Although children with acute lymphoblastic leukemia (ALL) have a high survival outcome, it is still challenging to treat adult patients. Inferior survival rates are primarily attributed to the high risk of relapse in adults, which in turn, is partly related to the adverse genetic makeup observed in many adult patients. The increased risk of relapse, however, is also due to the inadequate chemotherapeutic regimens that have historically been used to treat adults.
Studies have shown that adolescents and young adults with ALL have consistently shown superior survival when they are treated with a pediatric treatment regimen under the guidance of a pediatrician, compared with similarly aged patients treated with adult regimens and those who are cared for by oncologists who primarily treat adults. These findings have prompted pediatric or pediatric-inspired regimens to be offered to adults aged 39 to 60 years with ALL.1
After remission is achieved, a key component of pediatric ALL regimens is to include multiple doses of asparaginase, a bacterial enzyme derived from Escherichia coli and Erwinia chrysanthemi. Asparaginase reduces the concentration of extracellular asparagine, a nutrient for leukemic cells, via hydrolysis to form aspartic acid and ammonia.1,2
Administering asparaginase can be a challenge for oncologists, as this treatment is used almost exclusively in ALL, which is rare in adults. Oncologists may also lack familiarity with dosing and safety profiles, as toxicities associated with asparaginase are unique and not found in other types of chemotherapeutic agents.
In a paper published in Blood, coauthors Ibrahim Aldoss, MD, of the Gehr Family Center for Leukemia Research, Department of Hematology and Hematopoietic Cell Transplantation at the City of Hope Medical Center in Duarte, California, and Dan Douer, MD, of the Jane Anne Nohl Division of Hematology at the University of Southern California in Los Angeles, described experiences in managing some adverse effects associated with pegasparaginase, the long-acting pegylated form of asparaginase, in adult patients with ALL.1 Pegasparaginase is currently the only E coli-derived asparaginase available in the United States, and is the first-line treatment in most countries.1,2
“Using a pediatric regimen, or something similar, can improve survival in adults,” said Dr Douer, “but most oncologists do not have experience with this drug and are reluctant to use it because of the toxicities.”
He pointed out that for most of the adverse events that occur over the course of treatment, there is no need to stop the asparaginase, as most are nonfatal, manageable, and reversible. “More and more physicians are switching to a pediatric regimen with multiple doses, and one of our goals is to guide physicians and take away their fear of this drug, and direct them how to [manage] toxicity,” he said.
Most adult patients up to the age of 60 years can be treated with a pediatric regimen that includes asparaginase. “Some studies go up to age 55, but it isn’t clear what the upper age limit is,” said Dr Douer. “But after age 60, it does become more toxic.”
It may also be contraindicated in patients who are morbidly obese, as they are at a higher risk of severe liver toxicity.