Treatment of adolescents and young adults (AYA) with cancer in a multidisciplinary setting: on the way to a highly specialized AYA unit.

Further survival improvements of adolescents and young adults (AYA) with cancer are clearly affected by biological characteristics of the malignancies and age-specific needs. Multidisciplinary teams drawing expertice from both pediatric and adult cancer teams as well as clinical trials are required to meet the age specific needs of AYA patients with cancer. In 2011, the first AYA unit was established at the University Hospital Halle (Saale), where patients with newly-diagnosed cancer aged 15-25 are treated interdisciplinary by pediatric and adult oncologists. The enrollment into pediatric or adult clinical trials is controlled by age 18. Over the last 2 years, 19 AYA with cancer have been treated at the unit; and, in turn patients and their relatives reflected a high satisfaction with the offered novel health care approach. In the scope of the future Comprehensive Cancer Center at the University Hospital Halle (Saale), a complete ward is planned for all admitted AYA up to 25 years with cancer. The patients will be treated by a tumor-specialized multidisciplinary team of adult or pediatric oncologists and oncological surgeons. Therefore, we intend to establish a special teaching curriculum for physicians, nurses and psychosocial health care staff. Rather than age, cancer biology of a malignancy, surveillance data of late side effects as well as the age-specific needs of AYA patients will be crucial for best treatment options.

Management of oncology patients admitted to the paediatric intensive care unit of a general children's hospital - a single center analysis.

BACKGROUND: The improving prognosis of children with cancer has partially been attributed to the increasing importance of pediatric intensive care units (PICU). We analyze whether outcome of these patients on a PICU improved during the last decade and which factors may influence the outcome in our hospital. PATIENTS AND METHODS: The charts of all oncology patients admitted to the PICU between 1998 and 2009 have been reviewed retrospectively. The survival of patients admitted for life threatening complications has been correlated with basic data, organ failure and the PRISM score. The results of 2 consecutive treatment periods (1998-2003 and 2004-2009) were compared. RESULTS: 644 admissions of 226 patients were recorded. 79 admissions were performed because of potentially life threatening complications (Group A), 236 for monitoring (B) and 329 admissions for interventions (C). 62% of Group A patients and all Group B and C patients were discharged alive. Poor outcome was associated with admission >28 days after initial diagnosis, PRISM >10, organ failure >2 organs, sepsis, allogeneic stem cell transplantation, need for mechanical ventilation or for catecholamines. The PICU survival rate of Group A patients admitted between 2004 and 2009 (78%) was higher than in the period between 1998 and 2003 (48%). CONCLUSIONS: PICU provides essential services to support the pediatric oncology ward. Although children with cancer may have had benefit from advances in pediatric intensive care over the past decade, specific scoring systems for early identification of children with cancer needing PICU treatment are required. These systems might further improve PICU outcome in critical ill pediatric cancer patients.

Maintenance immunotherapy by repetitive low-dose donor lymphocytes infusions in a child with relapse state aml after allogeneic stem cell transplantation.

The treatment of a child with a relapsed state acute leukemia after allogeneic stem cell transplantation (allo-SCT) is a challenge. The authors report about a child with an acute myelogenous leukemia (AML), which relapsed after allo-SCT despite immunological intervention. It was further treated with a second line chemotherapy followed by an infusion of stem cells and donor lymphocytes. Because of an immense risk for a further relapse, an immunological maintenance therapy was also performed, consisting of repetitive infusions of low doses of donor lymphocytes combined with low-dose chemotherapy. Presently, the child is in continuous complete remission and has a good quality of life.

Common genetic variants in the interleukin-6 and chitotriosidase genes are associated with the risk for serious infection in children undergoing therapy for acute myeloid leukemia.

Infectious complications represent a substantial cause of morbidity and mortality in children undergoing therapy for acute myeloid leukemia (AML). Since it has been shown that alterations in innate immune pathways contribute to the risk for serious infections, we analyzed well-characterized variants in innate immune genes (TNF, IL6, IL8, MPO, CHIT, FCGR2A, TLR2, and TLR4) to determine their possible contribution to infectious complications during therapy for pediatric AML. The study population consisted of 168 North European Caucasian children enrolled on the clinical trial AML-BFM 93. We found an association between Gram-negative bacterial infection and common, functional variants in two genes, IL6 and CHIT. The risk for infection was significantly higher in children with the G allele in the IL6 promoter at -174 bp (P=0.026) and in patients with the H allele of CHIT (P=0.033). The promoter variant in IL6 has been shown to increase expression while the H allele disrupts both function and circulating levels. Our data suggest that variant alleles of both IL6 and CHIT could influence susceptibility to infection with Gram-negative bacteria in children undergoing therapy for AML. Follow-up studies, namely replication association studies and in vitro investigation of these common polymorphisms, are warranted to confirm these observations.

Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection.

