Serum carnitine levels and the relationship with fatigue scale in acute lymphoblastic leukemia in childhood

Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood. Cancer-related fatigue is one of the most common problems in children with ALL at the diagnosis and during the treatment. Fatigue is a subjective symptom. Various instruments are used for evaluating fatigue level. The Fatigue Scale Childhood which was developed by Hinds and Hockenberry; is a scale that measures cancer-related fatigue in children who are receiving cancer treatment. Carnitine is one of the cornerstones of energy metabolism. It has been proved, carnitine metabolism is impaired in many types of cancer, and secondary carnitine deficiencies can be observed during cancer treatment. In this study, we aim to figure out the effect of disease and the treatment on blood carnitine levels in leukemia pediatric patients', and the effects of carnitine levels on fatigue scale scores. We included 28 patients in group I who were diagnosed ALL after application to Bulent Ecevit University School of Medicine Pediatric Oncology Division and Ankara Child Health and Disease Hematology -Oncology Training and Research Hospital Pediatric Hematology -Oncology Department. Thirty healthy children for the control group in group II who applied Bulent Ecevit University School of Medicine Pediatric Outpatients Clinic. Additionally, we included 13 leukemia survivors in group III who are going on follow-up (at least six months off therapy) at Bulent Ecevit University School of Medicine Pediatric Oncology. After leukemia diagnosis in Group I, BFM ALL 2009 treatment protocole was started immediately. Blood samples for blood carnitine analysis were taken at the diagnose, at the end of Block IA, at the end of Block IB, and at the end of protocol M+HR1 block in group I . At the meantime, the childhood fatigue scale were applied. From the patient at group II and III, the blood work and fatigue scales were applied once at outpatient application. Carnitine analysis were done at Duzen Laboratories at Ankara. The whole blood count, hemogram, renal function blood tests, creatinine kinase, liver function blood tests were done at the time of carnitine blood sampling. Patients' height and weight were measured at the beginning of the study, and at the end of all treatment blocks in group I. BMI, height and weight z scores were calculated from the records. In group I, total carnitine level was 55.44±18.53 µmol/L, mean free carnitine level was 45.53 ±12.18 µmol/L, mean acyl carnitine level was 6.10±3.21, acly carnitine / free carnitine (AC/AF) ratio was 0.13±0.06 at the time of diagnose. In group II, total carnitine level was 46.25±9.4 µmol/L, mean free carnitine level was 30.19±8.59 µmol/L, mean acyl carnitine level was 6.36±2.65, AC/AF ratio was 0.19±0.096. In group III, total carnitine level was 49.92±8.88 µmol/L, mean free carnitine level was 39.59±17.49 µmol/L. At the time of diagnose, the total carnitine levels were higher in Group I than Group II, but no significant difference (p>0.05); free carnitine levels were significantly higher in Group I than Group II (p<0.001). There was no statistically differences about total and free carnitine levels between Group I and Group III (p>0.05). Total carnitine levels showed significant changes during treatment (p=0.003); total carnitine levels were statistically lower at the end of second part of remission induction blok that is Blok IB than at the time of diagnosis (p=0.000). Also, there is a significance at free carnitine changes during treatment similar with total carnitine levels (p=0.001), and free carnitine levels were significantly lower at the end of Blok IB rather then at the time of diagnosis (p=0.000). AC/AF ratio showed a significant increase between the diagnose and the end of protocol M+HR1 block (p=0.007). In Group I, regarding to rish groups there was no significantly differences about carnitine levels (p>0.05). In terms of fatigue scores, mean Fatigue Scale-Parent (FS-P)and Fatigue Scale-Adolescent (FS-A) scores at the time of diagnosis were higher in Group I than in Group II, but no statistically significant difference was found between Group II (p>0.05). But Fatigue Scale-Childhood (FS-C) scores were significantly higher both Group II and Group III (p=0.020). We found a weak negative correlation between low hemoglobin levels and FS-P scores in Group I (r=-0.250, p =0.036). When the FS-P scores were compared in terms of risk groups, higher scores were found at the time of diagnosis in the high-risk group and at the end of th protocol M+HR1 Block. No correlation was found between fatigue scores and blood carnitine levels in children with leukemia, despite significant changes in carnitine levels during treatment. As a result, blood carnitine levels in leukemic children change with chemotherapy; no relation was found with the fatigue scale scores. When the FS-P scores were compared regarding risk groups, higher scores were found at the time of diagnosis in the high-risk group and at the end of the protocol M+HR1 Block. No correlation was found between fatigue scores and blood carnitine levels in children with leukemia, despite significant changes in carnitine levels during treatment. As a result, blood carnitine levels in leukemic children change with chemotherapy; fatigue scores were found to be higher in the new diagnosed ALL patients at the time of diagnosis compared to both control group and children with ALL who were off-therapy at least six months. However, no correlation was found between the changes in the carnitine levels and the fatigue scale scores.