Case Report: Multifocal EBV-Associated Diffuse Large B-Cell Lymphoma in a Patient With 6-MP Associated Lymphopenia With TPMT Deficiency.

Introduction: EBV associated lymphoproliferative disorders (EBV LPD) are a known complication following solid organ or hematopoietic stem cell transplantation. The disturbance of the immune system leads to a lack of control of latent EBV-infected B-cells, as control by T-cells is mandatory to prevent uninhibited cell proliferation. EBV LPD in other settings is less frequent and etiology and pathogenesis are not completely understood.

Refining M1 stage in medulloblastoma: criteria for cerebrospinal fluid cytology and implications for improved risk stratification from the HIT-2000 trial.

Background: Medulloblastoma is the most common malignant paediatric brain tumour, and cerebrospinal fluid (CSF) dissemination (M1 stage) is a high-risk prognostic factor. Criteria for CSF evaluation and for differentiating M0 from M1 stage are not clearly defined, and the prognostic significance of M1 stage in this context is unknown.

Patients And Methods: CSF investigations from 405 patients with medulloblastoma of the prospective multicenter trial HIT-2000 (HIirnTumor-2000) were reviewed.

Nonmetastatic Medulloblastoma of Early Childhood: Results From the Prospective Clinical Trial HIT-2000 and An Extended Validation Cohort.

Purpose: The HIT-2000-BIS4 trial aimed to avoid highly detrimental craniospinal irradiation (CSI) in children < 4 years of age with nonmetastatic medulloblastoma by systemic chemotherapy, intraventricular methotrexate, and risk-adapted local radiotherapy.

Patients And Methods: From 2001-2011, 87 patients received systemic chemotherapy and intraventricular methotrexate. Until 2006, CSI was reserved for nonresponse or progression.

Treatment of Children and Adolescents With Metastatic Medulloblastoma and Prognostic Relevance of Clinical and Biologic Parameters.

Purpose To assess an intensified treatment in the context of clinical and biologic risk factors in metastatic medulloblastoma. Patients and Methods Patients (4 to 21 years old, diagnosed between 2001 and 2007) received induction chemotherapy, dose-escalated hyperfractionated craniospinal radiotherapy, and maintenance chemotherapy. Subgroup status and other biologic parameters were assessed.

MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties.

Background: Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup.

Intraventricular methotrexate as part of primary therapy for children with infant and/or metastatic medulloblastoma: Feasibility, acute toxicity and evidence for efficacy.

Background: To assess feasibility, acute toxicity, and efficacy of intraventricular methotrexate administered as part of the primary therapy in medulloblastoma.

Methods: From 2001 to 2007, 240 patients < 22 years from 61 treatment centres were registered. Patients received 2-3 cycles of intraventricular methotrexate with systemic chemotherapy in three different treatment arms of the prospective multicentre trial HIT2000 (150 children > 4 years with metastatic, 59 < 4 years with non-metastatic, 31 < 4 years with metastatic medulloblastoma).

Treatment of young children with CNS-primitive neuroectodermal tumors/pineoblastomas in the prospective multicenter trial HIT 2000 using different chemotherapy regimens and radiotherapy.

Background: Especially in young children, primitive neuroectodermal tumors of the central nervous system (CNS-PNET) and pineoblastomas are associated with an unfavorable outcome, and only a few prospective trials have been conducted thus far.

Methods: From January 2001 through January 2005, 17 eligible children aged <4 years with CNS-PNET not otherwise specified (n = 8), ependymoblastoma (n = 1), or pineoblastoma (n = 8) confirmed by central review were prospectively treated in the trial HIT 2000. In nonmetastatic disease (n = 11), up to 5 postoperative cycles of HIT-SKK systemic multiagent chemotherapy (8 months duration), followed by craniospinal radiotherapy (CSI), were given.

Treatment of adult nonmetastatic medulloblastoma patients according to the paediatric HIT 2000 protocol: a prospective observational multicentre study.

Background: Medulloblastoma in adulthood is rare. Knowledge is limited, and the efficacy and toxicity of chemotherapy--especially in nonmetastatic disease--is still elusive.

Methods: Seventy adults aged ≥21 years (median age: 28.

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.

Treatment of young children with localized medulloblastoma by chemotherapy alone: results of the prospective, multicenter trial HIT 2000 confirming the prognostic impact of histology.

This study was designed to confirm the previously observed favorable survival rates and prognostic factors in young children with nonmetastatic medulloblastoma (MB) treated with postoperative chemotherapy alone. Patients who received a diagnosis during the period January 2001 through December 2005 and who were aged <4 years received 3 cycles of postoperative systemic multiagent chemotherapy and intraventricular methotrexate. In cases of complete remission, treatment was terminated after 2 additional cycles of chemotherapy.

Outcome of 11 children with ependymoblastoma treated within the prospective HIT-trials between 1991 and 2006.

Ependymoblastoma is a rare malignant brain tumor of early childhood. Data on clinical behavior and optimal treatment strategies are scarce. We report on 11 consecutively treated children with centrally confirmed diagnosis of CNS ependymoblastoma, registered between February 1994 and October 2006 to the prospective GPOH-HIT multicenter brain tumor trials, and treated by multimodal regimens.

Ependymoma of the spinal cord in children and adolescents: a retrospective series from the HIT database.

Object: Reports on spinal cord ependymoma in children are rare. The aim of this study was to evaluate the clinical spectrum, treatment, and outcome of children with primary ependymoma of the spinal cord who were registered in the database of the pediatric German brain tumor studies Hirntumor (HIT) '91 and HIT 2000.

Methods: Between 1991 and 2007, 29 patients (12 male and 17 female, median age at diagnosis 13.

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.

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).

Role of radiotherapy in supratentorial primitive neuroectodermal tumor in young children: results of the German HIT-SKK87 and HIT-SKK92 trials.

Purpose: To assess the outcome of young children with supratentorial primitive neuroectodermal tumor (stPNET) treated by intensive postoperative chemotherapy alone compared with treatment with chemotherapy and delayed radiotherapy (RT).

Patients And Methods: From 1987 to 1992, children younger than 3 years of age with stPNET were enrolled in the HIT-SKK87 trial in Germany and Austria. After surgery, low-risk patients received maintenance chemotherapy before RT.

Treatment of early childhood medulloblastoma by postoperative chemotherapy alone.

Background: The prognosis for young children with medulloblastoma is poor, and survivors are at high risk for cognitive deficits. We conducted a trial of the treatment of this brain tumor by intensive postoperative chemotherapy alone.

Methods: After surgery, children received three cycles of intravenous chemotherapy (cyclophosphamide, vincristine, methotrexate, carboplatin, and etoposide) and intraventricular methotrexate.

Mediastinal T-cell lymphoma in a boy 7 years after treatment of supratentorial primitive neuroectodermal tumor.

Medulloblastoma/primitive neuroectodermal tumor (PNET) is one of the most common central nervous system tumors in children and requires aggressive multimodality therapy. The authors describe a patient who developed mediastinal T-cell lymphoma 7 years after treatment of supratentorial PNET. Despite a good tumor response, the patient died during induction therapy because of invasive pulmonary aspergillosis.

B-Cell lymphoproliferative disorder not associated with Epstein-Barr Virus in a child with relapsed acute lymphoblastic leukemia.

Lymphoproliferative disorder (LPD) is described in only a few children receiving chemotherapy for cancer. In all of them, an association between LPD and EBV (Epstein-Barr Virus) was found. We report on a patient who developed LPD not associated with EBV while receiving chemotherapy for relapsed acute lymphoblastic leukemia (ALL).