Leukemia Definition, Symptoms, Pathophysiology, Classification, Risk factors, Diagnosis and Treatment

 Leukemia                                                                   

The abnormal or excessive proliferation of hemopoietic stem cells/leucocytes is called Leukemia. It is a malignant disease of bone marrow, especially hemopoietic cells also called blood cancer especially affected white blood cells. Abnormal production of immature/band cells of myeloid and lymphoid series. These blood cells are not fully developed and are called blasts or leukemic cells and the Bone marrow, Lymph system form a group of malignant disorders affecting blood cells.

At first, Leukemia was described by anatomist and surgeon Alfred-Armand-Lous-Marie Velpeau in 1827, it more detailed description was given by pathologist Rudolf Virchow in 1845. Then a Pathologist Franz Ernst Christian Neumann found that the bone marrow of a deceased person with Leukemia was colored Dirty green-yellow as opposed to the normal red and this finding allowed Neumann to conclude that a bone marrow problem was responsible for the abnormal blood of people with Leukemia. In 1947, Boston pathologist Sidney Farber believed from his past experiments that aminopterin, a folic acid mimic, could potentially cure Leukemia in children. In 1962, researchers Emil J. Freireich, Jr. and Emil Frei III used combination chemotherapy to attempt to cure leukemia.

Definition:

Leukemia is a blood cancer that starts in blood-forming tissue, such as the bone marrow and causes large numbers of abnormal blood cells to be produced and enter the bloodstream.

Pathophysiology of Leukemia:

• Ø At the first point, a mutation occurs in DNA, and chromosomal abnormality like duplication, loss, and recombination error is found.
• Ø Combinations of these genetic defects cause reduced tumor suppressor gene expression and increased oncogene expression.
• Ø Then lack of cell growth inhibition, apoptosis, and overstimulation of cell division/growth is found in white blood cells and their precursors.
• Ø Neoplastic blood cells are incapable of regulated cell division.
• Ø Neoplastic cells uncontrollably divide in a monoclonal way that one neoplastic cell originates all successive cells.
• Ø In genes regulating differentiation/maturation, some cells are disrupted and some remain intact.
• Ø The disrupted cells cause slower disease progression, that call Chronic Myeloid Leukemia (CML)
• Ø when disrupted cells cause rapid division and build-up of existing neoplastic cells and show rapid disease progression it causes Acute Myeloid Leukemia (AML) and Acute lymphoid Leukemia (ALL).
• Ø The cells remain intact take time to mature further and show less rapid disease progression, which causes Chronic Lymphoid Leukemia (CLL).

Causes for Leukemia:  the reasons for Leukemia -

Genetic change: Results from transformations in the DNA. Certain changes can set off leukemia by initiating oncogenes or deactivating growth silencer qualities, and subsequently disturbing the guideline of cell passing, separation, or division.

Genetic circumstances: Down condition, Fanconi sickliness, Philadelphia movement,

Radiations: the realized causes are regular and fake ionizing radiation and a few synthetic substances, outstandingly benzene and alkylating chemotherapy specialists for past malignancies. Strontium 90, X-beam, X-ray, CT, and others

The utilization of tobacco is related to a little expansion in the gamble of creating intense myeloid leukemia in grown-ups.

Infection: Infections have additionally been connected to certain types of leukemia. For instance, human T-lymphotropic infection (HTLV-1) causes grown-up Lymphocyte leukemia. Epstein Barr infection connected to Burkitt's lymphoma

Cancer-causing agents: Aflatoxins, Cocktail utilization, 4-Aminobiphenyl, Pain relieving combinations containing phenacetin, Aristolochic acids, Arsenic and inorganic arsenic compounds, Asbestos, Azathioprine

Drugs: Fluoxetine, Paroxetine, Zantac, Losartan, Valsartan, Proton Siphon Inhibitors, Chloramphenicol, Phenylbutazone, and so on

Synthetic compounds/Ecological variables: formaldehyde (Formalin), Benzene, asbestos, vinyl chloride, radon, and arsenic, smoking, drinking

Symptoms of Leukemia:

• 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 our skin (petechiae)
• Excessive sweating, especially at night
• Bone pain or tenderness

Classification of Leukemia:

·      Acute Myeloid Leukemia (AML)

·      Acute lymphoid Leukemia (ALL)

·      Chronic Myeloid Leukemia (CML)

·      Chronic Lymphoid Leukemia (CLL)

Acute Myeloid Leukemia (AML): AML is the most common type of acute Leukemia in adults. It tends to progress quickly. It can affect any component of the blood and there are many subtypes of AML. Blood stem cells in the bone marrow form into either-

·      Lymphoid cells, which become white blood cells.

