Immunosuppression and Stem Cell Transplantation – How Are These Treatments Chosen? | Aplastic Anemia & MDS International Foundation Return to top.

Immunosuppressive therapy and stem cell transplantation are both used in treating bone marrow failure disease. Dr. Joseph Antin of Dana-Farber Cancer Center summarizes each method and how decisions are made on which treatment to use for aplastic anemia, MDS and PNH.

Immunosuppression and Stem Cell Transplantation – How Are These Treatments Chosen?

Aplastic Anemia

For around 80% of aplastic anemia patients, the underlying cause of the disease is immunologic – it’s an autoimmune disease. As with other autoimmune diseases like multiple sclerosis, lupus, or even rheumatoid arthritis, the body has misdirected its immune response. In the case of aplastic anemia, the immune system targets the bone marrow stem cells, which causes bone marrow failure. So an immunologically-based therapy has the potential to alleviate this immunologic defect. 

With patients for whom stem cell transplantation is not feasible – and there are different reasons for this -- immunosuppressive therapy is used, most often anti-thymocyte globulin (ATG), cyclosporine, or tacrolimus, and sometimes high dose cyclophosphamide.  These aren’t cures, and we don’t anticipate in an autoimmune disease that that immunosuppressive therapy will be curative. But it palliates the disease, and most patients still require long-term treatment with these immunosuppressive agents as the disease can easily recur, especially with events like pregnancy.

In 20 to 40% of aplastic anemia patients, there is significant stem cell loss, and immunosuppression does not offer much in the way of potential improvement.  In this situation, we will try to use stem cell transplantation if we have the option, as it is curative. Here, the treatment is giving a higher dose of immunosuppressive therapy, and then supply stem cells from a donor. Graft rejection can occur but it is uncommon with the intensive immunosuppression provided by the transplant conditioning regimen as well as the post-transplant immunosuppression.

A relatively new option for patients who have failed immunosuppressive therapy and are not eligible for a stem cell transplant is eltrombopag (Promacta®). Thus far, it has been shown to work in about 40% of this group. This is a marrow stimulant, that at least in the small number patients who have been studied, has been useful in stimulating blood cell production. Eltrombopag is a growth factor, which was originally developed to treat immune thrombocytopenic purpura (ITP). It mimics the effects of thrombpoeitin, which is a natural hormone that stimulates platelet production. There are some concerns about its use of because some patients develop mutated blood cells. But again, there are also concerns with ongoing immunosuppressive therapy -- patients developing PNH or MDS. So because of these scenarios, we prefer to do stem cell transplantation if possible.


For MDS, we typically try and do stem cell transplantation instead of immunosuppression. This is because MDS can sometimes progress to acute myeloid leukemia (AML) or on to progressive bone marrow failure. There’s really only one subset of MDS that responds well to immunosuppressive therapy – hypoplastic MDS – where’s there’s a nearly empty marrow, but the cells that remain are dysplastic cells.  So immunosuppressive therapy in this case does ameliorate cytopenias (low blood cell counts) and is not curative, but can be useful for older patients or those for whom transplantation is not an option.


PNH is more complicated because there are several manifestations of it – hemolysis, thrombosis, and bone marrow failure. Bone marrow failure in PNH is less responsive to immunosuppression. Here we use eculizumab (Soliris®) to reduce the risk of thrombosis (blood clots) and reduce hemolysis. This treatment is not curative and is often given for an extended term. Marrow transplantation is typically used in the setting of bone marrow failure, and there are scenarios where aplastic anemia enters the picture and complicates matters.  So immunosuppressive therapy is really only used in PNH when aplastic anemia also develops.

These are complex diseases with complex therapies which can have substantial risks. Stem cell transplantation can be curative, and the other therapies are not. But stem cell transplantation can’t and should not be used in every patient even though it is a potential cure. The other approaches can provide long term control of the disease, lessened the need for transfusion or even complete transfusion independent, and lessen the risk of complications from bone marrow failure.

Joseph H. Antin, MD

Position / Title: 
Professor of Medicine
Harvard Medical School

Dr. Antin received his MD from Cornell University in 1978, and postgraduate training in hematology and medical oncology at DFCI and Brigham and Women's Hospital. He subsequently served as director of the Bone Marrow Transplantation Service at BWH from 1987 to 1997. He now heads the Stem Cell Transplant Program of the Department of Medical Oncology at DFCI and BWH. He is a founding member and past president of the American Society of Blood and Marrow Transplantation and a past Chairman of the Steering Committee of the BMT Clinical Trial Network.

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