Treatment of Myelodysplastic Syndromes (MDS)

While all conditions classified as myelodysplastic syndrome (MDS) impact the way bone marrow functions, they encompass a variety of disorders. As a result, treatment depends on the type of MDS a person is experiencing.

Not all MDS therapies are appropriate for every patient with MDS. Options for MDS treatment include supportive care, low-intensity therapy, high-intensity therapy, and/or clinical trials.

Treatment Considerations

When discussing your MDS treatment plan with your healthcare provider, the so-called patient-related factors can be very important. Examples of patient-related factors include the following:

• How you were getting along with daily activities before the MDS diagnosis
• Other medical conditions you have
• Your age
• The financial costs of various treatments
• Which risks of treatment are acceptable to you

Characteristics of your particular form of MDS are also very important. Examples of specific characteristics and findings include the following:

• Markers and results of genetic testing of your bone marrow, which help determine the options available to you, the likelihood that your MDS will progress to leukemia, and what outcomes might be expected from certain therapies.
• How your MDS is impacting the number of healthy cells in your circulating blood
• How severe your disease is in terms of the number of immature “blast” cells in your marrow

Your goals for what you want to get out of treatment also factor into the plan. Examples of differing treatment goals include the following:

• Just to feel better
• Limit your need to have so many transfusions
• Improve your anemia, neutropenia, and thrombocytopenia
• Achieve a remission
• Cure your MDS

Watch and Wait

For patients who have a low-risk MDS as determined by the International Prognostic Scoring System, or IPSS, and stable complete blood counts (CBC), sometimes the best approach to therapy is observation and support, as needed.

In this case, you will need to be monitored for changes in your marrow that might indicate the progression of the disease. Regular CBCs, as well as bone marrow aspirate and biopsy, can be a part of monitoring.

Supportive Care

Supportive care refers to therapies used to treat and manage the MDS; these treatments can greatly improve a person's condition, but they stop short of actually attacking the cells causing the MDS.

Transfusions

If your blood counts begin to fall and you experience symptoms, you may benefit from a transfusion of red blood cells or platelets. The decision to have a transfusion will depend on other medical conditions you have and how you are feeling.

Iron Overload and Chelation Therapy

If you begin to require multiple blood transfusions each month, you may be at risk for developing a condition called iron overload. The high levels of iron in red blood cell transfusions can cause an increase in the iron stores in your body. Such high levels of iron can actually damage your organs.

Healthcare providers can treat and prevent iron overload from multiple transfusions using medications called iron chelators, which includes an oral therapy, deferasirox (Exjade), or an infusion called deferoxamine mesylate (Desferal). Practice guidelines by the National Comprehensive Cancer Network, or NCCN, offer criteria your healthcare provider can use to decide if you need iron chelation therapy.

Growth Factors

Certain people with MDS anemia may benefit from receiving growth factors medications called erythropoietin stimulation agents or proteins (ESAs). Examples of ESAs include epoetin alfa (Eprex, Procrit or Epogen) or the longer-acting darbepoetin alfa (Aranesp). These medications are given as an injection into your fatty tissue (subcutaneous injection). While these drugs are not helpful for all MDS patients, they may help to prevent blood transfusions in some.

Your healthcare provider may offer to start you on a colony stimulating factor, such as G-CSF (Neupogen) or GM-CSF (leukine), if your white blood cell count becomes low as a result of your MDS. Colony-stimulating factors help to boost your body to produce more illness fighting white blood cells called neutrophils. If your neutrophil counts are low, you are at a higher risk of developing a dangerous infection. Keep an eye out for any signs of infection or fever, and see a healthcare provider as soon as possible if you are concerned.

Low-Intensity Therapy

Low-intensity therapy refers to the use of low-intensity chemotherapy or agents known as biologic response modifiers. These treatments are mainly provided in the outpatient setting, but some of them may require supportive care or occasional hospitalization afterward, for instance, to treat a resultant infection.

Epigenetic Therapy

A group of medications called hypomethylating or demethylating agents are the newest weapons in the fight against MDS.

Azacitidine (Vidaza) has been approved by the FDA for use in all French-American-British (FAB) classifications and all IPSS risk categories of MDS.  This medication is generally given as a subcutaneous injection for 7 days in a row, every 28 days for at least 4-6 cycles. Studies of azacitidine have shown that approximately 50% of higher-risk MDS patients notice improvements and increased quality of life. Azacitidine often causes an initial drop in blood cell counts that may not recover until after the first one or two cycles.

Another type of hypomethylating agent that is used in therapy for MDS is decitabine (Dacogen). Very similar in structure to azacitidine, it is also FDA approved for all types of MDS. The treatment regimen was generally associated with low-intensity-type toxicities, and so it is also considered to be low-intensity therapy. Decitabine can be given intravenously or subcutaneously.

Immunosuppressive Therapy and Biologic Response Modifiers

In MDS, red blood cells, white blood cells and platelets are killed or die before they are mature enough to be released from the bone marrow into the bloodstream. In some cases, lymphocytes (a type of white blood cell) are responsible for this. For those patients, it may be effective to use a therapy that impacts the immune system.

Non–chemotherapy, low-intensity agents (biologic response modifiers) include anti-thymocyte globulin (ATG), cyclosporine, thalidomide, lenalidomide, anti-tumor necrosis factor receptor fusion protein, and vitamin D analogs. All of these have shown at least some in early trials, but many are in need of more clinical trials to understand effectiveness in different types of MDS.

People who have a particular type of MDS called 5q- syndrome, in which there is a genetic defect in chromosome 5, may have a response to a drug called lenalidomide (Revlimid). Typically, lenalidomide is used in patients with a low or low-intermediate IPSS risk MDS that are red blood cell transfusion dependent. In studies of lenalidomide, many patients had reduced transfusion requirements -- almost 70%, in fact -- but continued to experience low platelet and neutrophil counts. The benefits of treating higher-risk MDS, or subtypes other than 5q- syndrome with lenalidomide are still being studied.

High-Intensity Therapy

Chemotherapy

Certain patients with higher risk MDS, or FAB types RAEB and RAEB-T, may be treated with intensive chemotherapy. This chemotherapy, the same type that is used in the treatment of acute myelogenous leukemia (AML), aims to destroy the population of abnormal cells in the bone marrow that leads to MDS.

While chemotherapy may be beneficial in some MDS patients, it is important to consider that older patients with other medical conditions face additional risks. The potential benefits of the therapy must outweigh the risk involved.

Research is ongoing to compare the outcomes of intensive chemotherapy over those of azacitidine or decitabine.

Stem Cell Transplant

Patients with high-risk IPSS MDS may be able to achieve the cure of their disease with allogeneic stem cell transplantation. Unfortunately, the high-risk nature of this procedure limits its use. In fact, allogeneic stem cell transplant can have a treatment-related death rate of up to 30%. Therefore, this therapy is typically only used in younger patients who are in good health.

Current studies are investigating the role of non-myeloablative so-called “mini” transplants in older patients with MDS. While these types of transplants have traditionally been thought of as less effective than standard transplants, their decreased toxicity may make them an option for patients who would otherwise be ineligible.

Summary

Because of the different types of MDS and different patient types, there is no one-size-fits-all treatment. Therefore it is important for MDS patients to discuss all options with their healthcare team, and find a therapy that will provide them with the best benefits with the least amount of toxicity.

Clinical trials with newer therapies for MDS are underway, so stay tuned. For instance, ​ruxolitinib (Jakafi) is being investigated for the treatment of patients with low or intermediate-1 risk MDS.