Leukaemia is a cancer of the cells of the blood and blood-forming tissue such as bone marrow.

In patients with leukaemia, some blood-forming cells of the bone marrow are damaged and remain in an abnormal or immature form. As a result, these cells are unable to function properly.

Over time these leukaemic cells multiply and crowd out the normal cells of the bone marrow, which makes it hard for the blood to do its work.

For example, normal-functioning red blood cells carry oxygen in the body. When the number of red blood cells is reduced due to the oversupply of leukaemic cells, anaemia occurs which can result in feeling run down, tired, or short of breath.

Platelets, which are fragments of larger cells also found in the bone marrow, may also be affected. Platelets are necessary for normal blood clotting and clump together to prevent bleeding. A low level of platelets can lead to bruising and bleeding, especially in the skin, nose, and gums.

Under normal circumstances the blood forming cells of the bone marrow make white blood cells (WBCs) to fight infection caused by bacteria, viruses, and fungi. Very low levels of the healthy WBCs known as neutropenia, due to an oversupply of leukaemic cells, can increase the risk of infection.

Leukaemia literally means “white blood” in Greek and occurs when there is an excess of abnormal or immature WBCs. In some patients, these cells are so plentiful that the blood actually develops a whitish tinge.

If left untreated, leukaemia can cause bone marrow failure. This happens when the surplus leukemic cells overwhelm the bone marrow, enter the bloodstream, and eventually invade other parts of the body, such as the lymph nodes, spleen, brain, spine and liver.

Types of leukaemia

Leukaemias are grouped by how quickly the disease develops and by the type of WBC that is affected.

Acute leukaemias usually develop suddenly and worsen quickly. The blood cells are malformed and cannot carry out their normal function. Acute leukaemias require immediate and aggressive treatment.

Chronic leukaemias may exist for years before they are diagnosed or need to be treated. Early in the disease, people with chronic leukaemia may not have any symptoms. However, chronic leukaemias slowly worsen and cause symptoms as the number of leukemic cells in the blood rises.

Leukaemias are also classified by the cell lineage that gives rise to the disease.

The process of blood formation takes place in the bone marrow. Self-renewing cells called stem cells are responsible for making all the blood cells for the body. As these cells multiply, they develop into two types of cells: myeloid cells or lymphoid cells.

Lymphocytic leukaemia    develops in the lymphoid cell line,

Myeloid leukaemia           develops in the myeloid cell line.

There are several subtypes of Leukaemia based on the lineage of the leukemic cells each subtype has a different prognosis.

Chromosome analysis — also known as cytogenetics — of the bone marrow provides valuable information and is used to identify the subtype of AML. Each subtype is treated differently.

Geoff has Acute Myelomonocytic Leukaemia with  FLT-3 genetic variation (AMML FLT-3)

AML overview and insights

Acute myeloid leukaemia (AML) is the most common adult acute form of leukaemia. The incidence of AML rises dramatically in people over 55 years of age (median age of onset is 64 years). AML is also more common in white males than in any other population

AML is a cancer of the blood-forming tissues of the bone marrow, characterized by an increase in immature WBCs. Normally the bone marrow makes cells called “blasts” that mature into several different types of blood cells. See diagram above.

AML prevents the blasts from properly maturing.

Found in the blood and bone marrow, these mutated, leukemic blast cells multiply rapidly and crowd out normal blood cells.

People with AML become increasingly susceptible to bleeding and infection as the normal blood cells decrease in number and lose their ability to effectively defend the body against microorganisms. The onset of AML is usually quite sudden.

What causes AML?

Although the specific cause of AML is still not known, scientists believe that genetic, environmental, or immunology factors or viruses may be involved. However, please keep in mind that even if a virus is involved, AML is not contagious. There is no evidence to suggest an increased occurrence of the disease among people such as friends, family, and caregivers who have close contact with leukaemia patients. It is thought that rare genetic abnormalities may play a role in AML. In some families, people born with chromosome damage, such as Down’s syndrome, many carry genes that could increase their chances of developing AML.

Environmental factors such as high-dose radiation and exposure to toxic chemicals including benzene — commonly used in a variety of industrial applications — have been linked to AML. Some researchers believe that the increased incidence of AML in men may be related to occupational exposures.

People with immune-system deficiencies appear to be at greater risk for AML because of their body’s inability to resist foreign organisms.

There is also evidence that patients previously treated for cancer with certain chemotherapy agents and radiation therapy stand a higher chance of getting secondary leukaemia ( leukaemia that arises after therapy for another type of cancer), most commonly AML. The distinction is important because secondary AML, seen more often in elderly patients, is less responsive to chemotherapy.

Newly diagnosed patients not previously treated for cancer have what is called de novo AML and usually experience a more favourable response to chemotherapy than patients with secondary AML.

 

What are the signs and symptoms of AML?

The following are the most common signs and symptoms associated with AML. However, each individual may experience symptoms differently. These may include:

• Easy bruising
• Nonspecific fatigue or weakness
• Fever
• Petechiae (pinpoint-size, purplish-red spots)
• Bleeding gums
• Slow healing or prolonged bleeding of cuts
• Weight loss

Some people with AML do not notice any symptoms at all. Their AML may be discovered during a blood test or other diagnostic evaluation.

Diagnosing AML

The symptoms of AML sometimes resemble other blood disorders and medical problems.

A suspicion of AML may arise due to an abnormal complete blood test which may reveal low levels of platelets or haemoglobin, a protein carried by red blood cells, and an increase in the number of WBCs.

Patients with new onset leukaemia who have normal or elevated WBC counts may still be at high risk for infection. This can occur because the patient’s WBCs are abnormal and thus unable to fight off infections.

