Other leukemia symptoms in this phase include fatigue and reduced performance.

• Blast crisis (blast relapse): In this final phase of disease, the bone marrow releases large amounts of immature precursors of blood cells (called myeloblasts and promyelocytes) into the blood. This causes symptoms similar to those of acute leukemia. In most cases, patients soon die.

Chronic lymphocytic leukemia (CLL) also progresses slowly. Although the term “leukemia” is in the name, however, it is not a blood cancer, but a special form of lymphoma (malignant lymphoma).

Leukemia: Types

Leukemias are classified not only according to how quickly the disease progresses (acute or chronic), but also according to the cell type from which they originate (myeloid or lymphoid).

Accordingly, physicians distinguish different types of leukemias. The four most common forms are:

Leukemia form	Notes
Acute myeloid leukemia (AML)
Chronic myeloid leukemia (CML)
Acute lymphoblastic leukemia (ALL)
Chronic Lymphocytic Leukemia (CLL)

In addition, there are other types of leukemia that are very rare. One example is hairy cell leukemia.

Myeloid leukemia

Myeloid leukemias originate from the so-called myeloid progenitor cells in the bone marrow. These precursor cells normally develop into healthy red blood cells, platelets, and granulocytes and monocytes. The latter two are subsets of white blood cells.

However, when myeloid precursor cells degenerate and begin to grow uncontrollably, myeloid leukemia develops. Depending on its course, physicians distinguish between acute myeloid leukemia (AML) and chronic myeloid leukemia (CML). Both forms of blood cancer mainly affect adults. AML is much more common than CML.

You can read more about the two forms of myeloid blood cancer in the article Myeloid Leukemia.

Lymphatic leukemia

Lymphatic leukemias originate from different blood cell precursors than myeloid blood cancers: Here, the so-called lymphatic precursor cells degenerate. They give rise to the lymphocytes. This subgroup of white blood cells is very important for the targeted (specific) defense against foreign substances and pathogens (specific immune defense).

You can learn more about these two cancers in the article Lymphocytic Leukemia.

Hairy cell leukemia

Hairy cell leukemia (or hairy cell leukemia) is a very rare cancer. The same applies to it as to chronic lymphocytic leukemia: the name “leukemia” only indicates that the disease is like blood cancer. However, it is classified as lymphatic cancer (more precisely, as non-Hodgkin’s lymphoma).

The name “hair cells” comes from the fact that the cancer cells have hair-like extensions.

Hairy cell leukemia only occurs in adults. Men suffer from it significantly more often than women. The chronic disease is not very aggressive. Most patients have a normal life expectancy.

You can read everything important about this cancer in the article Hairy Cell Leukemia.

Leukemia in children

Leukemia is primarily a disease of adults: They account for about 96 percent of all patients. When leukemia develops in children, it is almost always acute lymphoblastic leukemia (ALL). Acute myeloid leukemia (AML) follows in second place. Chronic leukemias are very rare in children.

You can learn everything important about blood cancer in children in the article Leukemia in children.

Leukemia: Treatment

Leukemia treatment is adapted to the individual. Various factors play a role. In addition to the age and general health of the affected person, it is primarily the course of the disease, i.e. whether the leukemia is acute or chronic.

Treatment of acute leukemia

After the diagnosis “acute leukemia”, chemotherapy is usually started as soon as possible. This is considered the most important method of treatment for acute blood cancer. The patient is given special drugs known as cytostatics (chemotherapeutic agents). They prevent cancer cells (and other rapidly dividing cells) from growing. The damaged cells also do not multiply further. The body’s own control mechanisms recognize the diseased cells and break them down in a targeted manner.

Basically, the therapy proceeds in three phases, which together can extend over months and years:

1. Induction therapy: those affected receive strong chemotherapy that eliminates as many cancer cells as possible and alleviates the most severe symptoms. Treatment is usually given as an inpatient in a hospital.
2. Consolidation therapy: This is designed to “solidify” the success of induction therapy. Appropriately tailored chemotherapy eliminates any remaining cancer cells, if possible.
3. Maintenance therapy: The aim here is to stabilize the success of treatment and prevent a relapse (recurrence). Maintenance therapy varies greatly from person to person. In this phase, patients often take cytostatic drugs such as azacitidine in tablet form for at least a year.

