“I was starting my second batch of kids,” said Riegel, 63. “I really wasn’t planning on checking out early.”

Riegel has a 10 year old daughter, as well as a daughter who is 34 and a son who is 32 from his first marriage. With the prospect of myelodysplastic syndromes (MDS) looming, Riegel said he and his wife took the news very seriously and immediately started charting his blood counts.

A Vietnam veteran born in St. Louis, Riegel was living in Florida when he was originally diagnosed.

After being referred to hematologists and oncologists, Riegel’s hematologist insisted on a bone marrow biopsy. At that point, like so many MDS patients, Riegel was diagnosed with a disease he had never heard of.

“[My hematologist] explicitly told me not to go on the Internet, but of course I went to the Internet,” said Riegel. “For a while, I was really frightened.”

At the time of his diagnosis, Riegel was a department chair at Florida Atlantic University, but the fatigue from MDS increased until he decided he could no longer handle the stress of administrative duties for 12 months out of the year. Instead, his wife secured an administrative position at Missouri State University, and Riegel obtained a nine month teaching position there.

Riegel has taught at multiple universities, including the University of Guelph in Guelph, Ontario and Washington State University, as well as Florida Atlantic University and Missouri State University. He specializes in tourism marketing, destination development, and the business end of hospitality.

“I like teaching. I like doing research. I like the academic life,” Riegel said.

But MDS has definitely impacted his career. He has cut back to a nine month teaching schedule because physically teaching classes has become exhausting. In addition, Riegel now only teaches one or two classes in person and teaches as many as possible online.

One aspect of MDS that Riegel finds most frustrating is the subtlety of the disease.

“Let’s say you have really aggressive cancer or something like that, there’s immediate stuff to deal with,” Riegel said. “At least in my experience, this is sort of a gradual deterioration, and that’s so subtle sometimes.”

During a physical last year, Riegel’s doctor discovered melanoma on Riegel’s nose, and right away he was able to take steps to get it removed. However, there is no such quick fix with MDS.

Riegel is undergoing supportive care, and his blood counts are stable. However, he is too old for a bone marrow transplant, and due to a high concentration of iron in his blood, he cannot receive transfusions.

Additionally, Riegel has found subtle evidence that his energy has decreased. He can no longer climb multiple flights of stairs, and he now does one of his favorite chores, mowing the grass, over multiple days.

Although he has been experiencing changes in energy level, Riegel works to keep busy. Last summer was the first that he did not work in 20 years, and he admits his biggest mistake was allowing himself to become bored. This summer, he is working on writing and other academic responsibilities. He has planned to work on more than he will probably be able to complete, he admitted.

“I would hate to have the degree of disability to where I couldn’t work, and I know a lot of people who are at that stage. I’m fortunate to have the job I do,” said Riegel.

While the impact of MDS on Riegel’s life has been gradual, his response has been gradual as well, as he has eventually come to accept the reality. He suggests that dealing with MDS is a process that takes time.

“I think you’ve just got to somehow come to terms with it and realize it may shorten your life, but it may not, especially for those of us who were diagnosed young,” said Riegel. “Just figure out a way to go about your business.”

But Riegel above all maintains a level of perspective: “All that being said, it could be a lot worse.”

Researchers concluded that age alone should not be the deciding factor for treatment choice and that more elderly patients should be considered for targeted chemotherapies, such as Vidaza.

Elderly MDS patients generally have limited treatment options due to other age-related diseases, functional impairment, and poor tolerability or ineffectiveness of available therapies. Doctors may also be reluctant to actively treat MDS in this patient population. In addition, there is currently little data available showing improvement in survival in these patients if they receive treatment.

Vidaza is approved in the United States for all types of MDS patients. It generally delays disease progression of MDS to acute myeloid leukemia and improves overall survival in patients with higher-risk MDS.

In their analysis of an earlier Vidaza trial, researchers examined efficacy and side effects of Vidaza treatment in patients ages 75 years and older with higher-risk MDS.

Of the 87 elderly patients in the study, 38 received Vidaza treatment. They were given 75 mg/m² of Vidaza per day, injected below the skin, for seven days every 28 days.  Patients received a minimum of six Vidaza cycles, with 7.5 being the median number of Vidaza cycles.

Those patients who did not receive Vidaza treatment were assigned to one of three potential conventional care regimens: best supportive care, which included blood transfusions and antibiotics; low-dose chemotherapy; and intensive chemotherapy.

Researchers found that at two years, 55 percent of elderly patients who received Vidaza were alive compared to 15 percent who received conventional care regimens.

At the median follow-up of 17.7 months, the median overall survival of the Vidaza treatment group was not reached. The median overall survival of the conventional care regimen group was 10.8 months.

Of the patients who were dependent on blood transfusions at the beginning of the study, 43 percent of patients on Vidaza achieved transfusion independence compared to 22 percent of patients who received conventional care.

Vidaza was generally well tolerated. Side effects were similar in this patient population compared to patients younger than 75 years. The most common side effects were low platelet counts, low white blood cell counts, and infection for both the Vidaza treatment group and the conventional care regimen group.

Patients experienced Vidaza-related side effects during early treatment cycles. Side effects decreased with continued dosing.

For more information, please see the study in Critical Reviews in Oncology/Hematology (abstract) or a previous Beacon article about Vidaza treatments for elderly MDS patients.

Whether from his time fighting in the Vietnam War or teaching students the fundamentals of computer science and mathematics over 40 years as an adjunct professor at numerous Florida universities, Macfarlane is a man who is not afraid to confront tough situations. This includes his diagnosis with myelodysplastic syndromes (MDS).

It was May 2001 when Macfarlane’s private doctor first told him there might be something wrong. After running a few tests, the doctor told Macfarlane his blood cells were irregular.

