Leukemias

LEUKEMIAS

Leukemia is a cancer of the white blood cells that begins when the blood stem cells acquired mutation changes or proliferate in an uncontrollable manner, producing abundant abnormal white blood cell.  These abnormal cells are called leukemic cells. They are characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Over time, the leukemia cells crowd out normal blood cells so that they can’t do their jobs.

Bone marrow stem cells have the ability to transform into myeloid stem cells or lymphoid stem cells.  The lymphoid stem cells become lymphocytes, a type of white blood cells.  Myeloid stem cells become one of the three types of mature blood cells:

  1. Red blood cells that carry oxygen and other substances to all tissues of the body.
  2. White blood cells that have the function of fighting infection, cells, and diseases.
  3. Platelets that are the blood clotting forming cells and are effective in stopping the bleeding.

There are many different types of leukemia. They are grouped according to the type of blood stem cell they developed from. Lymphoblastic leukemias (usually known as lymphocytic leukemias in adults) develop from abnormal lymphoid stem cells. Myelogenous leukemias develop from abnormal myeloid stem cells.

The types of leukemia are further subdivided based on how quickly leukemia develops and grows. Acute leukemias start suddenly, developing within days or weeks. Chronic leukemias develop slowly over months or years.

There are different types of leukemia, including

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

Acute lymphoblastic leukemia (ALL) is the most common type of leukemia diagnosed in young children. Acute myelogenous leukemia (AML) is less common and usually occurs more often in girls than boys.

Rare types of childhood leukemias can also develop. These include chronic lymphoblastic leukemia (CLL) and chronic myelogenous leukemia (CML).

On this review, we will discuss Chronic lymphocytic leukemia(CLL). Chronic myeloid leukemia is discussed separately in this online educational guidance

  

Chronic lymphocytic leukemia, CLL

  • About 60,300 new cases of leukemia and about 24,370 deaths from leukemia (all kinds), estimates for 2018
  •  CLL is the most common adult leukemia in US
  • Persistent fatigue, weakness are symptoms of CLL
  • Rituximab (Rituxan) is the most common targeted therapy used to treat CLL

Chronic lymphocytic leukemia (CLL) is a leukemia of LYMPHOCYTES, a type of white blood cells- Derived from the lymphoid stem cells. It is the most common leukemia in adults. In CLL, the leukemia cells often build up slowly. Many people do not have any symptoms for at least a few years. Nevertheless, over time, the cells grow and spread to other parts of the body, including the lymph nodes, liver, and spleen.

 

How frequent his chronic lymphocytic leukemia?

 CLL is the most common adult leukemia in western countries, it is less common in Asia and relatively rare in Japan and Korea, even among Japanese people who immigrate to western counties.

The American Cancer Society’s estimates for leukemia in the United States for 2018 are:

About 60,300 new cases of leukemia and about 24,370 deaths from leukemia (all kinds)

About 20,940 new cases of chronic lymphocytic leukemia (CLL)

About 4,510 deaths from CLL

CLL accounts for about one-quarter of the new cases of leukemia. The average person’s lifetime risk of getting CLL is about 1 in 175 (0.57%). The risk is slightly higher in men than in women.

CLL mainly affects older adults. The average age at the time of diagnosis is around 70years. It’s rarely seen in people under age 40, and is extremely rare in children.

 

What are the types of chronic lymphocytic leukemia?

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are often considered different versions of the same disease because they are very similar. They both start in B Cells, may be slow growing (indolent) and usually occur in older adults.  T cell Chronic lymphocytic leukemia can occur rarely.They differ in where the lymphoma cells are found. In CLL, the lymphoma cells are mainly found in the blood and bone marrow. In SLL, the lymphoma cells are mainly found in the lymph nodes and spleen.

Chronic lymphocytic leukemia is often categorized accordingly to how fast and aggressive the disease is progressing.  Whether it grows very slowly- usually may take a long time before a patient needs treatment, or whether it grows faster and a more aggressive and serious disease. Distinguishing the two is very difficult but prognostic indicator such as proteins called ZAP-70 and CD38 are useful. If the CLL cells have low amounts of these proteins, leukemia tends to grow more slowly and have better long-term outcomes. In addition, These subsets may be distinguished by whether CLL cells express an unmutated or mutated immunoglobulin heavy-chain variable region gene (IGHV) which is part of the structure that forms antibodies-reflecting the stage of normal B cell differentiation from which they originate1,2. CLL cells that express an unmutated IGHV. Patients with CLL cells that express an unmutated IGHV typically have the more-aggressive disease than patients with CLL cells that express a mutated IGHV.

What are the risk factors for chronic lymphocytic leukemia?

Age.  9 out of 10 people with CLL are over age 50.

Chemical exposure. Agent Orange, a herbicide,  increases the risk of CLL. Radom exposure at home has also been linked to increase her risk.

Family history/chromosomal abnormalities /gene mutations

Gender.  CLL is more common in males and females.

Race. CLL is more common in North America any year none indication

 

What are the symptoms of chronic lymphocytic leukemia?

Many people with CLL/SLL don’t have symptoms that cause problems. Sometimes they have low red blood cell counts (called anemia) and low platelet counts (called thrombocytopenia) because the immune system starts to destroy some of these cells. The spleen and liver may become larger than normal and leukemia/lymphoma cells may spread to organs or tissues other than the lymph nodes (called extranodal spread).

