The continued improvement in diagnosis and treatment made possible by MRD, pharmacogenomics and new drug therapies has shifted the focus in ALL therapy toward reduction of both the immediate and long-term side effects of treatment. For example, a St. Jude team lead by Evans demonstrated that patients who lack the enzyme TPMT are more sensitive to thiopurine chemotherapy drugs and are more likely to suffer damage to the body's blood-producing cells. Evans subsequently discovered the genetic cause and developed a gene-based test that permits clinicians to identify children who should be treated with lower doses of this class of drugs while still receiving full therapeutic benefit. The overall improvements have led to more skilled use of cancer drugs, stem cell transplantation and treatment of ALL that invades the central nervous system, according to Pui.
"We are now testing the feasibility of omitting irradiation for all patients and reserving this treatment for only those children who suffer a relapse," he noted. "Irradiation of the brain can cause second cancers, hormonal disturbances and disruption of intellectual development as the child grows. So our omission of the use of irradiation should further reduce acute and long-term toxic side effects and improve outcome."
Coupled with the successes of the recent past, future treatment improvements promise to continually improve the survival rate of ALL, Evans said. For example, new drugs directed against the proteins made by genes linked to ALL will add to the options for treating this disease.
"Multiple breakthroughs at St. Jude and elsewhere have transformed ALL from a virtual death sentence into a disease that children can increasingly be expected to survive with minima
Source:St. Jude Children's Research Hospital