Acute Lymphoblastic Leukemia (ALL) in Infants

Acute lymphoblastic leukemia (ALL) is rare in infants. About 90 cases occur in children 1 or younger each year in the United States – about 3 percent of childhood ALL cases. Even the largest pediatric cancer centers may only see a few cases a year.

Diagnosis

Diagnosis of ALL involves a physical exam, medical history, blood tests, bone marrow aspiration and biopsy, and lumbar puncture. Tests will be run to determine the specific kind of ALL and identify chromosome changes, genes, proteins, and other factors involved in the leukemia. This information will have an impact on treatment approaches and predicted treatment outcome (prognosis).

Infant ALL is biologically different from ALL in older children. It is typically very aggressive. Most infants – as many as 80% -- have a rearrangement in a gene called MLL (mixed lineage leukemia). Another name for MLL is KMT2A.

Treatment

The main treatment for ALL in infants is chemotherapy with many different medicines. Treatment has different phases. It typically lasts about 2 years. Chemotherapy medicines may include cyclophosphamide, cytarabine, daunorubicin, dexamethasone, Erwinia asparaginase, etoposide, methotrexate, leucovorin, mercaptopurine, mitoxantrone, pegaspargase, prednisone, thioguanine, and vincristine.

Some patients may receive a hematopoietic cell transplant (also known as bone marrow transplant or stem cell transplant).

Physicians take a risk-stratified approach to treating infant ALL. In general, this approach means patients with a higher risk of relapse will receive more intensive treatment than those with lower risk.

When assigning a risk category, physicians consider:

• Presence or absence of MLL rearrangement: This rearrangement indicates a poorer response to therapy.
• Age: Infants closer to 1 typically respond better to treatment than infants younger than 6 months.
• Number of white blood cells: A very high white blood cell count at diagnosis indicates a poorer response to therapy.
• Timing of response to early therapy: If patients show a positive response to initial treatment, they are considered lower-risk.

Prognosis

The survival rate for infants with ALL is less than 50%.

Relapse

Infants with the MLL (KMT2A) rearrangement have a high risk of relapse. About two-thirds of infants will relapse within a year of diagnosis. At present, there are no treatment protocols for relapsed ALL in children younger than 1.

Side Effects of Treatment

Side effects vary among patients. The care team will work with families to try to prevent and/or lessen side effects as much as possible. The team will monitor side effects closely so that they can be treated. 

Infants are especially vulnerable to:

• Infections, particularly respiratory (such as respiratory syncytial virus (RSV))
• Mucositis (including mouth sores)
• Toxic effects on liver and kidneys
• Central nervous system damage

Research

Scientists and physicians continue to work closely in international cooperative groups to improve treatment options.

Clinical trials are underway to try new therapies designed to improve cure rates.

• One treatment approach under study adds 2 new anti-cancer drugs called bortezomib and vorinostat to the standard chemotherapy used to treat ALL in infants.
• Another study is evaluating using the drug azacitidine in combination with standard chemotherapy drugs.