Effect of methotrexate and doxorubicin cumulative doses on superoxide dismutase levels in childhood acute lymphoblastic leukemia
Abstract
Background Acute lymphoblastic leukemia (ALL) is the most
common malignancy in children. Chemotherapeutic drugs for
ALL such as methotrexate (Mtx) and doxorubicin produce
reactive oxygen species (ROS), a type of free radical. The ROS
can reduce levels of antioxidants in the body, including superoxide
dismutase (SOD). Decreased SOD levels can cause DNA, lipid,
and protein damage, which in turn may lead to adverse effects
and treatment failure.
Objective To determine the effect of Mtx and doxorubicin
cumulative doses on SOD levels in children with ALL.
Methods We conducted a retrospective cohort study in children
with ALL who underwent chemotherapy in Dr. Sardjito Hospital
in October 2011 who had completed the induction phase. Risk
factors for decreased SOD levels were analyzed by Cox regression
and hazard ratio, with a significant level of P <0.05.
Results Of 40 patients enrolled, Mtx ≥ 3000 mg/m2 significantly
decreased SOD levels (HR 9.959; 95%CI 2.819 to 35.183; P=0.001). However, doxorubicin ≥90 mg/m2 did not significantly
decrease SOD levels (HR 0.59 95%CI 0.194 to 1.765; P=0.34).
Conclusion Methotrexate is associated with decreased SOD levels
in children with ALL. However, doxorubicin is not associated with
decreased SOD levels in the same patient population.
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Published 2015-10-01
