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Cancer Types

Acute Myeloid Leukemia: What patients should know about

Materials of this image are taken from Vecteezy.com

May 24, 2024, 10:50

Acute Myeloid Leukemia: What patients should know about

What is Acute Myeloid Leukemia?

Acute myeloid leukemia (AML) is a severe and aggressive form of blood cancer characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. It is one of the most common types of leukemia in adults, with a significant number of new cases diagnosed annually in the United States. This comprehensive review article of AML covers everything about this cancer including its causes and risk factors, symptoms, current diagnostic modalities, treatment options, ongoing clinical trials, prognosis, and everything else that patients should know about their disease in 2024.

This image is taken from Cancer Research UK / Wikimedia Commons

Causes and Risk Factors

The exact cause of AML is not fully understood, but several risk factors have been identified:

Genetic factors: Certain genetic mutations and chromosomal changes are associated with AML.
Environmental exposure: Long-term exposure to benzene and certain other chemicals is linked to higher AML risk.
Radiation exposure: Previous radiation therapy or exposure to high levels of radiation can increase AML risk.
Previous chemotherapy: Treatment with certain chemotherapy drugs can lead to “secondary” AML.
Smoking: Tobacco use is a significant risk factor, as it exposes the body to benzene and other carcinogens.

Symptoms

Acute Myeloid Leukemia (AML) is characterized by a variety of symptoms that result from the proliferation of abnormal myeloid cells and the consequent reduction in normal blood cells. The symptoms of AML can be broadly categorized into general symptoms, symptoms caused by low numbers of blood cells, and symptoms due to the infiltration of abnormal cells in various body tissues.

General Symptoms of Acute Myeloid Leukemia

Fatigue and weakness, often due to anemia.
Fever, which may be related to infections due to decreased immunity.
Weight loss and loss of appetite, are common in many types of cancer, including AML.
Night sweats are another common symptom of AML.

Symptoms from Low Blood Cell Counts

AML leads to a decrease in the production of normal blood cells, causing:

Anemia, resulting in pallor, dizziness, and shortness of breath.
Neutropenia (low white blood cell count), increasing the risk of infections.
Thrombocytopenia (low platelet count), leading to easy bruising, bleeding gums, and frequent or severe nosebleeds.

Symptoms from High Numbers of Leukemia Cells

The accumulation of leukemia cells can lead to:
Bone or joint pain, due to the buildup of these cells in the bone marrow.
Swelling in the abdomen, from an enlarged spleen or liver.
Difficulty breathing, if the leukemia cells infiltrate the lung tissue.

Rare and Emergency Symptoms

Leukostasis, a medical emergency where high counts of leukemia cells clog blood vessels, potentially leading to stroke-like symptoms.
Disseminated intravascular coagulation (DIC), a condition causing both thrombosis and hemorrhage.

These symptoms are not exclusive to AML and can be caused by other conditions, making it essential for individuals experiencing these symptoms to seek medical evaluation for an accurate diagnosis.

Diagnosis

The diagnosis of acute myeloid leukemia (AML) involves a combination of clinical evaluation, blood tests, and bone marrow examinations. Here’s a detailed look at the diagnostic process based on the provided sources:

Initial Evaluation and Blood Tests

Physical Examination and Medical History

Doctors begin with a thorough physical examination and review of medical history, focusing on symptoms like fatigue, bruising, infections, and bleeding.
Blood tests are crucial in the initial stages. A complete blood count (CBC) is typically performed to check the levels of white blood cells, red blood cells, and platelets. In AML, there is often an increase in white blood cells, predominantly immature forms called blasts, and decreased red and platelet cells.

Bone Marrow Biopsy and Aspiration

Bone Marrow Tests

A definitive diagnosis of AML requires an examination of the bone marrow. Bone marrow aspiration and biopsy are performed to collect and examine marrow cells.
This procedure usually involves numbing a spot on the hip bone and extracting a small sample of bone marrow. The sample is then analyzed under a microscope to detect the presence of leukemic cells.

Molecular and Genetic Testing

Cytogenetic and Molecular Analysis

Further tests include cytogenetic analysis to look for chromosomal abnormalities and molecular genetic testing to identify specific gene mutations.

Common genetic tests check for mutations in genes like FLT3, NPM1, IDH1, IDH2, and others, which help in determining the subtype of AML and guiding treatment decisions.

Additional Diagnostic Tests

Immunophenotyping and Flow Cytometry

These tests are used to identify specific markers on the surface of leukemia cells, helping to distinguish AML from other types of leukemia and to classify the subtype of AML.

