Impact of Fusion Partners and Transplantation Benefit in Intensively Treated KMT2A-Rearranged Acute Myeloid Leukemia

KMT2A rearrangements are a frequent genetic abnormality associated with Acute myeloid leukemia (AML), historically linked to varied prognoses and outcomes. The prognosis for patients with this rearrangement remains controversial, necessitating further research to stratify risk and guide treatment.

In this retrospective study, a total of 3468 adolescent and adult AML patients were screened, and 181 patients harboring KMT2A rearrangements were analyzed. We used FISH, RT-PCR, and next-generation sequencing, including transcriptome and targeted panels, for diagnosis and mutation profiling. All patients received intensive chemotherapy. We evaluated overall survival and event-free survival using Kaplan-Meier and Cox regression models, with HSCT analyzed as a time-dependent variable.

The incidence of KMT2A-rearranged AML in our newly diagnosed cohort was 5.9%. Among the 181 patients included in the final analysis, 89 (49.2%) were male and 92 (50.8%) were female, with a median age of 33 years (range: 13-65). The distribution of fusion partners included KMT2A::MLLT3 (n = 39), KMT2A::AFDN (n = 27), KMT2A::MLLT10 (n = 25), KMT2A::ELL (n = 24), and others (n = 12). Seventy-four patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1). The median follow-up for survivors was 17.53 months (range 1.47-112.57), and the 3-year overall survival (OS) and event-free survival (EFS) for the entire cohort were 42.0% and 32.1%, respectively. Patients with KMT2A::ELL exhibited superior OS compared to other subtypes (3-year OS [ELL vs. non-ELL]: 59.8% vs. 39.3%, p = 0.023). Concomitant mutations did not significantly impact the prognosis of KMT2A-rearranged AML patients. In multivariate analysis, age and HSCT in CR1 were independently associated with OS and EFS (OS: HR = 1.022, p = 0.026 [age]; HR = 0.238, p < 0.001 [HSCT]; EFS: HR = 1.027, p = 0.002 [age]; HR = 0.155, p < 0.001 [HSCT]). Patients aged over 20 years were more likely to benefit from HSCT than those aged 20 years or younger (p < 0.001 [age > 20], p = 0.780 [age ≤ 20]).

Our study revealed the heterogeneous outcomes of KMT2A-rearranged AML patients and clarified the impact of HSCT across different age groups.