Introduction:
Leukemia is a group of cancers that appear in the cells that produce blood cells. It is a cancer of bone marrow and blood and is classified as an acute form of leukemia if it progresses fast without any treatment. Acute promyelocytic leukemia is a subtype of an acute form of leukemia known as acute myeloid leukemia (AML). It is one of the eight subdivisions of AML, and in myeloid leukemia, a cancerous change is seen in the marrow cell that usually forms certain blood cells, such as red blood cells, white blood cells, and platelets.
What Is Acute Promyelocytic Leukemia?
Acute promyelocytic leukemia (APL) is a type of blood cancer in which a marked increase in the type of white blood cells known as promyelocytes (immature white blood cells) can be seen. In acute promyelocytic leukemia and other forms of leukemia, the bone marrow (cell-forming tissue) gets filled with malignant (cancerous) cells. It cannot produce normal functional cells like RBCs, WBCs, and platelets. The distinctive symptom of acute promyelocytic leukemia is coagulopathy (impaired clot formation), which can lead to excessive bleeding and may also cause thrombosis (blockage of veins or arteries due to a blood clot).
What Is the Frequency of Acute Promyelocytic Leukemia?
Acute promyelocytic leukemia is seen in 10 percent of acute myeloid leukemia cases. It is found to be in one percent of all childhood leukemias, most commonly seen in children of Hispanic or Mediterranean descent, and has a lower incidence for African Americans. The average age of children with this condition is found to be 8 to 10 years, and it is uncommon in children younger than three years of age. The incidence of APL is the same in males and females. In the U.S.A, the occurrence of acute promyelocytic leukemia is found to be 1 in 250,000 people. If it is diagnosed, it is considered a medical emergency.
What Are the Causes of Acute Promyelocytic Leukemia?
Acute promyelocytic leukemia occurs due to a genetic mutation involving two genes PML gene on chromosome 15 and the RARA gene on chromosome 17. The alteration of genetic material between these chromosomes 15 and 17, which are written as (15;17). This leads to the fusion of the PML gene with the RARA gene, and the protein formed from this fusion is called PML-RAR-alpha. This type of mutation occurs during the life of a person and is present in certain cells. This type of fusion or change in genetic material is called somatic mutation.
The protein PML-RAR-alpha functions differently from the normal proteins of PML and RARA genes. The protein produced by the RARA gene, which is RAR-alpha helps in the maturation of white blood cells, and the PML protein produced by the PML gene acts as a tumor suppressor and prevents the abnormal growth and division of cells. Therefore the abnormal protein PML-RAR-alpha interferes with the functioning of PML and RAR-alpha proteins. This leads to the abnormal development of blood cells, which cannot get past the promyelocyte stage. This leads to the accumulation of promyelocytes in the bone marrow, and the normal development of white blood cells gets disturbed, leading to acute promyelocytic leukemia.
What Are the Symptoms of Acute Promyelocytic Leukemia?
Patients with acute promyelocytic leukemia usually feel a loss of well-being because of the underdevelopment of normal blood cells and the accumulation of leukemic cells in the bone marrow. Some of the common signs and symptoms seen in patients with acute promyelocytic leukemia include -
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Pale complexion due to anemia.
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Fatigue.
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Mild fever.
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Frequent minor infections.
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Weight loss.
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Enlarged spleen (splenomegaly).
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Enlarged liver (hepatomegaly).
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Loss of appetite.
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Discomfort in bones or joints.
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Neurological symptoms such as headache, confusion, and visual impairment.
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Bleeding due to a meager platelet count leads to black and blue bruises on the skin without any trauma or injury, red spots called petechiae, and prolonged bleeding from minor injuries.
Bleeding is commonly seen in this condition due to low platelet count and low clotting factors. The bleeding can also occur in the brain and lungs, which can be fatal. Additionally, severe infections may also be seen at the time of diagnosis, and this can be very serious when the bone marrow gets suppressed during the treatment phase.
When to See a Doctor?
Diagnosing acute promyelocytic leukemia is considered a medical emergency, and prompt treatment is needed. However, the early signs of this condition are difficult to recognize and may resemble other conditions. Patients are advised to seek medical assistance if some of the following symptoms are noticed such as -
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Unexplained fever.
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Unusual bleeding.
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Chronic fatigue.
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Pale complexion.
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Frequent infections.
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Bruising.
How Is Acute Promyelocytic Leukemia Diagnosed?
The diagnosis of acute promyelocytic leukemia is made by conducting some blood and bone marrow tests along with the clinical signs and symptoms of the patient, which include -
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Complete Blood Count - The initial test that is usually advised is CBC (total blood count). In this test, the blood sample is taken and assessed for any abnormal white blood cells, such as abnormal promyelocytes or leukemic blast cells, which indicates APL, and the diagnosis can be confirmed by examining the same cells in the bone marrow.
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Bone Marrow Examination - If the blood test indicates APL after a bone marrow biopsy is advised to confirm the diagnosis. In the biopsy, a sample of bone marrow is taken mainly from the back of the hip bone. The sample is then assessed in the lab for the number and type of cells, and the amount of blood-forming activity occurring in the bone marrow and the excessive number of blast cells in the bone marrow is an indication of acute promyelocytic leukemia.
Apart from that, additional tests such as immunophenotyping and cytogenetic tests provide information regarding the type, course, and best way to treat the disease. Additional tests such as X-rays, body scans, and ECGs (electrocardiograms) are also done to detect additional symptoms occurring in this condition.
What Is the Treatment for Acute Promyelocytic Leukemia?
Prompt diagnosis and treatment are required in case of acute promyelocytic leukemia (APL), as this can quickly develop into a life-threatening bleeding condition. The treatment for APL differs from other types of acute myeloid leukemia. The treatment usually involves non-chemo drugs such as all-trans-retinoic acid (ATRA), and additional treatment therapies include chemotherapy and platelet transfusions or other blood cells.
The treatment is usually divided into three phases such as -
1. Induction - This is the first part of the treatment, which includes drugs like all-trans-retinoic acid (ATRA) which is usually combined with one of the following-
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Arsenic trioxide (ATO) is a non-chemo drug.
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Chemotherapy with anthracycline drugs such as Daunorubicin or Idarubicin.
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Chemotherapy plus Arsenic trioxide (ATO).
2. Consolidation (Post-remission Therapy) - In this phase, when the APL is in remission, the remaining leukemia cells are getting rid of which the help of the same drugs given in the induction phase; however, the dosage may vary.
3. Maintenance - In this phase, low doses of drugs over a more extended period are given. However, there is no need for maintenance therapy in people with a low risk of leukemia and a good response to drugs such as ATRA plus ATO.
Conclusion
Acute promyelocytic leukemia is an uncommon condition that can be easily managed with current therapies. However, this has been linked with multiple deaths during the initial phase of the treatment due to bleeding complications. Therefore patients must be monitored closely by the healthcare providers and manage any complications caused by this condition.
