We consider the problems arising in clinical research on childhood acute lymphoblastic leukemia (ALL). Given the therapeutic progress achieved over the last few decades, any improvement in the outcome for the majority of children with ALL is difficult to assess with the usual size trials. Furthermore, the progress in genetics and molecular biology has now led to the identification of subgroups of children, typically with rare characteristics, for whom new treatments still await evaluation. For both these aspects of clinical research, there is an increasing need for international intergroup cooperation. After a discussion on the role of retrospective meta-analysis and randomized controlled trials in ALL research, we suggest that intergroup studies could be made more feasible, but still scientifically rigorous, by adopting a strategy of prospective meta-analysis. This strategy can be described as follows: i) different groups prospectively plan to ask the same randomized question within their protocols which may differ in other aspects, and to pool their data in order to evaluate treatment effect; ii) the management of the study can be de-centralized, by allowing each group to be responsible for conducting its own protocol. We would like to stimulate the debate on the methodological and practical aspects of research perspectives in ALL (and in pediatric oncology).