Acute Myelogenous Leukemia (AML)

Introduction

The speaker introduces the topic of acute myelogenous leukemia and encourages viewers to support their channel by liking, commenting, and subscribing.

Acute Myelogenous Leukemia

The speaker explains that acute myelogenous leukemia is a problem with hematopoiesis, the production of all blood cells. It starts with a cell called the hemocytoplast in the red bone marrow. The hemocytoplast differentiates into two cell lines: lymphoid stem cells and myeloid stem cells.

• The myeloid stem cell differentiates into red blood cells, platelets, and granulocytes.

• Granulocytes include neutrophils, eosinophils, and basophils.

• Lymphoid stem cells become B lymphocytes and T lymphocytes.

• In AML patients, myoblasts cannot differentiate into pro-myelocytes and functional white blood cells.

• This causes an overproduction of myoblasts that crowd out the bone marrow and cause problems throughout the body.

Causes of AML

The speaker discusses three potential causes of AML.

• DNA mutation can cause a cell to continue replicating without dying.

• Chemoradiation therapy can cause DNA mutations that lead to AML.

• Other genetic mutations can also lead to AML.

Causes of Acute Myeloid Leukemia

In this section, the speaker discusses the causes of acute myeloid leukemia (AML), including genetic abnormalities and bone marrow disorders.

Genetic Abnormalities

• AML can be caused by genetic abnormalities that allow for excessive DNA replication and cell division without cell death.

• Down syndrome is a genetic abnormality that has a high association with AML due to trisomy 21.

• A subtype of AML called acute promyelocytic leukemia (APL) is caused by a 15;17 translocation that forms a fusion gene called PML-RARA.

Bone Marrow Disorders

• Underlying bone marrow disorders such as myelodysplastic syndrome (MDS) or chronic myeloid leukemia (CML) can progress to AML over time.

• The presence of too many myeloblasts in the bone marrow can lead to decreased red blood cells and platelets.

Consequences of High Myeloblast Count

In this section, the speaker discusses the consequences of having a high count of myeloblasts in the bone marrow.

• High counts of myeloblasts in the bone marrow can take up space and hog nutrients for other cell lines, leading to decreased red blood cells and platelets.

• This can cause symptoms such as fatigue, shortness of breath, and increased risk of infections.

High Risk of Infections and Other Consequences of Acute Myelogenous Leukemia

The speaker discusses the consequences of acute myelogenous leukemia, including a high risk of infections, anemia, thrombocytopenia, bone pain, bruising and bleeding.

High Risk of Infections

• Due to the inability to undergo phagocytosis or kill parasitic worms or trigger inflammatory reactions.

• Downstream consequences include a high risk of infections leading to mortality.

• Infections can cause pneumonia, UTIs, cellulitis or abscesses.

Anemia

• Low red blood cell count leads to anemia.

• Anemia causes fatigue and paleness in skin color.

• Severe anemia may cause dyspnea.

Thrombocytopenia

• Low platelet count leads to thrombocytopenia.

• Thrombocytopenia increases the risk of bruising and bleeding.

• Bruising may present as petechiae, purpura or ecchymosis. Bleeding may occur in the nose (epistaxis), gums (gingival bleeding) or GI tract.

Bone Pain

• Expansion of bone marrow due to crowding by myoblasts causes bone pain.

• Bone pain may present as back pain, chest pain or limping.

These are the main points discussed in this section.

Oncological Emergencies

This section discusses oncological emergencies that can occur when the white blood cell count is too high, leading to clotting of blood vessels and downstream occlusive effects.

Leukostasis

• Occurs when the myeloblast count is greater than or equal to 100,000.

• Can cause blockage of blood flow to specific areas of the body, leading to hypoxemia.

• Symptoms may include headache, TIA, ischemic stroke, dyspnea, acute respiratory failure, vision changes or complete vision loss.

• More common in AML but can also occur in ALL.

Tumor Lysis Syndrome

• Can occur spontaneously or as a result of treatment for leukemia.

• Happens due to a high tumor burden and chemotherapy.

