Antineoplastic agents for pediatric anaplastic large cell lymphoma: Vinblastine is the most effective in vitro.

Anti-neoplastic effects of a total of 11 agents (adriamycin, briplatin, cytarabine, dexamethasone, etoposide, 4-hydroperoxycyclophosphamide, 4-hydroperoxyifosphamide, methotrexate, predonisolone, vinblastine, vincristine) were tested on 4 cell lines (DEL, Ki-JK, SR-786, SU-DHL-1) established from pediatric ALCL cases. The individual cell lines were treated with those agents at different concentrations (0.01 microM/L, 0.1 microM/L, 1 microM/L, 10 microM/L, 100 microM/L) for 1 h or 24 h, and their cellular growths were measured by the microculture tetrozolium (MTT) assay. Of those anti-neoplastic agents, methotrexate, vinblastine, and vincristine were highly effective on the cell growth inhibition in all these cell lines with time- and dose-dependent manner. Among them, vinblastine was found to be the most effective in 3 cell lines (DEL, Ki-JK, SR786) with 50% effective doses (ED50, concentrations causing 50% cell survival after treatment) ranging from 0.0016 to 1.27 microM/L for the 1-h treatment and 0.0002 - 0.59 microM/L for the 24-h treatment. Further experiments demonstrated that vinblastine treatment induced cellular apoptosis and caused severe disruption in mitotic spindle formation on these cell lines. The results support the protocol of ALCL 99 study, which uses vinblastine as one of the first-line anti-neoplastic agents for the high-risk ALCL patients in the pediatric age group.