Targeted therapeutics in treatment of children and young adults with solid tumors: an expert survey and review of the literature.

Although prognosis of children with solid tumors is steadily improving, long-term survival is not achievable in all patients, especially in patients with recurrent or refractory disease. Despite the increasing number of targeted therapeutics (TT), only very few TT have been introduced into clinical protocols. Accordingly, clinical experience concerning the efficacy and safety of these drugs is limited.

A long duration of the prediagnostic symptomatic interval is not associated with an unfavourable prognosis in childhood medulloblastoma.

Background: Due to the lacking specificity of symptoms making a correct diagnosis can be a challenge in children with medulloblastoma. This can lead to prediagnostic symptomatic intervals (PSIs) of several weeks to months. It is unknown whether the length of the PSI is associated with an inferior survival outcome in this population.

Long-term outcome and clinical prognostic factors in children with medulloblastoma treated in the prospective randomised multicentre trial HIT'91.

Purpose: To analyse long-term outcome and clinical prognostic factors in medulloblastoma.

Methods: We analysed 280 patients with medulloblastoma (3-18 years) included from 1991 to 1997 in the randomised multicentre trial HIT'91 comparing pre-('sandwich') and postradiation ('maintenance') chemotherapy (median follow-up of survivors for 10 years).

Results: In 187 patients with complete staging, overall survival (OS) was higher after maintenance compared to sandwich treatment for M0 (10-year OS 91% and 62%, p=0.

Prognostic relevance of clinical and biological risk factors in childhood medulloblastoma: results of patients treated in the prospective multicenter trial HIT'91.

Purpose: To identify better risk stratification systems in childhood medulloblastoma based on clinical factors and analysis of routinely processed formalin-fixed tumor material.

Experimental Design: Formalin-fixed paraffin-embedded tumor samples from well-documented patients treated within the prospective randomized multicenter trial HIT'91 were analyzed for DNA amplification of c-myc and N-myc (n=133) and mRNA expression of c-myc and trkC (n=104; compared with human cerebellum) using validated methods of quantitative PCR and reverse transcription-PCR. Results were related to clinical data and outcome.

[Desmoid tumors of the head and neck].

Desmoid tumors of the head and neck, also known as aggressive fibromatoses, are rare. They are soft tissue neoplasms arising from musculoaponeurotic structures and characterized of locally aggressive infiltration and recurrences. Complete surgical excision of desmoid tumors is considered to be the only effective method of cure.

Childhood pineoblastoma: experiences from the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91.

Objective: To analyze the outcome of children with pineoblastoma (PB), treated within the prospective multicenter trials HIT-SKK87, HIT-SKK92 and HIT91 of German-speaking countries.

Patients: We report on 11 children suffering from PB. Five children younger than 3 years of age received chemotherapy after surgery until eligible for radiotherapy (HIT-SKK87 and HIT-SKK92).

Near-total splenectomy for hereditary spherocytosis: clinical prospects in relation to disease severity.

We prospectively studied the efficacy of near total splenectomy (NTS) for managing hereditary spherocytosis (HS) based on haemoglobin (Hb), total bilirubin and splenic remnant regrowth in 30 children receiving NTS for HS between November 1996 and December 2004 (mean followup 3.6 years). Patients were classified into three severity groups.

Insulin-like growth factor-binding protein 4 in children with acute lymphoblastic leukemia.

Insulin-like growth factor-binding protein 4 (IGFBP-4) is a potent inhibitor of IGF-mediated cell proliferation. To investigate the functional relevance of IGFBP-4 in leukemia, we measured plasma IGFBP-4 levels and messenger RNA expression in leukemic cell clones of patients with acute lymphoblastic leukemia (ALL) and in control subjects. The IGFBP-4 levels of ALL patients at diagnosis were significantly lower than the levels of healthy control subjects.

Chronic natural killer cell lymphocytosis is associated with elevated cytotoxic activity of natural killer cells.

The authors describe a 16-year-old girl who has suffered from chronic natural killer cell lymphocytosis (CNKL) for 12 years. From age 4 years, she has shown a persistent lymphadenopathy and lymphocytosis. Clinically, she developed allergic skin involvement, thrombocytopenia, and peripheral polyneuropathy.

Insulin-like growth factor binding protein-2 at diagnosis of childhood acute lymphoblastic leukemia and the prediction of relapse risk.

Despite remarkable advances in the clinical outcome of most children with acute lymphoblastic leukemia, a substantial number of patients ultimately relapse or suffer from side effects of treatment. In the present study, we investigated components of the IGF system for their predictive value to identify patients with an increased risk of relapse. Serum levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-1, IGFBP-2, and IGFBP-3 were measured in 162 children with acute lymphoblastic leukemia treated by the Berlin Frankfurt Munster Study Group.

Familial urticaria pigmentosa associated with thrombocytosis as the initial symptom of systemic mastocytosis and Down's syndrome.

Most cases of urticaria pigmentosa are confined to the skin, but visceral involvement and/or haematological abnormalities have been observed. It is still a matter of debate whether all forms of mastocytosis are true neoplasias or reactive hyperplasias. Familial inheritance of urticaria pigmentosa is rare.

Loss of imprinting of IGF-II gene in children with acute lymphoblastic leukemia.

Insulin-like growth factor-II (IGF-II) is known to be involved in the regulation of growth, differentiation and cell death in normal human tissues. In a variety of human tumors, the IGF-II gene is overexpressed and considered to be a stimulator for tumor growth through autocrine and paracrine mechanisms. The IGF-II gene is normally parental imprinted, only the paternal allele being expressed in most tissues.

