Allogeneic hematopoietic stem cell transplantation could improve survival for pure CBF-AML patients with minimal residual disease positive after the second consolidation

2021 Update on MRD in acute myeloid leukemia: a consensus document from the European LeukemiaNet MRD Working Party

“…For patients who are: (1) MRD positive by MFC after 2 cycles of intensive chemotherapy, after consolidation chemotherapy, prior to stem cell transplantation, and/or after stem cell transplantation; 84,85 (2) MRD positive by ≥2% NPM1 mutant copies per ABL1 copies measured in BM or transcript levels of NPM1 or CBF fusions failed to reach a 3-4 log reduction in the same tissue after completion of consolidation chemotherapy (ratio of target copies / ABL1 copies between the sample at diagnosis and the sample after completion of consolidation chemotherapy, measured in the same tissue, preferably BM); 36,71,81,86,87 and/or Pre-transplant MRD positivity should not be viewed as a contraindication to stem cell transplantation (recommendation D26). 90 The panel recommends that patients with detectable MRD before alloHCT should be considered for myeloablative conditioning (recommendation D27) noting that other approaches such as post-alloHCT maintenance treatment or donor lymphocyte infusions may also reduce relapse risk.…”

“…demonstrated to have MRD relapse (either molecular or MFC), individualized treatment84 and/or conditioning regimen strategies should be considered, preferably as part of clinical trials, in an effort to reduce disease relapse (recommendation D22, Figure1). However, it should be emphasized that a single positive MRD test does not guarantee relapse and should not be used as the sole basis for clinical action.Patients with NPM1 or CBF AML who have stable molecular MRD detection at low level (MRD-LL) do NOT necessarily require a change in treatment (at EOT or during follow up) 81 (recommendation D23).…”

A venetoclax and azacitidine bridge‐to‐transplant strategy for NPM1‐mutated acute myeloid leukaemia in molecular failure

“…Among the advantages of MRD monitoring, the possibility to identify an impending relapse and enable early treatment intervention is clearly stated by the European LeukemiaNet (ELN) 2022 recommendations, defining the novel treatment setting of molecular failure (MF) 2,3 . The feasibility of systematic molecular monitoring to identify relapsing patients to allocate to pre‐emptive therapy has been demonstrated in the setting of acute promyelocytic leukaemia and has become routine practice also in other molecular categories 4,5 . Although important studies have addressed the point of pre‐emptive intervention in delaying or preventing haematological relapse in MRD‐positive (MRD pos ) AML patients, clinicians have little indications on how to act on MRD data and clinical trials to understand the role of early intervention in MF are ongoing 2,6,7 …”

“…2,3 The feasibility of systematic molecular monitoring to identify relapsing patients to allocate to pre-emptive therapy has been demonstrated in the setting of acute promyelocytic leukaemia and has become routine practice also in other molecular categories. 4,5 Although important studies have addressed the point of pre-emptive intervention in delaying or preventing haematological relapse in MRD-positive…”

The present and future of measurable residual disease testing in acute myeloid leukemia

“…[65][66][67] RUNX1-RUNX1T1 or CBFB-MYH11 Yes Measurement of fusion transcripts by qRT-PCR highly informative, but there is evidence that ultra-low levels of disease can be serially monitored. 34,[68][69][70][71][72] Other fusions such as KMT2A, DEK-NUP214, 73 MECOM Not specifically Smaller bodies of evidence but concept is sound. KMT2A has over 40 partners.…”