A new study has revealed that children with acute lymphoblastic leukemia (ALL) who had a certain gene variant experienced a higher incidence and severity of peripheral neuropathy after receiving treatment with the cancer drug vincristine.
Vincristine is widely used and an effective anticancer agent for treating leukemias in both adults and children. The dose-limiting toxic effect of the drug is peripheral neuropathy (damage to the nerves), characterized by neuropathic (nerve) pain and impaired manual dexterity, balance, and altered gait. Presently, there are no reliable means of identifying patients at high risk of vincristine induced neuropathy nor strategies to reduce vincristine toxicity.
Researchers performed a genome-wide association study to determine whether there are genetic variants associated with vincristine-induced neuropathy. The study included participants in 1 of 2 prospective clinical trials for childhood ALL that included treatment with 36 to 39 doses of vincristine. Genetic analysis and vincristine-induced peripheral neuropathy were assessed in 321 study patients from whom DNA was available- 222 patients (median age, 6.0 years) enrolled in 1994-1998 in a St. Jude Children's Research Hospital cohort; and 99 patients (median age, 11.4 years) enrolled in 2007-2010 in a Children's Oncology Group (COG) cohort.
Grade 2 (moderate) to grade 4 (life threatening) vincristine-induced neuropathy during therapy occurred in 28.8 percent of patients (64/222) in the St. Jude cohort and in 22.2 percent (22/99) in the COG cohort. The researchers found that an inherited variant in the gene CEP72 was associated with a higher incidence and severity of the cancer drug-related peripheral neuropathy in children with ALL. Among patients with the gene variant, 28 of 50 (56 percent) developed at least 1 episode of grade 2 to grade 4 neuropathy, compared with 21 percent (58/271) of other patients.
The authors wrote, "If replicated in additional populations, this finding may provide a basis for safer dosing of this widely prescribed anticancer agent."
The study is published in the 'JAMA'.