Cognitive deficits and psychopathological symptoms among children with medulloblastoma.

Children with medulloblastoma (MB) are predisposed for negative cognitive sequela, which has been widely identified in this population. The purpose of the present study was to explore cognitive deficits and psychopathological symptoms and analyse their relation among MB survivors. The Wechsler Intelligence Scale for Children and the Mini International Neuropsychiatric Interview (MINI-KID) was administered to 34 MB survivors to measure cognitive functioning and psychopathological symptoms. The MB survivors had lower global IQ (86.41 [79.70-93.13]) compared with the control population mean. We found impaired functioning in all IQ subscales in the MB survivors group, of which processing speed (84.15 [77.71-90.58]) was the most affected. Higher radiation dose and high-dose chemotherapy with stem cell rescue were significantly associated factors for lowered global IQ, while age at diagnosis, sex and time period from diagnosis were not significantly associated. Compulsive disorder, generalised anxiety, separation anxiety and posttraumatic stress disorder were significantly more prevalent in the MB survivor group than a group of 46 control participants. No correlation was found between the cognitive deficits and the psychopathological symptoms. Our results identify that MB survivors suffer from cognitive and psychopathological impairments, and these could exist independently from each other.

Trends and territorial inequalities of incidence and survival of childhood leukaemia and their relations to socioeconomic status in Hungary, 1971-2015.

The Hungarian Childhood Cancer Registry, a population-based national registry of the Hungarian Paediatric Haemato-Oncology Network founded in 1971, monitors the incidence and mortality of childhood cancer. Our aims were to carry out a longitudinal study to investigate the trends and spatial inequalities of incidence and survival of leukaemia, and the association between survival and deprivation in Hungary. All cases of childhood leukaemia and myelodysplasia were analysed (3157 cases, 1971-2015, age: 0-14 years). Time trends and the annual percentage change in direct standardized incidence and mortality were assessed. Survival and association with deprivation were assessed using the Kaplan-Meier method and Cox regression. Incidence rates of leukaemia (23.5-56.0/million) increased with an average annual percent change (AAPC) of 1%, determined by an increase in the incidence of acute lymphoblastic leukaemia (14.6-39.2/million, AAPC: 1.25%). Kaplan-Meier analysis showed a significant improvement in overall survival over the study period. Starting from 25% of cases surviving 5 years in the 70s; the overall 5-year survival reached 80% by 2010. Survival differences were observed with sex, leukaemia type and age at diagnosis. A reverse association was found in the survival probability of leukaemia by degree of deprivation. The Cox proportional hazards model verified a significant reverse association with deprivation [hazard ratio=1.08 (1.04-1.12)]. This is the first nationwide study to confirm the prognostic role of deprivation on the basis of a large cohort of patients with childhood leukaemia during a 45-year period. To maintain further improvement in treatment results, it is important to detect inequalities. Our results showed that deprivation may also be important in the survival of leukaemia.

[Importance of the National Childhood Cancer Registry in the field of paediatric oncology care in Hungary]. / Az Országos Gyermektumor Regiszter jelentosége a gyermekonkológiai ellátásban.

National Childhood Cancer Registry has been operated since 1971 by the Hungarian Paediatric Oncology Network. This Registry collects data on epidemiology, treatment modalities and effectiveness, as well as late follow-up of childhood cancers. An internet-based paediatric cancer registration and communication system for the Hungarian Paediatric Oncology Network has been introduced in April, 2010. The National Childhood Cancer Registry contains data of all paediatric cancer patients (0-18 yrs) who have insurance covered by the Hungarian Social Security Card. Creation (1971) and operation of the National Childhood Cancer Registry have been very important steps in the field of childhood oncology to evaluate the efficiency of paediatric oncology treatments as well as maximize return on medical investment.

[Antiangiogenic treatment of pediatric CNS tumors in Hungary with the Kieran schedule]. / Gyermekkori központi idegrendszeri daganatok érújdonképzõdés-gátló kezelésének magyarországi eredményei a Kieran-sémával.

