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Leukamia


OVERVIEW OF Leukamia :

  Leukaemia is formed in the blood forming cells such as white blood cells in the bone marrow. It leads to overproduction of white blood cells resulting in leukaemia.


STRUCTURE of Leukamia :

Lymphocytic: the cancer cells starts their proliferation in the lymphoid cells. This takes place in the lymphocytes.

Myeloid cells:

The myeloid cells are the cells which aids in the formation of the red blood cells, white blood cells and the platelets. The cancer cells developing in the myeloid cells gives rise to the myeloid leukaemia.

  • Acute lymphocytic leukaemia(ALL):

This is the most common type of leukaemia occurin in the young children. It alos can oocur in adults.

  • Acute myelogenous leukaemia(AML): It is more common among adults.

AML is a common type of leukemia. It occurs in children and adults. AML is the most common type of acute leukemia in adults.

  • Chronic lymphocytic leukaemia:

 With CLL, the most common chronic adult leukemia, you may feel well for years without needing treatment.

  • Chronic myelogenous leukaemia:

 This type of leukemia mainly affects adults. A person with the CML does not tends to have symptoms or signs for a month or years.

  • Other types of leukaemia:

Other, rarer types of leukemia exist, including hairy cell leukemia,    myelodysplastic syndromes and myeloproliferative disorders.

 


CAUSES :

Causes:

  • Age:
  • All leukaemias are common among elders. The acute lymphocytic leukaemia is more common among childres.
  • Gender – leukaemias are generally more common in males
  • Genetics – some timies the familial history of getting the disease is known.
  • Chemical exposure – being exposed to some chemicals and high levels of radiation may increase the chance of developing leukaemia. These factors account for only a very small proportion of all cases
  • Some forms of leukaemia are seen more commonly in people who have other bone marrow disorders. The most common disorders which behave in this way are myelodysplastic syndrome and myeloneoplastic syndromes.
  • Smoking and alcohol consumption
  • Radiations
  • Down’s syndrome.

 


PATHOPHYSIOLOGY :

In leukaemia the clone of malignant cells arises at any stage of maturation the  stage might imclude lymphoid, myeloid and pluripotent stage. It results in some rearrangement of DNA. External factors such as alkylating drugs, ionizing radiations, chemical and internal  factors such as chromosomal abnormalities lead to DNA changes.

Chromosomal rearrangements may alter the structure or regulation of cellular oncogenes. For example in the B cell lymphocytic leukemias chromosomal translocations might result in replacement of the genes which aids in light and heavy chain immunoglobulin synthesis next to the gene that regulate the normal cell division. This results in proliferation of lymphoblast.

As the proliferation might results in the misbehaving of the bone marrow and the bone marrow loses it function resulting in fprmation of cancer cells. Pancytopenia is typical and results in part

ocular involvement may occur prior to the diagnosis of leukemia, during the disease course, or as a sign of relapse. The ocular manifestations may be secondary to direct infiltration of the leukemic cells, as a result of abnormal systemic hematological parameters, opportunistic infections, or iatrogenic complications arising from chemotherapy.

 


COMMON CLINICAL SIGNS AND SYMPTOMS :

  • 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


DIAGNOSTIC :

The physician might concentrate on your health history and your symptoms:

  • Symptoms that is suggestive of leukaemia
  • Exposure do high doses of radiation
  • Genetic syndromes such as Fanconi anaemia, down’s syndrome, ataxia telengectiasis.
  • exposure to benzene
  • previous chemotherapy or radiation therapy
  • blood disorders
  • viral infections

physical exam:

the doctor might also check for any abnormal signs such as

swollen lymph nodes

fever

shortness of breathe

palpitations

feel the abdomen for enlarged organ

tenderness is felt in the skeleton

complete blood count:

   it measures the number and quality of white blood cells, red blood cells and platelets.leukamia might results in the abnormal cell counts

normal WBS value:4,00,000 -11,00,000 cells per micromiter.

Blood chemistry tests:

It measures the exposure to certain chemicals in the blood. The following are the chemicals which tends to rise in leukaemia:

  • blood urea nitrogen (BUN)
  • creatinine
  • phosphate
  • lactate dehydrogenase (LDH)
  • alanine aminotransferase (ALT)
  • aspartate aminotransferase (AST)
  • uric acid

bleeding and clotting factors examination:

  • fibrinogen level
  • prothrombin time (PT)
  • partial thromboplastin time (PTT)
  • international normalized ratio (INR)

cytochemistry:

it uses certain dyes and stains to view the structure of tissues, bone and bone marrow cells.

Immunophenotyping:

It is the of proteins expressed by the cells. It is the used to study the type of the leukaemia.

It is a specific antigen antibody reaction used to identify certain  proteins in tissues or cells. It uses monoclonal antibodies marked with fluorescent label or specific enzyme label that detect the mutual understanding of antigen to the antibody.

