OVERVIEW

What is acute promyelocytic leukemia?

Acute leukemia (AL) is a group of malignant clonal diseases originating from hematopoietic stem cells, divided into two main types: acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Acute promyelocytic leukemia (APL) is a clinically and biologically distinct variant of AML, characterized by a high early mortality rate, primarily due to bleeding caused by its distinctive coagulopathy.

Patients with APL not only endure physical suffering but may also experience significant psychological distress. However, it is crucial not to lose hope in treatment. If a family member or friend is diagnosed with APL, please provide them with ample emotional support and encourage them to pursue treatment actively.

How common is acute promyelocytic leukemia?

Geographically, APL accounts for 5%–20% of AML cases. In the United States, statistics show 600–800 new cases annually, while its incidence in China is approximately 0.23 per 100,000 people. APL is rare before the age of 10, predominantly affecting adults, with a median onset age of 44 and no gender predilection.

SYMPTOMS

What are the common manifestations of acute promyelocytic leukemia?

Patients typically exhibit symptoms related to complications of pancytopenia (i.e., anemia, neutropenia, and thrombocytopenia), including weakness, fatigue, infections of varying severity, and/or bleeding manifestations such as gum bleeding, ecchymosis, epistaxis, or menorrhagia.

Some patients may develop APL-associated coagulopathy, which is often an emergency. Without treatment, it can lead to pulmonary or cerebrovascular hemorrhage in up to 40% of patients, causing 10%–20% of early hemorrhagic deaths.

What serious consequences can acute promyelocytic leukemia cause?

Without treatment, APL is the most aggressive subtype of AML, with a median survival of less than 1 month. APL-specific pulmonary or cerebrovascular hemorrhage secondary to disseminated intravascular coagulation (DIC) can cause early death in 10%–20% of patients.

CAUSES

What are the common causes of acute promyelocytic leukemia?

Acute myeloid leukemia (AML) results from a series of genetic mutations in hematopoietic precursor cells. These mutations alter the normal growth and differentiation of hematopoietic cells, leading to the accumulation of large numbers of abnormal immature myeloid cells in the bone marrow and peripheral blood. These cells retain the ability to divide and proliferate but cannot differentiate into mature hematopoietic cells.

The cytogenetic hallmark of acute promyelocytic leukemia (APL) involves the translocation of the RARA locus on chromosome 17. The vast majority of APL cases carry the t(15;17)(q24;q21.1) mutation.

Who should be vigilant about acute promyelocytic leukemia?

Suspicion of acute promyelocytic leukemia should arise based on the characteristic morphology of leukemia cells, immunophenotype, or the presence of severe coagulation dysfunction.

DIAGNOSIS

What tests are needed for acute promyelocytic leukemia? What are the purposes of these tests?

Blood tests, bone marrow examination, cytochemistry, immunology, chromosome and molecular biology, blood biochemistry changes

• Blood tests: Routine examination for leukemia patients.

• Bone marrow examination: Bone marrow cell morphology is the basis for diagnosing acute promyelocytic leukemia. In typical APL cases, malignant promyelocytes usually account for more than 30% of myeloid cells in the bone marrow.

• Cytochemistry: Combines cells and chemistry to display chemical components and their distribution in intact leukemia cells, helping to differentiate types of acute leukemia. Abnormal promyelocytes typically show strong myeloperoxidase (MPO) positivity, while 1/4 of cases exhibit weak nonspecific esterase (NSE) reactivity.

• Immunology: Determines the origin of leukemia cells based on lineage-specific antigens. Specific immunophenotypes correlate with cell morphology and chromosomal changes. Immunophenotyping plays a supportive role in APL diagnosis. Typical findings include expression of CD13, CD33, CD117, and MPO, with absent or weak expression of CD34, HLA-DR, CD11b, CD14, CD64, and CD56. CD56 expression in a minority of patients suggests a poorer prognosis.