In Hungary a new oral antiangiogenic treatment was introduced in cases of primary chemoresistant or recurrent pediatric CNS tumors, called Kieran schedule. The early results of this treatment were analyzed. From 2010 at Semmelweis University on individual decisions a daily combined per oral treatment was introduced in pediatric patients with recurrent or progressive CNS tumor (Kieran schedule: thalidomid, celecoxib, etoposid and cyclophosphamid). Efficacy of therapy was analyzed in terms of demographic data, histology, side effects and tolerability in a retrospective manner. From 2010 through 2013, twenty patients were treated with Kieran schedule (medulloblastoma: 3, ependymoma: 5, anaplastic astrocytoma: 2, GBM: 4, plexus choroideus carcinoma: 1, central primitive neuroectodermal tumor: 1, optic glioma: 2, brainstem tumor: 2). Median treatment time and median progression-free survival were 0.60 and 0.61 years, respectively. Based on the preliminary analysis of a limited cohort of patients, the therapy was efficient in those cases of medulloblastoma, ependymoma, high-grade and optic gliomas, where the expected survival time was more than 3 months at start of treatment. Side effects were slight myelosuppresion in terms of previous therapy, 16% transient ischemic attack (TIA)-like episodes. During therapy patients could live their everyday life. Kieran schedule was well-tolerable and efficient with good quality of life in certain cases of pediatric CNS tumors.

[Paediatric oncology in Hungary]. / A gyermekonkológia helyzete Magyarországon.

The significance of paediatric oncology is increasing due to its increasing incidence and its leading role among the causes of mortality in children. The epidemiology, prophylaxis and therapy of paediatric malignancies in Hungary are discussed surveying the results and the most important tasks in the future.

[The role of chemotherapy in pediatric medulloblastoma]. / A kemoterápia szerepe a gyermekkori medulloblastoma kezelésében.

Medulloblastoma is one of the most frequent brain tumors in childhood. The mortality of medulloblastoma decreased significantly during the last few decades, which was the result of the better surgical and radiotherapeutic methods and of the development of chemotherapy. The aim of this publication is the critical review of the present chemotherapeutic treatment. The new therapeutic trials based on the molecular genetic mechanism of these tumors are also mentioned.

Effect of somatostatin analogue octreotide in medulloblastoma in xenograft and cell culture study.

BACKGROUND: The effect and possible timing of nonradiolabeled somatostatin analogue octreotide are still not determined in the treatment of medulloblastoma, while the presence of somatostatin receptor type-2 (SSTR2) is proved in the majority of medulloblastoma by several authors. PROCEDURES: Daoy, SSTR2A positive medulloblastoma cell culture was tested with octreotide in monotherapy and combined with cisplatin, etoposide, and vincristine. Daoy medulloblastoma mice xenograft was treated with octreotide alone. RESULTS: In monolayer cell culture high-dose octreotide (44 microM) resulted in mitotic inhibition with parallel increment of apoptosis. Combination with cytostatic drugs did not result in additive or synergistic effect, but vincristine was partially antagonized. In medulloblastoma xenograft, octreotide monotherapy (100 microg/kg/day for 10 days) resulted in partial tumor growth inhibition. CONCLUSIONS: High concentration of nonradiolabeled octreotide may have role in the treatment of medulloblastoma by long-term administration. Concomitant administration of octreotide with widely used cytostatic drugs against medulloblastoma will not have beneficial impact.

[Examination of somatostatin receptor expression in recurrent childhood medulloblastomas]. / A szomatosztatinreceptor-expresszió változásának vizsgálata recidiváló medulloblastomában.

Medulloblastoma is the most common malignant pediatric central nervous system tumor. Despite the adequate therapy the tumor often recurs. The primary medulloblastoma expresses somatostatin receptor-2 (SSTR-2), but so far we had no experience about the receptor status in recurrent tumors. The presence of SSTR-2 may have an important role in the early detection and treatment of recurrent medulloblastomas. Our aim was to examine the state of SSTR-2 expression in recurrent childhood medulloblastomas. We examined SSTR-2 expression by immunohistochemistry in primary and recurrent medulloblastoma samples of ten children treated with recurrent medulloblastoma at Semmelweis University, Departments of Pediatrics, between 1998 and 2004. All primary and recurrent tumors have been operated at the National Institute of Neurosurgery. We examined the intensity and the percentage of SSTR-2-positive tumor cells in the primary and recurrent tumor samples. All primary tumors were receptor-positive and SSTR-2 was also expressed in all recurrent medulloblastomas. In our samples the percentage of SSTR-2-positive tumor cells was 30-90%. As a positive in vivo control Octreoscan images were available in two cases. In these cases the results of immunohistochemistry and Octreoscan imaging seemed to correlate. As a conclusion, SSTR-2-positive recurrent tumors can be detected early by Octreoscan imaging, and the presence of SSTR-2 establishes the opportunity of applying somatostatin analogues (octreotide) in the treatment of recurrent childhood medulloblastoma.