“My red blood cells were the wrong size and the wrong shape,” Macfarlane told The MDS Beacon. Macfarlane’s doctor told him, “I suspect you either have leukemia or MDS,” to which Macfarlane said, “Leukemia doesn’t sound good,” but his doctor said, “It’s better than MDS because they can treat it.”

However, Macfarlane’s oncologist could not make a definitive diagnosis without a bone marrow biopsy, a procedure Macfarlane was skeptical about from the beginning.

Macfarlane recalled saying to his doctor, “Let me get this right: you want to hurt me to satisfy your curiosity?” He declined, deciding to put it off as long as possible. For Macfarlane, that meant four years.

Although he noticed he was becoming more tired, Macfarlane said what really alerted him to the fact that something might be seriously wrong was not a doctor’s visit. Instead, it was when the blood bank would no longer accept his blood. He was told his blood was too anemic.

“That’s not possible,” Macfarlane said. “There’s nothing red and dead that I don’t want to eat.”

Macfarlane has been donating blood since returning from Vietnam, calling himself a “multi-gallon blood donor.” If the blood bank was rejecting his blood, he decided something must really be wrong.

By 2005, his general fatigue had increased enough that ignoring the disease was no longer an option. He finally relented to the biopsy, which confirmed that Macfarlane’s disease was indeed MDS.

Macfarlane took the diagnosis as a challenge.

“My doctor told me I had two to three years to live,” Macfarlane said. “I’m going to prove that he’s a liar.”

With the prospect of fighting MDS looming, Macfarlane decided to move his life and career outdoors. Roughly a year after his diagnosis with MDS, Macfarlane told the university where he was teaching that he was not coming back. He opened a lawn maintenance company instead.

The decision resulted from Macfarlane’s love for the outdoors. “If I had my life to live over again, I would have studied biological sciences instead of mathematics and computer science, and I would have been a game warden because I want to be outdoors,” he said.

Although he enjoyed his lawn maintenance company, his MDS made overseeing the new business nearly impossible. “It’s a bad move when you have MDS. If you’re short of breath, [lawn care] is sort of the wrong business to be in,” Macfarlane admitted.

Luckily, Macfarlane’s younger son came back from Bible College, where he was studying to be a minister, and offered to run the business. Macfarlane did not hesitate. “I said, ‘That’s fine son, I want to go hunting,’ and that’s all I’ve done for the last three years. I was in the woods.”

Macfarlane has also been focusing his energy on his efforts to attain disability benefits for his MDS from the Veteran’s Administration (VA).

Macfarlane volunteered for duty in the Vietnam War in 1965 and served for 13 months as a sergeant for the United States Air Force security service. Macfarlane believes that his MDS was caused by his service in Vietnam and his exposure to the chemical Agent Orange.

Following his diagnosis, he learned while doing research into MDS that there might be a link between Agent Orange exposure and MDS. For MacFarlane, such a correlation is serious, since his exposure to the chemical while in Vietnam was high.

“The marines used Agent Orange all the time to beat back the bush. I was exposed pretty much all the time I was there. When the planes would fly over and spray it on you, you just sort of wiped it off,” Macfarlane said.

When Macfarlane approached the VA with his private oncologist’s diagnosis, the first thing he wanted to know was why his MDS had not been diagnosed sooner. He had been undergoing blood work for four years for his diabetes, but his VA doctor had never mentioned MDS.

Now, Macfarlane is working to obtain VA benefits in a system he calls “arbitrary and very, very random.”

The Board of Veteran Appeals ruled that Macfarlane’s MDS was caused by exposure to Agent Orange during his time in Vietnam. However, Macfarlane’s regional VA office in St. Petersburg, which decides the level of disability to award, ruled that Macfarlane’s disease is only a difficult form of anemia and, therefore, denied him disability.

For Macfarlane, the goal is to get MDS classified as a presumptive disease. Currently, the VA lists a number of diseases as presumptively caused by Agent Orange exposure that automatically entitle a veteran to benefits. However, MDS is not on the list.

However, AMVETS, a partner of the VA, maintains the VA does work to grant benefits to all qualified veterans, but the problem is that in most cases, veterans may not meet the requirements.

“If a veteran meets the requirements, [the VA] grants service connection,” said Denny Boller, a spokesperson for AMVETS. “It’s just that, unfortunately, the current law does not allow the VA to [automatically] grant MDS as service-connected at this time.”

Additionally, illnesses such as MDS occur naturally in a certain percentage of the population, even for those who were not exposed to herbicides like Agent Orange, and this makes the process of determining the cause more complicated, said a media spokesperson for the VA.

Nevertheless, Macfarlane says he will not stop seeking benefits, even in the face of news from his doctor that his MDS shows signs of progressing to chronic myelomonocytic leukemia.

“My hope and my prayer in all of this is not for me to get disability, but for the VA to finally say that this is a presumptive illness from exposure to Agent Orange in Vietnam,” Macfarlane said, “so that those who have come before me and those who come after me will not have to jump through these hoops to get to where I am, at this point.”

Macfarlane is working to appeal his latest denial of disability benefits from the undersecretary of veteran’s benefits in Washington, D.C. Although Macfarlane is frustrated, he remains committed to the fight.

According to Macfarlane, veterans with MDS or any other disease need to remember above all else: tenacity.

“Don’t be afraid who you write to or what you say to them,” Macfarlane advised. “I had bad advice from someone a long time ago who said you have to learn to be nice, and I said ‘No way am I going to be nice about this.’ Go get a private oncologist who is willing to take your side. If you find one who’s unwilling to take your side, go find another one.”

His advice to MDS patients in general is largely the same: Trust your doctor’s advice and stay healthy. Then you have a better chance of fighting this disease.

When asked about his future plans, Macfarlane said, “I’m going to be crazy, I’m going to be happy, and I’m going to hunt. He has applications in to hunt moose in Maine and elk in Kentucky. Macfarlane said that he hopes when MDS finally takes him, he’ll be at the top of a deer stand hunting. He also spends time with his grandson, Judah Ezekiel, whom he lovingly calls Boo Boo. Macfarlane added that in the end, “I am going to live until the day I die,” just like everybody else.

