Conclusions And Further Perspectives

Our review of thiopurines in the treatment of childhood ALL and genetic variants of the TPMT gene summarizes the current status and gives some clues in addition to the many and varied questions that remain to be answered. Despite considerable insights into thiopurine pharmacology that have been gained lasting recent decades leading to the development of novel strategies for improving efficacy and reducing toxicity of 6-MP as well as 6-TG administration in several institutional and collaborative ALL study groups, the validation of this information and its potential translation into clinical practice is still an ongoing process.

Most of the major institutional and collaborative study groups on treatment of childhood ALL extensively assess prognostic factors on a regular basis in prospective trials. It can be extremely helpful for advancing our current knowledge on thiopurines in childhood ALL, if the evaluation of data on thiopurine response would be included in these studies on a broader basis. Initially, collection and comparison of information from different large clinical trial populations of children with ALL exposed to different background as well as thiopurine treatment may truly help to more clearly define the critical issues associated with thiopurine therapy.

As a consequence, relevant results can be evaluated prospectively in future clinical trials. Clearly, the success of such potential cooperative ventures depends on the quality of interaction among the leading institutional and collaborative study groups. Moreover, it is necessary to arrive at a consensus for generating tools needed to develop a more detailed uniform approach for an improved assessment of thiopurine treatment in childhood ALL.

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