Acute Lymphocytic Leukemia - Treatment to Achieve Remission

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Side Effects and Complications

Side effects and complications of any chemotherapeutic regimen are common, are more severe with higher doses, and increase over the course of treatment. Toxicities can be reduced without loss of cancer-killing effects in some cases by administering the drugs for shorter duration.

Common Side Effects. Common side effects include:

• Nausea and vomiting. Drugs known as serotonin antagonists, such as ondansetron (Zofran) or granisteron (Kyril), can relieve these side effects in nearly all patients given moderate drugs and most patients who take more powerful drugs. In one study, nearly all patients who took a combination of dexamethasone (a steroid) in combination with ondansetron within 24 hours of chemotherapy experienced either a significant or complete reduction in nausea and vomiting.
• Diarrhea
• Hair loss
• Weight loss
• Depression

These side effects are nearly always temporary. Most patients are able to continue with normal activities for all but perhaps 1 or 2 days a month.

Serious Side Effects. Serious side effects can also occur and may vary depending on the specific drugs used. Infection from suppression of the immune system or from severe drops in white blood cells is a common and serious side effect. Patients should make all efforts to prevent them. The patient at high risk for infection may require very potent antibiotics and antifungal medications as well as granulocyte colony-stimulating factors or G-CSF (lenograstim, filgrastim) to stimulate the growth of infection-fighting white blood cells.

Other side effects include:

• Liver and kidney damage
• Abnormal blood clotting
• Allergic reaction
• Low blood sugar (hypoglycemia) -- a rare complication in young, thin children who are taking purine analogues such as mercaptopurine and thioguanine
• Shrinking of adrenal glands in children who take short-term, high-dose corticosteroids such as prednisolone

Long-Term Complications.

• Fatigue is very common after chemotherapy and can be significant and long-lasting.
• Combinations of intrathecal chemotherapy plus brain radiation in children can cause some serious complications, including seizures and problems in learning and concentration. Methotrexate is particularly toxic. (The effects of intrathecal chemotherapy alone on mental functioning, however, did not seem significant.) Seizures can often be treated successfully with anti-epilepsy medications.
• Late puberty. The effects of treatment in the brain can affect regions that regulate reproductive hormones, which may affect fertility later on.
• Bone loss can occur after chemotherapy, particularly with corticosteroids and after bone marrow transplantation. Drugs are available, particularly bisphosphonates, which may help reduce this risk.
• Pancreatic beta-cell damage. A 2004 study reported that children who have been off treatment for at least 1 year have a higher risk of impaired insulin response. This suggests that chemotherapy-induced beta cell damage persists after therapy has been stopped.
• Anthracyclines (doxorubicin, daunorubicin, epirubicin) have been associated with later development of heart failure. Of some encouragement, a 2000 study reported that low doses used for many ALL children may not pose a high risk to the heart. Some anthracyclines (DaunoXome, Myocet, Doxil) now come in tiny protective capsules that may reduce toxic effects.
• Mood disorders. According to a 2003 study, CNS radiation and MTX therapy were associated with an increased risk of mood disturbances (such as depression) among adult survivors of childhood ALL. This suggests that patients undergoing CNS radiation and MTX therapy may benefit from psychosocial support.

Review Date: 01/16/2007
Reviewed By: Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital