Ovarian Sertoli Leydig cell tumours in children and adolescents: an analysis of the European Cooperative Study Group on Pediatric Rare Tumors (EXPeRT).

Objective: To analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification.

Patients: Forty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies (n=23), French TGM protocols (n=10), Italian Rare Tumour Project (TREP) registry (n=6), and the Polish Pediatric Rare Tumour Study group (n=5).

A novel role for microphthalmia-associated transcription factor-regulated pigment epithelium-derived factor during melanoma progression.

Microphthalmia-associated transcription factor (MITF) acts via pigment epithelium-derived factor (PEDF), an antiangiogenic protein, to regulate retinal pigment epithelium migration. PEDF expression and/or regulation during melanoma development have not been investigated previously. Using immunohistochemistry, we determined expression of PEDF in common and dysplastic melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma (n = 102).

LASP1 is a novel BCR-ABL substrate and a phosphorylation-dependent binding partner of CRKL in chronic myeloid leukemia.

Chronic myeloid leukemia (CML) is characterized by a genomic translocation generating a permanently active BCR-ABL oncogene with a complex pattern of atypically tyrosine-phosphorylated proteins that drive the malignant phenotype of CML. Recently, the LIM and SH3 domain protein 1 (LASP1) was identified as a component of a six gene signature that is strongly predictive for disease progression and relapse in CML patients. However, the underlying mechanisms why LASP1 expression correlates with dismal outcome remained unresolved.

PTEN microdeletions in T-cell acute lymphoblastic leukemia are caused by illegitimate RAG-mediated recombination events.

Phosphatase and tensin homolog (PTEN)-inactivating mutations and/or deletions are an independent risk factor for relapse of T-cell acute lymphoblastic leukemia (T-ALL) patients treated on Dutch Childhood Oncology Group or German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia protocols. Some monoallelic mutated or PTEN wild-type patients lack PTEN protein, implying that additional PTEN inactivation mechanisms exist. We show that PTEN is inactivated by small deletions affecting a few exons in 8% of pediatric T-ALL patients.

Identification of novel NOTCH1 mutations: increasing our knowledge of the NOTCH signaling pathway.

Background: Alterations in the NOTCH1 signaling pathway are found in about 60% of pediatric T-ALL, but its impact on prognosis remains unclear.

Procedure: We extended the previously published CoALL cohort (n = 74) to a larger cohort (n = 127) and additionally included 38 Argentine patients from ALL IC-BFM to potentially identify novel mutations and decipher a stronger discriminatory effect on the genotype/phenotype relationship with regard to early treatment response and long-term outcome.

Results: Overall, 101 out of 165 (61.

Aberrant ZNF423 impedes B cell differentiation and is linked to adverse outcome of ETV6-RUNX1 negative B precursor acute lymphoblastic leukemia.

Differentiation arrest is a hallmark of acute leukemia. Genomic alterations in B cell differentiation factors such as PAX5, IKZF1, and EBF-1 have been identified in more than half of all cases of childhood B precursor acute lymphoblastic leukemia (ALL). Here, we describe a perturbed epigenetic and transcriptional regulation of ZNF423 in ALL as a novel mechanism interfering with B cell differentiation.

Learning from errors: when a low platelet count in neonate excludes immune thrombocytopenic purpura in mother.

This paper reviews the most common causes of thrombocytopenia in the newborn. It mentions few classification schemes that clearly characterize the most common causes, diagnosis and treatment approaches for neonatal thrombocytopenia. Particular attention is paid to inborn macrothrombocytopenia without congenital anomalies.

Doxorubicin or daunorubicin given upfront in a therapeutic window are equally effective in children with newly diagnosed acute lymphoblastic leukemia. A randomized comparison in trial CoALL 07-03.

Background: The anthracyclines daunorubicin (DNR) and doxorubicin (DOX) are among the most important drugs in the treatment of childhood acute lymphoblastic leukemia, however there are conflicting in vitro data about the comparative efficacy and equivalent doses of both anthracyclines. To address the question of in vivo efficacy of both anthracyclines, patients enrolled in the CoALL 07-03 trial were randomized to receive one single dose of either doxorubicin 30 mg/m(2) , daunorubicin 30 mg/m(2) , or daunorubicin 40 mg/m(2) upfront induction therapy.

Procedure: Children with newly diagnosed B-Precursor ALL or T-ALL were eligible for the randomized comparison.

Meta-analysis of randomised trials comparing thiopurines in childhood acute lymphoblastic leukaemia.

Mercaptopurine has been used in continuing treatment of childhood acute lymphoblastic leukaemia since the mid 1950s. Recent advances in the understanding of thiopurine pharmacology indicated that thioguanine (TG) might be more effective than mercaptopurine (MP). The US and UK cooperative groups began randomised thiopurine trials and agreed prospectively to a meta-analysis.

The long-term impact of in vitro drug sensitivity on risk stratification and treatment outcome in acute lymphoblastic leukemia of childhood (CoALL 06-97).

Background: In a study of childhood acute lymphoblastic leukemia (CoALL 06-97 study), the in vitro sensitivity of the patients' cells to prednisolone, vincristine and asparaginase was introduced as a new additional risk parameter for treatment stratification. In parallel in vivo treatment response was assessed by determining the presence and extent of minimal residual disease in a subset of patients (n=224). Here we report the long-term impact of in vitro sensitivity-based risk stratification according to survival and compare the results of in vitro sensitivity with in vivo response.

