Combining flow cytometry and WT1 assessment improves the prognostic value of pre-transplant minimal residual disease in acute myeloid leukemia

Early minimal residual disease assessment after AML induction with fludarabine, cytarabine and idarubicin (FLAI) provides the most useful prognostic information

“…For MFC analysis, bone marrow samples obtained at diagnosis were analysed with a broad panel of monoclonal antibodies. A positive MFC‐MRD in the follow‐up samples was defined by the presence of no less than 25 clustered leukaemic cells/10 5 total events (threshold of 0·025% residual leukaemic cells) (Guolo et al , ).…”

“…Patients presenting WT1 overexpression at diagnosis, defined as a number of WT1 copies/10 000 ABL1 greater than 1000, were evaluated for WT1 ‐MRD at TP1. A cut‐off of WT1 copies/10 000 ABL1 lower than 250 was chosen to define MRD negativity (Cilloni et al , ; Guolo et al , ). For patients with specific genetic abnormalities, such as NPM1 mutations and RUNX1‐RUNX1T1 or CBFB‐MYH11 rearrangements, MRD was assessed by reverse transcription polymerase chain reaction (RT‐PCR) at the same TPs (See Appendix S1 for MRD assessment techniques).…”

“…Although the clinical value of MFC‐MRD evaluation has been widely reported (Buccisano et al , ; Terwijn et al , ; Guolo et al , ), consensus on the most informative TPs and MFC threshold has not been reached yet and MRD status has been mostly evaluated in later phases of treatment to define indication for HSCT (Terwijn et al , ; Venditti et al , ), or to predict post‐transplant outcome (Guolo et al , ). Our study, which evaluated three different TPs, clearly shows that, for FLAI‐5 induction, early MRD assessment (TP1) is the strongest predictor of outcome.…”

Longitudinal minimal residual disease (MRD) evaluation in acute myeloid leukaemia with NPM1 mutation: from definition of molecular relapse to MRD‐driven salvage approach

“…Due to the low disease burden and normal blood cell count at the time of Mol-relapse, toxicity is reduced and, more importantly, a single course of MEC enabled all patients to achieve MRD negative status. As previously reported (Guolo et al, 2017), complete MRD clearance before allo-SCT profoundly affects outcome and should be the aim of modern rescue approaches.…”

<p>Strategies for minimal residual disease detection: current perspectives</p>

“…Finally, many papers reported the value of WT1 monitoring in the setting of HSCT, both before HSCT to assess the quality of the remission and therefore predict the outcome and after HSCT to predict relapse. [48][49][50][51][52] The data reported in this setting are quite strong and led several centers to adopt WT1-based pre-emptive immunotherapy with cyclosporine discontinuation and/or donor lymphocyte infusion in patients with increasing WT1 values after transplantation. 53,54 Finally, although many studies reported that the CBFB-MYH11 fusion transcript can persist at low level in patients during long-term remission after chemotherapy, only a few studies with small samples have addressed the detection of the CBFB-MYH11 fusion transcripts after allo-HSCT.…”