We defined clinically relevant time points for NPM1(mut) MRD assessment that allow for the identification of patients with AML who are at high risk of relapse. Monitoring of NPM1(mut) transcript levels should be incorporated in future clinical trials to guide therapeutic decisions.

Key Points• In FLT3-ITD-positive AML, high allelic ratio and ITD insertion site in TKD1 predict for low complete remission rates and poor survival.• In FLT3-ITD-positive AML, allogeneic HSCT in first CR outweighs the negative impact of high allelic ratio on survival.The objective was to evaluate the prognostic and predictive impact of allelic ratio and insertion site (IS) of internal tandem duplications (ITDs), as well as concurrent gene mutations, with regard to postremission therapy in 323 patients with FLT3-ITD-positive acute myeloid leukemia (AML). Increasing FLT3-ITD allelic ratio (P 5 .004) and IS in the tyrosine kinase domain 1 (TKD1, P 5 .06) were associated with low complete remission (CR) rates. After postremission therapy including intensive chemotherapy (n 5 121) or autologous hematopoietic stem cell transplantation (HSCT, n 5 17), an allelic ratio ‡ 0.51 was associated with an unfavorable relapse-free (RFS, P 5 .0008) and overall survival (OS, P 5 .004); after allogeneic HSCT (n 5 93), outcome was significantly improved in patients with a high allelic ratio (RFS, P 5 .02; OS, P 5 .03), whereas no benefit was seen in patients with a low allelic ratio (RFS, P 5 .38; OS, P 5 .64). Multivariable analyses revealed a high allelic ratio as a predictive factor for the beneficial effect of allogeneic HSCT; ITD IS in TKD1 remained an unfavorable factor, whereas no prognostic impact of concurrent gene mutations was observed. The clinical trials described herein were previously published or are registered as follows: AMLHD93 and AMLHD98A, previously published; AML SG 07-04, ClinicalTrials.gov identifier #NCT00151242. (Blood. 2014;124(23):3441-3449)

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