Improper supplementation habits of folic acid intake by Hungarian pregnant women: improper recommendations.

BACKGROUND: Neural tube defects (NTDs) are some of the most common congenital anomalies. Proper folic acid supplementation is a dominant risk factor, which has been shown to decrease the incidence of NTDs. In Canada, the incidence of neuroblastoma has presented a considerable decrease of 60% as a result of enrichment cereal grain flours with synthetic folic acid. The aim of this study was to investigate the effect of folic acid intake by pregnant women on the incidence of NTDs and neuroblastoma. METHODS: Regular folic acid intake has been recommended to pregnant women in Hungary since the eighties of the last century by health visitors eventually raking effect as an official protocol which had been released in 1997. During 2001, 2002 and 2003, folic acid intake habits of pregnant women were evaluated by health visitors, proving to be successful in collecting data from 95.06% of the pregnant women. The incidence of NTDs has been registered by the Hungarian National Centre of Epidemiology, Department of Human Genetics and Teratology. The Pediatric Cancer Registry provided the incidence of neuroblastoma in children. RESULTS: Consistent findings revealed a regular intake of supplementary folic acid products by 68.71% of the pregnant women. Out of these, 93.13% of pregnant women who were taking folic acid, started the supplementation after their 7 weeks of pregnancies, a time designated as the completion period of the development of the neural tube. The dose of folic acid supplementation was evaluated as less than 5 mg/day in 84.75% of the pregnant women. In Hungary, the incidence of NTDs has remained constant, while the incidence of neuroblastoma has shown constant slight increase in spite of the introduction of folic acid supplementation in 1997. CONCLUSIONS: Based on our experience, folic acid supplementation was initiated after the recognition of pregnancy and its application in a dose of lower than 5 mg/day neither decreased the incidence of NTDs nor did it have an effect on the neuroblastoma incidence. It is implicated that proper folic acid supplementation, which is started from the conception, can be achieved only with the enrichment of cereal grain flours.

Advanced pediatric inoperable thymus carcinoma (type C thymoma): case report on a novel therapeutic approach.

Although there has been considerable advancement in treatment techniques but still there are some illnesses that continue to exhibit a rather poor curability, such as thymoma. This report highlights the benefit of octreotide and prednisolone therapy in a 15-year-old girl, who was diagnosed with inoperable thymus carcinoma, with chemotherapy and radiotherapy being the last resort. The detection of type 2 somatostatin receptors on the surface of the tumor justified the introduction of treatment with somatostatin analog and prednisolone. Fortunately, after 6 months of this treatment, the tumor showed partial regression. However, 2 months later, somatostatin receptor negative metastases appeared; therefore, a switch over to imatinib became essential, because the tumor was CD-117 positive. Despite the therapy change, the patient's condition deteriorated owing to tumor progression.

[Imaging of pediatric brain tumors using somatostatin analogue 111Ih-DTPA-D-Phe1-octreotide]. / Gyermekkori agytumorok vizsgálata szomatosztatin-analóg (111In-DTPA-D-Phe1-octreotide) alkalmazásával.

