myelodysplastic syndromes (MDS) | Page 2 | Aplastic Anemia and MDS International Foundation

myelodysplastic syndromes (MDS)

Research Overview - Recent Past Progress and Projections for the Near-Term

Dr. Alan List is the president and CEO of Moffitt Cancer Center in Tampa, Florida. He is a senior member in the Department of Malignant Hematology and the Experimental Therapeutics Program. Prior to joining Moffi tt in 2003, Dr. List was a professor of medicine and director of the Leukemia and

Interview: 

Patients want to keep up to date with MDS research, but there are distinct phases —basic, translational, and clinical research. Can you explain what part of the process each area of research represents -- and can activity in one phase of research affect another?

For basic research, there are other terms we also use – such as preclinical, meaning research that precedes clinical testing, or bench research – research conducted in the laboratory. But basic research means that one is studying the features involved in the biology of the disease. This is generally done in a laboratory setting and may involve animal models.

One of the challenges we have in MDS basic research is that unlike solid tumors and leukemia, where there are cell lines that are propagated from the disease, we do not have reliable cells lines from MDS. With MDS, the bone marrow cells are often destined to die, which is the reason for peripheral blood cytopenias. So we rely upon studying fresh patient bone marrow specimens for that part of research. Basic research can involve evaluating molecular features of the disease. This would involve examining those nuclear components that drive the disease phenotype, such as the DNA, the expression of genes, and the proteins that are made from those genes. Or, we focus on biologic processes that are deregulated to see if there is a way to understand the disease biology and pathogenesis. This means understanding how the disease came to be, or also understanding what the weak point – the Achilles heel-- may be, so you can exploit that for a possible treatment.

Translational research is what bridges the basic discoveries to clinical research. It means determining the potential clinical application of the laboratory findings, in other words, testing them further for clinical development. Before proceeding to the clinical phase, you have to have assurance that you have a relevant target, that there is sufficient evidence that it will be relevant in the clinical setting, and that these may have therapeutic value. Translational research may involve looking at gene mutations across the DNA. If specific gene mutations are discovered in the basic side, what does that mean for the patient? We can look at outcomes for patients who have had those gene mutations to see their prognostic relevance. Or, the translational science may involve studying the mutation that turns on the activity of an enzyme in a critical regulatory pathway. With that, we want to know if we can inhibit this enzyme, and can we further discern its potential therapeutic benefit by testing such an inhibitor in an animal model with minimal toxicity. Then, if all looks good, it proceeds to further animal studies to identify possible side eff ects before the next stage which is clinical research. Clinical research involves the testing of a potential new therapeutic compound in individuals who have the disease.

There is a bi-directional influence at work between the different phases of research. Of course something that’s discovered in the laboratory may enter into clinical testing in the scenario just described. But the opposite also can occur. In the clinic, you can have a discovery that takes you back to further science basic research. Lenalidomide is a good example of this. In the laboratory, we saw it affected angiogenesis, which is important in MDS. But after the translational studies and the clinical phase, we found in our first MDS trial that there was a subset of MDS, i.e., those cases with chromosome 5q deletion, where it worked exceptionally well to suppress the clone. It was not until after its FDA approval, that we went back to the lab to find out what are the targets in deletion 5q that allowed lenalidomide to suppress the clone. Later, as patients failed lenalidomide, we went back and studied the mechanism underlying the development of resistance to the drug that was acquired over time. This is a good example why it is important to have the clinical investigators working closely with the basic scientists.

Have there been particular recent trends or directions in MDS research that have helped bring it to its present status?

When you look back over the last six to eight years, research gave rise to a much a better understanding of the biology underlying MDS and especially the molecular biology of the disease. Some of this was made possible by the sequencing of the human genome in 2000 and then innovation in technology that allows us now to survey the reading frames of the human genome quickly and at a reasonable price. This has in more recent years provided new insight to previously unrecognized gene mutations and learn more about which mutations may be driving the disease. We hope that this over time will translate into new therapeutics that will be specific to the genetic makeup of a given individual’s disease.

Another new area of focus is the role of innate immunity and its chronic activation in MDS. Innate immunity, or the so- called non-specifi c immune system, is normally the fi rst line of defense against host infection. However, in some diseases it is chronically activated, such as autoimmune disorders like rheumatoid arthritis. Recognition of its role in MDS led to a lot of new work in the laboratory to identity potentially new targets that can be exploited therapeutically. So it is two particular trends – the advances in understanding the molecular biology of MDS and the role of the activation of innate immunity.

