Katarzyna Muszynska-Roslan

AVASCULAR NECROSIS—AN ANTINEPOLASTIC TREATMENT RELATED TOXICITY: The Experiences of Two Institutions

Avascular necrosis (avn) is a complication of treatment for malignancies in children and adolescents. The authors present a two-center retrospective of experiences with avn in children treated for acute lymphoblastic leukaemia or non-Hodgkin lymphoma (8 from 191 patients with newly diagnosed disease in total of 19 sites). The median age at diagnosis was 16.6 years. Avn was observed in 4.1% of the group, higher among males than females (7/1), both during and after therapy. Early diagnosis of the process has enabled 7 patients to avoid surgical intervention. The increased incidence of avn, the multimodal character of symptoms, but unknown late consequences of avn showed that prospective studies of early recognition and proper therapy are needed.

Intellectual functioning of childhood leukemia survivors - relation to Tau protein - a marker of white matter injury

PURPOSE Chemo- and radiotherapy used in acute lymphoblastic leukemia (ALL) can influence on brain functioning in the future. In a prospective study we analysed the cognitive functions of ALL survivors in relation to Tau protein as a marker of white matter injury. MATERIAL AND METHODS Thirty-one survivors of childhood ALL (6.3 years after diagnosis); without the signs of CNS involvement, treated with chemotherapy alone, rested in first remission; underwent Intelligence tests- Wechsler Intelligence Scales (WISC-R, WAIS-R). Their results were analyzed in relation to the levels of Tau in cerebrospinal fluid (CSF) obtained during the treatment. RESULTS The analysis showed that all survivors attained the average scores in intelligence tests. A negative correlation was found between methotrexate (MTX) doses and Freedom from Distractibility (FFD). Females had higher values of Performance Intelligence Quotient (PIQ) than males. A negative correlation was noted of Tau protein levels obtained from the last CSF with: Total and Verbal Intelligence Quotient, PIQ, Perceptual Organisation Index and FFD but not with Verbal Comprehension Index. CONCLUSION Our results suggest the possibility of white matter injury during the treatment for ALL with chemotherapy alone. Elevated Tau protein level in CSF at the end of treatment might indicate future difficulties in neurocognitive functioning.

Body composition and bone mass in survivors of childhood cancer.

The number of survivors of childhood cancer has increased. Several studies in children and adults have shown relationships between lean mass (LM), fat mass (FM), and bone mineral content (BMC). The objective of the study was to examine the association between body composition and bone mass in young survivors of childhood cancer.

Little Evidence of Low Bone Mass in Acute Lymphoblastic Leukemia Survivors

Childhood acute lymphoblastic leukemia (ALL) survivors represent a specific group at risk for many health problems, including skeletal complications and osteoporosis. The objective of this study was to assess the risk of osteoporosis associated with the prevalence of low bone mass (according to the guidelines of the Pediatric Official Positions of the International Society for Clinical Densitometry 2007) in survivors of childhood ALL. The cross-sectional study was conducted in a cohort of 69 Caucasian children and adolescents (46 boys and 23 girls) aged 12.15 ± 0.5yr diagnosed with ALL and screened up to 5 yr after cessation of the treatment. Total body bone mineral content (TB BMC, g), total body bone mineral density (TB BMD, g/cm(2)), and lumbar spine BMD (LS BMD, g/cm(2)) were determined using dual-energy X-ray absorptiometry. Time interval from the completion of the treatment to the beginning of this study (subgroup I<2 yr or subgroup II>2 yr after treatment), methotrexate (MTX) doses (subgroup I-MTX ranging from 0.5 to 1.0g/m(2); subgroup II-MTX>2.0 g/m(2)), cranial irradiation (subgroup I-without radiotherapy (RTX) and subgroup II receiving RTX of 12-18 Gy), cumulative steroid dose, and impaired endocrine function were considered as potential factors affecting bone metabolism and included in the analysis. No differences were found in bone traits (BMC, TB BMD, LS BMD) in relation to examined risk factors. In multiple regression model that included therapeutical factors, a risk group and central nervous system irradiation were of an important influence on bone mass, and risk group predicted TB BMD in small degree. Risk group and irradiation status lost their significance after the inclusion of anthropometric, age-connected, and time-connected factors. This study suggests that ALL survivors are not at increased risk for low bone mass. However, from the clinical perspective all patients after childhood ALL should be screened for clinical signs, fracture history, and lifestyle risk factors for low bone mass and osteoporosis. They should be referred to bone density evaluation only as often as may be necessary from the clinical evaluation.