Anemia is common in low-risk MDS and is usually treated with transfusions, but MDS patients who are transfusion dependent typically have poor survival. EPO is a hormone used to treat anemia in MDS by promoting the production of red blood cells. EPO and other growth factors have been shown in previous studies to be successful in approximately one third of patients.

Researchers concluded that although the study was small, consisting of only 10 patients, the rate of response was good and the treatment was well-tolerated.

The study examined the use of immunosuppressants followed by treatment with EPO to increase red blood cell counts. The treatment regimen was tested in low-risk MDS patients who were resistant to EPO treatments and patients who had a low probability of response to EPO alone.

In the study, 10 patients were given daily, oral doses of the immunosuppressant agents CellCept (mycophenolate mofetil) and prednisone.

The treatment response of the patients was evaluated at 12 weeks.

For patients who still showed no red blood cell response at evaluation, the growth factor EPO was administered via subcutaneous injection for six weeks. If no response was observed, the EPO dose was increased.

Of the 10 patients treated, eight had received EPO before but had become nonresponsive and seven were receiving transfusions. One patient was hospitalized for pneumonia and removed from the study.

Of the remaining nine patients in the study, five experienced a response. Three of the five responsive patients experienced a major response, while the other two patients experienced a minor response.

Researchers reported that the treatment was well tolerated, with the most common side effect during the study being low-grade diarrhea. Also during the study, one patient who was diabetic required an increase in diabetes treatment and another patient was hospitalized for pneumonia.

The researchers highlighted that the patients included in the study had few alternative treatment options, with most of them being nonresponsive to EPO.

Researchers concluded that the study results were positive, but recommended a larger study to corroborate the findings.

For more information, please see the full study in the journal Haematologica. For more information on EPO treatment for anemia in MDS, please see previous related Beacon articles.

Vidaza is approved in the U.S. for all types of MDS patients, generally delays progression of MDS to acute myeloid leukemia, and improves overall survival. Revlimid is typically used to treat certain low- or intermediate-1 risk MDS patients.

The Phase 1 study results represented attempts by researchers to determine the maximum tolerated dose and the tolerability of the combination treatment in high-risk MDS patients by testing different dosing schedules.

Researchers described the study results of the combination therapy as “encouraging clinical activity.”

However, researchers did not initially expect such a positive response by patients to the therapy.

“We were surprised for 2 reasons: We anticipated that the combination might be more toxic than either agent used alone. As it turns out, it was not. And we were surprised that the efficacy appeared to be at least as good, if not better than either agent used alone in higher-risk MDS,” said Dr. Mikkael Sekeres, lead author of the study.

Researchers also concluded that the most effective “go-forward” dosage regimen was 75 mg/m² on days 1 through 5 for Vidaza and 10 mg on days 1 through 21 for Revlimid.

The study included 18 patients with a median age of 68. Patients received treatment on a 28 day cycle, with patients receiving a maximum of seven cycles. Patient response was evaluated at a follow-up length of seven months.

The overall response rate was 67 percent, with 44 percent experiencing a complete response, 17 percent experiencing hematological improvement, and 6 percent experiencing complete response in the marrow.

This compares to a response rate of 45 percent for Vidaza alone and 20 percent for Revlimid alone in higher-risk MDS patients.

During the study, there were no hematological side effects that limited dosage, and a maximum-tolerated dose was not reached. Non-hematological side effects included severe or life-threatening febrile neutropenia (temporarily lowered white blood cell levels) in five patients, cardiac toxicity in two patients, and central nervous system hemorrhages in two patients.

Several other Phase 1 and Phase 2 trials are also investigating the combination of Vidaza and Revlimid for the treatment of MDS.

For more information, please see the study in the Journal of Clinical Oncology.

Changing Roles

As you become a caregiver, your family or relationship roles may be shifting. You may be assuming control of more responsibilities, and at the same time, your loved one may be feeling a certain loss of control.

There may be an impulse to swoop in and take charge, in order to ensure your loved one can focus on only his or her health. But for many patients, this sudden transformation of roles can be upsetting, especially in the case of a son or daughter caring for a parent. It is helpful to be sensitive to the emotional impact your new role may have on your loved one and to discuss the tasks that you are taking over.

In other ways, you may also feel powerless. Being unable to control your loved one’s health may make you feel as if you are only a bystander and that you cannot do anything to help. However, there are many ways you can help your loved one get the best care possible, such as researching treatment options and ways of making your loved one comfortable as well as attending medical appointments with your loved one.

Communication and openness between you and your loved one is also a good way to combat these feelings of helplessness, since you both may have similar feelings.

Anxiety For The Future

When your loved one was diagnosed with MDS, your mind may have automatically jumped to the future. What does MDS mean for your loved one, and what does it mean for your own life? How will this affect your plans for the future? What can you do to prepare for what is to come?

Your loved one is most likely working through these very same thoughts and concerns, and communication can often help both of you cope.

Again, a sense of powerlessness may surround thoughts of the future, both for you and your loved one. As a result, both of you may feel fear or anxiety, and it is these shared concerns that you can focus on while supportting your loved one.

You can address these emotions by being open and honest with your loved one about fears and concerns. Although it may feel uncomfortable or frightening to discuss the future, your loved one may not have anyone else with whom to discuss these emotions. To your surprise, you may find that your loved one is more at peace with his or her future than you are. In the end, it can help both of you to talk through what may be a shared anxiety, or you may gain strength from knowing how your loved one feels.

Growing Through Being A Caregiver

Most caregivers are grateful for being able to be by the side of their loved one during his or her struggle with MDS. Although illness is always unfortunate, those who are involved can grow through the process by gaining a greater appreciation for life and by developing stronger relationships with the ones they love.