Induction therapy is sometimes so successful that practically no more cancer cells can be detected in the patient’s blood and bone marrow. Doctors then speak of remission. However, this does not mean that the leukemia has been cured. It is possible that individual cancer cells have survived. Therefore, further therapy steps (consolidation therapy) are necessary.

Other therapy options

Sometimes a stem cell transplant is also part of the leukemia treatment. Stem cells are the “mother cells” from which all blood cells are produced in the bone marrow. Before the transplant, it is necessary to destroy virtually all of the diseased person’s bone marrow and (hopefully) all of the cancer cells with high-dose chemotherapy (and possible total body irradiation).

Then the doctor transfers healthy stem cells as in a transfusion. The cells settle in the marrow cavities of the bones and produce new, healthy blood cells.

For such a stem cell transplant, the transferred stem cells often come from a healthy donor (allogeneic stem cell transplant). This can be a family member or a stranger.

To obtain the stem cells from the blood, blood is taken from the donor through the arm vein. In the so-called cell separator, the blood stem cells are filtered out of the blood (stem cell apheresis). The blood is then returned to the donor. The leukemia patient then receives the healthy blood stem cells. Stem cell donation takes only a few hours and is usually done on an outpatient basis without anesthesia. In rare cases, doctors remove the donor’s stem cells from the bone marrow under general anesthesia.

Many patients with acute lymphoblastic leukemia (ALL) receive radiation therapy in addition to chemotherapy. On the one hand, the physician irradiates the head as a preventive measure, since the cancer cells more frequently attack the brain. On the other hand, he uses radiation to specifically treat malignant lymph nodes, for example in the breast area.

Treatment of chronic leukemia

Doctors usually diagnose chronic myeloid leukemia (CML) in the chronically stable phase of the disease. The doctor then most often prescribes so-called tyrosine kinase inhibitors (such as imatinib, nilotinib, bosutinib or dasatinib). These drugs act very specifically against blood cancer cells: They inhibit growth signals in the cells. Ideally, this stops the disease for many years. The tyrosine kinase inhibitors are available as oral tablets, which patients usually take for the rest of their lives.

At the same time, the doctor regularly checks the blood and bone marrow. If, for example, the blood values or the patient’s condition deteriorate, this indicates that the CML is moving into the next phase (acceleration phase). The physician then changes the drug treatment: he prescribes other tyrosine kinase inhibitors. In this way, the disease can be returned to a chronic stable phase in many patients.

At any stage of the disease, it is possible for the condition of a patient to deteriorate significantly within a short period of time. Doctors then speak of a blast crisis. As in the case of acute leukemia, those affected usually receive intensive chemotherapy. In this way, doctors try to quickly reduce the signs of the disease. Once the condition has improved and stabilized, a stem cell transplant may be appropriate.

Some patients with CML are treated with interferons. These are messenger substances with which the cells of the immune system communicate with each other. They are able to inhibit the growth of cancer cells. However, interferons – like chemotherapy – are usually less effective in CML than the tyrosine kinase inhibitors described above.

This is not always true, however: tyrosine kinase inhibitors work best in patients whose cancer cells possess the so-called “Philadelphia chromosome”. This is the name given to a characteristically altered chromosome 22, which can be detected in more than 90 percent of all CML patients. The remaining patients do not have the altered chromosome. This is why treatment with tyrosine kinase inhibitors often does not work so well for them. It is then sometimes necessary to change the therapy and use interferons, for example.

For example, many patients receive chemotherapy plus so-called monoclonal antibodies (immunochemotherapy or chemoimmunotherapy). The artificially produced antibodies bind specifically to the cancer cells, thereby marking them for the immune system. Physicians occasionally use both forms of therapy separately.

If the cancer cells exhibit certain genetic changes, treatment with tyrosine kinase inhibitors may be useful. These drugs block a pathologically altered enzyme that promotes the growth of cancer cells.

If other treatments do not work or if there is a later relapse, (allogeneic) stem cell transplantation is sometimes an option. However, this risky treatment is only suitable for young people or people whose general health is good.

Accompanying measures (supportive therapy)

In addition to leukemia treatment with chemotherapy, radiation therapy and others, supportive measures are also very important. They serve, for example, to reduce symptoms of the disease and consequences of the treatment. This improves the patients’ well-being and quality of life enormously.

Increased susceptibility to infections is also a serious problem in leukemia. Both the disease itself and the chemotherapy weaken the immune system, making it less able to fight pathogens. This favors infections, which are then sometimes very severe, sometimes even life-threatening. For this reason, careful hygiene and an environment that is as germ-free as possible are very important for people with leukemia.

