Effect of topical oral G-CSF on oral mucositis: a randomised placebo-controlled trial.

Oral mucositis is a dose-limiting toxicity of intensive chemotherapy. It is caused directly by the cytotoxic effect of chemotherapeutic agents and indirectly by sustained neutropenia. Severe oral mucositis is an important predisposing factor for life-threatening septic complications during aplasia. It also reduces quality of life. At present, no effective causal prophylaxis or treatment against oral mucositis is established. We performed a prospective randomised placebo-controlled trial using topical oral r-metHuG-CSF (filgrastim) in high-grade lymphoma patients treated according to the B-NHL protocol, which contains high-dose methotrexate and causes severe oral mucositis (WHO grades I-IV) in >50% of patients. Between August 1996 and July 1997, a total of 32 chemotherapy cycles were documented in eight patients (four male, four female). Mucosal erythema and ulceration were recorded. All patients assessed their oral pain and impact on swallowing daily, using a subjective scale from no to maximal discomfort (1-10). In addition, oral mucositis was assessed according to the WHO score. Filgrastim was administered in 16 cycles as a viscous mouthrinse (carboxymethylcellulose 2%, oleum citrii) 4 x 120 microg/day from days 10 to 16. Sixteen cycles were given to control patients, of these 14 with placebo, and another two cycles with no treatment. Severe mucositis (WHO grade III/IV) was documented in 21 of 32 cycles (65.5%). A difference of borderline significance was observed for the reduction of maximum severity of oral mucositis between G-CSF vs placebo (P = 0.058), with a reduction of WHO grade IV of 50% (four G-CSF vs eight control). The number of days in hospital was reduced significantly in the G-CSF group (P = 0.02). In conclusion, topical oral G-CSF mouthrinses may be beneficial to reduce oral mucositis.

Characterization of five new cell lines derived from human primitive neuroectodermal tumors of the central nervous system.

Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood but only a few cell lines and animal models of this primitive neuroectodermal tumor (PNET) have thus far been established. Using specific cell culture conditions, we were able to derive four human MB cell lines (MHH-MED-1-4) as well as a cell line from a spinal PNET (MHH-PNET-5). The four MB cell lines grew in suspension as floating cell aggregates or as slightly adherent cells. They consisted of undifferentiated cells that did not express markers of late neuronal or glial lineages such as neurofilaments or glial fibrillary acidic protein. They also lacked expression of major histocompatibility complex class I or II antigens on the cell surface. All four MB lines were positive for vimentin and neuron-specific enolase, whereas synaptophysin, neural cell adhesion molecule, galactocerebroside, GD2, GD3, and the A2B5 antigen were expressed inconsistently. In contrast, MHH-PNET-5 grew as adherent monolayer and expressed major histocompatibility complex class I antigen. By cytogenetic analysis, the lines were near diploid with clonal aberrations. The MB lines showed no losses of chromosome arm 17p by either cytogenetic or microsatellite analyses. The cell line MHH-MED-2 exhibited double minute chromosomes, amplification of the c-myc gene, and overexpression of c-myc mRNA and protein. N-myc, p53, and Rb protein expression were unaltered. All four continuously passaged MB cell lines and the MHH-PNET-5 line were xenotransplanted s.c. into athymic mice; three of four MB lines and the spinal PNET line gave rise to tumors. These cell lines will be useful tools for biological and preclinical studies on PNETs.