• Intracellular contents such as potassium, phosphates and uric acid spill out causing harm to kidneys.

• Uric acid is nephrotoxic and can form urate crystals which deposit into the nephron causing damage.

• Phosphates combine with calcium forming calcium phosphate crystals like kidney stones which deposit into the kidney tubules causing damage.

• Precipitates acute kidney injury which can present as low urine output or high creatinine/bun levels.

Complications of Acute Myelogenous Leukemia

In this section, the speaker discusses the potential complications associated with acute myelogenous leukemia (AML).

Leukemia Cutis and Gingival Hyperplasia

• Deposits into the skin or mucosa can cause leukemia cutis or gingival hyperplasia.

• Leukemia cutis is a rare manifestation of AML that can be identified by its appearance on the skin.

• Gingival hyperplasia is another potential complication of AML that occurs when deposits are made in the gingiva.

Disseminated Intravascular Coagulation (DIC)

• DIC is a serious complication of AML that occurs when myoblasts release tissue factor and TPA enzymes.

• Tissue factor activates the extrinsic clotting pathway, leading to increased clotting and decreased clotting factors over time.

• TPA causes fibrinolysis, breaking down fibrinogen and fibrin strands, resulting in decreased ability to form stable clots.

• These effects lead to an increased bleeding risk, particularly in the brain or lungs.

Diagnosis of AML

• Diagnosis of AML involves identifying features such as high myeloblast count within bone marrow, fatigue, bone pain, and other symptoms.

Screening for AML

In this section, the speaker discusses the initial screening process for acute myelogenous leukemia (AML).

CBC with Peripheral Blood Smear

• A CBC with peripheral blood smear is a good screening test for AML.

• The test confirms or supports low red blood cells, low levels of platelets, and variable white blood cell counts.

• Tons of myeloblasts on a peripheral blood smear are indicative of AML.

Bone Marrow Biopsy

• A bone marrow biopsy is used to confirm the diagnosis of AML.

• Greater than 20 myeloblasts in the bone marrow is diagnostic for leukemia.

• Owl rods may be present in the bone marrow biopsy and are suggestive of APL subtype.

Prognostication and Treatment

In this section, the speaker discusses determining prognostication and treatment options for patients with AML.

Immuno Phenotyping

• Immuno phenotyping can determine if a patient has a specific subtype of AML, such as APL.

• This test looks at markers on the surface of cells to support the diagnosis.

Genetic Studies

• Genetic studies are more helpful than immuno phenotyping in determining prognosis and treatment options.

• These tests look at specific genetic mutations that can affect treatment decisions.

Conclusion

• Determining prognosis and treatment options is important after confirming an AML diagnosis.

Diagnosis of Acute Myelogenous Leukemia (AML)

In this section, the speaker discusses the diagnostic process for AML, including CBC with peripheral blood smear, bone marrow biopsy, immunohistochemistry, flow cytometry, and genetic studies.

Diagnostic Process

• Genetic studies are helpful in determining the specific subtype of AML and what type of treatment to institute.

• Karyotyping can be used to find abnormal chromosomes and translocations that suggest a subtype of AML.

• PCR can be used to identify specific fusion genes associated with certain subtypes of AML.

• CBC with peripheral blood smear is used to start off the diagnosis of AML.

• Flow cytometry is not very helpful in diagnosing AML but may be more useful for other types of leukemia.

Complications

• Tumor lysis syndrome can be tested for by looking for high levels of phosphates, uric acid, and potassium. Calcium levels should be low due to complexing with phosphates. Crystals formed from calcium phosphates and uric acid can cause acute kidney injury.

• DIC is another complication that can occur in AML. Coagulation parameters such as PTT, INR, fibrinogen, d-dimer, platelets and red blood cells should be monitored.

Conclusion

In conclusion, diagnosing AML involves a combination of tests including CBC with peripheral blood smear, bone marrow biopsy, immunohistochemistry flow cytometry and genetic studies. Genetic studies are particularly important in determining the specific subtype of AML which determines what type of treatment to institute. Complications such as tumor lysis syndrome and DIC should also be monitored.

