Acute Promyelocytic Leukemia: Symptoms, Causes, Treatment

Acute promyelocytic leukaemia (APL), also called APML or AML M3, is a rare but highly treatable form of blood cancer primarily affecting the bone marrow and blood cells. APL comprises about 7% to 8% of all adult AML cases. Normally, stem cells in the bone marrow produce blood cells, such as:

1. Red blood cells (erythrocytes) carry oxygen around the body

2. White blood cells (leukocytes) help fight infections

3. Platelets (thrombocytes) help form blood clots

Acute promyelocytic leukaemia is characterised by an abnormal accumulation of promyelocytes (immature white blood cells) in the bone marrow. These promyelocytes fail to mature into fully functioning blood cells, disrupting the normal balance of blood cell production.

Individuals with acute promyelocytic leukaemia may feel a loss of well-being. This may happen due to the accumulation of leukaemic cells in the bone marrow and the underproduction of normal blood cells. Acute promyelocytic leukaemia symptoms are generally non-specific and can resemble those of other types of leukaemia. Some of these symptoms include:

1. Fatigue: Individuals with this disease may experience fatigue and general weakness. It happens when there is a shortage of red blood cells due to leukaemia. 

2. Bleeding and Bruising: APL can interfere with the body’s ability to produce platelets, leading to problems with clotting. Signs of bleeding may include: 

1. Easy bruising

2. Prolonged bleeding from minor cuts

3. Frequent nosebleeds

4. Bleeding gums

5. Heavy menstrual periods

6. Hematuria (blood in the urine)

7. Petechiae (pinhead-sized red spots on the skin)

3. Mild Fever: Individuals with APL may have a weakened immune system, sometimes leading to mild fevers. 

4. Loss of Appetite: Some people may experience loss of appetite due to APL’s impact on the body’s metabolism.

5. Unexplained Weight Loss: Weight loss may occur due to loss of appetite, decreased food intake, or general weakness and fatigue that can accompany the disease. 

6. Frequent Infections: A decrease in healthy white blood cells can weaken the immune system. This makes individuals with APL more susceptible to infections. 

7. Pale Complexion: Anaemia (low red blood cell count) can cause paleness. A pale complexion may not be apparent in people with a dark complexion. 

8. Bone and Joint Discomfort: APL can cause bone and joint pain and discomfort. It may be felt as a dull ache or more intense discomfort.

9. Enlarged Spleen or Liver: Infiltration of leukaemic cells in the spleen or liver can disrupt their normal functioning and cause enlargement. This may cause pain or discomfort in the upper abdomen.  

10. Neurological Symptoms: Individuals with APL may experience neurological symptoms in rare cases when leukaemic cells invade the central nervous system. These symptoms may include headache, confusion, or visual changes. 

The primary acute promyelocytic leukaemia cause is a specific genetic abnormality known as the PML-RARA fusion gene. This gene results from a chromosomal translocation between chromosomes 15 and 17. 

1. In this translocation, a part of the PML gene on chromosome 15 and the RARA gene on chromosome 17 are fused. This fusion gene produces the protein PML-RARɑ.

2. Normally, the protein produced by the PML gene helps prevent the rapid division and growth of cells. 

3. The protein produced by the RARA gene helps white blood cells mature (differentiate) beyond the promyelocytic stage. 

4. However, the PML-RARɑ protein disrupts normal cell development and leads to the accumulation of immature promyelocytes.

5. Up to 98% of all APL cases result from PML-RARA gene fusion. The other few cases occur due to translocations involving the RARA or other genes. 

6. Since the chromosomal translocation occurs after conception, the condition is not inherited. 

Acute Promyelocytic Leukaemia Risk Factors

Several risk factors can lead to a higher risk of developing APL. Many individuals with APL do not have any known risk factors. Some common acute promyelocytic leukaemia risk factors include:

1. Chemotherapy: Individuals who undergo chemotherapy for previous cancer treatments have a greater risk of developing therapy-related APL. 

2. Ionising Radiation: High levels of ionising radiation, such as that experienced during radiation therapy or nuclear accidents, have been linked to an increased risk of developing APL.

3. Industrial Solvents and Toxic Agents: Long-term exposure to certain chemicals like benzene may increase the risk of developing APL. These chemicals are commonly found in certain industries, including petrochemical manufacturing, petroleum refining, and rubber manufacturing.

