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Detecting leftover NPM1-mutated leukaemia in the blood after the second course of chemotherapy identified patients very likely to relapse, and proved a better guide than genetics at diagnosis to who needs a transplant.
Prospective study within the AML17 trial of 346 patients with NPM1-mutated AML monitored by quantitative PCR for NPM1 transcripts in blood and marrow after each course.
Persistence of NPM1 transcripts in peripheral blood after the second chemotherapy course was found in 15 percent and predicted a three-year relapse rate of 82 percent against 30 percent when undetectable, with three-year survival of 24 versus 75 percent. The finding was the strongest independent prognostic factor.
Molecular monitoring of NPM1 now decides whether a patient with otherwise favourable-risk disease should go to transplant in first remission, and molecular relapse can be treated pre-emptively.