Immunohistochemistry:

It uses microscope to view the immunoperoxidase labels.

Flow cytometry:

The abnormal light is exposed to the light and it is analysed by the computer. This helps the physician to study about minimal residual disease that means there are blasts in the bone marrow that cannot be found using the standard lab test but they can be found isung more sensitive tests such as flow cytometry or polymerase chain reactions.

Cytogenic and molecular studies:

Cytogenic karyotyping:

It helps in the identification of the subtype of leukaemia and also major chromosomal abnormalities which can be found using microscope.

 

Fluorescence in situ hybridization:

It identifies chromosomal abnormalities and other genetic changes in the leukaemia cells or blasts cells. It used DNA probes labelled with fluorescent dyes.

Polymerase chain reaction:

It is used to find out the DNA mutations, inversions or deletions that are linked with certain types of leukaemia.

Bone marrow aspiration and biopsy:

During this test cells are removed from the bone marrow and they are tested in the lab.

 

Lumbar puncture:

 a lumbar puncture which is also called as spinal tap extract small amount of cerebrospinal fluid from the space around the spine and it is viewed under the microscope. CSF is the fluid that surrounds the brain and spinal cord and cushions the brain. It also checks whether the cancer cells has spread to the spinal fluid.

 

 

Lymph node biopsy:

A type of surgical biopsy also known as excisional biopsy in which the lymph node is completely removed. Sometimes the complete removal of the lymph node is difficult and hence a part of the lymph node is removed which is known as the core biopsy. It is used to find out how much fast that the cancer cell is growing.

Chest x ray:

It looks for:

Enlarged lymph nodes in the center of the chest which is called as mediastinal lymph nodes.

Enlarged thymus gland

Buildup of fluid between the lungs and the walls of the chest(called pleural effusion)

Lung infection(called pneumonia)

CT scan:

 A computed tomography special x ray equipment to reveal 3D and cross sectional images of organs, tissues, bones and blood vessels inside the body.

 

Magnetic resonance imaging:

It uses magnetic waves and radiofrequency waves tp view 3D pictures of the tissues and organs. It also can reveals the metastasis has happened or not.

Ultrasound:

It uses high frequenct sound waves to make the image structure in the body. It also checks if internal organs such as kidney, liver or spleen have been affected by leukaemia or  not.

 


TREATMENT AND PROGNOSIS :

Chemotherapy:

A chemotherapy is after the sugery or before the surgery to shrink the cancer cells. A chemotherapy is nothing but the delivery of drug intravenously

Radiation therapy:

It uses powerful x rays or emission of protons to destroy the cells. The radiation therapy also aids  in shrinkage of the cells and also relief the symptoms caused by the cancer.

Immunotherapy

it is a drug treatment that uses your immune system to fight cancer. Your body's disease-fighting immune system may not attack your cancer because the cancer cells produce proteins that blind the immune system cells from recognizing the cancer cells. This immunotherapy boos those cells and helps the body to fight against it.

  • Targeted therapy: This treatment uses drugs that are focused on a specific features of leukemia cells. Targeted therapies work by blocking the ability of leukemia cells to multiply and divide, cutting off the blood supply needed for the cells to live, or killing the cells directly. Targeted therapy is less likely to harm normal cells. Examples of targeted therapy include monoclonal antibodies (such as inotuzumab, gemtuzumab, , rituximab, obinatuzumab, alemtuzumab and tyrosine kinase inhibitors ruxolitinib , , gilteritinib
  • Hematopoietic cell transplant (also known as stem cell or bone marrow transplant): This procedure replaces the cancerous blood-forming cells that have been killed by chemotherapy and/or radiation therapy with new, healthy hematopoietic cells. These healthy cells are taken from you (before exposure to chemo or radiation therapy) or from a donor’s blood or bone marrow and are infused back into your blood. Healthy hematopoietic cells grow and multiply forming new bone marrow and blood cells that develop into all the different types of cells your body needs (red blood cells, white blood cells and platelets). In the case where the cells are taken from a different person (donor), the new immune system recognizes the cancer cells as foreign and kills them (similar to other immunotherapies).


PROGNOSIS :

The 5 year survival rate of leukaemia is 61.5%


PREVENTION :

Avoid smoking

Avoid alcohol consumption

Increases the physical activity- aids in digestion process

Drink lots of water

Avoid exposure to harmful radiations and chemicals


Medicines used in the Treatment :

 inotuzumab,

gemtuzumab,

rituximab,

obinatuzumab,

alemtuzumab

 tyrosine kinase inhibitors- ruxolitinib , , gilteritinib


REFERENCE :

https://www.cancervic.org.au/cancer-information/types-of-cancer/leukaemia/leukaemia-overview.html

https://my.clevelandclinic.org/health/diseases/4365-leukemia

https://www.cancer.ca/en/cancer-information/cancer-type/leukemia/diagnosis/?region=