This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and ...oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting.
The second tumour (ST) occurrence is a relatively uncommon late complication of radiotherapy but represents one of the most significant issues, especially in childhood oncology. We describe our ...experience with patients who developed second brain neoplasm following cranial irradiation in childhood.
We identified nine patients who received radiotherapy owing to central nervous system tumour in childhood and subsequently developed the second brain tumour. The full clinical and radiological documentation and histopathological reports were reviewed. Risk factors such as age at irradiation, latency period to ST diagnosis, radiotherapy doses and volumes and other therapy methods were evaluated. We correlated the ST location with the three levels of irradiation dose (high, >40 Gy; medium, 25-40 Gy; and low <25 Gy).
Five meningiomas and four gliomas occurred as the ST after the mean time of 11.7 years after radiotherapy. The average age of children during irradiation was 4.6 years. The shorter latency time to the ST induction was found in children treated with chemotherapy (9 years vs 17.2 years). Seven STs developed in the area of high and moderate dose (>25 Gy), only two low-grade gliomas appeared in the low-dose region.
Our data suggest that the STs usually develop in the brain tissues that received doses >25 Gy in patients irradiated at a young age.
The low-dose volume seems not to be so significant for second brain neoplasm induction. Therefore, the modern intensity-modulated radiotherapy technique could be safely applied in paediatric patients.
: HCC constitutes 25–30% of primary malignant liver tumors in children. Conventional surgical excision is not possible in more than 50% of patients. LTx has recently become an important therapeutic ...option for adults and children with primary liver tumors. The aim of this study was a retrospective analysis of the clinical and pathological data of children with HCC treated with LTx in relation to Milan criteria assessed at diagnosis and then immediately before transplantation, in comparison with a group of patients treated conventionally. Between 1990 and 2007 we have treated 21 children diagnosed with HCC. Patients were divided into two groups: group I, 10 children treated conventionally and group II, 11 children treated with LTx regardless of previous therapy. The outcome of our patients treated conventionally with resection and chemotherapy is very poor ‐ the disease‐free survival rate is 30%. In contrast, despite that only 3 children having fulfilled adult Milan criteria, early clinical results of LTx are much superior. Total hepatectomy followed by LTx is the main treatment option for the majority of children with HCC. Decisions on the type of surgical treatment is made individually, but very early in the course of treatment.
Nijmegen breakage syndrome The, I
Archives of disease in childhood,
05/2000, Letnik:
82, Številka:
5
Journal Article
Recenzirano
Odprti dostop
BACKGROUND Nijmegen breakage syndrome (NBS) is a rare autosomal recessive disorder. NBS-1, the gene defective in NBS, is located on chromosome 8q21 and has recently been cloned. The gene product, ...nibrin, is a novel protein, which is member of the hMre11/hRad50 protein complex, suggesting that the gene is involved in DNA double strand break repair. AIMS To study the clinical and laboratory features of NBS as well as the genotype–phenotype relation. METHODS Fifty five patients with NBS, included in the NBS registry in Nijmegen were evaluated. The majority of the patients were of eastern European ancestry. Most of them had shown a truncating 5 bp deletion 657–661 delACAAA. Four further truncating mutations have been identified in patients with other distinct haplotypes. RESULTS AND CONCLUSIONS Essential features found in NBS were microcephaly, usually without severe retardation, typical facial appearance, immunodeficiency, chromosomal instability, x ray hypersensitivity, and predisposition to malignancy. In 40% of the patients cancer was noted before the age of 21 years. Important additional features were skin abnormalities, particularly café au lait spots and vitiligo, and congenital malformations, particularly clinodactyly and syndactyly. Congenital malformations, immunodeficiency, radiation hypersensitivity, and cancer predispostion were comprehensible in case of dysfunctioning of DNA repair mechanisms. No specific genotype–phenotype relation could be found. Patients with the same genotype may show different phenotypes and patients with different genotypes may express the same phenotype. Specific mutations did not lead to specific clinical features.
Brain tumours are the most common solid tumours in children and adolescents. The increasing survival rate of these patients makes their follow-up and quality of life assessment an important task. The ...evaluation of the negative influence of anti-cancer treatment on their balance is the aim of this study.
The balance assessment was performed on patients who completed the treatment of CNS tumours and were disease-free at the time of the study. Eighty-eight patients aged 5 to 24 years participated in the study. Postural sway was recorded using Kistler force plate. Balance test parameters from two conditions: eyes open and eyes closed were calculated and compared with reference data. The severity of the balance disorders was scored for both conditions.
The balance disorders were generally not dependent on the localisation of the tumour. Only patients treated for posterior fossa tumours had a higher score (indicating pronounced balance deficit) in eyes closed condition comparing to others. The patients treated for spinal cord tumours seemed to have increased total sway path in comparison to others. The severity of the balance deficits tended to diminish in time.
These results suggest that the repair mechanisms of the CNS could overcome the problems inflicted by the illness and therapy.
This multicenter phase II study investigated temozolomide + irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma.
Patients received temozolomide 100-125 mg/m(2)/day ...(days 1-5) and irinotecan 10 mg/m(2)/day (days 1-5 and 8-12) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed ≥4 weeks and assessed by an external response review committee (ERRC). In a 2-stage Optimum Simon design, ≥6 responses in the first 15 evaluable patients were required within the first 4 cycles for continued enrollment; a total of 19 responses from the first 46 evaluable patients was considered successful.
Sixty-six patients were treated. Seven responses were recorded during stage 1 and 15 in the first 46 ERRC evaluated patients (2 complete responses and 13 partial responses). The objective response rate during the first 4 cycles was 32.6% (95% confidence interval CI, 19.5%-48.0%). Median duration of response was 27.0 weeks (7.7-44.1 wk). In 63 patients evaluated by local investigators, the objective response rate was 33.3% (95% CI, 22.0%-46.3%), and 68.3% (95% CI, 55.3%-79.4%) experienced clinical benefit. Median survival was 16.7 months (95% CI, 13.3-19.8). The most common grade 3 treatment-related nonhematologic adverse event was diarrhea (7.6%). Grade 3/4 treatment-related hematologic adverse events included neutropenia (16.7%), thrombocytopenia (12.1%), anemia (9.1%), and lymphopenia (9%).
The planned study primary endpoint was not met. However, its tolerability makes TEMIRI a suitable candidate chemotherapy backbone for molecularly targeted agents in future trials in this setting.
Seventy-four neuroblastoma patients were analyzed according to the clinical data including age, stage, bone metastases, primary tumor localization, tumor diameter, LDH, and serum ferritin. ...Histological examination of tumor specimens comprised calculation of proliferative index (PI) on slides stained with anti Ki-67 antibody and assessment of microvascular density (MVD) on anti-CD34 stained sections. Wide range of PI (1.5-79; median 37.8%) and MVD (41-385; median 172/mm2) values was observed. Significant relationship between higher PI and tumor diameter more than 5 cm (40.3 vs 37.2%) was found. Lower PI was found more frequently in stroma-rich tumors. Significantly higher median MVD was found in infant tumors and in smaller tumors <5 cm. Tendency to inverse relationship between PI and MVD was observed. The high values of both PI and MVD were found in some aggressive tumors in patients >1-year old. We evaluated the new parameter: proliferative-vascular index (PVI) as PVI=PIxMVD which ranged from 213-18333. Among eleven patients >1 year old, with PVI >7000, seven (64%) had a poor outcome within the mean period of 22 months. Our results suggest that the simultaneous estimation of proliferative activity and vascularity of neuroblastomas could be studied as a prognostic indicator. Further investigations are needed to confirm this finding.
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