Cancer survivors are increasing nowadays; many of them are highly motivated to seek information about dietary supplement use and complementary nutritional therapies to improve their response to treatment [1]. Leukemia and lymphoma therapy, especially in children, is the success story of contemporary cancer treatment. There is widespread consensus that, with survival projections as good as they are, the emphasis is shifting towards improving tolerability and reducing side effects from treatment. Children undergoing treatment for acute lymphoblastic leukaemia (ALL) receive multiagent chemotherapy; many of them (cytosine arabinoside, doxorubicin, cyclophosphamide, and methotrexate) are associated with free radical production may affect the antioxidant status during therapy [2]. Also hepatic and hematological complications are very common due to multiagent chemotherapy especially during the initial intensive period of induction; usually these complications cause discontinuation of therapy, prolong the duration of stay in hospitals, and may affect the overall prognosis and outcome of the disease. There is a debate about the concurrent use of antioxidants with cytotoxic therapies [3]. It is true that much remains unknown concerning antioxidants, their mode of action, and possible interaction. Vitamin E (alpha tocopherol succinate) as antioxidant has generated some interest as an adjunctive cancer therapy due to its remarkable lack of toxicity in vivo [4]. If given with omega 3 fatty acids of fish oil, it may prolong survival in patients with generalized malignancy [5]. Another antioxidant is N-acetylcysteine (NAC) which is the acetylated form precursor of L-cysteine and reduced glutathione. It was used as a mucolytic agent in respiratory illness as well as an antidote for acetaminophen hepatotoxicity but recently used as complementary therapy of cancer [6, 7].

This study was conducted on a cohort of 40 children with ALL (18 males and 22 females) with their ages ranging between 2 and 15 years. They were enrolled consecutively from the recently diagnosed cases of ALL at Pediatric Hematology and Oncology Unit of Mansoura University Children's Hospital, Mansoura, Egypt, in the period between November 2006 and July 2007. Diagnosis of ALL was done according to standard methods including morphological, cytochemical, and immunological evaluation. Patients were treated by the modified BFM 76/79 protocol of therapy [8]. Cases with serious complications that may necessitate cessation of chemotherapy for undetermined duration were excluded from the selection. Patients were randomly allocated into one of two groups. First group (Group I) included 20 patients (10 males and 10 females) who were supplemented with vitamin E in a dose of 400 IU/day orally and N-acetylcysteine (NAC) in a dose of 600 mg/day orally [9] in addition to chemotherapy from day one of treatment till the end of CNS intensification (Phase II of chemotherapy, for a period of almost two months). CNS intensification phase includes a combination of chemotherapy (intrathecal methotrexate age-adjusted doses on days 4, 11, 18, and 25) and cranial irradiation (1800 cGy in 10 fractions of 180 cGy per day). The second group (Group II) included 20 patients (8 males and 12 females) who received chemotherapy and radiotherapy without any supplementation. Informed consent was obtained from the parents prior to giving chemotherapy and any supplementation. Blood samples were collected from every patient at day 28 of induction and at the end of CNS intensification for estimation of Malondialdehyde (MDA) thiobarbituric acid reactive substance, serum glutathione peroxidase (Glu.Px), tumor necrosis factor alpha (TNF-α), and liver function tests (SGOT, SGPT). Blood was collected into heparinised tubes which were protected from light and processed immediately after sampling. At the time of collecting the blood samples, patients were free of any potentially confounding or interfering conditions, such as infections, fever, derangements of glucose, and lipid metabolism. Patients were evaluated for occurrence of any complications, for example, haematological complications like bone marrow (BM) hypoplasia (BM cellularity less than 30 000 at the end of either induction or CNS intensification phases), febrile neutropenia, need for blood or platelet transfusions (hemoglobin level less than 8gm/dL and platelet count less than 20 000/cmm, resp.), and toxic hepatitis (defined by elevation of liver enzymes, 2 to 3 folds after chemotherapy, with the exclusion of viral hepatitis and return to the normal range after suspending chemotherapy [10]).

Table 1 shows the median values and interquartiles of serum level of Glu.Px, MDA, and TNF-α in the two phases of therapy in both leukemia groups. There is a statistically significant increase in serum Glu.Px in group I (supplemented with vitamin E and NAC) compared to group II during phase II (P = .03). MDA is slightly decreased in group I after phase II of therapy but this decrease is statistically insignificant (P = .13). Serum level of TNF-α does not show any significant difference between both groups of patients after the two phases of therapy.

Many patients with cancer take antioxidant nutritional supplements during cancer treatment to alleviate treatment toxicities and to improve long-term outcomes, but little is known about the efficacy and safety of antioxidant use during cancer treatment [14]. Despite the considerable debate about the role of antioxidant status in cancer outcomes, very few studies have assessed changes in antioxidant status and oxidative stress. Among children undergoing treatment for cancer there was only one study, to our knowledge, that measured exposure and treatment outcome in pediatric oncology [15]. They found that children with ALL have altered antioxidant and micronutrient status at diagnosis and during treatment. Our results support this study; oxidative stress has been found to be increased during treatment and antioxidant status decreased as being measured by serum Glu.Px and MDA in the group of children with ALL who did not receive antioxidants. Antioxidant status was associated with treatment-related oxidative stress (febrile neutropenia and elevated liver enzymes). We observed a significant increase of serum Glu.Px in ALL patients receiving vitamin E and NAC after phase II of therapy in comparison to those who received chemotherapy alone without any supplementation. Although MDA decreased after phase II of therapy in group I of ALL patients, this decrease is not statistically significant; this could be explained, in part, by the relatively small sample size. Comparison of serum level of TNF-α did not show any difference between both groups of patients. These findings are consistent with the results of Portakal et al. [16], Ray et al. [17], and Mantovani et al. [18] who found an increase of oxidative stress during treatment in cancer patients as compared with control. Thus we may conclude that vitamin E and NAC supplementation had significantly decreased the level of free radicals resulting from oxidation as evidenced by increasing the level of GLu.Px and lowering level of MAD in ALL patients who took the supplementation.