E Coli-Asparaginase Superior to Erwinia-Asparaginase for Pediatric ALL
According to results recently published in the journal
Blood, asparaginase obtained from
Eschericia coli appears to improve survival compared to asparaginase obtained from
Erwinia chrysanthemi in children with acute lymphoblastic leukemia.
Acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin’s lymphoma (NHL) are cancers 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 tissue; and platelets, which help blood to clot. ALL and lymphoblastic NHL are characterized by uncontrolled production of immature lymphocytes (white blood cells), of which there are two types: B and T 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 red blood cells, platelets and other white blood cells.
Asparaginase, used in addition to chemotherapy, radiation and/or stem cell transplantation, has remained an important treatment component for pediatric ALL or lymphoblastic NHL. Asparaginase is an enzyme, or type of protein, that destroys an amino acid called asparagine. Asparagine is essential to all living cells for the production of many proteins. Cells can either internally produce asparagine or they can absorb asparagine from outside the cell, as it is obtained from a person’s diet and made available through the bloodstream to all cells in the body. Cancer cells, particularly lymphoma cancer cells, require more asparagine than normal cells, as they are continually replicating. Due to the high levels of asparagine needed by cancer cells, internal production, which is limited, cannot maintain the demands needed for replication. Thus, cancer cells rely on absorbing asparagine from outside the cell. Conversely, most normal cells do not grow and replicate near the rate of cancer cells, and can rely on internal production of asparagine to maintain necessary levels. Asparaginase destroys asparagine that is in the bloodstream, so that cells can only access asparagine that is produced internally.
There are two bacteria from which asparaginase can be isolated:
Eschericia coli (E coli) and
Erwinia chrysanthemi(Erwinia). No previous clinical trial has directly compared the two in the treatment of pediatric ALL or lymphoblastic NHL. Researchers from the European Organisation for Research and Treatment of Cancer-Children’s Leukemia Group (EORTC-CLG) recently conducted a clinical trial to directly compare safety and long-term outcomes between
E coli-asparaginase and
Erwinia-asparaginase as initial treatment in patients with pediatric ALL or lymphoblastic NHL. This trial involved 700 patients, 93% of whom had ALL, who were newly diagnosed.
Following initial therapy, 94.5% of patients treated with
E coli-asparaginase achieved a complete remission (disappearance of cancer) compared with 91% of patients treated with
Erwinia-asparaginase. Approximately seven years following therapy, the relapse rate was 1.5 times higher in the group of patients treated with
Erwinia-asparaginase. Overall survival at six years following therapy is 83.9% for patients treated with
E coli-asparaginase, compared to 75.1% in patients treated with
Erwinia-asparaginase. Coagulation (blood clotting) abnormalities occurred in 30.2% of patients who received
E coli-asparaginase, compared with only 11.9% of patients who received
Erwinia-asparaginase. There was no significant difference in any other side effects between the two groups.
These results indicate that asparaginase isolated from
E coli as opposed to
Erwinia may reduce the risk of a cancer relapse and improve long-term survival in pediatric patients with ALL or lymphoblastic NHL. Parents with children who have ALL or lymphoblastic NHL may wish to speak with their physician about the risks and benefits of
E coli asparaginase as a component of their treatment regimen. (Duval M, Suciu S, Ferster A, et al. Comparison of Eschericia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children’s Leukemia Group phase 3 trial. Blood. 2002;99:2734-2739.)
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