Analyses of transplantation outcomes for adult patients with mixed-phenotype acute leukemia Open Access

1. Allo-HSCT can promote durable survival in MPAL, with outcomes comparable to AML and ALL, especially when performed in first CR.

2. We established MPAL-PRO, a novel risk model that stratifies prognosis after allo-HSCT based on five pre-transplant clinical factors.

Mixed-phenotype acute leukemia (MPAL) is associated with poor prognosis. While allogeneic hematopoietic stem cell transplantation (allo-HSCT) can achieve long-term survival, optimal transplantation strategies remain unclear. We analyzed a national registry of adult MPAL patients who underwent allo-HSCT between 2008 and 2022 in Japan. Among 417 patients, median age at transplant was 44 years (interquartile range, 32–55), 61% were male, 20% were BCR-ABL1 fusion positive, and 66% were transplanted during the first complete remission (CR1). At 5 years post-transplant, overall survival (OS) was 54%, disease-free survival was 49%, relapse was 28%, and non-relapse mortality was 23%. Multivariate analysis identified older age (adjusted hazard ratio [aHR], 1.78, 95% confidence interval [CI] 1.11–2.84 for ages 50–59; aHR 2.65, 95% CI 1.54–4.55 for ≥60, both vs.<40 years), male sex (aHR 1.56, 95% CI 1.07–2.27), ECOG PS ≥2 (aHR 3.05, 95% CI 1.72–5.40), BCR-ABL1-fusion-negative status (aHR 1.64, 95% CI 1.02–2.64), advanced disease status (aHR 1.642, 95% CI 0.80–3.36 for CR2; aHR 4.01, 95% CI 2.61–6.15 for ≥CR3/non-CR, vs. CR1), and low conditioning intensity (aHR 2.49, 95% CI 1.21–5.13 for low transplant conditioning intensity [TCI], vs. high TCI) as adverse prognostic factors for OS. A propensity score-matched comparison with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) during the same period showed that MPAL did not have significantly worse prognosis than AML or ALL. These findings suggest that allo-HSCT offers long-term survival in MPAL, with outcomes not inferior to those of AML and ALL.