Serum Carnitine Levels in Childhood Leukemia Maria Rogalidou, MD,* Athanasios Evangeliou, MD, PhD,w Eftichia Stiakaki, MD, PhD,z Emmanouel Giahnakis, PhD,y and Maria Kalmanti, MD, PhD*w Summary: In patients with malignancies, the system of carnitine seems abnormally expressed. The serum total, free, and acyl carnitine levels in 40 children and adolescents with acute leukemia were determined using electrospray tandem mass spectrometry in 4 different phases of the disease: at the diagnosis, 1 year after the initiation of chemotherapy, at the end of treatment, and 2.4 ± 1.668 years after the completion of chemotherapy. The age, sex, hemoglobin values, serum biochemistry, somatometric features of the patients, and the risk group of the disease were examined. Although the carnitine levels were found higher in patients compared with the control group from diagnosis to treatment completion, statistically significant decrease in carnitine levels was observed in patients within different phases of the disease especially during induction and consolidation treatment (phase A to B) for both free and total (P = 0.023) carnitine. In addition, a statistically significant recovery in carnitine levels was observed between phase B (end of intensive chemotherapy) and D (some years after the completion of treatment) for free and total carnitine (P = 0.054 and 0.035, respectively). No statistical correlation was documented between the carnitine levels and somatometric parameters or other variables studied. In conclusion, a significant transient decrease in the levels of carnitine during the treatment was observed in children with acute leukemia. Further studies are required to clarify the role of carnitine status in patients with malignancies and possibly the necessity of carnitine supplementation during chemotherapy administration. Key Words: carnitine, chemotherapy, children, leukemia (J Pediatr Hematol Oncol 2010;32:e61–e69) C arnitine (4-trimethyl-amino-3-hydroxibutyric acid) is biosynthesized from the aminoacids lysine and methio- nine mainly in liver and kidneys and has the properties of vitamin. Carnitine has a very important role in the intermediate metabolism. It is responsible for the transport of long-chain fatty acids from cytoplasm to the inner site of mitochondria where they are broken down through b-oxidation resulting in the production of energy through the Krebs cycle . 1–4 Carnitine also takes part in the trans- port of peroxisomes including acetyl-CoA to the mitochon- dria for their oxidation in CO 2 and H 2 O in the Krebs cycle. 5,6 Other functions of carnitine are the regulation of the ratio of acetyl-CoA/CoA, 3,7 the storage of energy as acyl carnitine, 7,8 and the regulation of the toxic actions of the insufficiently metabolized acyl-groups with their elimina- tion as esters of carnitine. 9,10 The function of carnitine in the transport of mitochondrial long-chain fatty acid oxidation and regulation of the intramitochondrial acyl- CoA/CoA ratio are shown in Figure 1. Deficiency of carnitine has been described in physio- logic conditions such as pregnancy, aging, prolonged fasting 11,12 and in many pathologic situations as in patients with organic aciduria, 13,14 chronic renal failure, 15,16 several neurodegenerative diseases, 17–19 all type of diabetes, 9,20–22 and in patients treated with valproate and zidovudine. 23 L-carnitine is implicated also in the process of lipid meta- bolism and can influence the differentiation of myelomono- cytic cells. 24 In patients with malignancies, the carnitine system seems abnormally expressed both in tumor and nontumor tissues, 2 abnormal ratio of AC/AF may occur in all type of malignancies. The secondary deficiency of carnitine ob- served in patients with cancer can be explained as the result of metabolic changes which derive directly or indirectly from chemotherapy or from the neoplastic process itself. 1,25 In parallel with the changes in the metabolism of carnitine either from chemotherapy and/or from the disease itself in patients, there coexist other situations which could independently influence the metabolism of carnitine. Such situations are anorexia and cachexia which appear in 40% of cancer patients. 26,27 In an earlier study 1 concerning the nutritional status of children with cancer, it has been shown that inadequate intake of carnitine or its precursors could not be responsible for the insufficiency of carnitine. Metabolic changes that result from therapy and/or the neoplastic process may be responsible for that decrease. 1 The purpose of this study was to examine the serum levels of carnitine in children with leukemia at different phases of the disease and therapy: at the diagnosis, 1 year after the initiation of chemotherapy, at the completion of treatment, and months to years after the end of treatment. Do alterations exist in serum levels of carnitine at the diagnosis or during chemotherapy and if so what is the status after the completion of therapy? Patients’ characteristics such as age and sex, somato- metric features, peripheral blood parameters, serum bio- chemistry, and risk groups of the patients were also examined. Comparison with healthy controls from the same geographi- cal area was also performed. PATIENTS AND METHODS The study population included 40 children and adolescents (12 females and 28 males) diagnosed with acute leukemia in the Pediatric Hematology/Oncology Depart- ment of our Hospital. The patients received treatment according the Berlin-Frankfurt-Munster-ALL and AML Copyright r 2010 by Lippincott Williams & Wilkins Received for publication July 17, 2008; accepted November 11, 2009. From the Departments of *Paediatrics; yStatistics, University of Crete; wPediatrics Department, Aristotle University of Thessaloniki; and zDepartment of Pediatric Hematology-Oncology, University Hospital of Heraklion, Crete, Greece. Reprints: Maria Rogalidou, MD, K. Karamanli 42 Anatoli Ioannina, Greece 45500 (e-mail: rogalidoum@yahoo.com). ORIGINAL ARTICLE J Pediatr Hematol Oncol  Volume 32, Number 2, March 2010 www.jpho-online.com | e61