Plasma leptin and leptin receptor expression in childhood acute lymphoblastic leukemia.

Recently, leptin has been shown to play a regulatory role for differentiation within the myeloid and erythroid cell lineage, whereas results of its regulatory effects on lymphocytes and related tumor cells have been contradictory. To investigate whether leptin plays a role in acute lymphoblastic leukemia (ALL), we investigated the levels of leptin in plasma with enzyme-linked immunosorbent assays and the expression of the leptin receptor on malignant lymphoblasts with reverse transcriptase polymerase chain reaction (RT-PCR). At diagnosis, the leptin levels of bone marrow-derived plasma in children with ALL were found to be significantly lower than the levels of healthy control subjects (0.

Expression of components of the IGF signalling system in childhood acute lymphoblastic leukaemia.

Background: Alterations in the insulin-like growth factor (IGF) system have been reported for different tumours. They are of particular interest in the search for new prognostic and therapeutic approaches in cancer. In childhood acute lymphoblastic leukaemia (ALL) the amount of "tumour mass" at diagnosis can exceed 1 kg.

Gliomatosis cerebri: post-mortem molecular and immunohistochemical analyses in a case treated with thalidomide.

Gliomatosis cerebri (GC) is a rare tumor of the central nervous system (CNS) characterized by widespread diffuse infiltration of the brain and spinal cord by neoplastic glial cells. We report the case of a 17-year-old boy with a bioptically diagnosed fibrillary astrocytoma. The administration of thalidomide, which was suggested to be beneficial in the treatment of human cancers, had no substantial clinical effect on our patient.

[Factor VIII inhibitors in patients suffering from severe haemophilia A: problems of "very low" responders].

Without recognition of any inhibitor until now, low concentrations of factor VIII inhibitors (< 1 Bethesda unit (BU)/mL plasma) can be occasionally measured in patients with severe haemophilia A. The existence of so-called "very low" responders is assessed contradictorily due to a methodically caused inhibitor increase. Plasma from 10 patients with severe haemophilia A was incubated with human plasma or animal plasma from pig, cattle, or cat and assayed for factor VIII inhibitors.

CTGF (IGFBP-rP2) is specifically expressed in malignant lymphoblasts of patients with acute lymphoblastic leukaemia (ALL).

Connective tissue growth factor (CTGF) is a major chemotactic and mitogenic factor for connective tissue cells. The amino acid sequence shares an overall 28-38% identity to IGFBPs and contains critical conserved sequences in the amino terminus. It has been demonstrated that human CTGF specifically binds IGFs with low affinity and is considered to be a member of the IGFBP superfamily (IGFBP-rP2).

Postoperative neoadjuvant chemotherapy before radiotherapy as compared to immediate radiotherapy followed by maintenance chemotherapy in the treatment of medulloblastoma in childhood: results of the German prospective randomized trial HIT '91.

Purpose: The German Society of Pediatric Hematology and Oncology (GPOH) conducted a randomized, prospective, multicenter trial (HIT '91) in order to improve the survival of children with medulloblastoma by using postoperative neoadjuvant chemotherapy before radiation therapy as opposed to maintenance chemotherapy after immediate postoperative radiotherapy.

Methods And Materials: Between 1991 and 1997, 158 patients were enrolled and 137 patients randomized. Seventy-two patients were allocated to receive neoadjuvant chemotherapy before radiotherapy (arm I, investigational).

Familial clustering of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is considered a non-hereditary disorder. Evaluation of the few familial cases might provide insight into its aetiology and pathogenesis. We conducted a survey to identify familial LCH cases.

[EICESS 92 (European Intergroup Cooperative Ewing's Sarcoma Study)-- preliminary results].

Background: Ewing tumor patients' outcome is 50% to 60% with current treatment strategies. Questions concerning toxicity and secondary malignancies are of increasing importance.

Patients And Methods: 631 patients were registered with the German EICESS study center of the European Intergroup Cooperative Ewing's Sarcoma Study, 369 patients were randomized.

[Treatment concepts in osseous manifestations of Langerhans cell histiocytosis].

Introduction: Patients with Langerhans Cell Histiocytosis (LCH or Eosinophilic granuloma) were assessed from the orthopaedic point of view to give recommendations for the management of the disease.

Material And Methods: The results of 36 cases of histologically proven bony manifestations out of 48 treated cases were reviewed. A retrospective analysis of our treated cases with bony manifestations of LCH between 1970 and 1995 was performed.

[Genetic instability in osteoblastic tumors of the skeletal system].

In the histological differential diagnosis of osteoblastic bone tumors, several problems could not have been solved by conventional histological methods including immunohistology. Some well-known examples are the differential diagnosis between aneurysmal bone cyst and telangiectatic osteosarcoma and giant cell tumor versus giant cell-containing highly malignant osteosarcoma. As a new approach to these diagnostic problems, we analyzed the genetic instability in a larger number of bone-forming tumor-like lesions, benign and malignant osteoblastic tumors.

[Multiplication of chromosomes and primary leucocyte number in childhood ALL and hyperdiploid karyotype].

In the blast cells of children with acute lymphoblastic leukemia (ALL) more than 50 chromosomes can be observed in a quarter of cases. As a rule these children have a good prognosis. However, some of these patients develop a relapse of their basic disease.

von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.

Background: Thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome are severe microvascular disorders of platelet clumping with similar signs and symptoms. Unusually large multimers of von Willebrand factor, capable of agglutinating circulating platelets under high shear stress, occur in the two conditions. We investigated the prevalence of von Willebrand factor-cleaving protease deficiency in patients with familial and nonfamilial forms of these disorders.