Researchers at The University of Texas M. D. Anderson Cancer Center have found that when Gleevec is paired with high-dose chemotherapy, patients with Philadelphia-positive ALL have a more durable response than if they were treated with the standard therapy.
The Philadelphia-positive subtype, which accounts for one-fifth of ALL diagnoses, is extremely difficult to treat. Typically, two-year survival is only 12 percent to 28 percent following use of standard or high-dose chemotherapy, respectively, but is somewhat higher if a stem cell rescue is also used for patients who have a matched donor.
In a small study being reported at the annual meeting of the American Society of Hematology (ASH), the researchers found that 23 of 24 patients using Gleevec with high-dose chemotherapy had a complete response after a single three-week course, and the remissions have, so far, lasted up to 29 months after treatment.
To date, the two-year disease-free survival is 85 percent says the study's lead author, Deborah Thomas, M.D., assistant professor in the Department of Leukemia.
"This is a promising treatment that has provided very durable responses, but we need to accrue more patients with a longer follow-up before we can recommend the treatment universally," she says.
Both CML and this type of ALL are caused by a break in the so-called "Philadelphia" chromosome, named after the city where the abnormality was discovered. The defect arises when a portion of chromosome 9 exchanges genetic material with chromosome 22, causing the two genes to locate next to each other and jointly produce an abnormal protein that results in excessive production of white blood cells. The difference between CML and Philadelphia-positive ALL is the size of the protein produced by the translocated genes, but many of the basic mechanisms, as well as the course of the disease and the symptoms are the same, says Thomas.
Gleevec blocks production of the abnormal protein, thereby preventing the growth and reducing the number of abnormal blood cells.
While the drug works in CML without use of additional therapy, earlier studies of Gleevec as a single agent in previously treated Philadelphia-positive ALL did not show a lasting benefit. The study by M. D. Anderson researchers, however, suggests that concurrent use of the two therapies produces a synergistic effect that produces a dramatic response, says Thomas.
She notes that adding Gleevec to the treatment does not appear to add toxicity.
Thomas notes that while the majority of patients in the study have achieved remission without the use of a stem cell transplant, "it is too early to say that we may be able to forego stem cell rescue," she says.
Contact: Julie Penne, 713-792-0655; jpenne@mdanderson.org
Laura Sussman, 713-792-0655; lsussman@mdanderson.org