The loss or absence of minimal residual disease of <0·1% at any time after two cycles of consolidation chemotherapy in CBFB–MYH11‐positive acute myeloid leukaemia indicates poor prognosis

Abstract

No consensus has been reached on the relationship between CBFB-MYH11 copies and prognosis. Of 1525 acute myeloid leukemia (AML) patients, 58 with CBFB-MYH11-positive AML (16/58 patients with c-kit mutation) were retrospectively analyzed with a median follow-up duration of 29.8 (range: 4.8-74.4) months. Of these, 25/58 (43.1%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT), 10 of whom had the c-kit mutation. Of the 33 patients who did not undergo allo-HSCT, recurrence in patients with CBFB-MYH11/ABL level >0.1% at any time after two consolidation cycles was significantly higher than in patients with CBFB-MYH11/ABL level <0.1% (61.9% vs. 0%, P = 0.001); further, the 3-year relapse-free survival (RFS; 31.4% vs. 100%, P = 0.004) and event-free survival (EFS; 33.1% vs. 100%, P = 0.004) were significantly decreased in patients with CBFB-MYH11/ABL level >0.1% at any time after two consolidation cycles. The 3-year RFS and EFS rates were lower in patients who did not receive allo-HSCT than in those who did (31.4% vs 84.6%, P = 0.000; 31.4% vs. 80.8%, P = 0.001). CBFB-MYH11-positive AML patients with CBFB-MYH11/ABL level >0.1% at any time after two cycles of consolidation had poor prognoses, and allo-HSCT could improve their survival.

The consensus from The Chinese Society of Hematology on indications, conditioning regimens and donor selection for allogeneic hematopoietic stem cell transplantation: 2021 update

“…In addition, similar results were observed in patients with inv (16) AML. Duan et al reported in single center study that patients with CBFB-MYH11/ABL levels > 0.1% at any time after two consolidation cycles benefited more from allo-HSCT than from chemotherapy in terms of DFS (84.6% vs. 31.4%, p < 0.001) [ 16 ]. Emerging data also suggested the prognostic values of specific KIT mutations (mainly D816), especially in MRD negative status.…”

“…1. Acute myeloid leukemia AML (non-acute promyelocytic leukemia, non-APL): AML (non-APL) in CR1 Patients with intermediate- or adverse-risk AML according to ELN/NCCN risk stratification [ 9 ] Patients who achieve CR1 after > 2 cycles of therapy Patients with AML showing myelodysplasia-related changes or therapy-related myeloid changes Patients with favorable-risk AML showing any of the following features: failure to attain MMR (RUNX1-RUNX1T1 decrease> 3 log) after two consolidation cycles or loss of MMR within 6 months [ 15 , 63 ]; recurrence of a CBFB-MYH11/ABL level >0.1% at any time after two consolidation cycles [ 16 ]; D816 KIT mutation in CBF-AML [ 17 – 19 ]; FCM+ status after two consolidation CEBPAbi+ AML [ 20 ]; MRD+ status in NPM1+ AML AML (non-APL) ≥ CR2 Relapsed or refractory AML (non-APL): allo-HSCT as salvage therapy with individualized conditioning regimens APL Failure to achieve hematological CR by induction therapy Relapsed APL (molecular, cytogenetic, or hematological relapse) who remain PML-RARA-positive after reinduction …”

“…AML (non-APL) in CR1 Patients with intermediate- or adverse-risk AML according to ELN/NCCN risk stratification [ 9 ] Patients who achieve CR1 after > 2 cycles of therapy Patients with AML showing myelodysplasia-related changes or therapy-related myeloid changes Patients with favorable-risk AML showing any of the following features: failure to attain MMR (RUNX1-RUNX1T1 decrease> 3 log) after two consolidation cycles or loss of MMR within 6 months [ 15 , 63 ]; recurrence of a CBFB-MYH11/ABL level >0.1% at any time after two consolidation cycles [ 16 ]; D816 KIT mutation in CBF-AML [ 17 – 19 ]; FCM+ status after two consolidation CEBPAbi+ AML [ 20 ]; MRD+ status in NPM1+ AML …”

“…Patients with favorable-risk AML showing any of the following features: failure to attain MMR (RUNX1-RUNX1T1 decrease> 3 log) after two consolidation cycles or loss of MMR within 6 months [ 15 , 63 ]; recurrence of a CBFB-MYH11/ABL level >0.1% at any time after two consolidation cycles [ 16 ]; D816 KIT mutation in CBF-AML [ 17 – 19 ]; FCM+ status after two consolidation CEBPAbi+ AML [ 20 ]; MRD+ status in NPM1+ AML…”

Measurable Residual Disease Detected by Multiparameter Flow Cytometry and Sequencing Improves Prediction of Relapse and Survival in Acute Myeloid Leukemia

“…The MFC MRD can be monitored in the majority of AML patients with rapid turnaround time, but an established threshold with considerably high sensitivity and reproducibility is still an unmet clinical need (7,10). Conversely, although the PCR technique is highly sensitive, its application is limited to a fraction of AML patients who harbored specific genetic aberrations suitable for MRD detection, including RUNX1-RUNX1T1, CBFB-MYH11, and PML-RARa fusions, and NPM1 mutations (5,(11)(12)(13)(14)(15)(16). Notably, the next-generation sequencing (NGS) has introduced novel molecular markers for MRD assessment, and reliable criteria for their routine application in the clinical setting are under exploration.…”