·      Myeloid cells, which can become red blood cells, white blood cells, or platelets.

In AML, myeloid stem cells usually mature into abnormal myeloblasts or white blood cells. But they sometimes become abnormal red blood cells or platelets.

Acute Lymphoid Leukemia (ALL): All is more common in children. This type of Leukemia begins in the B or T lymphocytes, which are immature white blood cells. Lymphoid tissue makes up the immune system.

ALL can be also separated into the: Lymph nodes, Liver, Spleen

Chronic Lymphocytic leukemia (CLL): CLL accounts for about a third of leukemia diagnoses. It usually affects older adults. One form of CLL progress slowly. Symptoms may not appear until years after onset. Another form of CLL grows very quickly.

CLL begins in the B lymphocytes. As the abnormal cells proliferate, they crowd out the normal cells. More subtypes of CLL exist that affect other types of cells.

Chronic Myeloid Leukemia (CML): This type of leukemia is rare. Only 10 percent of leukemia are CML. Adults are more likely than children to get CML.

CML occurs when a genetic change turns the myeloid cells into immature cancer cells. These cells then grow slowly and overwhelm the healthy cells in the bone marrow and blood.

Hairy cell leukemia: hairy cell leukemia is a rare type of leukemia (HCL) because of how it looks under a microscope and affects fewer than 6000 people each year. It grows slowly. Some people live with the disease for many years before symptoms appear.

FAB Classification of Leukemia:

In the 1970s, a group of French, American, and British leukemia experts divided AML into 8 subtypes, M0 through M7, and divided ALL into 3 subtypes L1, L2, and L3 based on the type of cell leukemia develops from and how mature the cells are. This was based largely on how the leukemia cells looked under the microscope after routine staining.

Acute Myeloid Leukemia:   

• ·      M0:  Undifferentiated acute myeloblastic leukemia
• ·      M1:  Acute myeloblastic leukemia with minimal maturation
• ·      M2:  Acute myeloblastic leukemia with maturation
• ·      M3:  Acute promyelocytic leukemia (APL)
• ·      M4:  Acute myelomonocytic leukemia and Acute myelomonocytic leukemia with eosinophilia
• ·      M5:  Acute monocytic leukemia
• ·      M6:  Acute erythroid leukemia
• ·      M7:  Acute megakaryoblastic leukemia

Acute Lymphoid Leukemia:

·      L1:  Lymphoblastic leukemia with a homogeneous structure

·      L2:  Lymphoblastic leukemia with varied structure

·      L3:  Burkitt’s leukemia

Risk factors for leukemia:

Factors that may increase our risk of developing some types of leukemia include:

Previous cancer treatment: People who've had certain types of chemotherapy and radiation therapy for other cancers have an increased risk of developing certain types of leukemia.

Genetic disorders: Genetic abnormalities seem to play a role in the development of leukemia. Certain genetic disorders, such as Down syndrome, are associated with an increased risk of leukemia.

Exposure to certain chemicals: Exposure to certain chemicals, such as benzene — which is found in gasoline and is used by the chemical industry — is linked to an increased risk of some kinds of leukemia.

Smoking. Smoking cigarettes increases the risk of acute myelogenous leukemia.

Family history of leukemia: If members of our family have been diagnosed with leukemia, our risk of the disease may be increased.

Diagnosis of Leukemia:

Results from routine blood work can alert our healthcare provider that we may have an acute or chronic form of leukemia that requires further testing. Or they may recommend a workup if we have leukemia symptoms.

Diagnostic examinations and tests may include:

Physical exam: Our healthcare provider will ask about our symptoms and feel for swollen lymph nodes and an enlarged spleen or liver. They may also inspect our gums for bleeding and swelling. They may look for a skin rash associated with leukemia. that may appear red, purple, or brown.

Complete blood count (CBC): This blood test lets our healthcare provider knows if we have abnormal levels of red blood cells, white blood cells, and platelets. If we have leukemia, we'll likely have higher than normal counts of white blood cells.

Blood cell examination: Our healthcare provider may take additional blood samples to check for markers indicating leukemia cells or a specific type of leukemia. Flow cytometry and peripheral blood smear are additional tests our healthcare provider may order.

