Acute Myeloid Leukemia (AML)

Acute Myeloid Leukemia (AML) is a kind of acute leukemia (cancers of blood cells) that affects a group of white blood cells called myeloid cells, which develop into several mature blood cells such as red blood cells, white blood cells, and platelets. "Acute" means that if the leukemia isn't treated, it will likely worsen quickly. AML causes abnormal myeloblasts (a kind of white blood cell), red blood cells, or platelets to form in the bone marrow. When abnormal cells crowd out healthy cells, infection, anemia, and frequent bleeding can occur. The abnormal cells can also move to other body sections outside the bloodstream.

AML can be divided into various subtypes. The subtypes are determined by how far the cancer cells have progressed and how different they are from normal cells at the time of diagnosis.

AML develops when bone marrow cells' genetic material (DNA) changes. The cause of these genetic changes has yet to be discovered. The DNA of a cell includes the information that tells it what to do. Usually, the cell's DNA directs it to grow at a specific rate and die at a particular time. The cell mutations in AML tell the bone marrow cell to keep growing and dividing. Blood cell production becomes uncontrollable as a result of this. The bone marrow creates immature cells that develop into leukemic white blood cells with myeloblasts. These abnormal cells can accumulate and crowd out healthy cells because they cannot operate properly.

The French-American-British (FAB) classification and World Health Organization (WHO) classification are two of the most common approaches for classifying AML into subtypes which are:

• AML with minimal differentiation (FAB M0)
• AML without maturation (FAB M1)
• AML with development (FAB M2)
• Acute myelomonocytic leukemia (FAB M4)
• Acute monoblastic/monocytic leukemia (FAB M5)
• Pure erythroid leukemia (FAB M6)
• Acute megakaryoblastic leukemia (FAB M7)

Some of the factors may increase your chances of developing AML.

Increasing age: AML becomes more common as people get older. Adults 65 and older are more likely to develop AML.

Sex: AML is more common in men than it is in women.

Cancer treatment in the past: AML is more likely to occur in people who have received specific chemotherapy or radiation therapy types.

Radiation exposure: AML is more likely to develop in people exposed to high quantities of radiation.

Chemical exposure and poisoning: Exposure to certain dangerous chemicals such as benzene has been related to an increased risk of AML.

Smoking: AML has been related to cancer-causing substances found in cigarette smoke.

Other Blood Disorders: AML is more likely to occur in those with other blood diseases, such as myelodysplasia, myelofibrosis, polycythemia vera, or thrombocythemia.

Genetic Disorders: Down syndrome and other congenital abnormalities are linked to an increased risk of AML.

The following are some of the signs and symptoms of AML:

• Fever
• Breathing difficulties
• Anemia 
• Pale skin
• Infections
• Frequent bruising or bleeding
• Petechia (tiny red dots that appear under the skin brought on by bleeding)
• Weakness or exhaustion
• Loss of appetite or weight loss
• Bone or joint pain (If abnormal cells develop near or inside the bones)

Your doctor may use a variety of methods to diagnose AML and determine which subtype you have:

• Physical examination and asking detailed medical history
• Blood testing includes a complete blood count (CBC) and a blood smear. Most people with AML have increased white blood cells but reduced red blood cells and platelets. However, the number of white blood cells in the body can sometimes be below. Another finding of AML is the presence of blast cells, which are immature cells found in bone marrow but do not circulate in the blood.
• Bone Marrow Tests: A blood test can indicate leukemia, but a bone marrow test is usually required to confirm the diagnosis. Bone marrow aspiration and bone marrow biopsy are the two most common procedures. Both tests require a sample of bone marrow and bone and are sent to a lab for testing.
• Genetic Tests: To look for gene and chromosome mutations
• If you've been diagnosed with AML, you'll likely need more testing to detect if cancer has spread.
• Imaging tests and a lumbar puncture (a process for collecting and testing cerebrospinal fluid (CSF)) are among them.
• Lumbar Puncture (Spinal tap): In certain situations, it may be necessary to remove some of the fluid around your spinal cord to check for leukemia cells. Your doctor can collect this fluid by inserting a small needle into the spinal canal in your lower back.

Differential Diagnosis 

• Aplastic Anemia 
• Neuroblastoma 
• Pancytopenia
• Histiocytosis 
• Lymphoproliferative Disorders
• Megaloblastic Anemia 
• Myelodysplasia 
• Gaucher Disease
• Acute lymphoblastic Leukemia 

You may have complications if you have Acute Myeloid Leukemia (AML). The condition itself can cause these, or they can happen due to treatment.

• Weakened Immune System: It is a common complication of AML. This makes you more susceptible to infection, and any condition you have could be more severe than usual.

• Bleeding: Because of the low platelet (clot-forming cells) levels in your blood, you may bleed and bruise more frequently. Excessive bleeding is also possible. People with advanced AML are more likely to experience internal bleeding.

• Infertility: It is a side effect of several medications used to treat AML. This is usually just temporary, although it can be permanent in some cases.

AML can be treated in a variety of ways, including:

• Chemotherapy: Chemotherapy is the most common remission induction therapy, although it can also consolidate remission. Chemotherapy is a type of treatment that uses chemicals to eliminate cancer cells in the body. Because the medications kill many normal blood cells while destroying leukemia cells, people with AML usually stay in the hospital throughout chemotherapy treatments. It is possible to repeat chemotherapy if the initial round does not remission.

• Targeted Therapy: Targeted medication treatments are designed to target specific abnormalities found in cancer cells. Targeted medication treatments can kill cancer cells by inhibiting these abnormalities. Targeted therapy can be administered alone or combined with chemotherapy for induction and consolidation therapy.

• Chemotherapy in Combination with a Stem Cell Transplant: Consolidation therapy may involve a bone marrow transplant, commonly known as a stem cell transplant which can help restore healthy stem cells by replacing diseased bone marrow with leukemia-free stem cells. You get very high doses of chemotherapy or radiation therapy before transplant to eradicate your leukemia-producing bone marrow. Then you get stem cell infusions from a compatible donor (allogeneic transplant). If you were previously in remission and had your healthy stem cells kept for a future transplant, you can also receive your stem cells (autologous transplant).

• Other anti-cancer medications

The treatment you receive is often determined by the subtype of AML you have. Treatment usually consists of two stages:

• The first phase aims to eliminate leukemia cells from the blood and bone marrow, putting leukemia into remission. The term "remission" refers to the reducing or disappearing signs and symptoms.
• Post-remission therapy is the second step of treatment. Its goal is to prevent cancer from relapsing (returning). It involves eliminating any remaining leukemia cells that may or may not be active but can grow back.

Drugs that target specific regions of cancer cells have been developed in recent years. Targeted medications differ from regular chemotherapy (chemo) drugs in how they function and cause side effects. They can be beneficial even when chemo isn't, or they can be administered in conjunction with chemo to improve its effectiveness. Certain people with acute myeloid leukemia may be prescribed some of these medicines.

• FLT3 Inhibitors such as Midostaurin and Gilteritinib
• IDH inhibitors such as Ivosidenib and Enasidenib
• BCL-2 inhibitors such as Venetoclax
• Hedgehog pathway inhibitors such as Glasdegib
• Chemotherapeutic agents such as Cytarabine, Daunorubicin, Etoposide, Arsenic Trioxide, etc. 
• Antiemetic agens like Ondansetron, Granisetron, Palonosetron. 
• Antimicrobials such as Sulfamethoxazole and trimethoprim.
• Antifungals like fluconazole.