Leukemias

Adult Acute Promyelocytic Leukemia

Adult acute promyelocytic leukemia (APL) is an aggressive subtype of acute myeloid leukemia that accounts for 5% to 10% of all subtypes of acute myeloid leukemia. Unlike other forms of acute myeloid leukemia, APL occurs most often in adults about 40 years old and older rather than adults 65 years of age or older.

APL is a cancer of the blood and bone marrow characterized by an abnormal buildup of immature bone marrow cells called promyelocytes, which under normal circumstances mature into granulocytes, that is, white blood cells that fight infection. The abnormal accumulation of promyelocytes in bone marrow results in reduced production of red blood cells and blood platelets.

APL is caused by a genetic mutation involving a reciprocal translocation (an exchange of chromosome material) between the gene for promyelocytic leukemia (PML) on human chromosome 15 and the gene for retinoic acid receptor-alpha (RARa) on chromosome 17. The translocation is the result of abnormal breaks in chromosomes 15 and 17. Chromosomes are long, coiled pieces of DNA containing genes. They are found inside cells.

Symptoms and Diagnosis

As in any other leukemia, symptoms of anemia or signs of infection can occur. However, this leukemia’s most serious manifestation is a previous disposition to bleeding. Prompt treatment with all-trans-retinoic acid (ATRA) or arsenic trioxide (as discussed below under treatment) can reverse this bleeding tendency.

For a diagnosis, your doctor may take a bone marrow biopsy and send the specimen for flow cytometry (a technique for counting and examining microscopic samples of cells) and cytogenetic analysis (analysis of blood or bone marrow cells that reveals the organization of chromosomes) to distinguish APL from other forms of acute myeloid leukemia. However, for a definitive diagnosis, your doctor will order a test to identify the fused PLM/RARa gene, either a test known as polymerase chain reaction or fluorescent in situ hybridization, or other cytogenetic testing (analysis of cells and chromosomes of your blood or bone marrow).

Treatment

APL was first described in 1957, and until the 1970s, there was no effective treatment for APL and it had a 100% mortality rate. Today, however, APL patients generally have very good outcomes from treatment, with about a 70% to 75% cure rate. The treatment of APL differs from the treatment of all other subtypes of acute myeloid leukemia because this type of cancer responds to ATRA therapy. ATRA is a derivative of vitamin A. It activates the retinoic acid receptors inside promyelocytes in bone marrow and causes them to mature and thus stop multiplying. A serious or life-threatening group of symptoms known as APL differentiation syndrome or retinoic-acid APL syndrome, characterized by fever, weight gain, difficulty breathing and swelling in the feet or legs, can occur with ATRA and requires prompt diagnosis and therapy. A high dose of the steroid drug dexamethasone is used to treat this syndrome.

ATRA therapy can induce a complete remission in most patients with APL; however, it is usually given in combination with anthracycline-based chemotherapy to improve the patient’s chances of long-term survival. Survival is better with combination therapy because the combination of ATRA and chemotherapy increases the rate of complete remissions with significantly fewer relapses. Without chemotherapy, ATRA therapy alone may induce remission for only a short time. After a complete remission, combination therapy is generally followed by at least two additional rounds of anthracycline-based chemotherapy.

Patients who relapse after combination therapy or patients who cannot tolerate chemotherapy may be given arsenic trioxide, a liquid drug injected into a vein usually over one to two hours. Arsenic trioxide, like ATRA, may also cause APL differentiation syndrome or retinoic-acid APL syndrome. Arsenic trioxide is being studied in the initial treatment of patients with APL.

Stem-cell transplantation using stem cells from bone marrow, umbilical cord blood or placenta may be given to the small number of APL patients who have disease that persists at a minimal level after combination therapy.

Patients 60 years old or older are frequently given less intensive chemotherapy than younger patients because they may be vulnerable to toxic effects related to treatment. For truly frail older patients who are considered unfit for chemotherapy, arsenic trioxide therapy with or without ATRA therapy is considered a reasonable alternative to ATRA therapy plus chemotherapy.

Patients who are anemic will receive blood transfusions to treat anemia by restoring red blood cells.

Additional Sources of Information

 

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