You may find yourself becoming closer to your loved one in a way that may not have been possible before MDS. You are creating a shared experience that may change your perspective of both yourself and your loved one.

But even though you may be watching and empathizing with your loved one every step of the way, no one can experience MDS in the same way a patient does. By appreciating this difference, you can support your loved one with MDS while also respecting his or her thoughts and emotions during a difficult time.

For more information about caring for a loved one with MDS, please see Part 1 of the series, which is about making your own health a priority, Part 2, which is about attending doctor appointments, or Part 3, which is about coping with your feelings of loss and grief.

In their study, the researchers sought to discover the cause of death in low-risk MDS patients where the disease had not progressed to AML in an attempt to guide early therapy decisions.

Currently, the exact cause of death in the lower risk MDS population is not well understood. Low- and intermediate-1 risk MDS patients are typically only given supportive care, such as transfusions and growth factors, without therapeutic treatment.  They receive disease-slowing agents only if their disease shows signs of progressing, such as higher blast percentages in the bone marrow, increasingly low blood counts, or transfusion dependence.

“A large group of patients with lower risk disease are not offered therapy mainly because physicians believe that this is a benign condition,” said Dr. Guillermo Garcia-Manero, a study author. “We make the point of the need to develop targeted interventions for patients with low- and intermediate-1 MDS.”

The researchers analyzed the reported causes of death for 273 low- and intermediate-1 risk MDS patients who had been referred to the M.D. Anderson Cancer Center in Texas between 1980 and 2004.  The patients’ median age was 66 years.

Infection, bleeding, transformation to AML, and disease progression were defined as MDS-related causes of death. All other deaths were classified as non-MDS related.

Researchers found that 84 percent of patients died from MDS-related complications, rather than age-related reasons.

The most common MDS-related causes of deaths were infection (38 percent), bleeding (13 percent), and transformation to AML (15 percent).  Bleeding occurred mostly in the gastrointestinal tract, lungs, and central nervous system. The most common non-MDS-related cause of death was cardiovascular complications.

The median overall survival of the group was 59 weeks from the time of referral to the cancer center.

The researchers concluded that although the results needed to be validated with different low-risk MDS populations, improved patient survival could be accomplished through early therapeutic intervention.

They suggested low doses of agents such as Vidaza (azacitidine) and Dacogen (decitabine), combinations of Revlimid (lenalidomide) with growth factors, and other new treatment combinations may be potential treatment options for low-risk MDS patients.

For more information, please see the study in the journal Cancer (abstract).

You may feel reluctant to examine or talk about your emotions associated with grief and loss through MDS. It may feel like acknowledging the loss as a permanent reality. Emotions may also be too complicated to separate or examine all at once. However, it can help to reflect on your feelings or to have a support system with whom you can discuss your feelings.

Grieving As A Process

Grieving is a response to loss, and it is a changing process that is unique to each person.

As a caregiver, you have been involved in all aspects of your loved one’s life with MDS, and you may grieve with each small loss along the road – a negative reaction to transfusion or treatment, your loved one’s changing mindset, or progression of their disease. In that sense, your grief will most likely come and go in waves.

Especially as MDS progresses, your sense of loss surrounding the illness will progress and the grieving process may become more intense and complex.

Each caregiver will experience different losses and will grieve in a different way. You may find yourself grieving and re-grieving during each stage of MDS. You may feel fear, sadness, anger, depression, or even hopelessness.

Anticipatory Grief

In many cases, caregivers find themselves anticipating the ultimate grief to come. If you are experiencing anticipatory grief, you may also experience a strong sense of guilt, since you are grieving the loss of someone who is still alive. However, this expectation of grief is a completely natural coping mechanism.

You may grieve the loss of who your loved one “used to be” or dread the future loss so strongly it becomes a form of grief. Anticipatory grief allows you to prepare for the emotionally inevitable. Preparing for the death of your loved one can give you as well as other family and friends, the time to reflect upon any unresolved issues and seek support from others.

Although anticipatory grief is often an emotional reality for many caregivers, it is also important not to let that mental preparedness distract you from enjoying what time is left. It may feel like the loss is imminent, but you should remember that you still have the chance to spend meaningful time with your loved one.

Bereavement

While grieving the loss of a loved one, you may experience feelings similar to those you experienced leading up to the death of your loved one or your feelings may become much stronger.

Although grieving is unique to each person, there are five common stages of grieving: denial, anger, bargaining, depression, and acceptance. Each person will go through the stages in a different order and at a different pace, and some people do not go through every stage.

Grieving does not have to be limited to emotional pain. You may also experience physical symptoms, such as periods of crying, a lack of interest in eating, weight loss or gain, trouble concentrating, difficulty with sleeping, or a weakened immune system.

Each person grieves over the loss of a loved one for a different length of time. You may begin to feel better within weeks, months, or years. Even once the main period of mourning has ended, you may experience periods of sadness or grieving later on, particularly during holidays, birthdays, anniversaries, or other dates with special meaning to you and your loved one.

Methods Of Coping With Grief

Grief can be complicated, confusing, and difficult to control or predict. Acknowledging the uncertainty of grief can help you regain a certain amount of control over your emotions.

During times of grief, it is natural to experience a decrease in productivity or efficiency. It is equally natural for a feeling of numbness to prevent any real grieving to take place until the reality of the loss has set in.

You can deal with loss by continuing to take care of yourself physically; asking for help with housework, chores, or other activities; and finding ways to express your emotions, such as crying, engaging in a creative hobby, or attending a support group, where you can connect with people in similar situations.

On the other hand, you may deal with your grief best by working through things on your own, at your own pace, and without the involvement of others.

The most important aspect of grieving is that it is different for everyone, and not every coping mechanism is equally successful or applicable as a result.

Above all, express your emotions with your loved ones as best you can while you still have the chance. Even if it is difficult to put these emotions into words, telling a departing loved one how much they are loved can provide comfort in grief.

