When the physicist and Nobel Prize winner Marie Curie died in 1934, her blood was flooded by white blood cells. During her work as a researcher and the years of contact with radioactive substances, she had developed a leukemia. There are various causes and forms for the disease, which is also known as blood cancer. Learn here about these and you will be well versed in the popular examination topic Leukemia.

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Image: “CLL with Autoimmune Hemolytic Anemia” by Ed Uthman. Licence: CC BY 2.0

Image: “CLL with Autoimmune Hemolytic Anemia” by Ed Uthman. Licence: CC BY 2.0


This Disease Mechanism Leads to Leukemia

Leukemia occurs when the precursor cells of the leukocytes, ie the white blood cells, degenerate in the bone marrow. They begin to proliferate uncontrollably and are washed out into other lymphatic organs and the blood. This has two consequences. Firstly, that the flooded organs such as lymph nodes and spleen greatly increase, and secondly, that the precursors of normal blood cells are displaced in the bone marrow. This mechanism leads to anemia, thrombozytopenia and granulocytopenia with the corresponding consequences (weakness, hypoxia, tendency to bleed, and susceptibility to infections).

Note: Leukemia = pathological proliferation of the precursor cells of the white blood cells in the bone marrow with displacement of the precursor cells of the other blood cells.

Acute Leukemia

  • Disease of neoplastic leukocytes
  • Predominance of immature forms, especially blasts (myeloblasts or lymphoblasts) — disease defined > 20 % blasts in the bone marrow
  • Symptoms due to marrow failure secondary to leukemia infiltration causing pancytopenia — anemia, leukopenia, and thrombocytopenia

Etiology

  • Chromosomal abnormalities (e.g., Down Syndrome)
  • Ionizing radiation
  • Chemical exposure
  • topoisomerase agents (chemotherapy)
  • Age

Haematopoietic

hematopoietic

Classification of Leukemias

Leukaemias can be classified according to their rate of development (acute or chronic) and the prevailing cell type (leukemic or lymphatic). It is also possible to characterize whether the leukocyte count in the blood is altered or not (leukemic or aleukemic). The aleukemic form, ie without degenerated leukocytes in the blood, occurs only in the acute forms, not in the chronic forms. On the basis of this classification, four forms result.

Acute lymphocytic leukemia (ALL)

Acute lymphocytic leukemia is the most common type of leukemia in children (about 80%). The cause is usually unclear, but additional genetic syndromes such as trisomy 21 and chemical environmental toxins increase the risk. The ALL is distinguished by the fact that there are many different subtypes, which is why diagnostic immunophenotyping is necessary. This is a measurement of the surface markers of the leukocytes. The therapy, but also the survival depends on this subtype. Children have a higher survival probability than adults.

The symptoms are above all the typical changes that occur in the displacement of the other, “healthy” blood series in the bone marrow. These are frequent infections due to granulocytopenia, weakness and performance decline due to anemia and mucosal bleeding caused by thrombocytopenia. Especially in children, the leukemia cells can also infiltrate the skin and central nervous system, leading to brain nerve paresis and headache (so-called Meningeosis leucaemica).

Because of the great variability of the ALL, there is no uniform treatment. Above all, children and adolescents are treated in the course of studies. Depending on the risk factors (e.g., genetic or immunophenotypic characteristics), patients are divided into study groups. In addition to the symptomatic treatment of anemia and the other symptoms, chemotherapy attempts to push the degenerate cells back. In the case of a special risk or in the case of unsuccessful chemotherapy, bone marrow transplantation by a foreign donor can also be considered.

Note: Common in children, many subtypes (immunophenotyping necessary), bone marrow insufficiency (anemia, thrombocytopenia, granulocytopenia) in the foreground, therapy in study groups, intrathecal prophylaxis important.

Acute myelogenous leukemia (AML)

Image: "Gingivahyerplasia" by Lesion. Licence: CC BY-SA 3.0

Image: “Gingivahyerplasia” by Lesion. Licence: CC BY-SA 3.0

The causes of acute myelogenous leukemia are also often unclear. Known risk factors are ionizing radiation and exposure to benzene. It is the acute leukemia form of the adult, especially older adults in the 6th life decade and older are affected. Like ALL, this disease is characterized by the symptoms of bone marrow insufficiency. Rare to observe, but typical of this leukemia form, is the gingival hyperplasia.

The AML is subdivided into cytomorphological subtypes, named M0 to M7, by means of the FAB classification. Alternatively, there is a subdivision from the WHO. In approximately 30%, microscopic Auer rods are seen in the precursor cells of the leukocytes, the blasts, which are characteristic for the AML.