• Cytogenetics and molecular biology: Guides diagnosis and treatment. Classic APL shows t(15;17)(q22;q12). Variant APL accounts for 2%, including t(11;17)(q23;q12), t(5;17)(5q35;q12), t(11;17)(q13;q21), der(17), t(17;17)(q24;q12), t(4;17)(q12;q21), t(X;17)(p11;q21), t(2;17)(q32;q21), t(3;17)(q26;q21), t(7;17)(q11;q21), t(1;17)(q42;q21), etc. About 5% of APL patients have a normal karyotype. Conventional chromosome testing may also reveal additional abnormalities beyond t(15;17). Over 98% of APL patients carry the PML-RARα fusion gene, making its detection one of the most specific and sensitive diagnostic methods for APL, as well as a reliable indicator for treatment selection, efficacy evaluation, prognosis analysis, and relapse prediction.

• Blood biochemistry tests: Provides a comprehensive assessment of the condition.

Being diagnosed with acute promyelocytic leukemia can be difficult for anyone to accept, and some may even develop extreme thoughts. Others may feel guilty, believing they are burdening their families. At this time, family and friends must offer patients sufficient support and companionship, helping them adjust their mindset and quickly engage in treatment.

What are the variant subtypes of acute promyelocytic leukemia?

APL has two morphological variants: hypergranular and microgranular.

• Hypergranular: The most common variant, also called "classic" APL, accounting for about 75% of cases. On Wright-stained smears, these promyelocytes typically contain densely packed bright pink, red-blue, or dark purple cytoplasmic granules. Some may show Auer rods.

• Microgranular: Accounts for about 25% of cases. Under light microscopy, cells of this variant often exhibit bilobed nuclei with inconspicuous granules.

TREATMENT

Which department should I visit for acute promyelocytic leukemia?

Hematology.

Can acute promyelocytic leukemia be cured?

With modern standardized treatment, APL may currently have the highest cure rate among leukemia types, so active treatment is essential.

How is acute promyelocytic leukemia treated?

APL is a medical emergency with high early mortality, often caused by bleeding due to characteristic coagulopathy. Therefore, a critical aspect of APL treatment is that once APL is suspected based on cytological criteria, treatment with all-trans retinoic acid (ATRA) should begin immediately without waiting for cytogenetic or other tests to confirm the diagnosis. ATRA promotes terminal differentiation of malignant promyelocytes into mature neutrophils. However, ATRA must be combined with other drugs to achieve prolonged remission.

What are the treatment options for acute promyelocytic leukemia?

Currently, the most widely used approach is ATRA combined with anthracycline-based chemotherapy.

• For low- or intermediate-risk APL (initial white blood cell count < 10 × 10⁹/L), ATRA plus ATO (arsenic trioxide) can be used.
• High-risk patients are recommended to receive ATRA plus cytotoxic chemotherapy, with 80%–95% achieving complete remission.

DIET & LIFESTYLE

What should patients with acute promyelocytic leukemia pay attention to in their daily life and diet?

• At the onset of the disease or during the initial treatment, when the tumor burden is high, it is necessary to monitor drug efficacy and side effects. Patients should drink plenty of water and urinate frequently. If necessary, urine alkalization and medications to aid uric acid excretion should be used, while reducing the intake of high-purine foods.
• During the stable remission phase, daily life and diet can be similar to those of healthy individuals.
• In the advanced or severe stages, precautions should be taken to avoid infections and overexertion. If thrombocytopenia is present, physical activity should be reduced to minimize the risk of bleeding.
• During medication, attention should also be paid to the use of other drugs or herbal supplements, as they may interfere with treatment efficacy.

Does acute promyelocytic leukemia affect fertility?

The disease itself has little impact on fertility, but the medications can affect the fetus. Drugs may enter the fetal body and cause malformations. It is also not recommended to discontinue medication for the purpose of pregnancy.

PREVENTION

How to Prevent Acute Promyelocytic Leukemia?

Acute promyelocytic leukemia is the result of a series of genetic mutations in hematopoietic precursor cells, and the exact cause is unclear, so there is no highly effective prevention method. However, avoiding various carcinogenic factors (such as ionizing radiation and harmful chemicals) in daily life may reduce the risk of developing acute promyelocytic leukemia.