title: TH1 predominance is associated with improved survival in pediatric medulloblastoma patients.
abstract: Medulloblastoma, a primitive neuro-ectodermal tumor that arises in the posterior fossa, is the most common malignant brain tumor occurring in childhood. Even though 60-70% of children with medulloblastoma will be cured with intensive multimodal therapy, including surgery, radiotherapy, and chemotherapy, a significant proportion of surviving patients may suffer from long-term treatment-related sequelae. Therapeutic success is limited especially in younger children by radiotherapy-induced neurocognitive longterm deficits. In order to avoid or delay craniospinal radiotherapy, high-dose chemotherapy followed by autologous stem cell transplantation (HSCT) has become an established treatment modality. Data on the host immunologic environment in medulloblastoma patients are rare, notably data on cytokine expression and immune reconstitution in patients with medulloblastoma undergoing HSCT are lacking. In this present study, we therefore decided to prospectively assess immune function following 24 consecutive autologous HSCT in 17 children with medulloblastoma treated according to the German-Austrian-Swiss HIT-2000-protocol. TH1 predominance was found to be the most important factor for probability of survival. Already before HSCT, survivors showed higher IFNγ levels in sera as well as higher numbers of IFNγ-positive T-cells. After transplantation, this effect was even more pronounced. Patients with higher numbers of IFNγ- and TNFα-positive T-cells had a more favorable outcome at all analyzed time points. In addition, patients in complete remission (CR) before transplantation, known to have a better prognosis a priori, showed higher expression of IFNγ in T-cells. Taken together, this is the first report to demonstrate that high expression of IFNγ and TNFα in T-cells of medulloblastoma patients in the early post-transplant period correlates with a better prognosis. Our data point toward a potentially important influence of TH1-cytokine expression before and after transplantation on the survival of pediatric medulloblastoma patients.
authors.affiliation: Department of Pediatric Hematology, Oncology and Neurooncology, Pediatric Stem Cell Transplantation Program, University Children's Hospital Würzburg, Josef-Schneiderstrasse 2, Wuerzburg, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Wiegering
authors.forename: Matthias
authors.initials: M
authors.lastname: Eyrich
authors.forename: Stefan
authors.initials: S
authors.lastname: Rutkowski
authors.forename: Matthias
authors.initials: M
authors.lastname: Wölfl
authors.forename: Paul G
authors.initials: PG
authors.lastname: Schlegel
authors.forename: Beate
authors.initials: B
authors.lastname: Winkler
mesh_terms: D000293:Adolescent; D001932:Brain Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D008527:Medulloblastoma / Q000276:immunology* / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D033581:Stem Cell Transplantation; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma