Adult patients with poorly responding, non-favorable AML after initial induction therapy or those who have already relapsed are usually advised to undergo allogeneic stem cell transplantation – as a chance for long-term cure. An important step prior to this life-saving therapy has always been to bring the patient back into complete remission by high-dose chemotherapy.

The clinical trial compared the standard treatment with an alternative approach for high-risk AML patients

The goal of the randomized controlled trial led by Prof. Schetelig was to get patients to transplantation as soon as possible. This coined the name of this trial: ASAP. The team of researchers collected data from 276 patients (the intention-to-treat population) with a median age of 61 years who were divided into two groups. According to standard practice, group one was treated with prolonged chemotherapy before stem cell transplantation to achieve complete remission. Group two received a transplant after only a short 12-day conditioning period without the intention of achieving complete remission prior to transplantation. A prerequisite for stem cell transplantation was, of course, the availability of an HLA-compatible allogeneic donor.

The results of the trial are surprisingly clear

The common practice of achieving complete remission before transplantation shows no advantage in terms of overall success or overall survival. Moreover, patients in the alternative study arm not only achieved the same outcome - they also benefited from fewer side effects by not having to undergo lengthy high-dose chemotherapy and their median hospital stay was only half as long. “The results of our clinical trial challenge the international standard of leukemia therapy and were also surprising for us. They suggest that if an HLA-compatible stem cell donor is available, transplantation should take place as soon as possible, even if leukemia cells are still detectable in the patient's body,” says Prof. Schetelig. “Moreover, these results underscore the need for early initiation of donor search, possibly at the time of diagnosis but latest after receipt of genetic reports which show a non-favorable risk profile for AML.”

The implementation of the results in the clinic may benefit patients worldwide

Even with intensive chemotherapy, the previously targeted complete remission can only be achieved in about 50 percent of patients. If the corresponding treatment is unsuccessful, most patients have so far received a second intensive chemotherapy with correspondingly burdensome side effects, depending on their overall state of health. Immediate transplantation without a prior attempt at complete remission could not only reduce side effects and shorten hospital stays, but also allow more patients access to this potentially life-saving therapy. “This is especially true for countries with less comprehensive healthcare, where stem cell transplantation is often not performed after a failed complete remission, also for cost reasons. Eliminating this expensive intermediate step could therefore open up the possibility of stem cell transplantation to more AML patients worldwide, which in many cases is the only chance of a cure," explains Prof. Schetelig.

DKMS enables clinical research

"Normally, sponsors of clinical research pursue economic interests. It is unusual to conduct a clinical trial that questions the use of a standard medical intervention - usually it is the other way around. That’s why it’s necessary for nonprofit organizations like DKMS to also conduct clinical research. This way, we can ensure that patients receive the best possible treatment and that we actually advance patient care," says Dr. Alexander Schmidt, Global Chief Medical Officer at DKMS.

Currently, the DKMS Clinical Trials Unit is engaged in two additional clinical trials. One of these looks at the administration of two different drugs to prevent graft-versus-host disease. This trial compares whether standard therapy (anti-thymocyte globulins) makes a significant difference in outcome compared to the alternative drug (post-transplantation cyclophosphamide) (GRAPPA trial). The other randomized controlled trial examines the extent to which stem cell transplantation outcomes differ when patients receive the graft from either a single-mismatched unrelated donor or a haploidentical donor (HAMLET trial). In the coming years, we will increasingly hear about the results of these important research topics and their potential impact on patient care.