Imaging and Other Tests

While imaging tests like X-rays or CT scans are not typically used to diagnose AML, they may be employed to check for infections or organ enlargement as a result of the disease.
In cases where there is concern about the spread of leukemia to the central nervous system, a lumbar puncture may be performed to examine the spinal fluid for leukemia cells.

Treatment

The treatment landscape for AML has evolved significantly over the years, with advancements in chemotherapy, targeted therapy, stem cell transplantation, and supportive care measures. This comprehensive overview delves into the current treatment modalities for AML, highlighting recent advancements and ongoing clinical trials that promise to further revolutionize the management of this challenging disease.

Chemotherapy

Chemotherapy remains the cornerstone of AML treatment, typically administered in two phases:

Induction therapy, aimed at achieving remission, and consolidation therapy, intended to eliminate any remaining leukemia cells. The standard induction regimen, known as “7+3,” combines cytarabine administered continuously for seven days with an anthracycline drug given for three days.

Despite its effectiveness, this regimen is associated with significant toxicity, limiting its use in older or less fit patients. Recent efforts have focused on developing lower-intensity regimens, such as the combination of venetoclax, a BCL-2 inhibitor, with hypomethylating agents (HMAs) or low-dose cytarabine, which have shown promising results in this patient population.

Targeted Therapy

The discovery of specific genetic mutations driving AML has led to the development of targeted therapies. These drugs are designed to block the growth and spread of cancer cells by interfering with specific molecules involved in tumor growth and progression. For example, midostaurin and gilteritinib target FLT3 mutations, while enasidenib and ivosidenib inhibit mutations in the IDH1 and IDH2 genes, respectively. These targeted agents can be used alone or in combination with chemotherapy, offering a more personalized treatment approach with potentially fewer side effects.

Stem Cell Transplantation

Stem cell transplantation (SCT) offers the potential for a cure in selected patients with AML. Allogeneic SCT, where stem cells are obtained from a donor, is considered for patients at high risk of relapse or those who relapse after initial therapy. The procedure involves the administration of high-dose chemotherapy or radiation therapy to eradicate the patient’s diseased bone marrow, followed by the infusion of donor stem cells to rebuild healthy bone marrow. Advances in donor matching, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis have improved outcomes, making SCT an option for a broader range of patients, including older adults.

Supportive care

Supportive care is an integral part of AML treatment, aimed at managing the side effects of therapy and maintaining the patient’s quality of life. This includes the use of antibiotics and antifungals to prevent or treat infections, transfusions to manage anemia and thrombocytopenia, and the use of growth factors to stimulate blood cell production. Additionally, the management of treatment-related toxicities, such as mucositis, nausea, and vomiting, is crucial for ensuring that patients can complete their prescribed therapy.

Ongoing clinical trials

Ongoing clinical trials for acute myeloid leukemia (AML) are exploring a variety of new treatment approaches, including targeted therapies, immunotherapies, and novel drug combinations. Here are some of the key ongoing trials and research directions:

Targeted Therapy and Molecular Inhibitors in AML

FLT3 Inhibitors: Clinical trials are investigating FLT3 inhibitors as a key component in targeted therapy for relapsed and refractory AML. These inhibitors, such as quizartinib, crenolanib, and sorafenib, target specific genetic mutations in the FLT3 gene, which are common in AML patients.
IDH Inhibitors: Trials are also focusing on inhibitors targeting mutations in IDH1 and IDH2 genes. These drugs, like AG221, aim to block the abnormal function caused by IDH mutations, which can contribute to the growth of leukemia cells4.
Menin Inhibitors: A new class of drugs, menin inhibitors, are being tested for their effectiveness in treating AML. Revumenib, a menin inhibitor, has shown promise in early-phase clinical trials, achieving complete remission in some patients with advanced AML.

Immunotherapy Approaches

Novel Immunotherapies: Researchers are exploring innovative immunotherapy treatments, such as genetically modified T-cells programmed to recognize mutations specific to AML. These therapies aim to enhance the immune system’s ability to target and destroy leukemia cells.
CAR T-cell Therapy: Although primarily used in other types of leukemia, CAR T-cell therapy is being studied for its potential application in AML. This approach involves modifying a patient’s T-cells to better recognize and attack leukemia cells.

Combination Therapies and Other Approaches

Combination of Chemotherapy and New Agents: Trials are testing combinations of traditional chemotherapy with new molecular inhibitors to improve outcomes. For example, the combination of CPX-351 (liposomal cytarabine and daunorubicin) with new agents like Glasdegib is being evaluated for specific subtypes of AML.
Venetoclax Combinations: Venetoclax, a BCL-2 inhibitor, is being tested in combination with other agents like azacitidine and decitabine. These combinations are aimed at treating newly diagnosed or relapsed AML patients.
Master Protocols: Some trials are using a “Master Protocol” approach to test multiple therapies simultaneously. This method allows for the rapid assessment of several investigational treatments to determine the most effective ones for different AML subtypes.

