Substitution of Dexamethasone in ALL Treatment Leads to Fatal Side Effects

Substitution of Dexamethasone in Acute Lymphocytic Leukemia Treatment Regimen Leads to Fatal Side Effects

In children with acute lymphocytic leukemia, the substitution of dexamethasone for prednisone may cause severe side effects including death, with no apparent treatment benefit, according to a recent article published in the journal Cancer.

Acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, is a cancer of the bone marrow and lymph system. The bone marrow produces early blood-forming cells, called stem cells, which grow and mature into the three blood cell types: white blood cells, which fight infection; red blood cells, which carry oxygen to the tissues; and platelets, which help the blood to clot. ALL is characterized by uncontrolled production of immature lymphocytes, or white blood cells. These immature lymphocytes never mature enough to perform their specific function of fighting infection. In addition, these rapidly dividing cells crowd out and suppress the formation of other important blood cells such as the red blood cells, platelets and other white blood cells.

Standard initial treatment for patients with ALL includes multiple chemotherapy agents plus a glucocorticoid, usually prednisone or methylprednisolone. However, prednisone and methylprednisolone are not effective at penetrating the barrier surrounding the central nervous system (CNS). Therefore, researchers have been investigating other therapy combinations that are able to enter the CNS in order to kill any cancer cells that may be present. Dexamethasone, another glucocorticoid, has shown superior CNS penetration capabilities over prednisone or methylprednisolone. This fact has led to a clinical trial evaluating dexamethasone in place of prednisone or methylprednisolone for the initial treatment of ALL.

A multi-institutional clinical trial was recently conducted in which pediatric patients with ALL received a combination of chemotherapy agents plus prednisone or dexamethasone. Nearly 11% of patients receiving the regimen containing dexamethasone died due to complications from the treatment combination. In addition, nearly 32% of the rest of the patients receiving dexamethasone had life-threatening complications caused by the treatment combination. Conversely, less than 1% of patients receiving the combination containing prednisone died due to treatment complications. There was no benefit regarding anti-cancer responses with the use of dexamethasone versus prednisone.

These results clearly indicate that dexamethasone in place of prednisone for the initial treatment of ALL may drastically increase the risk of treatment related fatality. Although dexamethasone can penetrate the central nervous system in a superior manner compared to prednisone, no treatment benefits were found with dexamethasone. In addition, the risk of severe side effects from dexamethasone significantly outweighs any potential benefits that could be achieved with this treatment combination. (Cancer, Vol 88, No 8, pp 1964-1969, 2000)

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