Bone mineralization defects after treatment of acute lymphoblastic leukemia in children.

AIM: Aim of the study was to assess bone metabolism disturbances in children with acute lymphoblastic leukemia following cessation of chemotherapy. For this purpose we measured bone mineral density (BMD) and evaluated bone metabolism markers. METHODS: Seventy-five patients (37 female, 38 males, mean age 10.77±3.80 years) were included. Lumbar spine BMD was measured by dual energy X-ray absorptiometry and serum calcium, phosphorus, magnesium, alkaline phosphatase, parathyroid hormone and 25OH vitamin D levels were analyzed. For characteristics of all patients at diagnosis data were retreived from hospital records and analyzed retrospectively. RESULTS: A total of 18.66% (14 patients) of patients were osteoporotic (z score <-2 SD), 22.67% (17 patients) were osteopenic (z-score between -2 and -1 SD) and 58.67% (44 patients) presented normal z-scores (>-1 SD). There were no statisticaly significant differences between normal, osteopenic and osteoporotic groups for mean serum vitamine D (P=0.677), calcium (P=0.280), phosphorus (P=0.179), magnesium (P=0.675), ALP (P=0.092) and serum PTH (P=0.915) levels. According to ages (P=0.745) and gender (P=0.810) there were no significant differences in BMD. There were no significant differences between normal, osteopenic and osteoporotic patients for the total dose of prednisolone (P=0.334), dexamethasone, (P=0.734), methotrexate (P=0.911), granulocyte colony-stimulating factor (P=0.173) and cranial irradiation (P=0.912) they have received during chemotherapy. Bone fracture and aseptic necrosis rates were 12%, 8%, respectively. CONCLUSION: Osteoporosis and osteopenia are still observed in high rates after chemotherapy. We must be aware of this morbidity and must screen the patients for decreased BMD during the long duration of leukemia treatment. Supportive treatments should be evaluated to minimize these serious complications.

Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia.

WNT signaling has been implicated in the regulation of hematopoietic stem cells and plays an important role during T-cell development in thymus. Here we investigated WNT pathway activation in childhood T-cell acute lymphoblastic leukemia (T-ALL) patients. To evaluate the potential role of WNT signaling in T-cell leukomogenesis, we performed expression analysis of key components of WNT pathway. More than 85% of the childhood T-ALL patients showed upregulated ß-catenin expression at the protein level compared with normal human thymocytes. The impact of this upregulation was reflected in high expression of known target genes (AXIN2, c-MYC, TCF1 and LEF). Especially AXIN2, the universal target gene of WNT pathway, was upregulated at both mRNA and protein levels in ∼40% of the patients. When ß-CATENIN gene was silenced by small interfering RNA, the cancer cells showed higher rates of apoptosis. These results demonstrate that abnormal WNT signaling activation occurs in a significant fraction of human T-ALL cases independent of known T-ALL risk factors. We conclude that deregulated WNT signaling is a novel oncogenic event in childhood T-ALL.

Effects of malnutrition on oxidative burst functions and infection episodes in children with acute lymphoblastic leukemia.

INTRODUCTION: The aim of this study was to determine the effect of malnutrition on oxidative burst functions (OBF) of neutrophils in children with acute lymphoblastic leukemia (ALL). MATERIALS AND METHODS: Twenty-eight patients with ALL and thirty healthy controls were enrolled to the study. Thirteen patients with ALL were found to have malnutrition. While neutrophil OBF of ALL patients without malnutrition were studied both before induction chemotherapy and 3 months after, the same functions in ALL patients with malnutrition were studied both before induction chemotherapy and when the nutritional status improved. Control group were studied at admission and 3 months later. RESULTS: The OBF of ALL patients with and without malnutrition before induction chemotherapy were found to be significantly lower than the control group (P = 0.009), whereas the OBF were found to be similar in both patient groups with ALL (P = 0.27). The median infection episode rate and the duration of antibiotics therapy during the study period were similar in both patient groups with ALL. The repeated OBF of both patient groups with ALL were shown to increase to similar values with the control group in the third month of chemotherapy (P = 0.002). The median infection episode rate during the first month of chemotherapy was shown to decrease significantly during the third month of chemotherapy in both patient with ALL groups (P < 0.001). CONCLUSIONS: We have not been able to demonstrate an overt effect of malnutrition on OBF. However, our results still need to be verified via further larger scaled studies of OBF in leukemic children with and without malnutrition.

Spontaneous remission of acute lymphoblastic leukemia with mediastinal mass.

Spontaneous remission/regression of cancer is defined as partial or complete disappearance of malignant disease temporarily or permanently in the absence of medical treatment. This event is named as spontaneous regression for solid tumors and spontaneous remission for leukemia. The authors report the case of a girl aged 4 years and 3 months, who presented with mediastinal mass and leukemic findings in the bone marrow both of which reappeared after spontaneous regression and remission, respectively.

The effects of iron deficiency on neutrophil/monocyte apoptosis in children.

OBJECTIVES: Iron is essential for DNA synthesis; its deficiency may lead to impaired DNA synthesis and subsequent alterations in levels of apoptosis. Here, we have aimed to investigate effects of iron deficiency anaemia (IDA) on apoptotic response of phagocytic cells and to understand whether the effect is reversible after iron supplementation. MATERIALS AND METHODS: Forty-nine IDA patients and 26 healthy controls, aged between 6 months and 12 years with similar demographic status, were considered. Neutrophil- and monocyte-apoptotic responses of IDA patients and the control group were compared by flow cytometry. Then, IDA patients were provided with oral iron supplementation. On day 15 of iron therapy, neutrophil- and monocyte-apoptotic responses of IDA patients were rechecked and were compared to those of control group. RESULTS: Neutrophil- and monocyte-apoptotic responses in terms of early and late percentages of apoptosis, and percentages of necrotic cells, were significantly less in IDA patients compared to the control group. The significantly low apoptotic responses of IDA patients rose to levels of the control group by day 15 of iron therapy. Besides, the effect of IDA on apoptotic responses was found to be more enhanced in severe IDA patients that those of mild IDA patients. CONCLUSION: Correction of differences after iron supplementation therapy implies that IDA might be a cause for changes in neutophil- and monocyte-apoptotic responses. The impact of this diminution of apoptotic cellular function in IDA should be further investigated, with longitudinal studies, in order to document the impact of any severe and/or long-lasting IDA on autoimmunity and malignancy.