clinical topic updates

Maintenance Therapy Post Allogeneic Stem Cell Transplantation in High-Risk MDS and AML

by Andrew M. Brunner, MD


Although patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) may be cured with allogeneic stem cell transplantation, too many individuals ultimately relapse. Efforts to increase the post-transplant cure fraction include the investigation of potential maintenance therapies.

Expert Commentary

Andrew M. Brunner, MD

Assistant Professor of Medicine
Harvard Medical School
Assistant in Medicine, Division of Hematology and Oncology
Center for Leukemia, Massachusetts General Hospital Cancer Center
Massachusetts General Hospital
Boston, MA

“While post-transplant maintenance therapy is not currently a global standard of care, I do believe that there is a growing recognition that there are some patients with high-risk disease whose treatment cannot end with allogeneic stem cell transplantation.”

Andrew M. Brunner, MD

For a long time, allogeneic stem cell transplantation was seen as the end of treatment for patients with MDS and AML. After the transplant, immunosuppression would be tapered, and then, ideally, after some time, the patient would get far enough out to be considered cured. The sobering reality is that, even after transplant, too many patients with MDS and AML will relapse. Further, certain MDS and AML subgroups are much more likely to relapse than others; for example, the majority of those with TP53 mutations, unfortunately, will relapse post transplant.

When we think about the broad subject of post-transplant maintenance therapy, there are many considerations and arguments that can be made for each side of the issue. If you had a very well-tolerated therapy that lowered relapse rates, this might be a more favorable scenario and one in which the use of maintenance therapy could be entertained; however, maintenance therapies may also add toxicities and present other challenges. 

There may be some advantages to tailoring decisions about maintenance therapy to a patient’s mutation type. For example, in the prospective SORMAIN study, patients with FLT3-ITD–positive AML in complete hematologic remission were randomized to sorafenib or to placebo after transplant. Researchers concluded that sorafenib maintenance therapy improved relapse-free survival in these patients. Studies with more highly selective and potent FLT3 inhibitors are ongoing. 

One of the challenges is that it is not yet possible to identify and treat only those patients who absolutely require maintenance therapy. Take, for instance, a 50% cure rate with transplant alone. If you then treat the whole population with maintenance therapy, you would be “overtreating” the other half by giving maintenance therapy to patients who, in the end, would not actually need it. 

Another strategy that has been employed is hypomethylating agent maintenance therapy. Both azacitidine and decitabine have toxicity profiles that can be more challenging after transplant, and we must be aware of risks such as low blood counts and flares of graft-vs-host disease. I think that the use of azacitidine or decitabine as maintenance therapy has generally been limited to patients with the highest-risk features. And I think that decisions regarding implementing therapy should also involve the consideration of disease characteristics at diagnosis and before transplant (ie, detectable residual disease and persisting mutations such as TP53). Individuals with a high variant allele fraction before transplant are among the highest-risk patients. And so, for those patients, putting them on some type of maintenance therapy makes a lot of sense, because their outcomes can be so poor without it. 

While post-transplant maintenance therapy is not currently a global standard of care, I do believe that there is a growing recognition that there are some patients with high-risk disease whose treatment cannot end with allogeneic stem cell transplantation.


Burchert A, Bug G, Fritz LV, et al. Sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with FLT3-internal tandem duplication mutation (SORMAIN). J Clin Oncol. 2020;38(26):2993-3002. doi:10.1200/JCO.19.03345

El Chaer F, Borate U, Duléry R, et al. Azacitidine maintenance after allogeneic hematopoietic cell transplantation for MDS and AML. Blood Adv. 2021;5(6):1757-1759. doi:10.1182/bloodadvances.2020003839

Jacoby MA, Duncavage EJ, Chang GS, et al. Subclones dominate at MDS progression following allogeneic hematopoietic cell transplant. JCI Insight. 2018;3(5):e98962. doi:10.1172/jci.insight.98962

Keruakous AR, Holter-Chakrabarty J, Schmidt SA, Khawandanah MO, Selby G, Yuen C. Azacitidine maintenance therapy post-allogeneic stem cell transplantation in poor-risk acute myeloid leukemia. Hematol Oncol Stem Cell Ther. 2021;S1658-3876(21)00030-3. doi:10.1016/j.hemonc.2021.03.001

Köhler N, Ruess DA, Kesselring R, Zeiser R. The role of immune checkpoint molecules for relapse after allogeneic hematopoietic cell transplantation. Front Immunol. 2021;12:634435. doi:10.3389/fimmu.2021.634435

Oran B, de Lima M, Garcia-Manero G, et al. A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients [published correction appears in Blood Adv. 2021;5(6):1755-1756]. Blood Adv. 2020;4(21):5580-5588. doi:10.1182/bloodadvances.2020002544

More in MDS & AML



Update on Actionable Targets in the MDS and AML Disease Spectrum

Clinical Topic Updates by David Sallman, MD

Mutations in FLT3 and IDH1/IDH2 are among those that are currently actionable in acute myeloid leukemia (AML). Trials of novel agents and combinati...READ MORE



Genomic Landscape of MDS and AML: Current Perspectives

Clinical Topic Updates by Harry Paul Erba, MD, PhD

Myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are part of a disease spectrum that is beginning to enter into the precision medici...READ MORE



Higher-Risk MDS and AML: Need for Treatment Without Intensive Chemotherapy

Patient Care Perspectives by Guillermo Garcia-Manero, MD

The US Food and Drug Administration approval of lower-intensity treatments, including hypomethylating agents (HMAs) and targeted and/or immunomodul...READ MORE

More In Oncology

HER2-Positive Breast Cancer

HER2+ Breast Cancer: Discussing Treatment Options

Patient Care Perspectives by Sara M. Tolaney, MD, MPH


High-Risk Chronic Lymphocytic Leukemia: Insights and Approaches

Expert Roundtables by Jennifer R. Brown, MD, PhD; John C. Byrd, MD; and Susan O’Brien, MD