A landmark international clinical trial has found no benefit in giving intensive chemotherapy to induce remission before allogeneic hematopoietic cell transplantation (alloHCT) in patients with poorly responsive or relapsed acute myeloid leukaemia (AML). The study, known as the ASAP trial, challenges a long-standing clinical assumption that achieving remission is essential before transplantation.
The trial randomised 281 patients with AML who either failed initial induction therapy or experienced an untreated first relapse. Participants were allocated to receive either standard salvage chemotherapy—high-dose cytarabine plus mitoxantrone—or proceed directly to alloHCT using intensified conditioning. After five years, overall survival was virtually identical: 47.5% for the remission induction group and 46.1% for those transplanted straight away.
Genetics Prove Stronger Predictor of Outcome
Detailed analysis revealed that remission status before transplant did not significantly influence survival. Instead, genetics emerged as the decisive predictor. According to multivariable Cox regression modelling, the most powerful factors affecting long-term outcomes were genetic risk classification under ELN criteria, patient age, and existing comorbidities. Treatment approach, by contrast, had no measurable impact on overall survival.
For patients with adverse-risk AML profiles, these findings suggest that delaying transplantation to achieve remission through traditional chemotherapy may not offer an advantage—and could expose patients to further toxicity and hospital stays.
Implications for Future Treatment Strategies
The investigators concluded that immediate alloHCT following non-intensive disease control or watchful waiting should be considered a viable option for patients with refractory or relapsed AML. This approach may shorten hospitalisation time, reduce healthcare costs, and avoid unnecessary chemotherapy exposure.
Researchers also highlighted the urgent need for new bridging and maintenance strategies, including targeted drugs that can enhance post-transplant outcomes.
Reference
Stelljes M et al. Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial. Blood. 2025; https://doi.org/10.1182/blood.2025028730.
