Leukemia and Chronic Myeloid Leukemia


Leukemia is cancer of the blood cells.


There are three main categories of blood cells:

  • Red blood cells - erythrocytes. Life span: 100-120 days
  • Platelets - thrombocytes. Life span: 8-9 days
  • White blood cells
    • Life spans:
      • Neutrophils - 1 day
      • Macrophages - several months
      • Lymphocytes - weeks or months



Blood cells are formed from the stem cells, of which their primary base is in the bone marrow.

There are several types of WBCs, the main important types are neutrophils, macrophages (monocytes), and lymphocytes. There are two main types of lymphocytes, the T-cells and B-cells.

In leukemia it is usually the white blood cells which are at faulty. They don't mature (differentiate) properly and are not only non-functional but also proliferate uncontrollably, crowding out healthy blood cells in the bone marrow.

Initial affects of leukemia can be attributed to lower numbers of normal blood cells:

  • Anaemia - low RBC
  • Neutropenia - low neutrophils
  • Thrombocytopenia - low platelets
  • Pancytopenia - all blood cell types affected


There are four main types of leukemia

  • Acute myeloid leukemia
  • Acute lymphocytic leukemia
  • Chronic myeloid leukemia
  • Chronic lymphocytic leukemia

Acute vs Chronic

  • Acute – the leukemia cells are immature blood cells, and resemble stem cells
  • Chronic – the leukemia cells are almost mature blood cells, and resemble normal blood cells but do not function properly.
  • Acute leukemia is a fast-growing cancer that usually gets worse quickly. Chronic leukemia is a slower-growing cancer that gets worse slowly over time.

Myeloid vs Lymphocytic

  • Lymphocytic – the leukemia cells are of the lymphocyte origin (lymphocytes are the T-cells and B cells)
  • Myeloid – the leukemia cells of the myeloid origin – the myeloid cells can convert into the other non-lymphocyte type WBCs, as well as RBC and platelets.

Chronic myeloid leukemia (CML)

People with CML have an abnormal chromosome called the Philadelphia chromosome. It’s a mutation resulting in a cancer-causing gene (oncogene). This oncogene gives a stem cell instructions to make a dysfunctional tyrosine kinase, which leads to the development of CML.

CML does not interfere as much with the functioning of the other blood cells, so is generally less severe than acute leukemia.

There are three phases of CML - chronic, acute and blast phase. Patients usually present at the chronic phase, when treatment is very effective for most patients.

Since the introduction of tyrosine kinase inhibitor (TKI) therapy in 2001, CML has been transformed from a life-threatening disease to a manageable chronic condition for most patients. CML patients are living longer and experiencing fewer treatment side effects.


Phases of CML

Chronic phase

  • The chronic phase is when the leukaemia is most stable and still developing slowly.
  • Less than 10% of the blood cells are abnormal (blast cells).
  • Symptoms are mild and vague - fatigue, some weight loss, there may be a swolling due to an enlarged spleen.
  • Majority of people (90%) are in chronic phase when they are diagnosed.
  • Treatment
    • Biological therapy is the most common treatment for this phase using imatinib. Most people respond well and the CML can stay under control for several years.
    • Nilotinib may be used if imatinib does not work or it stops working after a period of time. CRUK

Accelerated phase

  • There are more immature blasts, 10% - 30% of the blood cells are immature blasts.
  • CML does not respond as well to treatment as CML in the chronic phase. ACS
  • Symptoms are more obvious, the enlarged spleen may cause uncomfortable/painful feeling to the left of the stomach, under the ribs.
  • Treatment
    • Imatinib is normally the first choice unless the patient has had it before.
    • Taking imatinib may put CML back into the more stable chronic phase for a time.
    • Nilotinib (Tasigna) or dasatinib (Sprycel) are alternatives if imatinib has already been tried.

Blast phase

  • More than 20-30% of the blood cells are blasts.
  • Many blast cells fill the bone marrow. There are also more blast cells in the blood. The leukaemic cells may also have spread to other organs.
  • There is often fever, poor appetite, and weight loss.
  • In this phase, the CML acts much like an aggressive acute leukemia.
  • Treatment
    • Imatinib (Glivec) if treatment naïve, or nilotinib or dasatinib.
    • Other options include:
      • chemotherapy with a combination of drugs that’s usually used for acute leukaemia
      • a bone marrow or stem cell transplant
    • Treatment to relieve symptoms include radiotherapy to shrink an enlarged spleen to reduce pain in the bones.



References

Handwritten Tutorials - Cells of the immune system

cancer.org

Cancer Research UK

BNF

Leukemia and Lymphoma Society

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