What are some current themes that you fi nd intriguing and feel have promise to shape future directions for MDS research?

In the last few years, we have been able to fi nd out more about some of the signaling pathways that are aberrantly activated in the MDS bone marrow cells that contribute to their early death, or impaired survival. One of those examples is a signaling pathway involving the TGF–beta family members that acts to suppress normal blood development. So discovering that this pathway is overactive in MDS is leading to new drugs that are in clinical development that interfere with the signaling of these aberrant pathways. One of agents is sotatercept, which neutralizes that activity of the TGF–beta family member called activin-A. Another one is an inhibitor of the TGF-beta Type 2 receptor made by Lilly. One trial has already started, and the second agent will begin clinical testing in MDS patients later this year.

What we’ve also learned is that activation of these signaling pathways occurs as a consequence of chronic activation of innate immunity. That has allowed the identifi cation of a number of new targets that lie upstream of TGF-beta that that can be exploited therapeutically. Certain innate immune effector cells get activated, called myeloid derived suppressor cells (MDSC) that is driven by high levels of a soluble infl ammatory protein and stimulant of MDSC, called S100A9. We have been able to dissect the components of this signaling axis to get to the more proximal part and bring along new therapeutics that might be eff ective. That’s a good example of where things are currently moving in MDS research.

Were there particular presentations at ASH 2013 you found be of particular interest?

At ASH, there were interesting things presented, including a study of oral rigosertib given to patients with lower-risk MDS, where they found that a good number of anemic patients who were dependent on transfusions became free of needing transfusions. That will go through further clinical development to test and validate the activity of the drug in this setting. I also was interested in a new drug – an inhibitor of energy metabolism targeting an enzyme called pyruvate dehydrogenase.

This wasn’t just in MDS, but in all advanced hematologic malignancies. In this study, they had three MDS patients in the trial that all had major responses, even one complete response. This agent, CPI-613 by Cornerstone Pharmaceuticals, will be interesting to follow to see how it develops further. There will be more about this at future meetings.

Moffitt recently announced results of a study (Wei) on control mechanisms for the development of MDS. What are ‘control mechanisms’ and what potential does this new study have for affecting the course of future investigation?

This relates to what I mentioned earlier about innate immunity activation. Dr. Wei is an immunologist that works closely with me in MDS. He had been studying one of the major eff ectors of suppression of immune response–the myeloid derived suppressor cells, known as MDSCs. It turns out that these are markedly expanded and activated in the bone marrow of MDS patients. They can account for as much as 30% of the cells in the bone marrow. What he showed is that they are directly suppressing blood production and causing the death of the bone marrow precursors, and they also are the source of all the inflammatory cytokines that we see in the bone marrow and blood of MDS patients.

What’s important is that if we remove those cells from the bone marrow, there is a restoration of the blood forming capacity in the laboratory. Of greater importance is the discovery of a soluble infl ammatory protein that triggers these cells to expand and grow in patients with MDS. It is S100A9, levels of which are more than fi vefold elevated in the plasma of MDS patients. It directly activates the MDSCs through a receptor called TLR-4 and also directly binds to white blood cell precursors in the bone marrow to activate their cell death. Knowing that, we next want to know if this is a potential cause or mediator driving development of MDS.

What was done next was the creation a mouse model that over expressed S100A9, making excess levels of the protein that approximated what was seen in MDS patients. These mice developed MDS within six months, with pancytopenia and bone marrow cells that were profoundly dysplastic, the hallmark of MDS. Now we know that that protein alone can drive the entire phenotype. So with this data, we have a new target that we can potentially exploit therapeutically by trying to neutralize it. Or, we can work on it from a diff erent perspective, that is, by blocking the signaling that it triggers This gets us closer to a driving factor of what causes MDS.

Because of the time it takes for research to have a direct impact on treatment, what is most important for patients who follow MDS research keep in mind?

We all would like to see the process accelerated – so we can test new ideas faster and get the right drugs in to the hands of the treating physicians and patients as fast as we can. It is a process that often moves slowly, taking many years. Patients may read about encouraging progress, but not realize the potential benefi t of a new therapy for many years. Patients can help accelerate the process is to consider participating in clinical trials when it’s right for them. That is precisely what moves the fi eld faster! None of the drugs we are using now would be there unless patients had participated in trials, and helped us to prove their activity and effectiveness.

Education Topics: 

Research Retrospective for AA&MDSIF 30th Anniversary - Dr. Mikkael Sekeres

Interview: 

What do you think are the most impressive or significant advances in MDS research and treatment over the last five years since our 25th anniversary? If you extend this back 30 years, to 1983 (when AA&MDSIF was founded), what does the longer perspective indicate?