Common chronic lymphocytic leukemia signs and symptoms include:

  • Fever or chills
  • Persistent fatigue, weakness
  • Frequent or severe infections
  • Losing weight without trying
  • Swollen lymph nodes, enlarged liver or spleen
  • Easy bleeding or bruising
  • Recurrent nosebleeds
  • Tiny red spots in your skin (petechiae)
  • Excessive sweating, especially at night
  • Bone pain or tenderness

 

What are the Stages of chronic lymphocytic leukemia (CLL)

Staging describes or classifies a cancer based on how much cancer there is in the body and where it is when first diagnosed. This is often called the extent of cancer. Information from tests is used to find out the size of the tumor, which parts of the organ have cancer, whether the cancer has spread from where it first started and where the cancer has spread. Your Oncologist uses the stage to plan treatment and estimate the outcome (your prognosis).

Staging of blood cancers like chronic lymphocytic leukemia (CLL) is different from that of other cancers because CLL does not form a solid tumour. CLL is a cancer of the cells in the blood and bone marrow, where new blood cells are formed. The stage of the disease is based on blood cell counts and if the cancer has spread to the lymph nodes, spleen or liver.

The 2 staging systems for CLL are the Rai staging system and the Binet staging system. Sometimes doctors talk about a risk group for CLL. The risk group describes how likely the CLL is to worsen and need treatment. If the CLL worsens, doctors will do more tests to see if the CLL has reached a new stage.

Rai staging system

Stage 0: characterized by absolute lymphocytosis (>15,000/mm3) without adenopathy, hepatosplenomegaly, anemia, or thrombocytopenia

Stage I: characterized by absolute lymphocytosis with lymphadenopathy without hepatosplenomegaly, anemia, or thrombocytopenia

Stage II: characterized by absolute lymphocytosis with either hepatomegaly or splenomegaly with or without lymphadenopathy

Stage III: characterized by absolute lymphocytosis and anemia (hemoglobin <11 g/dL) with or without lymphadenopathy, hepatomegaly, or splenomegaly

Stage IV: characterized by absolute lymphocytosis and thrombocytopenia (<100,000/mm3) with or without lymphadenopathy, hepatomegaly, splenomegaly, or anemia

 

Binet Classification

Clinical stage A: characterized by no anemia or thrombocytopenia and fewer than three areas of lymphoid involvement (Rai stages 0, I, and II)

Clinical stage B: characterized by no anemia or thrombocytopenia with three or more areas of lymphoid involvement (Rai stages I and II)

Clinical stage C: characterized by anemia and/or thrombocytopenia regardless of the number of areas of lymphoid enlargement (Rai stages III and IV)

 

 What are the point considerations in Treatment of Chronic Lymphocytic  Leukemia?

Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, Stage, patient age and the presence of other diseases, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is one of the most relevant advances in cancer therapy

You may be offered one or more of the following treatments:

Watchful waiting

Many people with CLL/SLL who don’t have symptoms or problems may be offered watchful waiting (also called active surveillance). The Oncologist team will carefully monitor the person with CLL/SLL and start treatment when symptoms appear or there are signs that the CLL/SLL is progressing.

 

Chemotherapy

Chemotherapy may be a treatment option for people with CLL/SLL.

CLL/SLL is often treated with one of the following combinations of chemotherapy drugs:

CVP – cyclophosphamide (Cytoxan, Procytox), vincristine (Oncovin) and prednisone

FC – fludarabine and cyclophosphamide

The following chemotherapy drugs may be given alone:

chlorambucil (Leukeran)

fludarabine (Fludara)

bendamustine (Treanda)

Bendamustine may be used if CLL/SLL comes back (recurs).

Steroids, such as prednisone or dexamethasone (Decadron, Dexasone), may be used alone to treat immune complications such as autoimmune hemolytic anemia or low platelet counts that develops in some people with CLL/SLL.

 

Radiation therapy

External beam radiation therapy may be a treatment option for CLL/SLL. It may be given to the parts of the body that contain lymphoma cells, such as certain groups of lymph nodes or the spleen. It is used to control symptoms that develop when the lymph nodes or spleen are larger than normal. Radiation therapy may also be given in addition to chemotherapy.

 

Targeted therapy

Targeted therapy uses drugs to target specific molecules (such as proteins) on the surface of cancer cells. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells while limiting harm to normal cells.

Targeted therapy is very useful in cases of CLL  associated with gene mutations or chromosomal aberrations such as:

  • Immunoglobulin variable-region heavy chain (IgVH) gene mutation status
  • Deletions of part of the short arm of chromosome 17 (del 17p). Found in 5-10% of patients with CLL
  • Deletions of the long arm on chromosome 11 (del 11q)
  • Trisomy 12, an additional chromosome 12
  • Deletion of the long arm of chromosome 13 (del 13q). Noted in 50% of cases of CLL

Rituximab (Rituxan) is the most common targeted therapy used to treat NHL. It is often used in combination with chemotherapy to treat CLL/SLL.

Other targeted therapy that may be offered to people with CLL/SLL are alemtuzumab (Campath), ibrutinib (Imbruvica), obinutuzumab (Gazyva) or ofatumumab (Arzerra).

 

Stem cell transplant

A stem cell transplant may be an option for some younger people with CLL/SLL that no longer responds to treatment (called refractory disease).

 

 

 

When life throws questions and decisions about you or family, what you need – quite simply – is information, answers, and direction. This online guide has been developed to provide you with clear and practical information about cancer.

The information in this document does not replace a medical consultation. It is for personal guidance use only. We recommend that patients ask their doctors about what tests or types of treatments are needed for their type and stage of the disease.

Sources:

American Cancer Society

The National Cancer Institute

National Comprehensive Cancer Network

American Academy of Gastroenterology

National Institute of Health

MD Anderson Cancer Center

Memorial Sloan Kettering Cancer Center

 

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