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When Rose Zumbiel was diagnosed with myelodysplastic syndrome at age 48, she was far from the average patient. Myelodysplastic syndrome, or MDS, tends to affect older individuals — average age at diagnosis: 71 — and occurs more often in men than women.
The condition can occur when stem cells in the bone marrow are damaged and may not properly mature into red blood cells that carry oxygen, white blood cells that fight infection or platelets that help blood to clot. In fact, until recently, MDS was sometimes called “preleukemia” because the disease can progress into acute leukemia.
Approximately 13,000 people in the United States are diagnosed with the disease each year.
“When I was diagnosed, they told me they did not even really have a name for what I had,” Zumbiel, now 69, recalls. “It was known as a rare blood disease.”
After beginning a regimen of low-dose aspirin to stave off heart disease, Zumbiel began to notice large bruises on her legs and thought the aspirin might be thinning her blood too much. Her family doctor ordered blood work, which came back normal. However, a second blood test several months later revealed a platelet count of 150,000 per microliter of blood, at the bottom of the accepted normal range of 150,000 to 400,000 per microliter. Eventually diagnosed with MDS by a hematologist, Zumbiel was left wondering how this happened to her.
EXAMINING LOW BLOOD COUNTS
“MDS is a result of damage to the DNA of the cells in the bone marrow. Those injuries accumulate during life,” says David P. Steensma, M.D., an associate professor of medicine at Harvard Medical School in Boston. “A 70-year-old person has more DNA changes than a 40-year-old, and a 40-year-old has more than a teenager. They occur randomly whenever a cell divides and DNA is copied, just as randomly as when medieval scribes used to transcribe manuscripts and accidently put the wrong letter in the wrong place. Most of the time, those mistakes have no major consquence, but, if by random chance the DNA is written in the wrong place on the wrong day, it can cause quite a dramatic change in bone marrow behavior — just like certain letter changes may change the meaning of a word.”
There are few clear risk factors for developing MDS, Steensma said. In addition to older age and male gender, prior treatment with chemotherapy or combination chemotherapy and radiation therapy may increase the likelihood of developing MDS, known as treatment-related MDS. Some evidence also indicates that genetic syndromes, smoking or environmental exposures, such as to the chemical benzene, can also increase risk.
Patients with low platelet counts (thrombocytopenia) might experience bruising, like Zumbiel did, or bleeding in the nose, gums or stool. According to Steensma, a low platelet count occurs in about one of every three cases of MDS and is the only dominant feature of the disease in 5 percent or fewer cases. “Low platelet counts are not a big problem until they get much lower, around 30,000 per microliter or below,” Steensma says.
The most common symptom of MDS is a reduced level of red blood cells, or anemia, seen in 70 to 75 percent of cases, says Thomas Prebet, M.D., Ph.D., an associate professor of hematology at Yale Cancer Center in New Haven, Connecticut. Symptoms of anemia include shortness of breath, unusual paleness and fatigue.
“Low red blood cell counts with larger-than-average red cells, called macrocytic anemia, is one of the hallmarks of MDS,” Prebet says. “More than two-thirds of patients with MDS will at one point of their disease require some transfusion of red blood cells.”
Joan Powell, 64, has become familiar with fatigue and transfusions since her diagnosis of MDS in 2014. Always a go-getter, Powell started consistently experiencing extreme fatigue and weakness. Her sister urged her to visit a doctor and get blood work done. The results revealed anemia, and the physician told her to go to the emergency department right away because she required a transfusion.
Normal hemoglobin levels are above 12 grams per deciliter for women and 13.5 grams for men. “My count was five,” Powell recalls. “I was in crisis mode. I was given three packs of blood, connected to a heart monitor and oxygen, and given a variety of tests. I was in the hospital for three days.”
“In these cases, having anemia is like living with a backpack of 50 pounds on your shoulders each minute of life,” Prebet says.

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Powell’s physicians ran a battery of tests in search of an explanation for her symptoms until they finally diagnosed her with MDS. “It was a shock to my world,” Powell says. “They told me it was not curable — treatable but not curable.”
Often, people with MDS have no symptoms and are diagnosed only after undergoing routine lab work. Sometimes diagnosis follows an infection in people found to have a low number of white blood cells called neutrophils, a condition called neutropenia, which increases risk of infection.
People with MDS may have issues with any one — or all three — of these types of blood counts.
TREATMENT FOR MDS