Starting with the 30 year perspective, the two greatest advances in MDS over the past 30 years are, first, the understanding of the disease on a population level and on a biologic level. In 1983, we really weren’t sure how many people in the US and worldwide actually had myelodysplastic syndromes. Up to that point, there had only been a few hundred patients who had been reported, and it was not until database studies began and the US government in 2001 began to formally track MDS that we realized how many people actually are living with the disorder in the US. We now know that approximately 15,000 people in the US are diagnosed with MDS annually, and anywhere from 50,000 to 100,000 people in the US are living with MDS at a given time. So, especially in the past 15 years, we have gained much knowledge that we didn’t have before.

We also have realized how incredibly complex MDS really is from a biological perspective. We may divide it into four or five subtypes, or even 10 subtypes (depending on the classification system used), but MDS really represents hundred of subtypes. That has helped in our thinking about prognosis and therapies for MDS.

A second area that has advanced in the past 30 years is for developing therapies specifically for MDS. It used to be that if you were diagnosed, your only options were blood transfusions or platelet transfusions. Now, we have three FDA-approved drugs for MDS and dozens of drugs that are being testing in clinical trials.  We have also moved into an era of combination therapies for MDS, and more patients each year are receiving curative therapy in the form of a bone marrow transplant for MDS. There has been a remarkable amount of progress in that time.

In the past five years, a study published in 2009 demonstrated that for the first time, an MDS drug, azacitidine, has provided a survival advantage. We have a rising number patients every year who are receiving a bone marrow transplant, and for the first time, there is recognition by Medicare of the use of bone marrow transplant in patients with MDS. There has been an explosion of information about the genetic basis for MDS. It is to the point now where we can detect genetic/molecular abnormalities in 80% of people with MDS.

At the same time, in the last five years, have there been setbacks or instances where you feel progress has not kept up with general expectations or predictions made five years ago?

Five years ago, I felt there would be another drug approved since the last one in 2006, and that has been a disappointment. Also, the flip side to our expanding knowledge of MDS is that we recognize that MDS represents a much more complex collection of diseases, that therapies therefore will never be “one size fits all,” and that truly targeted approaches will therefore only be applicable to a minority of MDS patients.

With MDS, is there a consensus on overall direction research will take or needs to take --- or is this as diverse as the areas of interest that individual researchers or research teams have?

We can agree on general themes for new investigations in MDS. We need to develop new drugs, and they should be targeted to these molecular abnormalities we are now detecting. We should be able to use these molecular abnormalities to predict which existing drugs are more or less likely to work in someone with MDS. We need to understand more about the impact of the disease on the population. Also, we need to continue to perform very complex analyses, like genomic analyses, to continue to understand the biology of the disease.

In 2009, we asked a similar panel if generalist hematologists/oncologists were adequately informed about bone marrow failure disease, and what could be done to bridge any gap between the generalists and researchers/specialists. What are your thoughts in 2013?

I think this is the same as five years ago—we must continue to emphasize to general internists or family medicine doctors that anemias or other cytopenias in older adults are not just a normal consequence of aging.  These abnormalities should be explored and patients should be referred to hematologists. This may increase even further the prevalence of MDS in the US, and treatment options exist regardless of the age of a patient.

About treatment, we have no misperception about the challenges patients face traveling long distances to a specialized treatment center such as Cleveland Clinic or similar ones across the country to receive therapy. Our focus is to develop a treatment plan over one or two visits and then maximize the patient’s quality of life by having the routine or ongoing therapy be conducted closer to their home.

Education Topics: 

ASH 2012 - Reviewing MDS Progress from Research and Clinical Perspectives

Dr. Sekeres is Director, Leukemia Program, Department of Hematologic Oncology and Blood Disorders, at the Cleveland Clinic Taussig Cancer Institute Cleveland, Ohio. In this interview, Dr. Sekeres reviews some of the more significant clinical and treatment-related findings presented at the December 2012 American Society of Hematology (ASH) Annual Meeting that would be of interest to MDS patients.

Interview: 

Were there any presentations at ASH 2012 on the clinical aspects of MDS that you think patients might find particularly interesting?

There is some evolution in the classification systems used for MDS. For years, we have used the International Prognostic Scoring System (IPSS) as the standard system for prognostication.  IPSS risk classifications help predict survival and determine what kinds of treatments will be used. The IPSS was recently revised – and there is a new system called the IPSS-R, signifying this revision. There were a number of abstracts presented that validated the IPSS-R, applying it to MDS patients in international medical centers to see if it could accurately predict survival in those patient groups. In fact, it worked in a variety of patient groups around the world!

