Expert Shares Insight on Impact of Bone Marrow Transplant on MDS Paradigm

Joseph Uberti, MD, PhD, associate professor of oncology and urology at Johns Hopkins Medicine

Joseph Uberti, MD, PhD

For patients with myelodysplastic syndrome (MDS), a bone marrow transplant is the only potentially curative option; however, this procedure is underutilized, according to Joseph Uberti, MD, PhD.

Patients with MDS are generally of an elderly population, yet age alone should not cause a treating physician to be wary of bone marrow transplant, explained Uberti, a medical oncologist at Karmanos Cancer Institute.

“The patients who undergo transplant can live a long time, they can live a good quality of life, and they don't have to worry about any lasting side effects,” he said.

The rates of transplant-related morbidity and mortality should also be considered, but a set of guidelines is in place for those who are eligible for this procedure.

OncLive: Please highlight the role of bone marrow transplant in MDS.

In an interview during the 2018 OncLive^® State of the Science Summit™ on Hematologic Malignancies, Uberti discussed the risk and benefit of a bone marrow transplant for patients with MDS.Uberti: Bone marrow transplant is an underutilized procedure for the treatment of [patients with] MDS. There are certain indications for which patients should be considered for transplant. [During my presentation], I also spoke about the outcomes for patients with MDS who undergo transplant. There are also criteria for when a patient should be considered for transplant. It is the only curative strategy for MDS and it remains so. We think it should definitely be utilized a little bit more.

What are some other factors that may lead to hesitation in doing a transplant?

One of the issues has been the age of patients who can go into transplant. This is a difficult procedure, but we've shown over and over that these patients can do well. We've transplanted patients who were up to 80 years old, and typically these patients range in the 70- to 75-year-old range. The age of a patient alone is not a criterion to not go to transplant. It's not so much chronologic age as it is biologic age. Are they functioning well? Do they have good hearts and lungs? If those are the indications for the patient, they can make it through a transplant safely for their underlying disease.There are a number of reasons why referring physicians don't use transplant that much for MDS. Age is certainly one of the factors. People have the misconception that older patients can't make it through transplant easily, but I showed data indicating that these patients can do just as well. The other perception is that we can't find donors for our patients. Now we have new donors available, which give us access for pretty much every patient. That has changed our ability to do transplants for many different patients who we couldn't treat before. These new donors have been very effective; it is almost as if they're a brother or sister providing the transplant for the patient.

One of the problems with MDS, again, is the age of the patients. They acquire all the comorbidities we all get as we age. They have heart problems, lung problems, and kidney problems. However, even in certain patient populations with these issues, we can still get them through a transplant.

What are the data or general outcomes for patients who undergo transplant?

Beyond transplant, are there any ongoing trials that are looking at MDS therapy?

How does MDS typically present?

The first thing we look at is performance status. We look at their lung function, cardio function, and kidney function. All of these need to be adequate before we proceed with the transplant. We also look at the overall frailty of the patient. Some of them are a little too weak and frail to have this procedure. There are specific guidelines for looking at frailty score. Can they walk? Can they take care of themselves? Do they have good family support? These are all important to consider. The status of the underlying disease is important. Some of these patients don't have a level of MDS that requires transplant.The outcomes look very promising for these patients. Registry data show that 50% to 60% of patients are alive 6 years after undergoing transplant. There is also no evidence of disease in these patients. We think there is a high cure rate attached to transplant. You especially need to compare this cure rate with that of patients who don't undergo transplant, which is 0%. We can use related-donor transplants, or we can use unrelated-donor transplants. They both give approximately the same outcome.Right now, transplant is really the sole treatment option that provides a possible cure for MDS. There have certainly been a number of investigational trials conducted and agents have been tested. There are drugs approved for MDS, such as hypomethylating agents. Lenalidomide (Revlimid) is approved for certain forms of MDS. None of these therapies are curative, but they definitely can improve outcomes.It is one of the many cancers that has an increase of risk as we age. It usually presents with cytopenia. The patient is usually anemic. There are other symptoms associated with it, such as shortness of breath and fatigue. If their white blood cell count goes down, there is an increased risk of infection. If their platelet count goes down, there is the increased risk of bleeding. The initial blood work that is done will show this. However, patients then need to have a bone marrow biopsy done to confirm the diagnosis of MDS.

Are there any molecular targets?

There is much more sophisticated means of testing over the last few years in MDS. There are cytogenetics we can use to help confirm the diagnosis. We can also do genetic and mutational analyses. All of these tools are available for us. We can effectively predict the prognosis, as well. There are cytogenetic abnormalities that can either improve the prognosis or make it worse. The more blasts you have in the bone marrow biopsy, the worse the prognosis will be. All of these factors are put into a score, which allows us to come up with a median survival.We've started to find some, but we haven't developed any targeted therapies yet. Certainly, the most important step is identifying them and understanding what role they play in the disease. Right now, we know they affect prognosis.