In the blood picture one often finds a so-called “Hiatus leucaemicus“, which means a lack of the middle development stages of the myeloid series. This characteristic is absent in chronic myelogenous leukemia. As with the ALL, the therapy is an intensive chemotherapy, which is to suppress the blasts, with the option for stem cell transplantation. In acute myelogenous leukemia, recurrence is more common than in ALL, which is why overall survival is relatively low (35%) without transplantation.

Note: Common in adults, older people, FAB classification, Auer chopsticks in blasts, hiatus leucaemicus, high recurrence rate

Chronic lymphocytic leukemia (CLL)

Chronic lymphocytic leukemia is the most common form of leukemia, which affects mainly older people. It is not curable, but can be well treated. The cause is a disturbed cell death in the B cells in the bone marrow, which leads to a massive proliferation of these cells. The displacement of other mature B-lymphocytes leads to increased susceptibility to infections, autoimmune diseases and tumors. There is a familial accumulation of CLL, suggesting a genetic defect.

Characteristic of the CLL is a lymph node swelling, which is often first symptom. In addition, skin changes may occur. The blood count and the number of lymph node stations affected are used for therapeutic planning and prognosis estimation, with liver and spleen also being considered a large lymph node station.

Image: "Blood smear in CLL" by VashiDonsk at the English language Wikipedia. Licence: CC BY-SA 3.0

Image: “Blood smear in CLL” by VashiDonsk at the English language Wikipedia. Licence: CC BY-SA 3.0

In microscopy, Gumprecht’s nuclear shadow is typical. These are lymphocytes, which burst when the blood streaks on the cover glass, since they are more fragile than healthy cells. The CLL is slow and rather benign, which is why an aggressive therapy is generally dispensed.

Note: Most common leukemia form, older people, B cell proliferation due to apoptosis loss, familial accumulation, lymph node swelling, gentle therapy

Chronic myelogenous leukemia (CML)

Chronic myelogenous leukemia affects rather people in the middle age of life. Disease mechanism is the degeneration of a blood-forming stem cell, with the result that excessive granulocytes are formed. Characteristic of the CML is the so-called Philadelphia chromosome, which originates from the chromosomes 9 and 22 by reciprocal translocation. It is found to 90% with the CML and is proving for the illness.

philadelphia-chromosom-svg_

Image: “Philadelphia-Chromosom – Translokation” by Master Uegly. Licence: CC BY-SA 3.0

The disease is divided into three phases: in the stable phase there are no symptoms or hardly any symptoms, leukocytosis and splenomegaly can occur. In the subsequent acceleration phase, symptoms such as fever, night sweat, loss of weight (B-symptomatics) occur more frequently in the blood, and more than 10% blasts are found in the blood. Finally, there is a blast crisis, which is like acute leukemia. The only curative therapy for the CML is the stem cell transplant, the more recent therapy option is the antibody Imatinib.

Note: Granulocyte expansion, Philadelphia chromosome, 3-phase course with blast crisis, stem cell transplantation as a cure

Process of Typification

For stem cell transplantation, one needs a suitable donor. In Germany, the non-profit organization DKMS (Deutsche Knochenmarkspenderdatei) introduces potential stem cell donors in a card index and also provides them internationally. Mapping is carried out by typization.

In a typization, the tissue characteristics of a person are registered, the HLA (human leukocyte antigen) characteristics. These are polypeptides that are located among the leukocytes. The HLA are decisive for the histocompatibility, ie the compatibility of foreign tissues among one another, and thus for the prevention of rejection.

By registering as many people as possible with different tissue traits, the probability for patients to find a suitable donor increases. For example, you can register on the DKMS website.

Review Questions

You will find the solutions below the questions.

1. In a 83-year-old woman, you notice lymph node swelling in the neck and armpits during a check-up. In the blood count you also have a leukocytosis of 55,000 gpt / l and anemia. In the microscopy of the blood smear you see so-called Gumprecht’s nuclear shadow. The patient has no complaints. Shortness of breath and diminished efficiency she takes back to their age and a femoral neck fracture 5 months ago. What is your preliminary diagnosis?

  1. ALL
  2. AML
  3. CML
  4. CLL
  5. Multiple Myeloma

2. You are cardiologist and want to prescribe phenprocoumone a 69-year-old man due to atrial fibrillation. He tells you to take imatinib and has been told to tell this when getting prescribed new medications because the drug has many interactions. Due to which disease is the man most likely to take the tyrosine kinase inhibitor?

  1. Chronic myeloid leukemia
  2. Colitis ulcerosa
  3. CREST syndrome
  4. Chronic lymphatic leukemia
  5. Conn syndrome

2. Which cell trait is typical of the acute myeloid leukemia?

  1. Auer rods
  2. Sternberg reed cells
  3. Gumprecht nuclear shadows
  4. Hela cells
  5. Jacket cells
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