One abstract that interested me was from a French group that took the IPSS-R and applied it specifically to patients who were on azacitidine (Vidaza®). This is important because both the IPSS and IPSS-R were developed around patients who did not receive any therapy for their MDS. So the goal was to find out if either of these systems could be used in patients who are receiving active treatment for their MDS. This French group showed that IPSS-R can be used to predict survival in patients who are treated with azacitidine, thus it is valid for a patient who is about to start azacitidine to use IPSS-R to predict how long that person will live.

However, keep in mind that IPSS-R is a new system, and doctors have to get used to using it just as much as patients need to get used to using it. In time, it may come to replace the IPSS,  but that would be a least a couple of years away, and quite possibly longer, before it is widely used.

What presentations on specific therapies did you find interesting?

One interesting report was an update about the drug romiplostin (Nplate®) which has been FDA-approved for patients with idiopathic thrombocytopenic purpura (ITP). Patients with ITP have a low platelet count, not because of a bone marrow problem, but due to an autoimmune problem in which the immune system is attacking the platelets.

This drug had been earlier studied in patients with MDS who also have a low platelet count and in the largest study, it was found that romiplostin did improve platelet counts in about 40 to 50% of MDS patients with low platelet counts.  This is good news, since we now have a drug that works for platelets in the way that growth factors like erythropoietin (Procrit®) or darbepoetin (Aranesp®) work for low red blood cell counts. Romiplostin can be considered a platelet growth factor, also called a thrombopoietic growth factor (TPO).

The problem was that while the randomized Phase 2 study was in progress, the data safety and monitoring board noticed that the patients receiving romiplostin seemed to have an increased blast percentage, and some of these patients progressed to leukemia. So the study was closed earlier than would have normally happened, and the last patients admitted to the study could not be fully evaluated as to whether they responded to romiplostin.

What I found significant was that the follow-up presented this year of patients from the original study who did or did not receive romiplostim reported that the percentage of patients progressing to leukemia was no different in the romiplostin group and the group treated with a placebo. In other words, with additional follow-up, there actually did not appear to be a higher risk of leukemia among MDS patients treated with romiplostim, compared to MDS patients not treated with the drug.

In a companion study from our group, we developed and validated a model to predict response in patients treated with romiplostin, based on prior platelet transfusion needs and blood levels of the hormone TPO. So just as there is a model to predict patient response for red blood cell growth factors such as erythropoietin, we now have a model to predict patient response with rominplostin. 

One of the more common drugs used to treat MDS is azacitidine, or Vidaza®. This is given as a shot under the skin or into the vein through an IV line. More recently, a pill form of azacitidine has been developed and studied in patients with lower-risk MDS. A clinical trial update on oral azacitidine in lower-risk MDS patients showed that approximately 40-50% of patients had improvements in their blood counts and/or in their requirements for red blood cell transfusions. This is an important preliminary study that has set the stage for the study that will determine whether oral administration of azacitidine will be FDA approved for treatment of lower-risk MDS.

What do you think patients would most want to know about the state of MDS treatment as it was presented and discussed at ASH 2012?

As we get better at discovering and defining the genetic underpinnings of MDS, the next step will be to see if patients with certain genetic abnormalities are more likely to respond to some drugs than other ones.  We are becoming more sophisticated at selecting patients who are more likely to respond to a certain drug.

There were presentations on new genetic abnormalities found in MDS, some validating findings previously reported and some identifying new findings. One of the major ones was an international collaboration reporting on over 700 patients with MDS, MDS/MPN overlap, or AML that had evolved from MDS. This study found that 20% of the patients had a genetic abnormality (called SETBP1) that happens to be the same found in a rare congenital syndrome of infants born with retardation and skeletal abnormalities. This was typical of discoveries in MDS presented at ASH 2012.

What do you think MDS patients would most want to know about the state of research as it was presented and discussed at ASH 2012?

I think it is important to point out that the quality and number of presentations on MDS were higher at this meeting than any ASH meeting I have attended over the past 20 years. Patients should fi nd it encouraging that there is so much good work going on in this fi eld. Although it will take time for these new discoveries to be translated into improvements in diagnosis and treatment for MDS, there is good reason to be optimistic that outcomes for our patients will improve in the coming years.

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.

Treating MDS Toolkit and Diagnostic Spectrum Reference Cards - Interest Form

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