Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) known as acute leukemia type M3. This type of leukemia is prone to combined bleeding, has an aggressive course, and previously had a very high mortality rate.
But in 1983, Academician Wang Zhenyi discovered that all-trans retinoic acid (ATRA) had a differentiation-promoting effect on APL cells, allowing the leukemic cells to “turn from good to evil”. In 1986, Dr. Wang succeeded in treating the first APL patient with ATRA, and in the same year, he successfully treated 24 APL patients. Since then, there has been a milestone progress in the treatment of APL. It has now become the best prognosis among the various subtypes of AML, with a long-term survival rate of up to 90% for near-cure acute leukemia.
The most important cause of APL is the formation of the PML-RARα fusion gene and other genes that form fusion genes with RARα, causing a series of gene regulatory changes in the body that lead to the development of the disease.
The three main symptoms of APL are bleeding, infection, and anemia. Anemia manifests as pale skin, weakness, dizziness, and loss of appetite; infection manifests as recurrent cold symptoms, fever, abdominal pain and diarrhea, and perianal abscess.
The bleeding symptoms of APL are very pronounced, often manifesting as large subcutaneous petechiae, commonly referred to as “bruises”. In severe cases, there are life-threatening signs of gastrointestinal bleeding or intracranial hemorrhage. Routine blood tests often reveal a decrease in white blood cells, hemoglobin and platelets. Therefore, APL is highly suspected when there is significant bleeding and the blood count is reduced.
APL requires urgent treatment, and when APL is suspected, it is a race to initiate treatment with retinoic acid immediately. This is because the early mortality rate in APL is 10%, and almost all deaths are due to intracranial hemorrhage. If you can treat it a minute earlier, you reduce the risk of bleeding by a minute.
All-trans retinoic acid (ATRA) is the standard of care, and ATRA induces differentiation of tumor cells into mature cells and has no killing effect on normal cells. Therefore, the mechanism of action is completely different from other antitumor drugs that have a cell-killing effect.
Of course, ATRA has side effects, and one that requires special attention is the possible development of vincristine syndrome during treatment, which manifests as fever, weight gain, musculoskeletal pain, respiratory distress, and even death. After the appearance of related symptoms, ATRA should be discontinued and therapeutic measures should be taken to be able to control the symptoms.
Arsenic agents were also first identified by Chinese scientists as a potent agent for APL. Retinoic acid therapy, arsenic, and some consolidation chemotherapy can provide long-term survival for most patients, and generally do not require bone marrow transplantation, greatly reducing the cost of treatment for patients. Arsenic is also effective in controlling the disease if a relapse does occur. The total cost of treatment is less than for other types of leukemia. Also, patients are more tolerant of treatment because the treatment regimen has less impact on normal cells. Allogeneic hematopoietic stem cell transplantation may be considered for patients with multiple relapses.
For patients with APL, the two key things are early detection and regular therapy, with cure rates of more than 90%. Therefore, we confidently believe that APL is a curable class of acute leukemia.