In patients with acute myeloid leukemia, prior to transplantation of non-patient (allogeneic) blood stem cells, attempts have been made to suppress the disease with high-dose chemotherapy to such an extent that leukemia cells are no longer detectable (complete remission). In a large-scale nationwide study, which was largely financed by the non-profit organization DKMS, a research team was able to show for the first time that the complete remission previously aimed for does not bring any significant advantage for overall survival and disease-free survival. Rather, the study indicates that if an HLA-compatible donor (matching tissue characteristics – human leukocyte antigens – on the surface of the white blood cells) is available, a 12-day preliminary chemotherapy followed by an immediate transplantation brings comparable treatment results with fewer side effects and shorter hospital stays .
“The results of our study shake an international standard of leukemia therapy and were also surprising for us,” emphasizes study leader Prof. Johannes Schetelig. “They suggest that if an HLA-compatible stem cell donor is available, the transplantation should take place as quickly as possible, even if leukemia cells are still detectable in the patient’s body. Immediate transplantation without first attempting to completely reverse the disease can reduce overall side effects and shorten hospital stays.”
“Allogeneic stem cell transplantation is the most effective treatment option for patients with refractory or recurrent AML. Even with intensive chemotherapy, the previous complete remission that has been sought so far can only be achieved in about 50 percent of those affected. If the corresponding treatment is not successful, patients in Germany often receive further therapies with similarly unsatisfactory chances of success. Alternatively, the goal of complete remission can be dispensed with and a stem cell transplant can be offered after appropriate pretreatment,” says first author Prof. Matthias Stelljes, head of the bone marrow transplant department at the University Hospital in Münster. “In other countries with less comprehensive health care, stem cell transplantation is often no longer carried out after a failed complete remission, also for cost reasons. Abandoning this cost-intensive intermediate step could thus open up the possibility of a stem cell transplant to more AML patients worldwide, which in many cases is the only chance of a cure.”
The study treated 276 adult AML patients who were scheduled for allogeneic stem cell transplantation due to poor response to initial chemotherapy or relapse. A donor had already been found for all patients or the search for a donor was well advanced. The study participants were randomly divided into two groups of approximately equal size. Group 1 was attempted to achieve complete remission in preparation for transplantation. In group 2 patients, if a donor was available, a 12-day preparatory therapy followed by immediate transplantation. In the first group, a complete remission was achieved in 46 percent of the patients. In 5 percent of those affected, a second attempt was made to achieve complete remission using high-dose chemotherapy; the remaining patients received preparatory therapy and stem cell transplantation without this further attempt. In group 1, the median time to start of transplantation was eight weeks. In the second group, the transplantation took place after an average of four weeks.
The leukemia-free survival one year after transplantation showed no significant differences between both groups (69% vs. 71.5%), as did the overall survival one year and three years after study inclusion (71.9% vs. 69.1% and 54 .2% vs. 51%).
“The perspective shown for AML therapy of reducing side effects and hospital stays with the same good treatment results is trend-setting,” says Prof. Michael Albrecht, Medical Director of the Carl Gustav Carus University Hospital. “The current study is an impressive example of the fact that cancer research in Dresden is now providing impetus from which patients around the world are benefiting. Just 25 years ago, hardly anyone would have thought that possible!”
Publication:
M. Stelljes et al.: In Patients with Relapsed/Refractory AML Sequential Conditioning and Immediate Allogeneic Stem Cell Transplantation (allo-HCT) Results in Similar Overall and Leukemia-Free Survival Compared to Intensive Remission Induction Chemotherapy Followed By Allo-HCT: Results from the Randomized Phase III ASAP Trial. Blood (2022) 140 (Supplement 1): 9–11. https://doi.org/10.1182/blood-2022-159962
About the DKMS:
The DKMS is an international non-profit organization whose goal is to give as many blood cancer patients as possible a second chance at life worldwide. She was founded in Germany in 1991 by Dr. Peter Harf and since then has ensured that more and more patients receive a life-saving stem cell donation. More than 11.5 million potential donors are registered in the DKMS, and to date the organization has arranged more than 100,000 stem cell donations. Apart from Germany, DKMS is active in the USA, Poland, UK, Chile, India and South Africa.