If the blood test results look suspicious, the doctor will request a bone marrow biopsy in which a sample of bone marrow is taken from the hip bone or another large bone. Because it measures the blast count, a biopsy is the only sure way to determine whether leukaemia cells are in the bone marrow. This is especially important because AML is defined by greater than 30% blasts in the bone marrow, whereas a normal blast count is less than 5%.

The doctor will likely conduct various other tests to assess general health — for example, heart, liver, and kidney function. These assessments are important to ensure that a patient is not particularly prone to side effects from the planned treatment regimen.

Expectations for recovery

The prognosis for recovery from AML varies from patient to patient. Characteristics such as age and general health and the AML subtype are key factors.

Significant progress has been made in the fight against AML. Though primary causes of concern continue to be chemotherapy-related toxicities and life-threatening infections, many of today’s AML patients can anticipate a positive outcome.

Treatment aims for a complete remission. This means that there is no evidence of the disease and the patient returns to good health with normal blood and marrow cells.

Oncology centres across the country report increasing numbers of patients who are in complete remission at least 5 years after diagnosis of their disease

How is AML treated?

AML requires a more aggressive treatment regimen than other types of cancers. AML patients need to be treated right away and will begin their regimen within hours or days of diagnosis. Most patients with AML will receive chemotherapy while in the hospital.

AML treatment requires extended hospitalization due to the use of strong drugs that severely suppress the immune system. Hospitalization also provides patients with access to a total-care approach, integrating a network of disciplines that include a hematologist/oncologist; nursing, pharmacy, and laboratory services; and other supportive staff. The goals of treatment are to attain a complete remission and, with further treatment, to eradicate the disease and achieve a cure.

Induction chemotherapy

The first phase of treatment is called induction chemotherapy. The primary goal of induction chemotherapy is to kill the leukemic blasts that take over the bone marrow and crowd out normal stem cells. This restores the bone marrow to normal function, allowing it to produce healthy cells.

Induction chemotherapy involves the use of several drugs in combination (in Geoff’s case cytarabine 2/day on day 1,3,5 &7 plus  idarubicin on day 1,2 &3 and Midostaurin 2x per day from day 8-15 ).

While chemotherapy destroys many normal stem cells in the bone marrow, those that do survive now have ample space to resume normal and active development.

Complete remission is defined as less than 5% blasts in the bone marrow and no blasts circulating in the blood. In addition Platelets and normal WBCs must show evidence of recovery. Many patients experience a complete remission with this type of treatment regimen.

On day 28 of the Induction cycle another bone marrow biopsy will be performed. If the blasts are more than 5%, a second course of induction chemotherapy may be given.

Consolidation therapy

Once complete remission is achieved, consolidation therapy is usually given to prevent relapse and to eradicate any residual or remaining leukaemic cells from the blood and bone marrow. This is necessary in order to achieve a permanent cure.

Without consolidation therapy, complete remission lasts only about 4 to 8 months. Consolidation therapy consists of further chemotherapy and/or stem cell transplantation (from bone marrow or blood).

A stem cell transplant is used to introduce healthy blood-producing cells into the patient’s marrow to restore the immune system and allow normal blood cell production.

Treatment for patients who relapse

Although most patients with AML will achieve a remission, some will experience a relapse — a return of the disease. Relapse often occurs because the leukaemia cells have become resistant to drug treatment. However, bone marrow transplantation is a treatment option shown to prolong survival in many patients who have experienced a relapse.

AML treatment and the risk of infection

When chemotherapy is used to target and destroy fast-growing cancerous cells, it can also kill healthy cells, including the WBCs that protect the body against infection. WBCs are very important because they are continually on the lookout for signs of infection. When an invading organism does appear, the WBCs have a variety of ways by which they can attack.

When functioning normally, here is how several WBCs protect the body against infection:

• Neutrophils are the most abundant type of WBCs, and are the first to rush to the site of an infection and attack foreign antigens
• Monocytes mature into macrophages that act as scavengers to rid the body of worn-out cells and other debris. Macrophages also secrete a wide range of powerful chemicals that work to “activate” other immune system cells
• Dendritic cells are the least abundant, but most potent, type of WBC. They act as observers and messengers who go to the site of infection, collect pertinent information, and “coach” the immune system on how to react to infection
• T cells direct and regulate the body’s immune responses or attack cells that are infected or cancerous
• B cells produce antibodies, which are proteins that bind to antigens and mark them for destruction

See the “About the Immune System” for a fuller explanation of the types and functions of the Immune system.

Neutropaenia

Patients undergoing chemotherapy frequently experience neutropaenia, a condition that occurs when the number of neutrophils is abnormally low.

Neutropaenia can significantly increase the risk of infection. In fact, 40% of AML patients over the age of 60 experience serious infections following induction chemotherapy.

The high rate of infection is the primary reason the healthcare team will closely monitor the immune system, using blood tests that measure the levels of various cell types. As part of this process, they monitor the neutrophils, the normal neutrophil range is 2-7.5.

Neutrophils are monitored because they are the most abundant type of WBC. Since neutrophils are the first to rush to the site of an infection and attack foreign organisms, lack of neutrophils (neutropaenia) is an indication that the body may be unable to successfully defend itself against infection.

Treatments to help fight infection AND boost the immune system

Antibiotics are used to treat an infection once it occurs and are sometimes given to prevent infections.

In addition, G-CSF  is given as a daily injection  until the Neutrophil count begins to climb G-CSF helps to increase the body’s production of  WBCs (neutrophils, Monocytes/macrophages and dendritic cells) thereby helping activate the body’s natural defences against infectious organisms such as bacteria, viruses, and fungi.

 

Information and diagrams sourced from Leukine.com, editing by JRSH, formatting by LHH