Cooperative study group for childhood acute lymphoblastic leukaemia (COALL): long-term results of trials 82,85,89,92 and 97.

In this study, the long-term outcome of 1818 patients treated in five consecutive clinical trials (the cooperative study group for childhood acute lymphoblastic leukaemia (COALL) 82, 85, 89, 92 and 97) from 24 cooperating centres in Germany is reported. The probability of event-free survival (pEFS) improved significantly from the first two trials conducted in the 1980s (COALL 82 and COALL 85) to the three trials conducted in the 1990s (COALL 89, 92 and 97) (P=0.001).

Treatment of neuroblastoma with human natural antibodies.

Unlabelled: Serum of healthy individuals may contain natural antibodies which are able to induce complement dependent cytotoxicity against neuroblastoma. The prevalence of cytotoxic activity in serum of neuroblastoma patients is low compared with age matched healthy children which indicates a role of natural cytotoxic antibodies in immunosurveillance of neuroblastoma. Based on these findings we selected plasma of blood donors with a high in-vitro cytotoxic activity against LA-N-1 neuroblastoma cells.

A simplified method of antibiotic lock therapy for Broviac-Hickman catheters using a CLC 2000 connector device.

Introduction: We report a simplified method of performing antibiotic lock therapy (ALT) based on a disposable central venous catheter (CVC) hub device, CLC 2000, enabling an open-ended CVC to be flushed with normal saline solution without heparin.

Methods: ALT was administered through a CLC 2000 connector for recurrent CVC-bloodstream infections (BSI) by the same organism in four patients and for CVC colonization in five patients.

Results: The antibiotic concentration obtained in the lumen of the CVC with ALT was 2,500-fold higher than the minimum inhibiting concentration of targeted bacteria for patients treated with vancomycin, 2,500-80,000-fold higher for patients treated with teicoplanin, and 10,000-fold higher for the patient treated with amikacin.

Epidemiologic analysis of 1,442 children and adolescents registered in the German germ cell tumor protocols.

Background: Germ cell tumors (GCTs) constitute a heterogeneous group of tumors that significantly vary with respect to their clinical presentation and biology. The objective of this analysis was to analyze a large population-based pediatric cohort of GCTs and to evaluate the parameters age, sex, site of the tumor, histology, and potential correlations between these parameters.

Procedure: Between 1981 and 2000, 1,442 patients were prospectively enrolled onto the German protocols for testicular and non-testicular GCTs.

Incidence of childhood cancers in Poland in 1995-1999.

Background: The annual rate for childhood cancers in developed countries amounts to 105-130 new cases per 1 million children. The Polish population aged 0-17 years is estimated at approximately 10 million children and adolescents, thus ca. 1100-1300 new cases can be expected every year.

Serial evaluation of the oncological pediatric risk of mortality (O-PRISM) score following allogeneic bone marrow transplantation in children.

The O-PRISM score was introduced for risk assessment in children transferred to intensive care following BMT. The aim of this study is to determine the prognostic value of a serial evaluation of the O-PRISM score. Ninety-three children, 58 allogeneic-related and 35 unrelated BMT, were evaluated.

Management of germ cell tumors in children: approaches to cure.

The introduction of cisplatinum chemotherapy and current advances in the surgical treatment have resulted in a dramatic improvement of the prognosis of children with malignant germ cell tumors (GCT). Cisplatinum chemotherapy generally results in sufficient systemic tumor control, but local relapses may still occur in patients who did not receive adequate local treatment. Therefore, the therapeutic consideration must take into account age, primary site of the tumor, and its histology.

Genetic analysis of childhood germ cell tumors with comparative genomic hybridization.

Background: Germ Cell Tumors (GCTs) in children and adolescents constitute a clinically and histologically heterogeneous group of tumors. Compared to GCTs in adults, the numbers of GCTs in children analyzed with cytogenetic and molecular genetic techniques is limited. However, the data available to date reveal a pattern of cytogenetic aberrations different from that in adults.

Diagnostic value of alpha 1-fetoprotein and beta-human chorionic gonadotropin in infancy and childhood.

This article provides a comprehensive review of the current literature and summarizes the experience of the German cooperative protocols for nontesticular germ cell tumors (MAKEI) on the use of alpha 1-fetoprotein (AFP) and beta-human chorionic gonadotropin (beta-hCG) for diagnostic evaluation in pediatric oncology. Based on this evaluation, this review proposes guidelines for the initial diagnostic work-up for children with clinically suspected secreting tumors. AFP and beta-hCG represent the characteristic tumor markers of malignant epithelial liver tumors and malignant germ cell tumors (GCT).

Can busulfan replace fractionated total body irradiation as conditioning regimen for allogeneic bone marrow transplantation in children with acute lymphoblastic leukemia.

The results of allogenic bone marrow transplantation (allo-BMT) in 26 children with ALL treated with the same initial- and relapse-BFM-protocols, but transplanted in different centers (Poznań, Wroclaw, Hannover) after conditioning with two different regimens have been compared. Ten children (6 in Poznań, 4 in Wroclaw) were conditioned for BMT with busulfan and cyclophosphamide when fractionated TBI (FTBI) was not available there. Sixteen children obtained FTBI and etoposide (11 in Hannover, where in children with ALL exclusively chemoradioconditioning regimen has been employed, and 5 in Poznań).