Through international projects and aid programs, DKMS gives even more people worldwide access to life-saving therapy. In addition, the DKMS is involved in the fields of medicine, science and research in order to improve the chances of recovery for patients. In its high-performance laboratory, the DKMS Life Science Lab, the organization sets global standards for the typing of potential stem cell donors in order to find the perfect match for a transplant.
German Cancer Research Center (DKFZ)
With more than 3,000 employees, the DKFZ is the largest biomedical research facility in Germany. More than 1,300 scientists at the DKFZ research how cancer develops, record cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods with which tumors can be diagnosed more precisely and cancer patients can be treated more successfully.
At the Cancer Information Service (KID) of the DKFZ, those affected, interested citizens and specialist groups receive individual answers to all questions on the subject of cancer.
Together with partners from the university clinics, the DKFZ operates the National Center for Tumor Diseases (NCT) at the Heidelberg and Dresden sites, and the Hopp Children’s Cancer Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translation centers at seven university partner locations. The combination of excellent university medicine with the top-class research of a Helmholtz center at the NCT and DKTK locations is an important contribution to transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.
The DKFZ is funded 90 percent by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg and is a member of the Helmholtz Association of German Research Centers.
University Hospital Carl Gustav Carus Dresden
The University Hospital Carl Gustav Carus Dresden offers medical care at the highest level of care. As a maximum-care hospital, it covers the entire spectrum of modern medicine. The university hospital brings together 20 clinics and polyclinics, four institutes and ten interdisciplinary centers that work closely with the clinical and theoretical institutes of the medical faculty.
With 1,295 beds and 160 places for the day treatment of patients, the Dresden University Hospital is the largest hospital in the city and at the same time the only maximum care hospital in East Saxony. Around 860 doctors cover the entire spectrum of modern medicine. 1,860 nurses look after the well-being of the patients. Important treatment focuses of the university hospital are the care of patients suffering from cancer, metabolic and neurodegenerative diseases.
Germany’s largest comparison of hospitals by the news magazine “Focus” certifies that the University Hospital Carl Gustav Dresden has excellent treatment quality. The Dresden university medicine therefore occupies second place in the Germany-wide ranking.
Medical Faculty Carl Gustav Carus of the Technical University of Dresden
The Dresden University Medicine, consisting of the Carl Gustav Carus Medical Faculty and the University Hospital of the same name, has specialized in research in the areas of oncology, metabolic, neurological and psychiatric diseases. In these areas of focus, the overarching themes of degeneration and regeneration, imaging and technology development, immunology and inflammation, as well as prevention and healthcare research are of particular interest. International exchange is a prerequisite for cutting-edge research – the Dresden University Medicine lives this idea with employees from 73 nations and numerous cooperations with researchers and teams all over the world.
Helmholtz Center Dresden-Rossendorf (HZDR)
The Helmholtz-Zentrum Dresden-Rossendorf (HZDR) conducts research in the fields of energy, health and matter. The focus here is on the following questions:
- How do you use energy and resources efficiently, safely and sustainably?
- How can cancers be better visualized, characterized and treated effectively?
- How do matter and materials behave under the influence of high fields and in the smallest dimensions?
To answer these scientific questions, the HZDR operates large infrastructures that are also used by external measurement guests: Ion Beam Center, Dresden High Magnetic Field Laboratory and ELBE Center for High-Power Radiation Sources.
The HZDR is a member of the Helmholtz Association, has five locations (Dresden, Freiberg, Grenoble, Leipzig, Schenefeld near Hamburg) and employs almost 1,200 people – around 500 of them scientists including 170 doctoral students.