For more information about caring for a loved one with MDS, please see Part 1 of the series, which is about making your own health a priority, Part 2, which is about attending doctor appointments, or Part 4, which is about understanding your loved one’s perspective.

In some cases, the physical fight with MDS can leave a loved one too exhausted to fully focus on medical details. Making the most of every visit with the doctor can therefore become a caregiver’s responsibility.

Be Prepared

Anticipation and preparation can often be the key to a successful medical visit, which means knowing exactly where to go, who to see, why the visit is taking place, and what needs to get done at the appointment.

It may be helpful to keep a notebook at home in which you can write information and questions that you want to remember for the next medical appointment.

Keep track of all medications and dosages, as well as a schedule of treatments, transfusions, or other supportive care. It may be helpful to write everything down, or to bring medication containers to appointments.

Record all symptoms and side effects, specifically those that are new or changing, or that the doctor mentioned previously. Although it is a doctor’s responsibility to always ask about symptoms, if you or your loved one do not mention a symptom, then the doctor cannot know about it or do anything about it.

Stay vigilant about pain management. It is important to remember that in this day and age, your loved one does not need to suffer through pain because there are many ways to manage it. By asking the doctor for ways to manage the pain, your loved one can focus on healing or enjoy a better quality of life. A doctor should always ask about pain levels, but it is both you and your love one’s job during an office visit to keep the doctor aware of any and all aches and pains.

Keep a running list of questions for the physician. This way, you will not forget your questions when you are at the appointment. It can be very frustrating to leave the doctor’s office and realize that you forgot to ask a question.

In addition, collecting and organizing a patient’s medical information to bring to doctor appointments can help you and your loved one feel more in control of your loved one’s medical future. Writing down all questions, concerns, and anything else the doctor should know beforehand also ensures that no one loses track of what they want to accomplish at a doctor visit.

It Is Normal To Be Confused

At any doctor appointment about MDS, there will most likely be a lot of information to absorb. Therefore, it is important to take notes, use a recorder, or otherwise ensure that all information given by the doctor can be remembered, understood, and utilized.

Your primary role as a caregiver at a medical appointment is to make sure that everything surrounding your loved one’s illness is clearly understood or documented so that you can research it when you get home. If you do not understand something, ask the physician to clarify. If a doctor cannot answer questions or concerns to you or your loved one’s satisfaction, ask for other resources to find these answers. You should not give up until both you and your loved one are satisfied with your understanding of the details concerning your loved one’s MDS and treatment.

Know What To Ask

The best way to make sure that you get all the information you and your loved one need to know is to plan what questions to ask beforehand, especially if the appointment is the first following diagnosis. Some key questions to remember include:

• What subtype of MDS does he or she have?
• How severe is the MDS?
• Will he/she need more tests?
• What is his/her prognosis?
• What is his/her risk of progressing to leukemia?
• What are the treatment options?
• Can any treatments cure his/her myelodysplastic syndrome?
• Which treatment would be the best for him/her? Why?
• How will he/she know that the treatment is working? How long will it take to start working, and will it ease his/her symptoms?
• Is the treatment new or experimental, or is it well-tested?
• What are the potential side effects of each treatment? How long will they last?
• Are there any trials you would recommend? Why?
• How much will treatment cost? Will insurance cover it?
• He/she has other health conditions. How can he/she best manage them together?
• Are there any diet or health restrictions that he/she needs to follow?
• Are there any brochures or other printed material that we can take? What Web sites do you recommend?

Additionally, you can also ask questions specific to your role as a caregiver, such as:

• Are there any symptoms I should keep track of?
• How can I help my loved one prepare for treatment?
• What side effects of treatment should I watch for?
• How can I help my loved one feel better during and between treatments?
• Can I be there during treatment?

Be An Advocate For Your Loved One

Above all, it is important for you to be an outspoken advocate as your loved one battles MDS. At no time is this more necessary than when dealing with medical and health care professionals.

Diagnosis was probably the first time you heard the words “myelodysplastic syndromes.” By finding the best MDS specialists or health care teams in your area and investigating MDS treatments, trials, and developments online or through health care professionals, you can help give your loved one the edge over MDS.

Helping your loved one through doctor visits is one of the most important ways you can show your loved one that you are there to make sure he or she does not have to face MDS alone.

For more information about caring for a loved one with MDS, please see Part 1 of the series, which is about making your own health a priority, Part 3, which is about coping with your feelings of loss and grief, or Part 4, which is about understanding your loved one’s perspective.

The study authors speculated that MDS with trisomy 11 may represent an early evolving stage of acute myeloid leukemia (AML) rather than simply intermediate-risk MDS, due to the high frequency of transformation into AML.

The chromosomal abnormality known as trisomy 11 in MDS patients is rare, and its impact on disease progression is not yet fully understood. However, there is evidence that it may be an indicator of a more aggressive form of MDS and associated with a poor prognosis. MDS with trisomy 11 is currently classified as intermediate-risk MDS.

“Trisomy 11 is very rare and there were no studies except a few case reports out there. People do not understand the significance,” said Dr. Sa Wang, a study author. “MDS has so many different cytogenetic alterations and most are classified under the intermediate category. It makes people aware that not all “intermediate” MDS are born equal.”

The study examined 17 MDS patients from a hematological database with trisomy 11 either as a single abnormality or in conjunction with two or more other chromosomal abnormalities. Overall survival of the trisomy 11 patients was compared with that of the general MDS population within the database. The median age of the group was 71.

Following diagnosis, the patients in the study group had received both supportive care as well as other treatment agents, including thalidomide (Thalomid), Vidaza (azacitidine), and Dacogen (decitabine).

The median overall survival of the trisomy 11 patients was 14 months. The general intermediate-risk MDS population was observed to have a median overall survival of 28 months. The survival rate for trisomy 11 patients was more similar to high-risk MDS, which is associated with a median survival of 10 months according to researchers.