4. Age: While APL can occur at any age, it is most often diagnosed around 40. The disease is very rare before the age of 20.

5. Gender: APL affects men slightly more frequently than women. The reason for this gender difference is not well understood.

Acute promyelocytic leukaemia can not always be prevented. However, there are general strategies that can help promote an individual’s health and reduce the risk of developing various types of cancer, including APL. These include:

1. Maintain a Healthy Lifestyle: Healthy choices can improve general health and reduce cancer risk. These lifestyle choices include eating a well-balanced, nutritious diet, exercising regularly, avoiding tobacco use, and limiting alcohol consumption. 

2. Hydration: Drink plenty of fluids, primarily water, to stay well-hydrated. Adequate hydration is important for maintaining overall health. 

3. Food safety: Follow proper food safety practices to minimise the risk of foodborne illnesses when the immune system is weak. This includes:

1. Thorough cooking of meat, fish, and eggs 

2. Cooking fruits and vegetables before eating them

3. Eating only pasteurised cheese, yoghurt, and milk

4. Practising good hygiene during food preparation

4. Following Work Safety Guidelines: Individuals must follow safety guidelines if they work in an industry that involves exposure to chemicals linked to APL. These may include wearing appropriate protective equipment and adhering to recommended protocols to minimize exposure.

5. Regular Medical Screenings: Regular screenings and checkups can help identify signs or symptoms of APL at an early stage. It can also allow prompt management of health concerns. 

The exact diagnosis of the type of leukaemia can help doctors estimate how the disease will progress and determine the appropriate treatment approach. Acute promyelocytic leukaemia diagnosis starts with a physical exam and the patient’s medical history. Other tests performed to diagnose APL include:

1. Blood Tests: The doctor will collect a blood sample to analyse the complete blood count (CBC). CBC provides information about an individual’s level of blood cells. In APL, the CBC may reveal abnormal levels of white blood cells, red blood cells, and platelets.

2. Lab Tests: The doctor may perform several lab tests to diagnose the condition as per acute promyelocytic leukaemia pathology outlines. These tests include: 

1. Karyotyping: The test helps the doctor examine an individual’s complete set of chromosomes. The cells are stained, and a pathologist examines them under a microscope to identify genetic problems. 

2. Polymerase Chain Reaction (PCR): A sample of blood or bone marrow cells is studied to examine certain changes in the structure or function of the individual’s genes. 

3. Flow Cytometry: In this test, bone marrow cells are suspended in a fluid and passed before a laser beam. It helps doctors analyse the chemical and physical characteristics of cells.  

4. Fluorescence In-situ Hybridisation (FISH): Certain areas of the chromosomes are stained to detect and locate a specific DNA sequence. 

5. Next-generation Sequencing: The test allows doctors to analyse DNA and RNA samples of multiple genes simultaneously. 

3. Bone Marrow Tests: These involve the extraction of a small sample of spongy marrow inside the bones (biopsy) or liquid marrow (aspiration) from the hipbone. The sample is examined under a microscope to assess the presence of abnormal promyelocytes. 

How to Prepare for Doctor’s Consultation?

By preparing for a doctor’s consultation appointment, individuals can help ensure they make the most of their appointment and address any concerns effectively. The following are some tips to help individuals prepare:

1. Compile Medical History: Individuals must write their medical history, past illnesses, treatments, or surgeries. 

2. Write the Symptoms: Patients must be prepared to give information about the symptoms they experience. 

3. Enlist Medications: They should include information about medications, vitamins, or supplements they are taking. This will help the doctor understand any potential drug interactions. 

4. Make a List of Questions: It helps to enlist the questions the patient wants to discuss with their doctor. This helps ensure they cover all the important topics during their appointment.

What to Expect from the Doctor?

