Comprehensive assessments and related interventions to enhance the long-term outcomes of child, adolescent and young adult cancer survivors - presentation of the CARE for CAYA-Program study protocol and associated literature review.

BACKGROUND: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. METHODS: The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. DISCUSSION: CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. TRIAL REGISTRATION: Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).

Preoperative selective embolization with vascular coiling of giant sacrococcygeal teratoma.

Sacrococcygeal teratoma is one of the most common congenital tumors. Its optimal management requires interdisciplinary care by obstetricians, radiologists, pediatric surgeons, and neonatologists. Early surgery entailing complete tumor excision is the main therapy aim, but a substantial risk of life-threatening complications remains, especially uncontrollable intraoperative hemorrhage. To reduce the risk of bleeding in a female neonate with a giant sacrococcygeal teratoma, we successfully coil-embolized the tumor's main feeding arteries. Her subsequent complete surgical resection was uneventful, and the child is well with favorable reconstructive and functional status of all involved and adjacent organ systems.

Multi-color polymer pen lithography for oligonucleotide arrays.

Multi-color patterning by polymer pen lithography (PPL) was used to fabricate covalently immobilized fluorophore and oligonucleotide arrays with up to five different components. The oligonucleotide arrays offer a virtually unlimited inventory of orthogonal binding tags for self-assembly of proteins as demonstrated by use of the arrays to monitor cell-protein interactions of MCF7 cells.

[Studies and Publication Practice in Pediatric Hematology and Oncology in Germany--An Analysis of the Period 1970-2006]. / Studien und Publikationspraxis in der PädiatrischenHämatologie und Onkologie in Deutschland--Analyseder Jahre 1970­2006.

BACKGROUND: Several therapy optimization studies (TOSs) for the treatment of hematologic and oncologic disorders in children and adolescents have been conducted in Germany. The publication of research results is necessary to ensure that future studies are well designed and based on relevant and unanswered questions. This retrospective cohort study was conducted to analyze the study- and publication practice in this field. METHODS: All study protocols in the field of the pediatric oncology and hematology in Germany were collected. Relevant data from study protocols were extracted, beginning with 1) general information about the study protocol, and 2) information about each methodological trial. In a second step, the publication practice was characterized by searching in electronic databases and by contacting principal investigators. Relevant Data of each publication was extracted. RESULTS: The research activity has increased significantly in the past few years. The found publication rate of 85% represents an outstanding publication practice. Additionally, German, as being the main publication language a few decades ago, has been almost completely replaced with English. An acceptable methodological conduct was observed in the analyzed study protocols. DISCUSSION AND CONCLUSION: Studies have been principally based on the concept of TOS, without considering a detailed breakdown into each methodological trial. A markedly subdivision of studies into methodologically identifiable trials would allow a clear definition of their parameters, while increasing transparency of the study conduct and its results.

Outcomes of mismatched and unrelated donor hematopoietic stem cell transplantation in Fanconi anemia conditioned with chemotherapy only.

Fanconi anemia (FA) is a genomic instability syndrome associated with bone marrow failure, myelodysplastic syndrome (MDS), and/or acute myeloid leukemia (AML) requiring hematopoietic stem cell transplantation (HSCT) to restore normal hematopoiesis. Although low-intensity fludarabine-based preparative regimens without radiation confer excellent outcomes in FA HSCTs with HLA-matched sibling donors, outcomes for FA patients with alternative donors are less encouraging, albeit improving. We present our experience with 17 FA patients who completed mismatched related or unrelated donor HSCT using a non-radiation fludarabine-based preparative regimen at Charité University Medicine Berlin. All patients engrafted; however, one patient had unstable chimerism in the setting of multi-viral infections that necessitated a stem cell boost to revert to full donor chimerism. Forty-seven percent of patients developed grade I acute graft-verus-host disease (aGVHD). No grade II-IV aGVHD or chronic graft-versus-host disease of any severity occurred. At a median follow-up of 30 months, 88 % of patients are alive with normal hematopoiesis. Two patients died of infections 4 months post-transplantation. These results demonstrate that short-term outcomes for FA patients with mismatched and unrelated donor HSCTs can be excellent using chemotherapy only conditioning. Viral reactivation, however, was a major treatment-related complication.

[Germline mutations in children with cancer - leopoldina meeting report, september 26, 2014, jesuit monastery merzhausen]. / Keimbahnmutationen bei krebskranken Kindern - Symposium der Leopoldina am 26.09.2014 im Jesuitenkloster Merzhausen bei Freiburg.

Under the umbrella of the Leopoldina, National Academy of Science Germany, a one-day workshop took place with experts from Pediatric Oncology, Human Genetics, Jurisprudence and Science Ethics. Professor Dr. Matthias Brandis, former head of the Clinic of Pediatrics and Adolescent Medicine, Albert-Ludwigs-University Freiburg, encouraged the authors to organize this workshop near Freiburg and provided professional and logistic support. Professor Dr. Matthias Brandis serves as the chairmen of our pediatric-gynecological section within the Leopoldina.

T-cell receptor Vß skewing frequently occurs in refractory cytopenia of childhood and is associated with an expansion of effector cytotoxic T cells: a prospective study by EWOG-MDS.

