AML transplant or not

Arguably one of the more prominent areas of debate during the 2025 annual EBMT meeting was the role of allogeneic stem cell transplantation (allo-SCT) in adult patients with acute myeloid leukemia (AML). In this video, Prof Charles Craddock from the University of Warwick in the UK, discusses how improvements in the pre- and post-transplant management of these patients can lead to better outcomes.

Nowadays, an allo-SCT is considered standard of care for most fit, adult AML patients up to the age of 75 years. The latter has become possible by an increased availability of donors through expanded unrelated panels and by the fact that post transplantation anti-GVHD prophylaxis (e.g., with cyclophosphamide) allows for the use of haploidentical donors. In this light, it is important that tissue typing is done at diagnosis in all newly diagnosed adult AML patients and that an urgent unrelated donor search is started.

When looking at ways to improve outcomes for AML patients undergoing an allo-SCT, it is important to remember that relapse continues to be the most important cause of transplant failure. In this respect, the focus should be to maximize the graft versus leukemia effect, while in the meantime minimize the toxicity of the treatment. 

Multiple clinical studies around the globe have been set up to determine the best conditioning regimen for AML patients prior to an allo-SCT. In younger, fit patients (<50 years), the BMT-CTN 0901 study convincingly demonstrated that a myeloablative conditioning regimen (MAC) leads to a better overall survival and a lower relapse risk than a reduced intensity regimen (RIC). As such, a MAC should be preferred in this setting, especially for patients who are MRD-positive prior to transplantation. In older patients, who are unfit for MAC, several clinical trials are looking into effective, less intensive conditioning regimens. Prime examples of this are the FIGARO trial evaluating conditioning with fludarabine, amsacrine, cytarabine and busulphan, or the EBMT led study evaluating conditioning with thiotepa, busulfan and fludarabine. 

While these studies may bring some incremental improvements, Prof Craddock is not convinced that a major breakthrough will come from better conditioning. Instead, a crucial area of research should be the development of therapies that bring patients in complete response and MRD-negative prior to transplantation. In this respect, several clinical trials are ongoing evaluating the potential of venetoclax-based regimens in this setting.

A second are of intensive research consists of maintenance therapy after an allo-SCT in adults with AML. In this respect, the MORPHO study demonstrated a higher relapse free survival for participants with detectable FLT3-ITD MRD pre- or post-SCT who received gilteritinib.² Importantly, however, gilteritinib is not EMA approved in this setting. In contrast, quizartinib is approved and by extrapolating data from MORPHO, quizartinib maintenance should be seen as a standard of care in MRD-positive patients harboring a FLT3-ITD mutation. An alternative option could consist of sorafenib, but this treatment is generally poorly tolerated by AML patients. Th ongoing AMADEUS trial is currently evaluating azacitidine post transplantation, while the VIALE-T study will evaluate the combination of venetoclax and azacitidine after an allo-SCT in adult AML patients. Taken together, these 2 studies will include about 1,400 patients illustrating the fact that the AML community is actively investing in the design of randomized controlled study.

With the advent of effective maintenance strategies, it is becoming increasingly important to treat patients with a conditioning regimen and provide them with a good GVHD prophylaxis treatment so that they remain fit enough to receive maintenance therapy. With respect to GVHD prophylaxis, the BMT CTN 1703 study demonstrated a significant benefit in GVHD- and relapse-free survival with the addition of cyclophosphamide to post-transplant tacrolimus-mycophenolate mofetil.³ However, in Europe the standard GVHD prophylaxis consists of anti-thymocyte globulin (ATG) and is not based on tacrolimus.  In this light, 2 rapidly recruiting trials are underway evaluating the added value of cyclophosphamide to ATG as GVhD prophylaxis after an allo-SCT.