More information about completed and ongoing trials for AML can be found here – clinicaltrials.gov

Prognosis

Acute myeloid leukemia (AML) prognosis is influenced by several factors, including patient age, genetic mutations, and specific disease characteristics.

Key Prognostic Factors

Age: Younger patients generally have a better prognosis. The overall survival rate for patients under 20 is higher and it significantly drops for older patients, particularly those over 60.

Genetic Mutations: Certain genetic mutations can significantly impact prognosis. For example, mutations in FLT3, NPM1, and CEBPA genes are important for determining the course of the disease and the response to treatment.

Disease Subtype: Specific subtypes of AML, such as acute promyelocytic leukemia (APL), have a much better prognosis due to effective targeted therapies.

Impact of Treatment Response

Initial Treatment Response: Achieving complete remission with initial treatment is crucial for a favorable prognosis. Patients who do not achieve remission have a poorer outlook.

Measurable Residual Disease (MRD): The presence of MRD after treatment is a strong predictor of relapse. New technologies that improve the detection of MRD can lead to better disease management and improved patient outcomes.

Recommendations for Management

Clinical Trials: Participation in clinical trials is strongly recommended to access new therapies and contribute to research, potentially improving prognosis.

Tailored Treatment: Treatment plans should be personalized based on genetic findings and disease characteristics to optimize outcomes.

Patient’s Survivorship

Patients who have undergone treatment for cancer face a myriad of challenges during and after their treatment, which can affect their physical, emotional, and social well-being. Understanding these challenges is crucial for implementing effective coping strategies and seeking appropriate support. Here’s an overview of common problems faced by cancer survivors and recommendations on how to address them.

Watch this inspiring story of Tamara an AML survivor from Moffitt Cancer Center.

Physical Challenges

Fatigue and Weakness: Persistent fatigue is a common issue that can significantly impact daily activities and quality of life.

Recommendation: Engage in light physical activity and prioritize rest. Consult with a healthcare provider for management strategies tailored to individual needs.

Risk of Infection: The immune system can be weakened by cancer treatments, increasing the risk of infections.

Recommendation: Practice good hygiene and avoid exposure to infectious agents. Stay up to date with vaccinations as recommended by a healthcare provider.

Organ Dysfunction: Treatments such as chemotherapy can cause long-term damage to organs like the heart and kidneys.

Recommendation: Regular monitoring and follow-up care with healthcare providers to manage and mitigate organ dysfunction.

Secondary Cancers: Some treatments increase the risk of developing a second cancer.

Recommendation: Adhere to recommended screening schedules for early detection.

Infertility: Certain treatments can affect fertility.

Recommendation: Discuss fertility preservation options with a healthcare provider before starting treatment.

Emotional and Psychological Challenges

Anxiety and Depression: Survivors may experience significant emotional distress, including anxiety and depression.

Recommendation: Seek support from mental health professionals. Consider therapies such as cognitive-behavioral therapy (CBT) and mindfulness-based stress reduction (MBSR).

Fear of Recurrence: Worrying about cancer returning is common among survivors.

Recommendation: Engage in activities that promote a sense of control, such as regular follow-up appointments and healthy lifestyle choices. Support groups and counseling can also be beneficial.

Social and Practical Challenges

Financial Strain: The cost of cancer treatment can lead to financial difficulties.

Recommendation: Explore financial assistance programs offered by various organizations. Discuss payment plans and financial counseling options with healthcare providers.

Employment Issues: Returning to work can be challenging due to ongoing health issues or treatment side effects.

Recommendation: Understand your rights under employment laws. Seek accommodations through human resources departments.

Survivorship Care

Survivorship Care Plans: A personalized document summarizing diagnosis, treatment, and follow-up care recommendations is crucial for managing long-term health.

Recommendation: Request a survivorship care plan from your healthcare team. Use it to guide discussions with primary care providers and specialists.

Lifestyle Modifications: Adopting a healthy lifestyle can improve long-term health outcomes.

Recommendation: Incorporate a balanced diet, regular physical activity, and smoking cessation into your lifestyle. Seek guidance from healthcare professionals on specific recommendations.

Support Services: Accessing support services can help address the multifaceted challenges of survivorship.

Recommendation: Utilize resources such as support groups, counseling, and survivorship programs offered by cancer centers and community organizations.

Conclusion

AML is a serious and rapidly progressing form of leukemia that requires immediate medical attention. Advances in understanding the genetic basis of the disease have led to more targeted therapies, improving outcomes for some patients. Ongoing research and clinical trials continue to seek more effective treatments for AML.