MDS sub-types | Aplastic Anemia and MDS International Foundation

MDS sub-types

Therapies

There are many therapies and approaches doctors use to treat bone marrow failure disease patients. Some treatments are used for several different diseases. Others are used only for aplastic anemia, MDS or PNH. Every person's condition is unique, and each situation is different. That's why your health care team must look carefully at your specific case before recommending what's right for you.

Pediatric MDS

Interviews with the Experts – MDS We Don’t Often Think About Specialists Speak about MDS Subtypes Having a Lower Profile

Interview: 

What is pediatric MDS, and why is it seldom mentioned in larger discussion about MDS?

Pediatric MDS, like adult MDS, is a clonal myeloid malignancy that is typically fi rst spotted as cytopenias (low blood counts). It’s a stem cell disorder in the bone marrow that results in disturbances  in blood cell differentiation and apoptosis (cell death). It is distinguished from acute myeloid leukemias (AML) by having a relatively low percentage of blasts (immature blood cells in the bone marrow). There’s really no difference in the definition of MDS as it applies to children or adults – the only thing that makes it a different category is the age of the patient. The reason it’s seldom mentioned in overall discussions of MDS is because of a far lower incidence than the adult age group and particularly, the older adult age group. The other interesting point is that within pediatric myeloid malignancies, pediatric MDS is a much smaller proportion than it is for adult myeloid malignances. Less than 5% of pediatric myeloid malignancies are MDS, whereas it’s much higher in for adult myeloid malignancies.

There are several classification systems used for identifying subtypes and their potential severity and risk levels of MDS in the adult patient population. Do these classifications also apply to pediatric MDS?

That’s a good question. They can apply and we do our best to apply those classification systems. We have attempted to fit pediatric MDS into the World Health Organization (WHO) classification system, but it’s not optimal for this. This is because there are certain subtypes of MDS, for example, refractory anemia with ringed sideroblasts (RARS), that don’t occur in children. Another interesting point is that one-third to one-half of children with MDS has an associated constitutional abnormality that can play a large part in the child developing MDS. The most common ones are Down Syndrome and inherited bone marrow failure diseases such as Fanconi Anemia. Those are difficult to classify in the adult systems because they generally don’t take inherited abnormalities into account.

Another issue is that familial MDS is not uncommon in children with MDS. Many young MDS patients will have siblings who also have MDS. We have had a few families we have treated with familial monosomy 7-related MDS, and that doesn’t occur on the adult side. Finally, some of the subsets of cytogenetic abnormalities that occur in MDS are very different in children. A larger proportion of children have monosomy 7 compared to adults, and a much small proportion of children have the 5q-minus variant – this one is almost never seen in children.

Do the several different treatment approaches (watch and wait, supportive care, active treatment including stem cell transplantation) used in adult MDS apply to pediatric MDS?

They typically don’t apply. Our approach on the pediatric side is to take the patient to an allogeneic bone marrow transplant as soon as possible because it’s a much different set of circumstances. For younger children, a bone marrow transplant, like adults, is the only potential curative therapy for MDS. Because children are often in a better position to handle the intensity of bone marrow transplant therapy, and because the potential upside of number of years of life that can be extended is much higher, we usually try right away to find a bone marrow transplantation option for a pediatric MDS patient.

Has there been any promising recent research with regard to pediatric MDS?

Because pediatric MDS is so heterogeneous, most of the research occurring is more in the conditions that can predispose to MDS, or make it more likely for pediatric MDS to occur. For example, with Down syndrome-related MDS, there have been striking advances in the understanding of what causes it and the development of different treatments that can help. There have also been advances in understanding the genetic causes of various bone marrow failure syndromes. But those haven’t yet translated into better therapies for pediatric MDS once it develops - bone marrow transplant remains the treatment of choice.

What do parents of children diagnosed with pediatric MDS most need to know?

There are two points here. We consider pediatric MDS to be a curable condition as long as a patient can have an allogeneic bone marrow transplant. Just like with recurrent MDS, bone marrow transplantation doesn’t guarantee a cure. However, the proportion of pediatric patients for which we can find a suitable donor and who can tolerate a transplant is so high that we can reasonably be very optimistic about pediatric patients diagnosed with MDS.

It’s also important to say that any parent of a child diagnosed with a rare blood or bone marrow malignancy like pediatric MDS should be treated at a specialized pediatric oncology center. It should one that has a lot of experience with these conditions and that also has a collaborative relationship with their adult oncology colleagues, who see many more cases of MDS and can be a great source of expertise and advice.

