Response to chemotherapy estimates by FDG PET is an important prognostic factor in patients with Ewing sarcoma.

BACKGROUND: Response to chemotherapy is a prognostic factor in patients with Ewing sarcoma (ES); the role of FDG PET to predict response in these patients has not been thoroughly investigated. We evaluated the diagnostic accuracy and the potential of FDG PET to predict response to chemotherapy (CHT). MATERIALS AND METHODS: We analyzed data of 50 patients with ES (median age 12.6 years). All patients were treated with neoadjuvant CHT, and underwent surgery for local control. All patients had (18)F-FDG PET/CT at diagnosis and after induction CHT, prior to local control. We compared response assessed by histopathology with FDG PET using standard uptake values (SUVs). RESULTS: Median SUV at diagnosis (SUV I) was 5 (range 1.2-17), and median SUV after neoadjuvant chemotherapy (SUV II) was 1.8 (range 0-8.4). Median SUV II/I ratio was 0.3 (range 0-1). SUV at diagnosis was significantly lower in patients with good histological response than in patients with poor histological response (median 3.8 vs. 7.2, p 0.02). We found a significant correlation between SUV II and outcome; the positive predictive value of an SUV II ≤ 2.5 for favorable response was 84.21 %, and the median SUV II was significantly higher in patients with disease progression (2.3 vs. 1.6, p = 0.04). In multivariate analysis, necrosis and SUV II were significant predictors of outcome. CONCLUSIONS: (18)F-FDG PET demonstrates high diagnostic accuracy for response to initial chemotherapy in patients with ES and it correlates with outcome. The role of FDG PET in predicting response and outcome should be further investigated.

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.

Cerebrospinal fluid IL-6, TNF-α and MCP-1 in children with acute lymphoblastic leukaemia during chemotherapy.

The aim of the study was to investigate the levels of cerebrospinal fluid (CSF) cytokines during chemotherapy of acute lymphoblastic leukaemia (ALL). Examination of 12 ALL child (6 boys and 6 girls) patients evidenced significant increases in interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1) after induction treatment and significant increases in IL-6, tumour necrosis factor-α (TNF-α) and MCP-1 levels during the consolidation phase, as compared to their values at the time of diagnosis. There were no significant differences in CSF IL-6, TNF-α and MCP-1 concentrations after therapy. Our data suggest that standard ALL treatment may cause a subclinical inflammation and neurotoxicity.

Cerebrospinal fluid changes in the excitatory amino acids concentration caused by the standard treatment of acute lymphoblastic leukaemia in children do not correlate with their later cognitive functioning.

The aim of this study was to ascertain whether changes in the concentrations of cerebrospinal fluid excitatory amino acids (EAAs) contribute to neurotoxicity of the standard acute lymphoblastic leukaemia (ALL) treatment protocols. We found a statistically significant increase in glutamate and aspartate in 12 ALL patients during their treatment. Cognitive functioning was examined in all patients at an average of 3.7 years after the disease diagnosis. Importantly, the levels of EAAs during the therapy were not correlated with the results of the cognitive test. This study suggests that standard ALL treatment-induced neurotoxicity may not lead to persistent neurocognitive deficits.

Relationship between insulin-like growth factors (IGF-I and IGF-II), IGF-binding proteins (IGFBP-3, IGFBP-2), leptin and anthropometric parameters (height, body mass index) during antileukaemic treatment in children.

PURPOSE: The aim of the study was to estimate the anthropometric parameters and their relationship to serum levels of IGF-I, IGF-II, IGFBP-3, IGFBP-2 and leptin before and during intensive antineoplastic treatment for acute lymphoblastic leukaemia in children. MATERIAL AND METHODS: In 46 children in median age 6.6 years (range from 1.6 to 16) we evaluated at the time of diagnosis, after protocol I and after intensive treatment, height, body mass index (BMI) and IGF-I, IGF-II, IGFBP-3, IGFBP-2 and leptin. RESULTS: Height SDS lowered in successive points of analysis whereas BMI SDS rose after protocol II. IGF-I SDS was low and similar at each point, IGF-II SDS and IGFBP-3 SDS values augmented progressively and IGFBP-2 SDS was significantly elevated before treatment and lowered (but not normalized) during the therapy. Leptin SDS was elevated, especially after protocol I. CONCLUSION: Leukaemia and its treatment affect directly growth factors, its binding proteins and leptin production leading to growth retardation and overweight.