AML and Treatment

This section discusses the treatment of Acute Myeloid Leukemia (AML).

Chemotherapy for Non-APL Subtype

• The primary treatment for AML is chemotherapy.

• Induction chemotherapy, consolidation chemotherapy, and maintenance chemotherapy are used to achieve complete remission.

• Cytarabine and Idarubicin/Donnarubicin are the preferred chemotherapeutic agents.

Chemotherapy for APL Subtype

• All-trans retinoic acid and arsenic are used to promote differentiation in patients with APL subtype.

• The goal is to differentiate myoblasts into promyocytes and then into white blood cells like neutrophils, eosinophils, and basophils.

• Differentiation syndrome can occur as a rare side effect.

Diagnosis of AML

This section discusses the diagnosis of Acute Myeloid Leukemia (AML).

Symptoms

• Symptoms include fatigue, fever, weight loss, easy bruising or bleeding, bone pain, and frequent infections.

Physical Examination Findings

• Gingival hyperplasia is a physical examination finding associated with AML.

Clinical Examination Findings

• Leukostasis is a clinical examination finding associated with AML.

Laboratory Tests

• Elevated D-dimer levels indicate fibrinolysis in patients with AML.

• Platelets get consumed along with red blood cells leading to degradation products.

DIC and Tumor Lysis Syndrome

This section discusses DIC (Disseminated Intravascular Coagulation) and Tumor Lysis Syndrome.

DIC

• DIC occurs due to the consumption of platelets in patients with AML.

Tumor Lysis Syndrome

• Tumor lysis syndrome is associated with AML.

• Fibrinolysis and consumption of platelets, red blood cells occur in this disease.

Treatment Options for AML

In this section, the speaker discusses the treatment options for Acute Myeloid Leukemia (AML), including chemotherapy and bone marrow transplant. They also cover the management of complications associated with AML.

Chemotherapy Options

• Chemotherapy is a common treatment option for AML.

• Two chemotherapeutic options are available: 7+3 regimen and FLAG regimen.

• The 7+3 regimen involves administering cytarabine and an anthracycline over seven days followed by three days of no treatment.

• The FLAG regimen involves administering fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF).

Bone Marrow Transplant

• Bone marrow transplant is another treatment option for AML patients who have poor prognostic findings or have failed chemotherapy.

• The goal of a bone marrow transplant is to create a new hemocytoplast that will produce functional white blood cells, red blood cells, and other cell lines.

Management of Complications

• Complications associated with AML include DIC, leukostasis, and tumor lysis syndrome.

• Leukostasis is characterized by having more than 100,000 white blood cells or myeloblasts clogging up arteries in various parts of the body.

• Cytoreduction is necessary to treat leukostasis quickly. This can be achieved through hydroxyurea or leukapheresis.

• Tumor lysis syndrome is commonly associated with chemotherapy.

Overall, this section provides an overview of the different treatment options available for AML patients as well as how to manage complications associated with the disease.

Understanding Tumor Lysis Syndrome

In this section, the speaker explains the importance of avoiding uric acid in patients with tumor lysis syndrome and how to prevent acute kidney injury.

Uric Acid and Purines

• Uric acid comes from purines.

• Uric acid causes kidney damage and nephrotoxicity.

• The goal is to avoid acute kidney injury by inhibiting the conversion of purines into uric acid.

Allopurinol and Rasburicase

• Allopurinol inhibits the conversion of purines into uric acid.

• Rasburicase helps convert uric acid into allantoin, which is less toxic to the kidneys.

• Giving both drugs can reduce the risk of acute kidney injury.

Flushing Out Crystals

• Keeping patients hydrated helps flush out crystals and prevent crystal formation.

• IV fluids can help keep kidneys continuously flushing out crystals.

Overall, it's important to keep patients properly hydrated, inhibit the conversion of purines into uric acid using allopurinol, convert uric acid into allantoin using rasburicase, and flush out crystals through IV fluids.