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The only potential cure for MDS is stem cell transplantation. However, this often requires a high-intensity preparative conditioning regimen, which limits the number of people healthy enough to undergo the procedure. Transplantation can be done for patients who are under age 75, are otherwise healthy and have a matched donor.
Usually, people with MDS undergo treatments to reduce or manage symptoms, known as palliative or supportive treatments. The use of specific therapies often depends on whether the disease is classified as lower or higher risk. This is based on several characteristics found in the blood and bone marrow, including the number of immature cells (called blasts) and blood counts, as well as the results of studies looking for chromosomal and genetic abnormalities.
“If a patient has lower-risk MDS with a low risk to progression of leukemia, we think the disease will potentially have a long duration and evolution, and we try to focus on the management of the cytopenias (a reduction in the number of blood cells) and delay more aggressive treatments,” Prebet says. “In higher-risk cases with a higher risk to progression of leukemia, we have to use active treatment more systematically and more quickly.”
Although Zumbiel’s platelet counts remained manageable for many years after her diagnosis, they eventually dropped below 30,000 per microliter, and her hematologist recommended a platelet transfusion.
“Unfortunately, the half-life of platelets is very short,” explains Kebede H. Begna, M.D., an assistant professor of medicine at Mayo Clinic in Rochester, Minnesota. “Even newly synthesized platelets only usually survive about 14 days, meaning that individuals may require multiple transfusions.”
Transfusions are often required in patients with low red blood cell counts, too. Powell calls the red blood cell transfusions she undergoes every 4 to 6 weeks her new normal. “My life has begun centering around MDS,” she says.
For each transfusion, she travels to the hospital for an 8- to 9-hour outpatient procedure. The frequent visits have made her close with the staff and nurses and opened her eyes to the generosity of people who donated the blood that flows into her veins with each transfusion, she says.
Frequent transfusion carries several risks, however. “Platelet transfusions can cause allergic reactions, fever or hives,” Steensma said. “Over time, recurrent platelet transfusion exposes the body again and again to foreign platelets and the body may start to form antibodies — that is called being platelet refractory or alloimmunized.” Alloimmunization can also occur in patients undergoing transfusions for red blood cells.
Patients who undergo multiple red blood cell transfusions per month also run the risk of developing iron overload, Prebet said. Excess iron can be stored in important organs such as the heart and liver and, down the road, impair function. Treatment for iron overload may depend on a person’s life expectancy. In people with lower-risk disease, iron overload can be treated with removal of the blood, or phlebotomy.
This cannot be done in patients who are anemic. In addition, two FDA-approved iron chelators are commonly used for anemia related to MDS. Intravenous Desferal (deferoxamine) is given via a pump, often during nighttime rest. The second iron chelator Deferasirox comes in two tablet forms: Exjade, dissolved in juice or water once daily, or Jadenu, taken once daily on an empty stomach or with a light meal.
White blood cells cannot be transfused, though. “White blood cells’ job is to recognize what is you and what is foreign, so if we put your white cells into me, they would be very confused and vice versa,” Steensma says.
For low white blood cell counts, recombinant human granulocyte colony-stimulating factor or recombinant human granulocyte–macrophage colony-stimulating factor can be used to stimulate production of a patient’s own white blood cells.
Low-intensity chemotherapy may also be given to patients with MDS in an attempt to change bone marrow cells so they produce normal red blood cells, white blood cells and platelets.
After undergoing a platelet transfusion, Zumbiel began receiving Vidaza (azacitidine), a low-intensity chemotherapy shown to increase survival and improve quality of life in patients with MDS. Six months of treatment brought her platelet count back up to about 57,000 per microliter. The two other FDA-approved chemotherapies used for MDS are Dacogen (decitabine) and Revlimid (lenalidomide).
In between transfusions, Powell takes a hematopoietic growth factor called Procrit. Hematopoietic growth factors promote growth and development of blood cells but are not always effective in people with MDS.
HOPEFUL FOR THE FUTURE
Despite the promising treatments being explored in oncology, it is difficult to know what the future holds for patients with MDS. “There have been some exciting new drugs in solid tumors, like immune checkpoint inhibitors, but those tend not to be as effective in MDS or leukemia, especially as single agents,” Steensma says.
More work also needs to be done toward understanding the disease and identifying genetic mutations that might provide a target for treatment. “In MDS, there are more than 40 different genes that have been found to be mutated in the bone marrow, and no single gene is mutated in more than 20 percent of patients,” Steensma says. “That is a real problem for designing targeted therapies, since no single drug is likely to work for a large proportion of patients.”
Begna hopes to begin to more effectively harness next-generation sequencing — now used to classify patients and provide prognosis — to understand the characteristics of the different forms of leukemia cells associated with MDS.

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Two drugs under study, sotatercept and luspatercept, trigger a hematologic response, improving red cell counts in about 60 percent of patients with mutations in the transforming growth factor–beta signaling pathway, according to Prebet. “It will not be used for all patients, but in patients with MDS harboring ring sideroblasts and/or an SF3B1 mutation, there is some real hope that this medication will have some efficacy,” he says.
Like MDS treatments, Powell and Zumbiel both face uncertain futures.
Powell’s disease is currently considered lower risk, and her experience has inspired her to become more active in the MDS community. She is involved with the Aplastic Anemia and MDS International Foundation’s Patient Advisory Committee on Clinical Trials (PAACT+), which was designed to bring a patient voice to the industry and academic researchers focusing on rare bone marrow disorders.
“In this group, we are able to have well-rounded conversations with patients, caregivers, doctors, nurses and researchers to let people know that this disease exists [and] what it is like and to find out more about what they are doing to help us,” Powell says.
After living for two decades with MDS, Zumbiel has begun to consider herself cured. Shortly after receiving definitive confirmation of her MDS diagnosis with chromosomal tests, her platelet counts began to recover, with her most recent counts upward of 180,000 per microliter.

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She credits her physician and her prayers to Saint Padre Pio for her recovery. “I am always a mess when I go for my blood counts, but you have to just trust your doctors and pray that you are strong enough to get through it,” Zumbiel said. “Whatever happens, you can take it!”