Human mannose-binding protein (MBL) is a component of innate immunity. To capture the common genetic variants of MBL2, we resequenced a 10.0 kb region that includes MBL2 in 102 individuals representing four major US ethnic groups. In all, 87 polymorphic sites were observed, indicating a high level of heterozygosity (total pi=18.3 x 10(-4)). Estimates of linkage disequilibrium across MBL2 indicate that it is divided into two blocks, with a probable recombination hot spot in the 3' end. Three non-synonymous SNPs in exon 1 of the encoding MBL2 gene and three upstream SNPs form common 'secretor haplotypes' that can predict circulating levels. Common variants have been associated with increased susceptibility to infection and autoimmune diseases. The high frequencies of B, C and D alleles in certain populations suggest a possible selective advantage for heterozygosity. There is limited diversity of haplotype structure; the 'secretor haplotypes' lie on a restricted number of extended haplotypes, which could include additional linked SNPs, which might also have possible functional implications. There is evidence for gene conversion in the region between the two blocks, in the last exon. Our data should form the basis for conducting MBL2 candidate gene association studies using a locus-wide approach.

Clinical double-blind trial on the dermal tolerance and user acceptability of six alcohol-based hand disinfectants for hygienic hand disinfection.

Six commercially available alcohol-based hand rubs [AHD 2000, Desderman, Mucasept A, Manorapid (Poly-Alkohol, Spitacid, and Sterillium] were investigated in a clinical double-blind trial involving 10 participants who had no previous experience of using hand rubs (Group 1), and seven who had substantial professional experience of using hand rubs (Group 2; virology laboratory staff). Group 1 was studied for one week with 20 applications on day 1 and then five applications per day for six days. Transepidermal water loss, dermal water content and superficial sebum content of the skin were measured before and after the seven-day application of the products, as well as user acceptability (self-assessment of smell, speed of drying, emolliant effect, skin dryness). Group 2 used each preparation twice for two weeks in a random sequence, and carried out self assessment at the end of each fortnight. Transepidermal water loss (mean baseline: 18.7 g/m(2)h), dermal water content (mean baseline dorsum: 75.6) and superficial sebum content (mean baseline dorsum: 4.8 microg/cm(2)) did not change significantly. In both groups assessments of the smell and the speed of drying did not reveal any significant differences between the six products. Sterillium had the best emollient effect of all products (P<0.05; Wilcoxon test and Mann-Whitney-U test) and was significantly better than Desderman, AHD 2000, and Mucasept A, causing less skin dryness after seven days use in Group 1 (P<0.05; Mann-Whitney-U test). Manorapid caused significantly less dryness than Spitacid, AHD 2000, and Mucasept A in Group 2 after the first use, but no significant difference was observed after the second use. Thus alcohol-based hand rubs that contain emolliants, irrespective of the type of alcohol (n-propanol, iso-propanol or ethanol), are well tolerated and do not dry out or irritate the skin. Personal assessments showed significant differences for the emolliant effect and the extent of dryness. Both factors are very important, as user acceptability has an impact on compliance. Sterillium is the only hand disinfectant containing mecetronium etilsulphate which has been shown to have an emolliant effect. Future research should focus on user acceptability in order to improve compliance.

Intensive chemotherapeutic regimens against acute leukemia transiently suppress asthma symptoms but do not lead to long-term relief.

In some very rare cases children suffer from a combination of asthma and a malignant disease. This study investigated whether intensive chemotherapy might have a positive effect on asthma in these special cases and whether asthma generally relapses after completion of chemotherapy. The authors monitored clinical outcome and lung function of 43 children with acute lymphoblastic leukemia and non-Hodgkin lymphoma who received chemotherapy at the University Children's Hospital of Greifswald between 1993 and 1998. Cytostatic chemotherapy was administered according to the German treatment protocols. Two of the 43 patients had asthma before leukemia was diagnosed. During the course of chemotherapy, asthma symptoms diminished promptly after beginning of chemotherapy but asthma was rediagnosed after completion of chemotherapy in both cases. The third patient developed asthmatic symptoms shortly after completion of chemotherapy for the first time. It can be stated that chemotherapy does not essentially cure asthma. Therefore, it seems mandatory to perform follow-up lung testings after chemotherapy, especially in patients with asthma.

Ectopic cervical thymus in a 12-year-old boy: a case report.

The case of a 12-year-old boy with ectopic cervical thymus is reported. This is a rare differential diagnosis in cervical tumors in childhood. The clinical symptoms might present as complications; in rare cases malignant transformations have been reported. The diagnosis ectopic cervical thymus can be achieved only histologically. Due to possible malignant transformation, it is mandatory to excise this thymus tumor totally.

Antibiotic sequential therapy for febrile neutropenia in pediatric patients with malignancy.

Children suffering malignant diseases can experience phases of bone marrow depression during intensive chemotherapy. The influence of antibiotic sequence therapy on the course of diseases was examined in 41 pediatric patients with malignant diseases. Inclusion criteria were neutropenia (ANC < 500/microL), rectal body temperature over 38.5 degrees C, and increased C-reactive protein (CRP, cutoff > 5.0 mg/L). The first stage of therapy comprised the following antibiotics: piperacillin, teicoplanin, and gentamicin. In stage 2 imipenem, teicoplanin, and tobramycin were administered. Fluconazole was the antifungal drug of choice in stages 1 and 2. In the first level of antibiotic therapy 68% of the patients showed a positive reaction. The C-reactive protein was a sensitive parameter, which significantly decreased with 3 days of therapy. A total of 72% of the bacteriological smears were sterile. All patients survived the septic phase.