Acute myeloid leukemia (AML): Disease risk but not remission status determines transplant outcomes – new ASAP long-term results

(Press-News.org) The selection of patients for allo-HSCT and the best approach to bridging patients to transplantation is continuously discussed by experts. The first results of the ASAP study (ASAP standing for “as soon as possible”), published in 2024, have already attracted considerable attention [2]. ASAP questions existing treatment standards for AML and was the first randomized controlled trial to compare remission induction with salvage chemotherapy prior to allo-HSCT – which represents the current standard of care (SOC) – against an alternative approach of immediate transplantation after intensified conditioning combined with non-intensive disease control strategies such as less aggressive chemotherapy or simple monitoring of leukemic proliferation. These two groups are referred to as the SOC arm and the alternative treatment arm, respectively.

ASAP: Transplantation as soon as possible

The now published long-term analysis [1] supports the initial results of the ASAP trial [2]. The findings suggest, that a transplantation as soon as possible yields comparable treatment outcomes as remission induction – with shorter hospital stays and reduced exposure to chemotherapy [1]. “The results question the international standard of leukemia treatment. We no longer need to give all patients a very aggressive chemotherapy to reduce the tumor burden ahead of transplantation when regimens with good anti-leukemic activity are used for conditioning on the days prior to stem cell transplantation,” says Prof. Dr. Johannes Schetelig, coauthor of the study.

The results  were based on a median follow-up of 61 months in the patient cohort: The induction of remission in the SOC arm (5-year OS: 47.5%) compared to immediate transplantation in the alternative treatment arm (5-year OS: 46.1%) showed no overall survival (OS) advantage in AML patients, which were poorly responsive to initial treatment or with untreated relapse [1]. Since non-inferiority could not be demonstrated formally, immediate transplantation will not replace the common SOC but can be considered more often today [1]. One argument in favor of proceeding directly to transplantation without remission induction is that patients who received intensive salvage chemotherapy in the SOC arm spent one month longer in hospital and experienced more adverse events [1].

Age and AML genetics are the most important risk factors influencing survival

The long-term follow-up of ASAP additionally analyzed treatment success according to risk classification and genetic subgroups. Both age and AML genetics were identified as the most important baseline risk factors influencing survival. AML genetics were classified according to the ELN 2022 criteria [1].

The overall survival probabilities at 5 years (5-year OS) from randomization in the different risk groups independent from treatment arm were [1]:

66% with favorable risk AML, 53% with intermediate risk AML, and 34% for adverse risk AML. When both the ELN risk and the treatment were taken into account, the 3-year overall survival was 77% for patients with favorable/intermediate AML with watchful waiting in the alternative treatment arm (N = 49) versus 66% for patients transplanted with complete remission in the SOC arm in the same risk group (N = 49) [1].

An important step towards precision medicine in transplantation

“In summary, it can be concluded that survival after allo-HSCT in AML patients is less influenced by remission induction or bridging strategies and more influenced by intrinsic disease biology,” concludes Prof. Schetelig. Interestingly, reducing the pre-transplant leukemia burden did not translate into improved survival when intensive cytotoxic regimens were used, challenging a common assumption in treatment planning [1].

The uncertain benefits of inducing remission prior to allo-HSCT are in contrast to the fundamental impact of AML genetics. Favorable risk AML was associated with higher survival rates compared to adverse risk AML. These findings are consistent with previous reports on the prognostic impact of the ELN 2022 classification in patients undergoing allogeneic stem cell transplantation [1]. “But the data of the ASAP trial also demonstrate that tolerable novel bridging therapies and posttransplant maintenance for more personalized strategies are urgently warranted, especially for adverse risk AML, to improve outcomes after allo-HSCT,” summarizes Prof. Dr. Johannes Schetelig. “These findings open the door for future research to identify specific AML subgroups – a key step towards precision medicine in transplantation.”

 

DKMS fosters scientific progress

The ASAP study, initiated and realized by DKMS, reflects the focus on various areas of innovation to fight blood cancer from every angle. "It is our declared goal to improve the survival and healing chances for patients with blood cancer by investing in research to enhance current treatments and explore innovative approaches,” highlights Dr. Elke Neujahr, Global CEO DKMS.

As an international non-profit organization, DKMS places special importance on scientific questions that are not driven by commercial interests. This includes research that helps to enable access to holistic treatments worldwide, or that critically examines the use of current standard treatments. DKMS partners with medical experts across continents to foster scientific progress, funds research projects on an international level, conducts clinical trials, and honors outstanding scientific work with the DKMS Mechtild Harf Science Award. With the DKMS John Hansen Research Grant the organization supports actively young scientists with innovative approaches in the field of blood cancer (current application deadline: November 20, 2025). Find out more about all scientific information at DKMS Professionals’ Platform.

 

1 Stelljes, M. et. al. Disease risk but not remission status determines transplant outcomes in AML: long-term outcomes of the ASAP trial. Blood 2025 Jul 30:blood.2025028730. doi: 10.1182/blood.2025028730 Online ahead of print.

2 Stelljes, M. et al. Remission induction versus immediate allogeneic haematopoietic stem cell transplantation for patients with relapsed or poor responsive acute myeloid leukaemia (ASAP): a randomised, open-label, phase 3, non-inferiority trial. Lancet Haematol. 2024;11(5):e324-e335. doi: 10.1016/S2352-3026(24)00065-6

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