Eleven patients (69 percent) progressed to AML within a median of five months.

Researchers concluded that MDS with trisomy 11 should be classified as high-risk MDS instead of its current classification as intermediate-risk. They added that as such it requires a more aggressive treatment course.

For more information, please see the study in the journal Leukemia (abstract).

How to Understand Your Lab Results And What They Mean – The Leukemia & Lymphoma Society (LLS) is sponsoring an event to help blood cancer patients understand their blood test results. Dr. Thomas Butler will be leading the discussion on March 17 from 7 p.m. to 8 p.m. at the Virginia Hospital Center in Arlington, VA. This event is free, and light refreshments will be served. To attend, please register through the LLS by March 15.

MDS Webinar: Treating Lower-Risk MDS – The Aplastic Anemia & MDS International Foundation (AA&MDSIF) is sponsoring a webinar, including lecture and case studies, to present current treatment options for lower-risk MDS patients. Dr. Mikkael Sekeres of the Cleveland Clinic will explain the differences between higher-risk and lower-risk MDS, review the factors that influence specific treatment decisions, and discuss treatments that are under development. The webinar will be held on Thursday, March 18 beginning at 3 p.m. EST. For more information or to register, please see the AA&MDSIF Web site.

For a more detailed listing of MDS-related events, please check the MDS Beacon Events Calendar.

Thrombocytopenia (low platelet levels) can be an unfavorable prognostic factor for MDS survival. Increased thrombocytopenia is often linked to a shorter time to AML progression. Platelet transfusions are currently the only available treatment option for thrombocytopenia. Transfusions carry a set of risks including alloimmunization, allergic reaction, infection, and lung injury. Alloimmunization is a type of immunity that often makes platelet transfusions ineffective.

Nplate is a protein consisting of a peptide and an antibody (peptibody) that increases platelet production. The drug has shown to be effective in clinical trials in increasing platelet production in healthy individuals and patients with chronic immune thrombocytopenia.

Researchers studied the efficacy and safety of Nplate for treating thrombocytopenia in low- and intermediate-1 risk MDS patients.

The study included 44 patients, all of whom completed at least four weeks of treatment. Patients were divided into four groups that received 300, 700, 1,000, and 1,500 µg Nplate respectively, administered subcutaneously once a week for three weeks, with follow-up assessment during the fourth week. Patients who completed the four-week treatment could continue taking Nplate during an extension phase lasting up to one year.

All 44 patients completed the four-week treatment phase. Researchers found that patients in all four groups experienced an increase in platelet counts during the treatment phase. Twenty patients (45 percent) achieved a complete or major platelet response. The share of patients who achieved a complete or major platelet response was similar across the different treatment groups.

Patients who entered the extension phase were also evaluated for response duration. Of the 44 patients treated, 41 entered the extension phase. A durable platelet response was achieved by 46 percent of the patients. The median treatment duration for the patients who achieved a durable response was 37 weeks.

Nearly all patients (98 percent) experienced side effects, with the most common being fatigue, diarrhea, and headache. Severe side effects were experienced by 39 percent of patients, and one patient withdrew from the study as a result of adverse side effects.

Side effects in 39 percent of patients were attributed to Nplate, and 11 percent experienced severe Nplate-related side effects. All patients who experienced severe side effects received the highest Nplate dose of 1,500 µg.

Researchers found that achievement of platelet response was independent of the dosage. Based on the study results, 700 µg was selected as the dosage to use in future studies.

Researchers also noted that the study design lacked a control group, and suggested future studies to further analyze the safety of Nplate in MDS patients.

For more information on the study, please see the study in the Journal of Clinical Oncology (abstract). For information in the interim results, please see the related MDS Beacon article.

Patients lean or even depend on their caregiver, and yet as a caregiver, you are also going through an emotionally and physically difficult time as you watch a loved one struggle with MDS and as you do all that you can to help.

One of the best ways to help your loved one is by finding the balance between caring for your loved one while also taking care of yourself. It can be tempting to focus all of your energy and strength on your loved one’s needs. However, staying healthy is the first step in tackling the challenges of caring for a loved one with MDS. Taking care of yourself gives you the strength to take care of someone else.

Over the next few weeks, The MDS Beacon will address many important aspects of caring for MDS patients in a series of articles. This article includes key tips for keeping yourself healthy while caring for your loved one. Future articles in this series will focus on additional issues important to caregivers, including tips for attending doctor visits with your loved one, coping with your feelings of loss and grief, and understanding your loved one’s perspective as they are going through this difficult time.

Keep Your Body Healthy

Keep your immune system strong. Continue with regular doctor check-ups and any regular medications. It’s important for a caregiver to keep track of any previous health problems while staying on the lookout for any new symptoms that may develop, especially stress-related symptoms. Stress can affect your body, emotions, and behavior. It also weakens the immune system, making your body more susceptible to viruses like the common cold. Symptoms of stress include headaches, back or chest pain, high blood pressure or heart disease, an upset stomach, difficulty sleeping, anxiety, depression, irritability, lack of focus, over eating or under eating, or increased smoking or drinking.

Eat a balanced diet. This is especially important if you eat with your loved one, since someone with MDS needs to maintain a healthy diet. To increase energy, avoid soft drinks and candy in favor of nuts, beans, whole grains, fish, green vegetables, bananas, dried fruit, and yogurt. To help improve your mood, eat foods that make you release endorphins like chickpeas or dark chocolate.

Exercise. Any type of muscle activity, even something brief like stretching or dancing around the kitchen, can increase energy. Ideally, a caregiver should try to maintain at least 30 minutes of physical activity about four times a week. This can be anything from running to yard work to playing outside with a pet (more exercise ideas).