During a consultation for acute promyelocytic leukaemia, the doctor may ask several questions to understand the patient’s medical history, symptoms, and overall health. While the specific questions may vary, the following are some common ones to expect:

1. What symptoms are you experiencing?

2. When did you first experience these symptoms?

3. How severe are your symptoms?

4. Are these symptoms continuous or occasional?

5. Does anything seem to improve or worsen these symptoms?

6. Have you undergone treatments for any previous cancers?

7. Do you smoke or consume alcohol? If yes, how much?

8. Do you currently take any medications, supplements, or herbal remedies?

9. How are your symptoms affecting your daily life?

Questions to Ask the Doctor

During a consultation appointment, patients must ask questions to understand their diagnosis, treatment options, and what to expect moving forward. The following are some questions they may consider asking their doctor:  

1. What is the cause of my symptoms?

2. What tests will I need for diagnosis?

3. Is there a cure for the disease?

4. What are the treatment options available for APL? Which one do you recommend?

5. Are there any acute promyelocytic treatment guidelines to be followed?

6. How long will the treatment last?

7. Are there any available clinical trials that I should consider?

8. What are the expected side effects of the recommended treatment, and how will they be managed?

9. How will my treatment be monitored and evaluated? 

10. Are there any dietary or exercise recommendations to support my treatment and overall well-being?

11. What is the long-term outlook for APL? Are there any potential late effects or complications I should be aware of?

12. Should I seek a second opinion?

Patients should feel free to ask any other questions or address their concerns.

Even though APL is a subtype of AML, the treatment for APL differs from other subtypes of AML. The specific treatment plan may vary depending on the patient’s age, overall health, and APL risk classification. The disease is characterised into two risk categories based on the white blood cell count during diagnosis. These categories include:

1. Low risk: White blood cell count of 10,000/microlitre or less

2. High risk: White blood cell count above 10,000/microlitre

Treatment Phases for Acute Promyelocytic Leukaemia

Acute promyelocytic leukaemia treatment typically involves three distinct phases to manage the disease effectively. These treatment phases for APL include:

1. Induction: This initial treatment stage aims to reduce the number of leukaemia cells and induce remission.

2. Consolidation: After achieving remission in the induction phase, the consolidation phase aims to keep the disease in remission and eliminate any remaining leukaemia cells. 

3. Maintenance: The maintenance phase helps sustain remission and prevent relapse.

Common treatment options for APL include:

1. All-Trans Retinoic Acid (ATRA): This non-chemo drug is the most important component of APL treatment and is usually administered orally. It promotes the maturation of leukaemia cells by eliminating the PML-RARɑ protein. ATRA helps induce remission in about 8 in 10 individuals with AML. However, it may be combined with other treatments for long-lasting remission. 

2. Arsenic Trioxide (ATO): ATO is another non-chemo drug administered intravenously. It can be used in combination with ATRA or as a standalone treatment. According to studies, the combination of ATRA and ATO for low-risk APL is superior to the previous standard of care involving chemotherapy. 

3. Chemotherapy: In addition to ATRA and arsenic trioxide, chemotherapy drugs may be used to enhance the effectiveness of treatment. Anthracycline-based chemotherapy regimens, such as daunorubicin or idarubicin, are commonly used in the induction phase to reduce the number of leukaemia cells rapidly.

4. Bone Marrow Transplantation: Since APL has high cure rates, it is not the first treatment option. A bone marrow transplant is only considered for patients who relapse or are resistant to therapy. 

5. Supportive Care: Supportive care measures are implemented throughout treatment to manage side effects and prevent complications. This may include platelet transfusions to address bleeding tendencies and antibiotics to prevent or treat infections.

Please Note: The selection of the treatment approach is based on the patient’s condition and the treating doctor’s opinion. 

Cost of the Acute Promyelocytic Leukaemia

The cost of acute promyelocytic leukaemia in India is generally influenced by numerous factors including patient’s age, treatment technique used, type and location of the hospital, insurance coverage, diagnostic tests and many more.

To know the exact cost of acute promyelocytic leukaemia, one must consult their healthcare provider or the below mentioned table provides an approximate cost of various treatment techniques used to treat acute promyelocytic leukaemia.

Acute Promyelocytic Leukaemia Survival Rates 

The survival rates for acute promyelocytic leukaemia have significantly improved in recent years. With the current treatment protocols, the overall survival rates for APL are quite promising. 

1. The 2-year survival rate is as high as 97% in patients receiving ATRA-ATO treatment. 

2. The 2-year APL-free survival rate for patients receiving ATRA chemotherapy is 90%. 

However, it is important to remember that survival rates are general statistics and cannot predict an individual’s outcome.

