Aplastic anemia is a rare blood disorder in which blood stem cells fail to produce enough blood cells, including red blood cells and platelets. Patients with aplastic anemia are prone to life-threatening conditions ranging from severe infections to dangerous bleeding or heart failure. The condition can be managed for a short time using immunosuppressive medications, but hematopoietic stem cell transplantation is the only cure. Patients who receive a transplant typically do very well, and studies estimate that the 5-year survival rate after transplantation ranges from 96-100%.
These favorable outcomes are built on decades of research to fine-tune the transplant process for patients with aplastic anemia. Prior to transplant, the patient’s own blood cells must be depleted by a conditioning regimen like total body irradiation or a cytotoxic drug called cyclophosphamide. Patients also receive drugs as prophylaxis for graft-versus-host-disease, a common transplant complication where donor cells attack healthy tissues in the recipient. Over the years, recommendations for conditioning regiments and prophylactic drugs have shifted as researchers have learned more about the disease. Dr. Daniel Olivieri and his colleagues in the Clinical Research Division highlight how these recommendations have changed and what problems remain for treating aplastic anemia in a retrospective study published in Blood Advances.
The teams study analyzed medical records from over 600 patients that received hematopoietic stem cell transplants to treat aplastic anemia at Fred Hutch between 1970 and 2024. They separated the patients into three groups based on whether their donor cells came from a relative or a stranger and whether they were HLA-matched. HLA, or human leukocyte antigens, are proteins that are expressed on nearly all cells of the body. Having a close HLA match greatly reduces the risk of the transplanted cells (the graft) attacking the patient’s own cells (the host). Of the patients analyzed, 65% of them received HLA-matched related donor cells, 18% received HLA-matched unrelated donor cells, and 17% received HLA-mismatched donor cells. Importantly, they found that survival outcomes across all three groups improved over time, reflecting the impact of continuing research efforts into treating aplastic anemia.
First, the authors describe how treatment and outcomes have shifted for patients receiving HLA-matched cells from related donors. The conditioning and graft-versus-host-disease prophylaxis regimens for HLA-matched related donor recipients have evolved over time. In the 1970s, patients first began receiving cyclophosphamide and methotrexate for graft-versus-host-disease prophylaxis and conditioning. In the 1980s, cyclosporine and horse anti-thrombocyte globulin were added to the regimen. Since then, the standard approach at Fred Hutch has been conditioning with cyclophosphamide and anti-thrombocyte globulin to enable engraftment, followed by graft-versus-host-disease prophylaxis with cyclosporine and methotrexate. Notably, rates of graft rejection have dramatically dropped from 21% in the 1970s to just 2% in the 1990s, and no patients have died from graft rejection since 1991. Survival outcomes have improved just as dramatically. In the 1970s, the 5-year survival rate after transplant was just 56%. This rate improved to 84% for patients that received a transplant between 2000-2010.
HLA-matched unrelated donor transplants have become more common over time as transplant outcomes have improved. Conditioning and prophylaxis regimens are slightly different for unrelated donor transplants but typically use some combination of cyclophosphamide, cyclosporine, total body irradiation, anti-thrombocyte globulin, fludarabine, or a thrombopoietin receptor agonist. Overall, graft rejection has remained rare, occurring in only 3% of patients, and no deaths have been attributed to graft rejection since 1992. Over the same period, long-term outcomes have improved substantially, with 5-year survival increasing from 25% in the 1980s to 70% in the 2000s, again highlighting the impact of ongoing research in this area.
HLA-mismatched donor transplants are riskier, and relatively few of them have been performed at Fred Hutch compared to the other two types of transplant. Nevertheless, survival outcomes of these transplants have improved from 15% in the 1970s to 70% in the 2000s, and graft rejection has dropped since the 1980s, as well.
Overall, transplant outcomes for aplastic anemia patients have improved dramatically over time. The authors attribute this to several changes since the 1970s, including the use of better antibacterial and antifungal agents, better monitoring for infectious agents in donor cells, advances in the conditioning and prophylaxis regimens, and better transplant practices and infrastructure. Still, some challenges remain. For example, a majority of recipients develop some form of graft-versus-host-disease, so ongoing clinical trials at Fred Hutch and elsewhere are evaluating new treatments to prevent this complication.
This work was supported by funding from the National Institutes of Health.
Fred Hutch/University of Washington/Seattle Children’s Cancer Consortium Members Drs. Megan Othus, Phuong Vo, Roland Walter, Shivaprasad Manjappa, and Sioban Keel contributed to this work.
Olivieri D, Othus M, Vo P, Walter RB, Manjappa S, Basom R, Storb R, Keel S. 2026. Allogeneic hematopoietic cell transplantation for aplastic anemia: a single institution experience across 6 decades. Blood Adv. 2026 Apr 28;10(8):2661-2675. doi: 10.1182/bloodadvances.2025018548.
Kelsey Woodruff is a PhD candidate in the Termini Lab at Fred Hutch Cancer Center. She studies how acute myeloid leukemia cells remodel the sugars on their membranes to reprogram cancer cell signaling. Originally from Indiana, she holds a bachelor's degree in Biochemistry from Ball State University. Outside of lab, you can find her crocheting and enjoying the Seattle summers.