Get plenty of rest. Generally, an adult needs around eight hours of sleep a night. Missing an hour of sleep every night for eight nights in a row can make the brain as sleep-deprived as if it had stayed awake all night long. You can also try to nap when your loved one does to catch up on missed sleep, or practice meditation and other relaxation exercises during the day (more sleep tips).

Keep Your Mind Healthy

Take a break. Even spending just a few minutes watching TV, reading, working on a favorite hobby, or doing relaxation exercises can increase energy and help you refocus on caring for your loved one.

Let go of the less important things. Although it may be difficult to cut some things from your daily routine, health should become the top priority for both you and your loved one. Let go of less important activities or concerns for the time being: order takeout instead of cooking dinner, vacuum and dust less frequently, do not worry about folding the laundry immediately or do it while watching TV, and organize mail into piles of important mail that needs to be dealt with quickly and mail that can wait.

Ask others for help. Often, family and friends want to help but do not know how. A caregiver can reasonably ask for help with any basic task including cooking, cleaning, childcare, yard work, and running errands. If you receive too many phone calls or emails asking how your loved one is doing, consider choosing a family member or friend who can notify others of your loved one’s health. Keep that person informed, and ask them to tell others about updates. You can also create an email mailing list so that you can update everyone with one quick email, or start a blog or web page on CaringBridge or CarePages. There is a limit to what any one person can do, and asking for help can keep you healthy, as well as possibly relieving any guilt your loved one may feel for depending entirely on you for care.

Stay in touch with family and friends. Illness has a tendency to make people feel isolated, including for caregivers. Whether by phone, email, or a coffee date, preserve outside relationships separate from your loved one to help you stay strong and to get support.

Be honest about your emotions. Caring for a loved one with MDS can make you feel scared, angry, guilty, lonely, or sad, as well as a host of other complicated emotions. In many cases, your loved one is going through similar emotions. Talking about your feelings together can bring you closer together as a team against MDS. If you do not feel comfortable talking with your loved one, try talking to friends or family or seek counseling. Also, caregiver support groups can provide an opportunity for camaraderie and support from individuals in similar situations. However, seek professional help if you or your loved one have signs of severe depression or anger.

Long-term, maintaining your own health makes you more effective as a caregiver, giving you the energy and strength to provide the best care possible for your loved one as they fight MDS. The key is to remember that by taking care of yourself, you are also indirectly caring for your loved one.

For more information about caring for a loved one with MDS, please see Part 2 of the series, which is about attending doctor appointments, Part 3, which is about coping with your feelings of loss and grief, or Part 4, which is about understanding your loved one’s perspective.

The findings were presented at the 51st Annual American Society of Hematology (ASH) meeting and exposition in December.

MDS patients aged 80 years and above make up 30 to 35 percent of all MDS patients. These patients are usually not candidates for chemotherapy, even at low doses, because older patients typically do not respond well to the side effects of chemotherapy. Instead, they generally only receive supportive care, which may help improve quality of life but does not treat MDS.

However, this analysis showed that response rates, survival, and side effects associated with Vidaza may be similar in MDS patients of all ages.

Researchers collected data on 41 MDS patients ages 80 years and older who were treated with Vidaza at hematology clinics in France. Vidaza was given to these patients on a compassionate use basis, where the drug was given to seriously ill patients with few or no treatment options before Vidaza was officially approved in France.

Two dosing regimens were used. The first dosing regimen was given to 54 percent of the patients and followed the European Medicines Agency-approved schedule of 75 mg/m² of Vidaza for seven days every four weeks.

The second dosing regimen was given to 46 percent of the patients and was identified as less intensive, following a schedule of 75 mg/m² of Vidaza for five days every four weeks, or in some cases less than 75 mg/m² a day.

Patients received a median of four cycles of treatment within a median follow-up time of 12 months.

Of the patients being analyzed, the overall response rate was 34 percent, which is comparable to the response rate in patients less than 80 years old. Six of those patients (15 percent) achieved a complete response, and two patients (5 percent) achieved a partial response.

The median overall survival rate was 17 months, similar to the 15 month survival of patients less than 80 years old. However, five patients (12 percent) died before the completion of four cycles of treatment, which is also similar to the rate for patients less than 80 years (10 percent).

The most common drug-related side effect in both age groups was a condition characterized by both fever and a low number of white blood cells.

The study did not report whether Vidaza delayed progression of MDS to acute myeloid leukemia in patients at least 80 years old.

Researchers concluded that Vidaza treatment in MDS patients 80 years and older was associated with significant overall response and survival rates, comparable to those observed in patients less than 80 years.

Unlike with chemotherapy, Vidaza did not cause an increased drug-related toxicity in patients 80 years and older when compared with MDS patients less than 80 years, according to researchers.

For more information, see abstract 1773 at the ASH Meeting Web site. For information about the safety and effectiveness of Dacogen (decitabine) in elderly MDS patients, see a related Beacon article.

The risk of developing MDS increases with age, and older patients make up a large share of all MDS patients.  Older cancer patients, however, often find it particularly challenging to deal with the side effects of many cancer drugs.

For these reasons, physicians who treat MDS are particularly interested in knowing whether a potential MDS treatment is both effective and safe for older patients.

Dacogen is one of several drugs the U.S. Food and Drug Administration has approved in recent years for the treatment of MDS.

Dr. George F. Geils, the author of the findings presented at the ASH meeting, analyzed data from two recent clinical trials of Dacogen.  The goal of this analysis was to assess the efficacy and safety of Dacogen in two subgroups of older patients: patients aged 65 to 75 years, and patients aged 75 years and older.

The data from the two clinical trials were examined for overall response rate, duration of response, time to response, transfusion independence, and tolerability.

In one trial, patients were given Dacogen intravenously at 20 mg/m² for five consecutive days every four weeks.

In the other trial, patients received Dacogen intravenously at 15 mg/m² over three hours every eight hours for three consecutive days every six weeks.