Recurrent and Secondary MDS

Interviews with the Experts – MDS We Don’t Often Think About Specialists Speak about MDS Subtypes Having a Lower Profile

Interview: 

Is MDS that returns after treatment(s) have successfully controlled it considered recurrent MDS?

The idea of the recurrent MDS is exactly that. If a patient’s MDS has been treated into remission or even controlled and stabilized from an earlier state and then starts to progress with symptoms,
worsening blood counts, and worsening bone marrow studies, that is recurrent MDS. Recurrent MDS can happen after supportive approaches, after medical treatments, and even after an allogeneic stem cell transplant. So, I think of recurrent MDS to mean progression or re-emergence of MDS after a period of remission or managed stability.

Is the frequency of recurrent MDS known, and is a certain type of patient more likely to experience it?

To date, this has not been well studied, but what we do understand is that the large majority of  patients with MDS who have periods of disease stability or respond to treatments will eventually recur. Most supportive care or active medical treatments are more temporary treatments and are not permanent or curative.

Is it known why recurrent MDS happens?

The simple answer is that the MDS is a progressive bone marrow failure disorder, and over time, it tends to get worse for most patients. The medical therapies we have do work for many patients, but because they are not curative, their MDS will often become resistant to the treatment. We do know a lot more about MDS than we did just 10 years ago. We understand that there is a series of genetic events (mutations) that occur in the development of MDS and their accumulation can also be associated with the progression or recurrence of the disease. So even when a treatment works
for awhile, it is possible that the responding MDS will obtain additional genetic events that render it resistant to the very same treatment. There are certainly many groups working on understanding the development of mutations in hopes of finding better treatments.

Is anything done differently when it comes to treating a recurrent case of MDS?

MDS, like all blood and bone marrow cancers, can go into remission and then recur. Once bone marrow and blood cancers recur, we don’t think of them as being curable by medical treatments. So when patients have recurrent or progressive MDS, we often explore the possibility of whether
an allogeneic stem cell transplant might be something appropriate for them. Not all patients are good candidates for a stem cell transplant, but many are.

If stem cell transplantation is the only cure for MDS, does that mean recurrent MDS cannot occur in someone who undergone a transplant and no longer has MDS symptoms?

It needs to be stressed that an allogeneic stem cell transplant is not a guaranteed cure. Not all transplants are successful. So, in fact, many patients will have recurrent MDS following a stem cell transplant. Efforts continue to try to lower the chance of MDS returning after a stem cell transplant, but still somewhere between one third and one half of patients will eventually have their MDS return even after a potentially curative stem cell transplantation. So stem cell transplants aren’t the answer for all patients or all types of MDS.

What do patients who are post-treatment most need to know about recurrent MDS? Is there anything they can do to lessen the chances of this occurring?

We don’t have really good answers here. I strongly encourage all patients and families to play active roles in monitoring their condition and frequently be seen and evaluated by their medical team. Blood cell counts have to be monitored because changes in these are often the fi rst sign of a recurring
MDS. Also, they should take the necessary steps improve and maintain their overall health. This means plenty of rest, staying physically active, and working towards a balanced and healthy diet. What we’ve found through the years is that patients who are in good overall physical health tend
to better tolerate different treatments. It is also important to maintain a very active dialog with your physician and treatment team to help manage the disease and to build a solid understanding of what is going on with your body and bone marrow so you are ready to face any changes in your bone marrow that may occur post-treatment.

What is the difference between de novo MDS and secondary MDS?

De novo MDS refers to an MDS that has arisen without an obvious or specifi c cause. Secondary MDS tend to have two general categories: the first is MDS that seem to have arisen or grown out of another bone marrow failure disorder or bone marrow cancer. For example, there are aplastic anemia patients with very low blood counts, and at times, we see a population of MDS cells that can develop. This may also occur related to other bone marrow problems like having an underlying  myeloproliferative disorder with a background of MDS cells as well.

The second defi nition relates to the MDS being related to previous cancer therapies, including chemotherapy and radiation therapy. So the language we use to describe the secondary MDS types has evolved over time into the “therapy-related MDS” and “MDS arising from or associated with another primary bone marrow disorder.” People tend to hear a bit more about the therapy-related MDS.

By what degree is secondary MDS less frequently seen than de novo MDS?

Secondary MDS makes up a small fraction of all the cases of MDS – many studies looking at the frequency suggest 5-15% of the cases are therapy-related.

What are the known risk factors for developing de novo secondary MDS?

The risk factors for therapy-related MDS really relate to the previous therapies that patients have undergone. Certain chemotherapies have a high incidence that are often associated with therapy-related MDS, and of course, radiation exposure is also felt to be a risk factor for developing MDS.