Association of collagen type I alpha1 gene polymorphism with bone density in survivors of childhood cancer--preliminary report.

A candidate gene, involved in the regulation of bone mass is the COLIA1 gene encoding type I collagen, the major protein of bone matrix. The disease per se, the age of its onset and treatment options might exert an impact on bone mineralization in survivors of childhood malignancy. We examined possible allelic influences of COLIA1 gene polymorphism on BMI, BMD spine and total body in 41 survivors (15 girls) of childhood cancer (the mean age 8.9 years). Genotype distribution was 33 (80.5%) SS and 8 (19.5%) Ss. There were no differences in SDS BMD and SDS BMI between patients with SS and Ss genotype. A tendency towards lower SDS values of BMD spine and BMI was observed (not significant). In conclusion, our preliminary observations suggest that COLIA1 genotype may affect bone accrual in a population treated for childhood cancer. Further investigations in a greater population are needed.

[Investigations of thyroid function in children and adolescents after treatment of Hodgkin's disease].

Radiotherapy focused on the neck, upper mediastinum or cranium can raise the risk of thyroid dysfunction. The influence of radio- and chemotherapy on thyroid morphology and function after treatment of Hodgkin's disease in 31 children and acute lymphoblastic leucaemia in 36 children was evaluated. Clinical examination, estimation of blood TSH, FT4 levels as well as ultrasonographic scan were performed. In the group of children with Hodgkin s disease the blood level of ATG Antithyreoglobulins andMAB, microsmal antibodies were estimated. The results of clinical examination were normal in all patients. Thyroid function tests were also normal, except for one case with elevated TSH values (22.76 microIU/ml) and decreased FT4 values (0.65 ng/ml). Three patients (9.7%) with Hodgkin s disease and three (8.5%) with ALL (only one had cranial radiotherapy) had an abnormal image of thyroid in ultrasonography (hypoechogenicity, heterogenous ultrasound scan, solid nodule). The results of our investigations indicate that abnormalities found in the ultrasound scan in children and adolescents with Hodgkin's disease in whom treatment has been terminated, can be a first prodrome of thyroid pathology.

Results of IDA-FLAG programme in the treatment of recurrent acute myeloblastic leukaemia--preliminary report.

BACKGROUND: Unsatisfactory treatment results of acute myeloblastic leukaemia inspire the search for new drugs, characterised by higher efficiency and lower toxicity. The aim of the study was the assessment of the efficiency and side effects associated with the implementation of IDA-FLAG protocol. MATERIAL AND METHODS: The assessment of treatment results and undesirable effects was based on the material of 4 children with the relapse of acute myeloblastic leukaemia, after a total of 6 IDA-FLAG protocols. RESULTS: Complete remission was obtained in 2 (50%) children, with mean remission time of 13.5 months. One of the children underwent the transplantation of haematopoietic cells from unrelated donor. The main side effect observed was bone marrow aplasia. Leucopenia, granulocytopenia, thrombocytopenia and anaemia persisted for approx. 20 days. Apart from haematological symptoms, the following were also observed: the symptoms of intolerance after ARA-C, aspergillosis of paranasal sinuses and lungs and severe coagulation disorders. CONCLUSION: IDA-FLAG protocol may be recommended for use in children with AML relapse and the undesirable effects observed are acceptable.

[Vaccination against hepatitis B in children with chronic hematologic diseases treated with immunosuppression]. / Szczepienia przeciw wirusowemu zapaleniu watroby typu B u dzieci z przewleklymi chorobami krwi leczonych immunosupresyjnie.

Prevention of hepatitis B infection is an important factor in the successful management of cancer and aplastic anaemia cases. Our result suggested that children with Hodgkin's disease and solid tumors vaccinated during early stage of immunosuppressive therapy are good responders to hepatitis B vaccine. Active immunisation with hepatitis B vaccine (Engerix B), was also effective in children with leukaemia after completing immunosuppressive therapy. Protective levels of antibodies remained 6 years after vaccination. Vaccination according to shortened schedule (0-10-20 days) was not effective in these children. Passive immunisation is indicated in children with chronic neoplastic haematological diseases during immunosuppressive therapy. In 6 children the lack of seroconversion after vaccination was due to immune disorders.