[Clinical characteristics and prognostic analysis of adult KMT2A-associated acute myeloid leukemia].
AI interpretation is pending for this paper.
Open original publication →What the AI sees
Not AI summarized yet.
Research significance
Pending deeper interpretation.
Source abstract
Objective: To explore the clinicobiological characteristics and prognostic impact of different fusion partners of KMT2A in acute myeloid leukemia (AML) . Methods: The clinical features of 303 patients with KMT2A-associated AML who received treatment between January 2014 and August 2024 were retrospectively analyzed to investigate prognostic differences among fusion partner subgroups. Results: Among 303 patients with KMT2A-associated AML, the median age was 41 (16-82) years. KMT2A-PTD accounted for 18.2% (55/303), whereas KMT2A rearrangements (KMT2Ar) were observed in 81.8% (248/303). Among KMT2Ar AML patients, the complete remission (CR) rate after a course of induction treatment was 65.3% (162/248), whereas the 2-year overall survival (OS) rate and cumulative incidence of relapse (CIR) were 52.6% (95% CI: 46.3% -59.7% ) and 55.4% (95% CI: 44.8% -61.6% ), respectively. Prognoses varied across partner gene subtypes; the KMT2A::AFDN subgroup (n=69) had the poorest 2-year CIR of 68.5% (95% CI: 55.4% -78.5% ), whereas the uncommon KMT2Ar subgroup (n=31) had a 2-year CIR rate of 43.2% (95% CI: 24.8% -60.3% ). The group with KMT2A::MLLT3 and EVI1 overexpression (n=18) exhibited a significantly higher 2-year CIR, at 66.7% (95% CI: 38.5% -84.2% ) versus 44.0% (95% CI: 30.1% -57.0% ) for those with KMT2A::MLLT3 who did not show EVI1 overexpression (n=53) (P=0.018). Among patients with KMT2A-PTD, the CR rate after a course of treatment was 60.0% (33/55) ; venetoclax-based therapy yielded a significantly higher CR rate compared with nontargeted therapy: 86.7% (26/30) vs 28.0% (7/25) (P<0.001), with a 2-year OS rate of 68.7% (95% CI: 36.1% -87.1% ) versus 53.9% (95% CI: 32.2% -71.4% ) (P=0.035), and 2-year CIR rate of 34.2% (95% CI: 15.9% -53.5% ) versus 78.7% (95% CI: 54.2% -91.0% ) (P=0.002). Compared to low-intensity chemotherapy, intensive chemotherapy resulted in a significantly lower CR rate: 40.7% (11/27) versus 78.6% (22/28) (P=0.004), accompanied by a higher 2-year CIR[72.3% (95% CI: 47.6% -86.8% ) versus 41.7% (95% CI: 20.6% -61.6% ), P=0.017]. Among transplant patients, those undergoing hematopoietic stem cell transplantation (HSCT) in CR1 (n=156) had better outcomes than those transplanted in non-CR1 (n=62), with a 2-year OS rate of 74.1% (95% CI: 66.9% -82.0% ) versus 52.0% (95% CI: 40.6% -66.7% ) and 2-year CIR of 27.3% (95% CI: 20.0% -34.9% ) versus 91.9% (95% CI: 80.8% -96.7% ), respectively (both P<0.001). Multivariate Cox regression analysis showed that achieving CR after one induction cycle (HR=0.54, P<0.001; HR=0.67, P=0.010) and receiving allo-HSCT (HR=0.17, P<0.001; HR=0.41, P<0.001) were favorable prognostic factors for OS and CIR. KMT2A::AFDN was an adverse prognostic factor for both OS (HR=1.51, P=0.029) and CIR (HR=1.56, P=0.006) . Conclusion: In KMT2Ar AML, the KMT2A::AFDN subtype was associated with adverse prognosis, whereas concomitant EVI1 overexpression significantly increased the risk of relapse in KMT2A::MLLT3 subgroup. allo-HSCT in CR(1) significantly improves prognosis in these patients. The KMT2A-PTD group showed poor response to conventional intensive chemotherapy but achieved significantly improved prognosis with venetoclax-based therapy.