Retrospective cohort study reveals disease biology rather than donor type drives transplant outcomes in KMT2A-rearranged AML, indicating a need for biology-driven risk stratification.
Key Points
To assess whether donor selection or underlying disease biology and measurable residual disease status primarily dictate post-transplant outcomes in patients with KMT2A-rearranged acute myeloid leukemia in complete remission.
Retrospectively analyzed 241 consecutive patients with KMT2A-rearranged AML who received a first allogeneic hematopoietic stem cell transplantation in complete remission (192 haploidentical, 29 matched sibling, 20 matched unrelated donors).
Evaluated the prognostic impact of donor platforms, KMT2A fusion partners, cooperating mutations, remission status (CR1 vs. ≥CR2), and pre-transplant measurable residual disease (MRD) via multiparameter flow cytometry (MFC) and RT-qPCR over a median follow-up of 28.4 months.
Overall 2-year overall survival (OS) was 80.0% and leukemia-free survival (LFS) was 78.9%, with no significant differences observed across donor platforms or major KMT2A fusion partners.
Inferior OS and LFS were independently predicted by NRAS mutations (OS HR 2.70, P = 0.003; LFS HR 2.37, P = 0.008), transplantation in ≥CR2 (OS HR 2.71, P = 0.005; LFS HR 2.40, P = 0.012), and pre-transplant concurrent MRD positivity (MFC+/RT-qPCR+).
An integrated biologic risk model stratified patients into high- and low-risk groups, showing 2-year OS of 50.4% versus 85.6% and LFS of 48.6% versus 84.6% (both P < 0.0001).