Goals for chronic myeloid leukemia TK inhibitor treatment: how little disease is too much?

Tyrosine kinase inhibitors, now numbering 5 for the treatment of Philadelphia chromosome-positive leukemia, have proven ability to reduce clonal disease burden rapidly, dramatically, and durably, especially in chronic myeloid leukemia in the chronic phase. Deep molecular remissions are likely in most chronic phase patients and expectations on timing of response have been developed, validated as best as possible, and evolved over time. Increasing attention has been given to the initial decline of Bcr-Abl1 transcripts and the ultimate depth of molecular remission, overshadowing but not displacing the traditional role of cytogenetic response. This chapter reviews the evolution of response milestones for chronic phase chronic myeloid leukemia and tries to answer the question of how little disease is too much.