Is the treatment for childhood solid tumors associated with lower bone mass than that for leukemia and Hodgkin disease

Background: Cancer disease and its therapy (e.g., chemotherapeutic agents such as glucocorticoids, methotrexate, antymetabolities, cranial and local irradiation) may severely disturb normal growth, bone mineral acquisition, and skeletal development because most individuals go through the stages of rapid growth when childhood cancer is diagnosed. Procedures: To identify factors associated with reduced bone mineral density (BMD) in survivors of childhood cancer the authors examined 114 patients (70 males) who had been treated for acute lymphoblastic leukemia (ALL; n = 43), Hodgkin disease (HD; n = 35), and solid tumors (ST; n = 36) twice. Median age at diagnosis was 8.4 years; at the consecutive examinations it was 12.8 and 16.3 years, respectively. To assess bone density we used dual-energy x-ray absorptiometry (DXA). Results: In the first examination, patients with a history of steroid therapy had higher total and spine BMD and higher BMI (body mass index) than those who were not given steroids. At the end of the follow-up, no differences were found in BMD between subgroups, although BMI was still higher in both ALL and HD patients than in those with ST. Conclusions: Patients treated for solid tumors have reduced bone mass. Low BMI and local irradiation seem to be the factors responsible for reduced BMD in children treated for ST. The use of steroids does not disturb bone mass accumulation in patients treated for childhood malignancies. However, a long-term effect of cancer treatment on osteoporosis risk remains to be determined.

Negative correlation between cerebrospinal fluid tau protein and cognitive functioning in children with acute lymphoblastic leukemia

The aim of the study was to assess whether cerebrospinal fluid tau protein is associated with cognitive changes in children with acute lymphoblastic leukemia (ALL). Examination of 38 ALL patients revealed a statistically significant increase in tau protein on treatment day 59 and at two points during consolidation phase. Cognitive functioning was examined in 19 patients at an average of 3.7 years after diagnosis. The level of tau at the initiation of maintenance therapy was negatively correlated with verbal abilities measured on an intellectual scale. The study suggests that standard ALL treatment may cause a decline in cognitive functioning. Pediatr Blood Cancer 2009;53:105–108.

Does Q223R Polymorphism of Leptin Receptor Influence on Anthropometric Parameters and Bone Density in Childhood Cancer Survivors

Childhood cancer survivors are in augmented risk for developing obesity. For many factors leptin and leptin receptor gene polymorphism play an important role in the development and metabolism not only of fat, but also, bone tissue. The aim of the analysis was to find the relationships between Q223R, leptin levels, and anthropometric parameters. Patients and Methods. In the study 74 cancer survivors participated (ALL n = 64, lymphomas n = 10), and the control group consisted of 51 healthy peers. Leptin blood concentration was determined by ELISA method. To estimate leptin receptor gene polymorphism, RFLP method was used. Bone mineral density (BMD) and content (BMC), fat, and lean tissue measurements were obtained by DXA. Results. We found no correlations between serum leptin concentrations and anthropometric parameters nor BMD. Serum leptin concentrations were significantly lower in the group of cancer survivors compared to controls; however, in those overweight from examined group we found leptin levels higher than those in nonoverweight. Genotype Q223R was not associated with higher leptin levels, BMI, BMD, body fat or lean tissue. Conclusion. To our knowledge, this is the first report describing the relationship between BMD and Q223R polymorphism in childhood cancer survivors. Further analysis, based on a larger group of patients, is needed to confirm these findings.

Bone mineral density, thyroid function, and gonadal status in young adult survivors of childhood cancer.