Malignant solid tumors and leukemias are the second most common causes of death in childhood. The most frequent pediatric solid tumors are brain tumors. Brain tumors, especially medulloblastoma should be treated by surgery, irradiation and chemotherapy. However, chemotherapy has only moderate effect. Pediatric brain tumors, especially medulloblastomas, express somatostatin receptors. The aim of this study was the investigation of the expression of somatostatin receptors in pediatric brain tumors for diagnostic and therapeutic purpose. Fifty-six scintigraphic imagings (111In-DTPA-D-Phe1-octreotide) made in 45 children treated with brain tumor at the Unit of Oncology of the 2nd Department of Pediatrics, Semmelweis University. The diagnosis was medulloblastoma in 21 cases (46.7%). MRI scans have been performed parallel with the Octreoscan images. Octreoscan images were positive in 27 of 56 (48.2%) cases. The 27 positive Octreoscan images consisted of 16 medulloblastomas, 4 ependymomas, 4 astrocytomas and 3 glioblastomas. In 37 (66.1%) cases the results of Octreoscans were the same as those of the MRI scans. However, in 19 scans (33.9%) the outcome was different. Octreoscan imaging is not suitable for differential diagnosis in pediatric brain tumors, including medulloblastomas. Isotopes specifically binding to the somatostatin receptors (111In-DTPA-D-Phe1-octreotide) can be applied in medulloblastomas for diagnosis and follow-up treatment. In Octreoscan-positive tumors the Octreoscan images establish the opportunity to somatostatin analogue and/or specifically targeted radiation therapies.

Identification of the Fanconi anemia complementation group I gene, FANCI.

To identify the gene underlying Fanconi anemia (FA) complementation group I we studied informative FA-I families by a genome-wide linkage analysis, which resulted in 4 candidate regions together encompassing 351 genes. Candidates were selected via bioinformatics and data mining on the basis of their resemblance to other FA genes/proteins acting in the FA pathway, such as: degree of evolutionary conservation, presence of nuclear localization signals and pattern of tissue-dependent expression. We found a candidate, KIAA1794 on chromosome 15q25-26, to be mutated in 8 affected individuals previously assigned to complementation group I. Western blots of endogenous FANCI indicated that functionally active KIAA1794 protein is lacking in FA-I individuals. Knock-down of KIAA1794 expression by siRNA in HeLa cells caused excessive chromosomal breakage induced by mitomycin C, a hallmark of FA cells. Furthermore, phenotypic reversion of a patient-derived cell line was associated with a secondary genetic alteration at the KIAA1794 locus. These data add up to two conclusions. First, KIAA1794 is a FA gene. Second, this gene is identical to FANCI, since the patient cell lines found mutated in this study included the reference cell line for group I, EUFA592.

[Alternative therapy in childhood cancer]. / Alternatív terápia a gyermekonkológiában.

INTRODUCTION: In Hungary there are as many as 300 children diagnosed with malignant tumor each year. Along with the traditional treatments, alternative remedies have been increasingly applied in the past two decades despite the availability of the more complex and more effective malignant tumor treatments. AIMS: The authors attempted to find out about the applied alternative remedies for childhood cancer outside the traditional treatments, to determine how frequently they were applied and to examine what psychological factors had lead to their application. PATIENTS: Children's parents, getting active treatment and also the ones that have been rehabilitated at the II. Department of Pediatrics, Semmelweis University. RESULTS: 60 percent of the 34 children being examined were getting several kinds of therapy. The most frequently applied alternative remedies were the following: nature products, diet supplements, herbs, diet changes. The parents' choice was mainly influenced by other parents' opinions (42%), frequently appearing commercials in media (26%) and their current financial background (23%). The authors have found on the base of their research that the general aim of parents was: to help their own incapability to help (31%), to make sure about the efficiency of the treatment (45%). CONSEQUENCES: Independently of demographic or clinical facts the use of alternative remedies are excessively widespread and popular with children having tumor. Thus it is not advisable or reasonable to absolutely refuse them since they are quite widespread and people tend to strongly believe in them. As for doctors, they are to give professional advice and help with choosing the alternative remedies that are not harmful or even more, the ones that can make traditional treatments more effective.

[Folic acid supplementation for pregnant women in Hungary]. / A magyarországi várandósok folsavszedési szokásai.