Many also receive antibiotics to prevent or treat bacterial infections. Active substances against fungal infections are known as antifungals.

Other complaints can also be treated specifically, for example anemia by means of a blood transfusion and pain with suitable painkillers.

Nutrition in leukemia

In principle, experts advise a diet that is as gentle as possible in order to avoid complaints such as nausea and vomiting. A diet that is very high in meat is often stressful, which is why vegetables and fruit are more suitable in leukemia. It is important to eat a balanced diet and avoid animal fats.

Leukemia: course and prognosis

In individual cases, the prognosis for leukemia depends on various factors. First and foremost are the type of cancer and the stage of the disease at the time of diagnosis. Depending on whether the leukemia is in the initial or final stage, there is a clear difference in what happens or how the disease develops. How well the patient responds to therapy also has an impact on prognosis.

Other factors that influence life expectancy and chances of cure in leukemia are the patient’s age and general condition, as well as any concomitant diseases.

Chances of cure

Is leukemia curable? How does one die from leukemia? Does acute leukemia mean a quick death? These and other questions are asked by many patients and their relatives. In principle, in the case of acute leukemia, the blood cancer is curable. The earlier the leukemia is discovered and treated, the greater the chances of cure and survival. This is especially true for younger patients. However, a cure is not likely without treatment such as chemotherapy.

Even if the cancer can be pushed back, a relapse (recurrence) often occurs later, even months and years later. Especially in the case of an early relapse, the chances of cure decrease. Leukemia patients then have to be treated again. Sometimes doctors choose a more aggressive therapy or other treatment methods.

In chronic leukemia, the cancer cells multiply more slowly than in acute forms of cancer (exception: blast crisis in CML) – and usually for years. For this reason, treatment is usually less intensive, but must be continued over the long term.

Although chronic leukemia cannot generally be cured (the only chance of this is in the case of risky stem cell transplantation), in many patients the therapy alleviates the symptoms and slows down the progression of chronic leukemia. Thus, the life expectancy of chronic leukemia is somewhat higher than that of the acute form. Nevertheless, chronic leukemia is also fatal in some cases.

Exactly how high the life expectancy is for the different types of blood cancer, i.e. acute or chronic leukemia, depends on the age at which the disease develops and cannot be determined in general terms.

Leukemia: examinations and diagnosis

The first point of contact when blood cancer is suspected is the family doctor. If necessary, he or she will refer the patient to a specialist, for example, a specialist in blood diseases and cancer (hematologist or oncologist).

Medical consultation and physical examination

The doctor first takes the patient’s medical history (anamnesis). This involves asking how the person feels in general, what complaints he or she has and how long these have existed. Information about any other illnesses that are currently present or have occurred in the past is also important. In addition, the doctor inquires, for example, about medications the person is taking and whether there are any known cases of cancer in the family.

This is followed by a thorough physical examination. Among other things, the doctor listens to the lungs and heart, measures blood pressure and feels the liver, spleen and lymph nodes. The results help the doctor better assess the patient’s general condition.

Blood test

Depending on how high the value for leukocytes is, it may be possible to conclude that leukemia is present. In the case of leukemia, it is rather unlikely that there are too many red blood cells.

Furthermore, the doctor determines the so-called MCH value, which indicates how much hemoglobin (Hb, “red blood pigment”) the individual red blood cells carry. Hemoglobin is particularly important because the iron it carries carries oxygen through the blood to all tissues and organs.

For example, if the MCH level is lower than normal, this indicates anemia. However, since there may be other reasons for anemia, physicians who suspect leukemia use an iron serum test to determine whether iron deficiency anemia is present, for example. In this case, the iron level in the blood would be significantly lower than normal. In leukemia, it is possible for iron to accumulate in the blood without being incorporated into hemoglobin. There is then too much iron in the blood – a high iron value is present.

Pathologically altered blood values such as an increased number of white blood cells and too few red blood cells are a possible indication of leukemia. However, abnormal blood values are also typical of many other diseases. Therefore, further differential diagnostic tests are usually required.

Every blood test that clarifies a blood disease also includes the determination of the erythrocyte sedimentation rate (ESR). The sedimentation rate indicates how quickly the red blood cells sink in a non-coagulable fluid. This in turn provides information about whether, for example, an inflammation or other serious disease is present. In leukemias, the blood sedimentation rate is usually significantly elevated.