Acute Promyelocytic Leukaemia Prognosis 

Without treatment, the prognosis of APL is very poor. Most people without treatment survive less than a month after diagnosis due to complications like bleeding and infections. However, with modern treatment, the prognosis has significantly improved. Acute promyelocytic leukaemia relapse rate has also decreased with these treatment options. The prognosis can vary depending on several factors, including:

1. High WBC count 

2. Advanced age

3. Male gender

4. Elevated serum creatinine (waste products in the blood)

5. Fibrinogen levels (a protein that helps with blood clotting)

Acute promyelocytic leukaemia itself or its treatment can give rise to various complications. Close monitoring and timely interventions by a healthcare team can help minimise these complications and improve outcomes for individuals with APL. The complications of acute promyelocytic leukaemia include:

1. Coagulopathy: A significant complication of APL is the risk of bleeding and clotting abnormalities. This happens due to the decreased platelets and clotting factors in APL patients. 

2. Infections: APL may disrupt the production of healthy white blood cells, weakening the immune system. This makes individuals more susceptible to infections.

3. Differentiation Syndrome: A potentially life-threatening complication that can occur during APL treatment, particularly in the early stages. It occurs when leukaemia cells release chemicals in the bloodstream and cause symptoms like:

1. Fever

2. Fluid retention

3. Respiratory distress

4. Low blood pressure

5. Kidney damage

4. QT Interval Prolongation: It is a heart rhythm disorder caused by drugs such as ATO. The drug’s effect on electrolyte levels can cause fast heartbeats, leading to sudden fainting or seizures. 

5. Hyperleukocytosis: The complication occurs when there is an excessive increase in the number of abnormal promyelocytes in the blood. 

Risks of Delayed Treatment

Since acute promyelocytic leukaemia is a fast-growing cancer, it can lead to several risks and complications if treatment is delayed. Delayed acute promyelocytic leukaemia complications include:

1. Organ Dysfunction: Acute promyelocytic leukaemia causes leukaemic cells to infiltrate organs like the spleen, liver, lungs, and central nervous system. If treatment is delayed, the risk of organ dysfunction may increase. 

2. Increased Bleeding and Blood Clotting:  APL can disrupt the body’s normal blood clotting mechanisms, leading to a higher risk of bleeding. Delayed treatment can exacerbate these bleeding tendencies. Additionally, abnormal clotting can occur, increasing the risk of blood clots forming in blood vessels (disseminated intravascular coagulation).

When to See a Doctor?

If an individual suspects acute promyelocytic leukaemia, it is crucial to see a doctor promptly, even if the disease is unlikely to be the cause. The following are some specific symptoms that people should look out for:

1. Chronic fatigue

2. Frequent infections

3. Unexplained fever

4. Excessive bleeding or bruising

5. Pale skin

6. Bone or joint pain

The treatment for APL can make patients feel tired and weak. Eating a healthy diet is important to support overall well-being and help manage potential side effects of treatment. Here are some general dietary guidelines that may be beneficial: 

Foods to Eat

Patients should focus on eating nutrient-rich foods, which include:

1. Protein: It heals the body and strengthens the immune system. Sources include:

1. Fish

2. Poultry

3. Lean red meat

4. Eggs

5. Peas

6. Beans 

2. Carbohydrates: Foods rich in carbohydrates provide energy. Sources include:

1. Vegetables

2. Whole grains

3. Beans

3. Good Fats: It helps the body use energy and carry vitamins around the body. Sources include:

1. Vegetable oil 

2. Avocados  

Foods to Avoid

APL patients should avoid or limit foods like:

1. Sweets

2. Beverages

3. Salty snacks

These items often have low nutritional value and may result in weight gain and other health issues.

Acute promyelocytic leukaemia is a subtype of acute myeloid leukemia characterized by the rapid proliferation of abnormal promyelocytes. With advances in treatment, the prognosis for APL has significantly improved. Treatments like all-trans retinoic acid and arsenic trioxide offer high remission and survival rates.

Looking for a platform to help you navigate your APL journey? Trust the HexaHealth team to provide expert care and support throughout your APL treatment. We offer comprehensive evaluations and access to cutting-edge treatments to enhance patients’ quality of life. Get in touch with us TODAY!

Suggested Reads