INTRODUCTION: Neural tube defects are common major congenital anomalies. Folic acid supplementation has been shown to reduce the incidence of neural tube defects. In 2003, incidence of neuroblastoma has decreased with 60% in Canada as a result of enriched cereal grain flours with synthetic folic acid. The aim of this study was to investigate the effect of the practice of the folic acid intake by pregnant women (based on the Hungarian recommendation) to the incidence of neural tube defects and neuroblastoma. METHODS: The practice of folic acid supplementation was examined by questionnaires filled according to the documentation of health visitors. The data were worked up by computer. The incidence of neural tube defect was obtained from the data of the Hungarian Congenital Anomalies Registry, however, the data of National Health Insurance Company are also given. The incidence of neuroblastoma was the data of the Hungarian Pediatric Tumor Registry. Regular folic acid intake has been recommended to pregnant women in Hungary, since the eighties of the last century. An official protocol had been released by the Obstetric and Gynecologic Professional Board in 1997. In this paper, the authors report the Hungarian pregnant women's folic acid intake in years of 2001, 2002 and 2003. These years were chosen, because according to the data of the Hungarian Pediatric Cancer Registry 45% of the neuroblastoma cases are less than 1 year old, and 45% of them are 1-5 years old at the time of diagnosis. The authors succeeded to collect the data from 95% of the pregnant women during these years (271,748 women). RESULTS: Based on the statistical analysis of the collected data, 69% of the pregnant women were regularly taking folic acid products in Hungary, however, the dose of the daily intake was below 5 mg. 93% of the pregnant women started the folic acid intake after their 7th weeks of pregnancy The incidence of neural tube defects was constant, and the incidence of neuroblastoma slightly increased during the above mentioned period. CONCLUSIONS: This work highlighted that, the folic acid intake to prevent neural tube defects was started too late, because the formation of neural tube is finished on 28. day of pregnancy. 85% of the pregnant women used less amount of folic acid than 5 mg/day. The increasing number of planned pregnancies would allow to start folic acid intake earlier. However, based on international experience, the enrichment of cereal grain flours with synthetic folic acid could provide optimal results.

Expression and prognostic examination of heat shock proteins (HSP 27, HSP 70, and HSP 90) in medulloblastoma.

Expression of heat shock proteins (HSPs) is of prognostic significance in several tumor types. HSP expression levels were determined in medulloblastomas and tested whether HSPs expression was associated with prognostic parameters. Expression of antiapoptotic HSP 27, HSP 70, and HSP 90 was investigated by immunohistochemistry, on paraffin-embedded sections from 65 patients. Expression of HSPs was validated on internal vascular controls and by Western blotting analysis. Sample evaluation was based on the estimated percentage of HSP positive tumor cells. For survival analysis Kaplan-Meier method, for statistical analysis chi2 test, univariate analysis, and log rank test were applied. Expression of HSPs varied in medulloblastomas. On the basis of the average expression rate of HSPs, at HSP 27 and HSP 90 with a 10% cut off, and at HSP 70 with a 70% cut off 2 groups were created. The amount of expression of any of the HSP types was not significantly associated with known prognostic factors (age of patient, extent of resection, presence of metastasis) and histologic subtype. After an average follow-up period of 4.30 years, no significant difference was observed in survival depending on the expression of HSP 27 or HSP 70 or HSP 90. The high expression of HSPs indicates that these proteins are potential therapeutic targets.

Hungarian experience with Langerhans cell histiocytosis in childhood.

The Langerhans cell histiocytosis (LCH) in children is relatively rare and the long-term analysis of therapy results has not been done yet in Hungary. The aim of this study was to investigate the incidence, clinical features, prognostic risk factors, and treatment results of children's LCH in Hungary in a 20-year period. Children less than 18 years of age with newly diagnosed LCH in Hungary were entered in this study. Clinical data of all children with LCH were reported to the National Childhood Cancer Registry in Hungary from 1981 to 2000. The clinical files were collected and abstracted for information regarding age at diagnosis, gender, disease characteristics, treatment, and outcome of treatment. Median follow-up duration of surviving patients is 10.98 years. Between January 1981 and December 2000, 111 children under 18 years of age were newly diagnosed with LCH in Hungary. The annual incidence of LCH in children younger than 18 years of age was 2.24/million children. The male-female ratio was 1.36:1; the mean age was 4 years 11 months. Thirty-eight children had localized disease and in 73 cases systemic dissemination was found already at the time of diagnosis. Twenty-two patients were treated only by local surgery, 7 by surgery with local irradiation, and 5 children got only local irradiation. In 2 cases remission was achieved with local steroid administration. Seventy-five patients received chemotherapy. In the 20 years of the study 14 children died, 9 due to the progression of the disease. Sixteen patients had relapse with a mean of 2.16 +/- 1.29 years after the first diagnosis. Three patients with relapse got chemotherapy generally used in lymphoma and remission was achieved. The overall survival of all patients (n = 111) was 88.3 +/- 3.1% at 5 years and 87.3 +/- 3.2% at 10 and 20 years. Childhood LCH is a well-treatable disease and the survival rate is high. Even disseminated diseases have a quite good prognosis in childhood.