In addition to the blood cells, the doctor assesses other blood parameters in the laboratory, such as kidney values and liver values. These values indicate how well these two organs are working. If leukemia is confirmed later on and the patient’s kidney and/or liver values are poor, this must be taken into account when planning treatment.

The laboratory also checks whether there are signs of infection with bacteria, viruses or fungi in the blood. These germs may also be responsible for some symptoms, such as an increased white blood cell count, fever and fatigue.

Whenever leukemia is suspected, it is necessary to examine the patient’s bone marrow in detail. To do this, the doctor takes a bone marrow sample under local anesthesia using a special needle, usually from the pelvic bone (bone marrow puncture). In the laboratory, the physician examines the number and appearance of the bone marrow cells. In the case of typical changes, leukemia can be clearly detected.

An indication of anemia caused by leukemia is, for example, an increased number of reticulocytes. These are precursor cells of the red blood cells. Experts suspect that the body tries to counteract the lack of erythrocytes by producing more reticulocytes.

Sometimes the bone marrow tissue can even be used to determine the form of the disease. In addition, the physician examines the cells for changes in their genetic material. For example, there is the “Philadelphia chromosome” in chronic myeloid leukemia.

Adults and older children usually receive a local anesthetic before the bone marrow is harvested. For younger children, a brief anesthetic is appropriate. The procedure usually takes about 15 minutes and can be performed on an outpatient basis.

Further examinations

For example, the doctor examines internal organs (spleen, liver, etc.) using ultrasound. He may also perform a computed tomography (CT) scan. This imaging procedure is suitable for additionally assessing the bones. This is important if the doctor suspects that the cancer cells have spread not only in the bone marrow, but also in the bone itself. Other examination methods include magnetic resonance imaging (MRI) or scintigraphy.

In acute lymphoblastic leukemia (ALL) and some subtypes of acute myeloid leukemia (AML), cancer cells sometimes affect the brain or meninges. Possible signs of this are headaches as well as neuronal deficits such as visual disturbances and paralysis. The doctor then takes a sample of the spinal fluid (lumbar puncture) and analyzes it in the laboratory. An MRI is also helpful in detecting cancerous involvement of the brain.

Leukemia: Causes and risk factors

The causes of the various forms of blood cancer have not yet been clearly established. However, experts have identified several risk factors that promote the development of leukemia. These include:

Age: The development of acute myeloid leukemia (AML) is influenced by age: The risk of developing the disease increases with age in acute leukemia. The same is true for chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). In contrast, acute lymphoblastic leukemia (ALL) occurs mainly in childhood.

Smoking: Smoking is responsible for about ten percent of all leukemia cases, experts estimate. For example, active smokers are 40 percent more likely to develop acute myeloid leukemia (AML) than people who have never smoked. In former smokers, the risk of contracting the disease is still 25 percent higher.

Ionizing radiation: This refers to various high-energy rays, for example radioactive rays. They damage the genetic material – especially in those body cells that divide frequently. These include the hematopoietic cells in the bone marrow. As a result, leukemia sometimes develops. The higher the dose of radiation that affects the body, the greater the risk of leukemia.

X-rays are also ionizing. However, experts believe that an occasional X-ray examination will not cause leukemia. Nevertheless, X-rays should only be taken if absolutely necessary. This is because the damage that the rays do to the body usually adds up over the course of a lifetime.

Chemical substances: Various chemical substances increase the risk of leukemia. These include benzene and other organic solvents. Insecticides and herbicides are also suspected of promoting blood cancer.

This connection is confirmed for certain drugs that are actually used to treat cancer (such as cytostatics): in the long term, they promote the development of leukemia. Before they are used, doctors therefore carefully weigh up the benefits and risks of such drugs.

Viruses: Certain viruses (HTL viruses I and II) are involved in the development of a very rare form of leukemia. This so-called human T-cell leukemia mainly affects people in Japan. In Europe, this blood cancer variant is very rare.

Other forms of leukemia such as AML, CML, ALL and CLL develop without any involvement of viruses or other pathogens, according to current knowledge.

Leukemia: Prevention

Since the actual causes of leukemia are largely unclear, few if any preventive measures can be defined. Doctors advise minimizing the risk factors. A healthy lifestyle and abstaining from tobacco and excessive alcohol, for example, can already help. Especially if you are older, take advantage of regular preventive checkups. In this way, for example, early, unspecific signs can be clarified in good time.