Platelet drug shows clinical benefits for severe, unresponsive aplastic anemia | Aplastic Anemia & MDS International Foundation Return to top.

Eltrombopag, a drug that was designed to stimulate production of platelets from the bone marrow and thereby improve blood clotting, can raise blood cell levels in some people with severe aplastic anemia who have failed all standard therapies.

About one-third of aplastic anemia cases do not respond to standard therapy, a combination of immune-suppressing drugs. Although bone marrow stem cell transplantation is an option for some, patients without a matched donor have few treatment options. The findings of this new clinical study, carried out by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, suggest eltrombopag could be a second-line therapeutic option for them.

“Eltrombopag and Improved Hematopoiesis in Refractory Aplastic Anemia,” was published online July 5 in the New England Journal of Medicine. 

Eleven of 25 participants enrolled in this phase 2 study showed improved production of at least one type of blood cell (red blood cell, white blood cell, or platelet) after 12 weeks of oral eltrombopag therapy. Among the seven volunteers who continued taking the pills long-term (8-32 months), six eventually showed an improvement in all three types of blood cells, and were able to maintain safe blood counts without needing red blood cell or platelet transfusions. Overall the drug was well tolerated, with few side effects.

The research team in the NHLBI Hematology Branch tested eltrombopag because this drug had previously been shown to boost platelet levels in both healthy people and people with reduced platelets due to hepatitis C infection or immune thrombocytopenia, blood disorders that like aplastic anemia result in low platelet counts and increased risk of bleeding.

The encouraging finding in this study was improvement in red blood cell and white blood cell counts in some aplastic anemia patients, suggesting that the drug can stimulate bone marrow stem cells and perhaps have wider utility than initially predicted.

AA&MDSIF interviewed Cynthia Dunbar, M.D., senior investigator in the NHLBI’s Hematology Branch and a coauthor on the study, to comment on the study’s findings and implications for future clinical studies with eltrombopag.

Platelet drug shows clinical benefits for severe, unresponsive aplastic anemia

What is Eltrombopag?

Eltrombopag is a chemical designed to bind to and activate the receptor for thrombopoietin, a cytokine produced by the body essential for production of platelets and it now appears also hematopoietic stem cells. Eltrombopag can be given orally and has been approved by the FDA for treating chronic immune thrombocytopenia (ITP)

How does it work?

It appears to stimulate hematopoietic stem cells to multiply, as well as stimulate increased production of platelets from platelet precursor cells.

How is it given and for how long?

It is given orally as a pill once or twice a day. Some patients with ITP have been treated with the drug for years. In our aplastic anemia trial several patients have been on the drug for over two years.

Is Eltrombopag being used for both children and adults?

In ITP, trials have been carried out in children, but it is not yet FDA-approved for children. The aplastic anemia trial reported in New England Journal of Medicine included only adults. However, we are designing a new trial for patients with refractory aplastic anemia that includes children. We also currently have a trial open for patients with new onset aplastic anemia combining eltrombopag with standard ATG and cyclosporin treatment, and this trial enrolls children.

How long before patients see response?

Most patients did not begin to respond until after 12 weeks of treatment, and did not reach their maximum response for a year or more.

What if there is no response? Are patients still able to try other therapies?

As far as we know there are no reasons that patients would not be able to try other therapies. Some patients that failed eltrombopag treatment on our trial went on successfully to have allogeneic stem cell transplantation.

Are there any side effects?

Very few. At very high doses some patients can become jaundiced and in some patients there is liver inflammation that necessitates lowering the dosage.

Are you still enrolling patients for any trials with Eltrombopag?

Yes, we are carrying out several trials at present. We have one for previously untreated moderate aplastic anemia in adults, another for refractory aplastic anemia in adults (an extension of the published study), and a trial for combining eltrombopag with ATG and cyclosporine in children and adults with previously-untreated aplastic anemia.

One of the trials is also for patients with low- or intermediate-risk MDS.

Do you have a timeline for the Phase 3 clinical trial period and how soon Eltrombopag could be possibly be approved for treatment of aplastic anemia?

It is difficult to predict. We hope that given the long-term safety data from the ITP trials, and the rarity of aplastic anemia, approval may be hastened.

The complete citation for the article is:
Eltrombopag and Improved Hematopoiesis in Refractory Aplastic Anemia

Matthew J. Olnes, M.D., Ph.D., Phillip Scheinberg, M.D., Katherine R. Calvo, M.D., Ronan Desmond, M.D., Yong Tang, M.D., Ph.D., Bogdan Dumitriu, M.D., Ankur R. Parikh, M.D., Susan Soto, B.S.N., Angelique Biancotto, Ph.D., Xingmin Feng, M.D., Ph.D., Jay Lozier, M.D., Ph.D., Colin O. Wu, Ph.D., Neal S. Young, M.D., and Cynthia E. Dunbar, M.D.

N Engl J Med 2012; 367:11-19 July 5, 2012

Learn more about the 20 active studies recruiting for eltrombopag at

Learn more about clinical trials.


Cynthia Dunbar, MD

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Position / Title: 
Senior Investigator
National Institutes of Health, National Heart, Lung, and Blood Institute

Cynthia Elizabeth Dunbar, M.D., is head of the Laboratory of Molecular Hematopoiesis in the Hematology Branch at the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health (NIH). Dr. Dunbar came to the NHLBI as a postdoctoral fellow in the laboratory of Arthur Neinhuis in 1987, became a principal investigator in 1993, and has been head of the Molecular Hematopoiesis Lab since 2000.

Dr. Dunbar’s research group investigates the mechanisms by which stem cells develop and differentiate into other cell types, particularly in relation to hematopoiesis, which governs the formation of new blood cells. Using cell lines and animal models, her research goal is to gain insight into the factors that control stem cell development. Such insight will aid in manipulating and modifying hematopoietic stem cells for applications in gene therapy, stem cell transplantation and other clinical interventions. Applying the knowledge gained from her stem cell work, Dr. Dunbar also conducts detailed preclinical studies aimed at improving the delivery and effectiveness of gene therapy interventions for blood-related disorders.

Dr. Dunbar earned a Bachelor of Arts from Harvard University in Cambridge, Mass., in 1980 and a Doctor of Medicine from Harvard Medical School in Boston in 1984; she subsequently completed her medical internship and residency at Boston City Hospital, and hematology fellowship training at the University of California, San Francisco.

Dr. Dunbar has authored more than 200 peer-reviewed scientific and review articles, and has given dozens of invited lectures and presentations about her work. She is the Editor-in-Chief of the journal BLOOD, the flagship publication of the American Society of Hematology.

Areas of expertise: Stem cells and stem cell therapy, gene therapy.

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