Childhood leukaemia incidence in Hungary, 1973-2002. Interpolation model for analysing the possible effects of the Chernobyl accident.

The incidence of childhood leukaemia in Hungary has yet to be reported, although data are available since the early 70s. The Hungarian data therefore cover the time before and after the Chernobyl nuclear accident (1986). The aim of this study was to assess the effects of the Chernobyl accident on childhood leukaemia incidence in Hungary. A population-based study was carried out using data of the National Paediatric Cancer Registry of Hungary from 1973 to 2002. The total number of cases was 2204. To test the effect of the Chernobyl accident the authors applied a new approach called 'Hypothesized Impact Period Interpolation'-model, which takes into account the increasing trend of childhood leukaemia incidence and the hypothesized exposure and latency times. The incidence of leukaemia in the age group 0-14 varied between 33.2 and 39.4 per million person-years along the observed 30 year period, and the incidence of childhood leukaemia showed a moderate increase of 0.71% annually (p = 0.0105). In the period of the hypothesized impact of the Chernobyl accident the incidence rate was elevated by 2.5% (95% CI: -8.1%; +14.3%), but this change was not statistically significant (p = 0.663). The age standardised incidence, the age distribution, the gender ratio, and the magnitude of increasing trend of childhood leukaemia incidence in Hungary were similar to other European countries. Applying the presented interpolation method the authors did not find a statistically significant increase in the leukaemia incidence in the period of the hypothesized impact of the Chernobyl accident.

Incidence and survival of central nervous system involvement in childhood malignancies: Hungarian experience.

Direct extension and hematogenous metastasis of primary non-CNS malignant tumors to the CNS are rare complications in children. The authors analyzed the incidence and outcome of these complications in Hungary. During a 14-year period between 1989 and 2002, 406 patients younger than 18 years were studied at Semmelweis University, Second Department of Pediatrics, in Budapest. Among the 406 patients with non-CNS solid tumors, nine hematogenous metastases and five direct tumor extensions to the CNS occurred. Primary tumors included rhabdomyosarcoma, neuroblastoma, tumors of the Ewing sarcoma family, non-Hodgkin lymphoma, and malignant chordoma. Mean interval between the initial diagnosis and the diagnosis of CNS involvement was 11.4 months. Despite intensive treatment, the mean survival after detection of CNS involvement was 10.4 months. The frequency of CNS involvement in non-CNS tumors is low, with a very poor survival.

Fermented Wheat Germ Extract Reduces Chemotherapy-Induced Febrile Neutropenia in Pediatric Cancer Patients.

PURPOSE: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. METHODS: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. RESULTS: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). CONCLUSIONS: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.

Fermented wheat germ extract reduces chemotherapy-induced febrile neutropenia in pediatric cancer patients.

PURPOSE: An open-label, matched-pair (by diagnosis, stage of disease, age, and gender) pilot clinical trial was conducted to test whether the combined administration of the medical nutriment MSC (Avemar) with cytotoxic drugs and the continued administration of MSC on its own help to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers compared with the same treatments without MSC. METHODS: Between December 1998 and May 2002, 22 patients (11 pairs) were enrolled in this study. At baseline, the staging of the tumors was the same in each pair (mostly pTNM = T2N0M0), with the exception of two cases in which patients in the MSC group had worse prognoses (metastasis at baseline). There were no significant differences in the average age of the patients, the length of treatment time (MSC) or follow-up, the number of patients with central venous catheters, the number of chemotherapy cycles, the frequency of preventive counterneutropenic interventions, or the type and dosage of antibiotic and antipyretic therapy used in the two groups. RESULTS: During the treatment (follow-up) period, there was no progression of the malignant disease, whereas at end-point the number and frequency of febrile neutropenic events significantly differed between the two groups: 30 febrile neutropenic episodes (24.8%) in the MSC group versus 46 (43.4%) in the control group (Wilcoxon signed rank test, P < 0.05). CONCLUSIONS: The continuous supplementation of anticancer therapies with the medical nutriment MSC helps to reduce the incidence of treatment-related febrile neutropenia in children with solid cancers.