Bone marrow biopsy (bone marrow aspiration): Our healthcare provider may perform a biopsy if we have an abnormal white blood cell count. A long needle inserted into our bone marrow (usually in our pelvic bone) draws out fluid during the procedure. The fluid sample gets tested in a lab for leukemia cells. A bone marrow biopsy helps determine the percentage of abnormal cells in our bone marrow, confirming a leukemia diagnosis.

 Imaging and other tests: Our doctor may order a chest X-ray, CT scan, or magnetic resonance imaging (MRI) scan if symptoms indicate leukemia has affected our bones, organs, or tissue. The leukemia cells don't show up on imaging.

Lumbar puncture (spinal tap): Our healthcare provider may test a sample of spinal fluid to see if leukemia has spread to the spinal fluid surrounding our brain and spinal cord.

Treatment:

Treatment for our leukemia depends on many factors. Our doctor determines our leukemia treatment options based on our age and overall health, the type of leukemia we have, and whether it has spread to other parts of our body, including the central nervous system.

Common treatments used to fight leukemia include:

Chemotherapy: Chemotherapy is the major form of treatment for leukemia. This drug treatment uses chemicals to kill leukemia cells. Depending on the type of leukemia we have, we may receive a single drug or a combination of drugs. These drugs may come in a pill form, or they may be injected directly into a vein.

Targeted therapy: Targeted drug treatments focus on specific abnormalities present within cancer cells. By blocking these abnormalities, targeted drug treatments can cause cancer cells to die. Our leukemia cells will be tested to see if targeted therapy may be helpful for, us.

Radiation therapy: Radiation therapy uses X-rays or other high-energy beams to damage leukemia cells and stop their growth. During radiation therapy, we lie on a table while a large machine moves around, directing the radiation to precise points on our bodies. We may receive radiation in one specific area of our body where there is a collection of leukemia cells, or we may receive radiation over our whole body. Radiation therapy may be used to prepare for a bone marrow transplant.

Bone marrow transplant: A bone marrow transplant, also called a stem cell transplant, helps reestablish healthy stem cells by replacing unhealthy bone marrow with leukemia-free stem cells that will regenerate healthy bone marrow. Before a bone marrow transplant, we receive very high doses of chemotherapy or radiation therapy to destroy our leukemia-producing bone marrow. Then we receive an infusion of blood-forming stem cells that help rebuild our bone marrow. We may receive stem cells from a donor or we may be able to use our own stem cells.

Immunotherapy: Immunotherapy uses our immune system to fight cancer. Our body's disease-fighting immune system may not attack our cancer because the cancer cells produce proteins that help them hide from the immune system cells. Immunotherapy works by interfering with that process.

Engineering immune cells to fight leukemia: A specialized treatment called chimeric antigen receptor (CAR)-T cell therapy takes our body's germ-fighting T cells, engineers them to fight cancer, and infuses them back into our body. CAR-T cell therapy might be an option for certain types of leukemia.

Clinical trials: Clinical trials are experiments to test new cancer treatments and new ways of using existing treatments. While clinical trials give us or our child a chance to try the latest cancer treatment, treatment benefits and risks may be uncertain. Discuss the benefits and risks of clinical trials with our doctor.

Prevention for leukemia:

we could have seen claims that specific food varieties, supplements, or different items can decrease our gamble of malignant growth. While that could sound enticing, we ought to know that most of those cases aren't upheld by enough logical examination.

There are a couple of food varieties with some proof that they could forestall a few tumors. A large portion of these food varieties is a sound expansion to any eating routine, so trying them positively can't do any harm.

Until more examination is done that tracks down unambiguous ways of forestalling leukemia, the best strategy is to

diminish the gamble factors we have some control over. There are a couple of ways of life transforms we can make to diminish our gamble of leukemia. These means

can likewise diminish our gamble of different kinds of malignant growth. They include:

Stop smoking: Smoking builds the gamble of various kinds of malignant growth, including leukemia. Never smoking or stopping smoking will bring down our gamble of leukemia.

Keep a moderate weight: Having weight is one more gamble for leukemia that we have some control over. Doing whatever it may take to keep a moderate weight can diminish our gamble of leukemia. We can begin by fostering a proper eating regimen and making active work part of our daily existence.

Try not to take in specific synthetics: The synthetic compounds benzene and formaldehyde are known to expand our gamble of leukemia. These synthetics can be tracked down in certain working environments and structures. If conceivable, staying away from these synthetic compounds can bring down our gamble of leukemia.