Immunosuppressive therapy (IST), consisting of antithymocyte globulin and cyclosporine A, is effective in refractory cytopenia of childhood (RCC), suggesting that, similar to low-grade myelodysplastic syndromes in adult patients, T lymphocytes are involved in suppressing hematopoiesis in a subset of RCC patients. However, the potential role of a T-cell-mediated pathophysiology in RCC remains poorly explored. In a cohort of 92 RCC patients, we prospectively assessed the frequency of T-cell receptor (TCR) ß-chain variable (Vß) domain skewing in bone marrow and peripheral blood by heteroduplex PCR, and analyzed T-cell subsets in peripheral blood by flow cytometry. TCRVß skewing was present in 40% of RCC patients. TCRVß skewing did not correlate with bone marrow cellularity, karyotype, transfusion history, HLA-DR15 or the presence of a PNH clone. In 28 patients treated with IST, TCRVß skewing was not clearly related with treatment response. However, TCRVß skewing did correlate with a disturbed CD4(+)/CD8(+) T-cell ratio, a reduction in naive CD8(+) T cells, an expansion of effector CD8(+) T cells and an increase in activated CD8(+) T cells (defined as HLA-DR(+), CD57(+) or CD56(+)). These data suggest that T lymphocytes contribute to RCC pathogenesis in a proportion of patients, and provide a rationale for treatment with IST in selected patients with RCC.

Key treatment questions in childhood acute lymphoblastic leukemia: results in 5 consecutive trials performed by the ALL-BFM study group from 1981 to 2000.

Between 1981 and 2000, 6 609 children (<18 years of age) were treated in 5 consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria, and Switzerland. Probability of 10-year event-free survival (survival) improved from 65% (77%) in study ALL-BFM 81-78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: 1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk ALL patients and eliminated in non-high-risk non-T-ALL patients, if it was replaced by high-dose and intrathecal methotrexate; 2) omission of delayed reintensification severely impaired outcome of low-risk patients; 3) 6 months less maintenance therapy caused an increase in systemic relapses; 4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; 5) condensed induction therapy resulted in a significant improvement of outcome; 6) the daunorubicin dose in induction could be safely reduced in low-risk patients; 7) intensification of consolidation/reintensification treatment led to considerable improvement of outcome in high-risk patients.

[DGRW-Update: musculo-skeletal diseases]. / DGRW-Update: Erkrankungen des Muskel-Skelettsystems.

BACKGROUND: Orthopedic rehabilitation is a major entity in rehabilitation. Due to coming demographic changes and its challenges concerning mobility of elderly patients it will increase. The criticism on orthopedic rehabilitation in Germany focuses on its missing evidence in therapeutic eff ectiveness especially in chronic low back pain. This overall-criticism is actually no more valid as there are a number of studies showing eff ectiveness of orthopedic treatment in rehabilitation if psychosocial comorbidities are respected and treatment is focussed on occupational training and eintegration. GOALS: This overview describes the actual situation in orthopedic rehabilitation and its research. RESULTS: The need for orthopedic rehabilitation will increase over the next years due to demographic changes. Important fi elds in orthopedic rehabilitation research are chronic low back pain, new rehabilitation models with focus on occupational reintegration, rehabilitation in elderly and following joint surgery as well as the analysis of health-care-system changes due to disease related groups.

Hematopoietic stem cell transplantation for advanced myelodysplastic syndrome in children: results of the EWOG-MDS 98 study.

We report on the outcome of children with advanced primary myelodysplastic syndrome (MDS) transplanted from an HLA-matched sibling (MSD) or an unrelated donor (UD) following a preparative regimen with busulfan, cyclophosphamide and melphalan. Ninety-seven patients with refractory anemia with excess blasts (RAEB, n=53), RAEB in transformation (RAEB-T, n=29) and myelodysplasia-related acute myeloid leukemia (MDR-AML, n=15) enrolled in the European Working Group of MDS in Childhood (EWOG-MDS) 98 study and given hematopoietic stem cell transplantation (HSCT) were analyzed. Median age at HSCT was 11.1 years (range 1.4-19.0). Thirty-nine children were transplanted from an MSD, whereas 58 were given the allograft from a UD (n=57) or alternative family donor (n=1). Stem cell source was bone marrow (n=69) or peripheral blood (n=28). With a median follow-up of 3.9 years (range 0.1-10.9), the 5-year probability of overall survival is 63%, while the 5-year cumulative incidence of transplantation-related mortality (TRM) and relapse is 21% each. Age at HSCT greater than 12 years, interval between diagnosis and HSCT longer than 4 months, and occurrence of acute or extensive chronic graft-versus-host disease were associated with increased TRM. The risk of relapse increased with more advanced disease. This study indicates that HSCT following a myeloablative preparative regimen offers a high probability of survival for children with advanced MDS.

Analysis of risk factors influencing outcome in children with myelodysplastic syndrome after unrelated cord blood transplantation.

We describe 70 children with myelodysplastic syndrome (MDS) (refractory cytopenia (n=31) and refractory anemia with excess blasts (n=30) or blasts in transformation (n=9)) who received umbilical cord blood (UCB) transplantation with a single UCB unit and a myeloablative conditioning regimen. Approximately 20% of children had secondary MDS. Median age at transplantation was 7 years and the median follow-up was 3 years. The day-60 probability of neutrophil recovery was 76%; recovery was faster after transplantation of matched or 1-locus mismatched UCB, irradiation-containing conditioning regimen, cell dose >6 × 10(7)/kg and monosomy 7. Risks of treatment failure (recurrent disease or death) were lower in patients with monosomy 7 and transplantations after 2001. The 3-year disease-free survival (DFS) was 50% for transplantations after 2001 compared with 27% for the earlier period (P=0.018). Transplantations after 2001 occurred within 6 months after diagnosis and used UCB units with higher cell dose. DFS was highest in patients with monosomy 7 (61%) compared with other karyotypes (30%), P=0.017. These data suggest that transplantation of mismatched UCB graft is an acceptable alternative for children without a matched sibling or suitably matched unrelated adult donor.

A novel HLA-B allele, B*14:10, identified by haplotype-specific sequencing.

A novel HLA-B allele, HLA-B*14:10, differs from HLA-B*14:08 by three nucleic acid substitutions.