A Pilot Study Investigating the Relationship Between Diet and Oxidative Stress in Infants Receiving Therapy for Acute Leukemia

Abstract 4228

Pediatric leukemia patients undergoing treatment are often malnourished due to nausea, food aversions, and mucositis. Clinical observations suggest that poor nutrition worsens outcomes for this patient population. Oxidative stress may be a key intermediary linking nutrition and clinical outcomes. Previous reports suggest that diet may modulate the balance of cellular pro- and antioxidants and that oxidative stress may influence the efficacy of cancer treatment. Taken together, these data suggest that dietary changes might modulate oxidative stress and consequently impact the efficacy of therapies used to treat children with cancer.

We hypothesize that age-appropriate nutrition may augment oxidative stress induced by chemotherapy and improve patient response to therapy. To address this hypothesis, we commenced a pilot study evaluating the interrelationship between nutrition and oxidative stress in children who are receiving therapy for leukemia. Twenty-four hour dietary recalls were completed and analyzed using the Minnesota Nutrition Data System for Research (NDSR) dietary analysis program to ascertain nutritional information, including caloric intake and dietary antioxidant consumption. Accordingly, the levels of pro- and anti-oxidants in mononuclear cells isolated from peripheral blood were quantified to measure oxidative stress. Levels of the reactive oxygen species (ROS) superoxide and hydrogen peroxide were measured with dihydroethidium (HE) and 2′,7′-dichlorofluorescin diacetate (DCF-DA) staining, respectively. As oxidative stress results from an imbalance of pro- and anti-oxidants, the quantity of the most common cellular antioxidant glutathione (GSH) was also measured by monochlorobimane staining.

Assessments of nutrition and oxidative stress were completed for each patient at regularly scheduled intervals over a six month period. The first assessment occurred either before the patient received chemotherapy or during a prolonged break from chemotherapy whereas later assessments were conducted one month, two months, and six months after the patient began or resumed chemotherapy. Consequently, changes in nutrition and oxidative stress were monitored in response to treatment.

To date, analyses have been completed for 12 patients. The median age of our patient population at the time of enrollment is 28.5 months. The oldest patient was 53 months at the time of enrollment and the youngest patient was 22 months. Seven patients are male and 6 are female. All subjects are receiving therapy for acute lymphoblastic leukemia (ALL); 7 have been diagnosed with standard risk ALL and 6 have been diagnosed with high risk ALL.

Preliminary results show that ROS were increased in mononuclear cells isolated from the majority of subjects during the course of their treatment. An increase was defined as a two-fold or greater elevation in ROS at any subsequent visit compared to the baseline visit. An increase in superoxides was detected in 72.7% of patients (8 of 11). Also, an increase in hydrogen peroxide was detected in 50% of patients (6 of 12). Interestingly, the antioxidant GSH was decreased in mononuclear cells isolated from many of our patients during the course of their treatment. A decrease was defined as a drop in the quantity of GSH at all subsequent visits compared to the baseline visit. A decrease in GSH was seen in 50% of patients (6 of 12) and 33% (4 of 12) demonstrated a decrease in GSH coincident with an increase in both superoxides and hydrogen peroxide. This increase in ROS and decrease in GSH suggests that the majority of our patients experience oxidative stress during therapy.

To investigate the impact of diet on oxidant status, NDSR software was used to compare the consumption of dietary antioxidants, such as vitamins A, B3, C, and E, selenium, and glutamic acid, to the corresponding amounts of ROS from the same visit. The strongest correlation was between vitamin C consumption and hydrogen peroxide levels. An inverse relationship between vitamin C consumption and hydrogen peroxide levels was apparent in 58.3% of patients (7 of 12). Though this data is preliminary, our hope is that the findings from this pilot study will begin to illuminate the relationship between diet and oxidative stress in pediatric leukemia patients and justify future work which will aid in devising dietary interventions that will modulate oxidant status to favor improved survival of children with leukemia.