Introduction During the last years, changes in the diagnosis and treatment have caused a significant increase of the number of young adults who experienced cancer in childhood. This enlarging population is affected by many health problems, including multiple hormone deficiencies and bone mineral deficits. This is the first polish study assessing bone mineral density and endocrine status in young adult cancer survivors. Material and methods A total of 76 long-term survivors treated for pediatric cancer were identified. The mean age at the time of study was 24.1 ±3.5 years. Bone mineral density and TSH, fT3, fT4, FSH, LH, estradiol and testosterone level were assessed for each patient. Results Nine subjects were diagnosed with subclinical hypothyroidism. We found higher level of TSH in the study group, in comparison with control group (p = 0.015). Eighteen patients had increased level of FSH. In the study group higher number of patients with high FSH level was found in comparison with the control group (p = 0.049). A low BMD was observed in 7 patients whereas mild BMD deficits were found in 19 participants. Conclusions In conclusion, our data show that young adult cancer survivors might experienced various hormonal problems including low bone mass, thyroid impairment and gonadal dysfunction. Some of the patients required treatment, but they were not diagnosed before this study. There is the lack of proper clinical assessment among adult childhood cancer survivors in Poland. Therefore, we demonstrated the need for a comprehensive plan for longitudinal follow-up for late effects in these population.

Outcome of refractory and relapsed acute myeloid leukemia in children treated during 2005–2011 – experience of the Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG)

Aim of the study Recent studies showed relatively better outcome for children with refractory (refAML) and relapsed acute myeloid leukemia (relAML). Treatment of these patients has not been unified within Polish Pediatric Leukemia/Lymphoma Study Group (PPLLSG) so far. The goal of this study is to analyze the results of this therapy performed between 2005–2011. Material and methods The outcome data of 16 patients with refAML and 62 with relAML were analyzed retrospectively. Reinduction was usually based on idarubicine, fludarabine and cytarabine with allogenic hematopoietic stem cell transplant (alloHSCT) in 5 refAML and 30 relAML children. Results Seventy seven percent relAML patients entered second complete remission (CR2). Five-year OS and disease-free survival (DFS) were estimated at 16% and 30%. The outcome for patients after alloHSCT in CR2 (63%) was better than that of those not transplanted (36%) with 5-year OS of 34% vs. 2-year of 7% and 5-year DFS of 40% vs. 12.5%. Second complete remission achievement and alloHSCT were the most significant predictors of better prognosis (p = 0.000 and p = 0.024). The outcome of refAML children was significantly worse than relAML with first remission (CR1) rate of 33%, OS and DFS of 25% at 3 years and 53% at 2 years, respectively. All survivors of refAML were treated with alloHSCT after CR1. Conclusions The uniform reinduction regimen of the documented efficacy and subsequent alloHSCT in remission is needed to improve the outcome for ref/relAML children treated within PPLLSG. The focus should be on the future risk-directed both front and second line AML therapy.

Total antioxidant status (TAS) in childhood cancer survivors

Total antioxidant status (TAS), and the influence of treatment and correlation between TAS and parameters involved in metabolic syndrome (MS) in pediatric cancer survivors were evaluated. One hundred children and adolescents were studied. Twenty-five survivors received radiotherapy, 12 were obese or overweight. Additionally, we analyzed TAS in eight children with acute lymphoblastic leukemia (ALL) at diagnosis and during treatment after remission induction. The control group consisted of 22 healthy children. Serum concentrations of TAS, glucose, cholesterol, HDL-cholesterol, triglycerides, fibrinogen and insulin were measured. In cancer survivors, independently of diagnosis and kind of treatment (radiotherapy anthracyclines administration), the mean serum TAS did not differ significantly from the control group. No correlations were observed with age at the time of diagnosis or interval after the end of treatment. TAS values did not correlate with traits of the metabolic syndrome. In a group of eight patients with ALL at diagnosis and after induction of remission, TAS values were lower than in the control and cancer survivor groups. Antioxidant status was not found to be deteriorated in children after anticancer treatment, irrespective of diagnosis or kind of treatment, which might indicate sufficient antioxidant prevention. However, the possibility of the development of MS and cardiovascular disease in adulthood indicates the need for future studies.