(A) Suggested management algorithm for patients with AML with a molecular MRD target. [1] ELN favorable risk patients with <4-log reduction in NPM1-mutant transcripts after first induction are shown to benefit from a CR1 allograft,⁴  and any positivity in the peripheral blood (PB) after second induction is associated with a very high risk for relapse.³  [2] MRD positivity > 200 copies per 10⁵ABL (ie, molecular persistence) and serially increasing transcript levels after treatment (ie, molecular progression) reliably predict relapse.⁷  [3] At the end of treatment, patients with CBF AML with high or serially increasing transcript levels are destined to relapse (relevant thresholds are >500 copies [per 10⁵ABL] of RUNX1/RUNX1T1 in the BM or >100 copies in the PB, and > 50 copies of CBFB/MYH11 in the bone marrow [BM] or >10 copies in the PB).⁷  Salvage according to (C) should be considered for these patients, although there is no evidence that this improves outcome. Conversely, patients with low copy numbers below these thresholds can be safely monitored according to (B). [4] Although CBF patients with an early unfavorable MRD response have a higher risk for relapse, there is insufficient evidence to warrant treatment change⁷ ; however, this may prompt initiation of an early donor search. Salvage may be considered in cases with extremely poor early response or if there is an increase while on treatment (ie, molecular progression). [5] Although there is no evidence that standard-risk patients who remain MRD positive benefit from transplant, this is a reasonable approach and is adopted in the current NCRI AML19 and MyeChild01 protocols. (B) Suggested algorithm for sequential monitoring after treatment. Patients with conversion to MRD positivity, confirmed on a second sample with >1-log rise, should be diagnosed with molecular relapse and treated as shown.⁷  (C) Possible peri-transplant management strategy. [1] Patients with an NPM1 mutation without FLT3 ITD who have transcript levels below 1000 copies in the BM or 200 copies in the PB have a very good outcome after allograft, it is uncertain whether these patients benefit from salvage chemotherapy.⁸⁹  [2] Patients with high levels of MRD after salvage, without an adequate response to donor lymphocyte infusion (DLI), as well as those to whom these standard therapies cannot be given should be considered for investigational approaches. Figure by Richard Dillon, NCRI Group.