In both trials, the overall response rate was higher for the 65 to 75 age group (38 percent and 16 percent) than for the 75 and older age group (23 percent and 9 percent).

More patients in the 65 to 75 age group achieved transfusion independence in both studies (39 percent and 43 percent, respectively) than patients in the 75 and older age group (15 percent and 21 percent, respectively).

However, patients aged 75 years and older responded more rapidly in both trials (72 days and 93 days, respectively) than patients aged 65 to 75 years (84 days and 101 days, respectively). In addition, the older patients showed a more durable response in both studies (554 days and 295, respectively) than their slightly younger counterparts (343 days and 226 days, respectively).

The most common side effects were moderate to severe anemia (low red blood cell levels), leukopenia (number of white blood cells outside of normal range), neutropenia (low white blood cell levels), and thrombocytopenia (low platelet levels). There were no reported cases of neutropenia in patients aged 75 years and above.

Dr. Geils, the author of the ASH study, concluded that Dacogen was effective and generally well-tolerated by both subgroups of older MDS patients. He further concluded that, based on his data analysis, physicians need not place undue weight on a patient’s age when considering whether or not Dacogen is an appropriate treatment.

Likewise, Dr. Geils believes the results of his study support further research into the efficacy and safety of Dacogen in elderly and other high-risk MDS patients.

For more information, please see abstract 2792 at the ASH Meeting Web site.

The research results were published in the official journal of the Multinational Association of Supportive Care in Cancer.

Infections are a serious risk to MDS patients undergoing treatment. Many physicians prescribe antibiotics or antifungal treatments preemptively to prevent infections from developing during MDS treatment.

Sporanox is the traditional initial option for antifungal treatment in high-risk MDS and acute myelogenous leukemia (AML) patients. Vfend was approved to treat fungal infections in 2002, but it has not been previously tested in high-risk MDS or AML patients.

The study evaluated the efficacy and safety of antifungal prevention with Vfend or Sporanox in 123 patients, all of whom were randomly assigned one of the two drugs. Of those evaluated, 29 patients had MDS and 94 had AML as their underlying disease.

Both drugs were given intravenously. Vfend was given at 400 mg every 12 hours for two doses, followed by 300 mg every 12 hours. Sporanox was given at 200 mg twice a day for two days, followed by 200 mg once daily.

None of the patients receiving Vfend developed fungal infections, while two of the patients receiving Sporanox developed fungal infections, a rate of 4 percent. The overall response rate was comparable for the two drugs, a rate of 69 percent for Vfend and 56 percent for Sporanox.

The most common side effect for both drugs was moderate to severe liver malfunction, at a rate of 11 percent for Vfend and 9 percent for Sporanox. Visual and auditory hallucinations were also experienced by patients receiving Vfend at a rate of 10 percent. Vfend was associated with a higher rate of side effects, particularly adverse liver functions and the development of hallucinations. All side effects were resolved after the discontinuation of the study drug.

“Patients with increased bilirubin before the start of chemotherapy will have higher chances to develop side effects,” said Dr. Gloria Mattiuzzi, a researcher for the study. Bilirubin is a product of hemoglobin found in bile. Increased bilirubin levels may be an indication of liver problems.

Researchers concluded that Vfend and Sporanox are both very effective in the prevention of fungal infections in patients with high-risk MDS and AML. Due to its exceptional efficacy, Vfend was identified as a good alternative to Sporanox in preventative antifungal treatment.

For more information, please see the study in Supportive Care in Cancer (abstract).

The findings were presented at the 51^st annual American Society of Hematology (ASH) Meeting and Exposition in New Orleans on December 8.

Trisenox is an FDA-approved therapeutic agent for the treatment of certain types of leukemia. It is currently being studied for use in the treatment of high- and low-risk MDS. In vitro studies, which are those performed in controlled environments like test tubes or Petri dishes, have shown that the efficacy of Trisenox in tumor cells can be increased by combining Trisenox with vitamin C.

The Italian researchers studied the effects of Trisenox in combination with vitamin C in MDS patients. The study included 44 patients with a median age of 71. Of these patients, 23 were assessed as having low- or intermediate-1 risk MDS and 18 as high- or intermediate-1 risk MDS.

Trisenox was given intravenously at a dose of 30 mg for five days, followed by 25 mg given twice weekly for 15 weeks. Vitamin C was given intravenously at 1000 mg within 30 minutes of each Trisenox transfusion.

Response was evaluated after two and four months of treatment. Ten patients showed a clinical response, which is a rate of 23 percent.

The response rate was 35 percent for lower- risk MDS patients and 6 percent for higher-risk patients. In eight of the 10 respondents, response was evident within the first eight weeks of treatment.

Twenty-three patients discontinued treatment due to disease progression, severe adverse effects, adverse events unrelated to drug use, and withdrawal of consent.

The most common drug-related side effects were severe neutropenia (low white blood cell count) and thrombocytopenia (low platelet count), at rates of 45 percent and 23 percent respectively.

The authors concluded that Trisenox is tolerable and active in the treatment of MDS. They noted that vitamin C did not increase the response rate nor the toxicity of Trisenox.

The authors also observed that the drug regimen was least tolerated in elderly and higher-risk MDS patients.

For more information, please see abstract 943 at the ASH Meeting Web site.

For MDS, Revlimid is typically used as a treatment for low- or intermediate-1 risk patients, especially those who require red blood cell transfusions and have del-5q. A del-5q mutation is a chromosomal abnormality characterized by a missing ‘q’ arm of chromosome 5. The recommended starting dose for MDS patients is 10 mg Revlimid daily, but the dose is lowered if patients experience severe side effects during treatment.

This study investigated the efficacy and safety of a low dose Revlimid regimen (5 mg daily) as compared to the recommended 10 mg dosing.

The study included 138 patients with transfusion-dependent low- or intermediate-1 risk MDS and del-5q. Patients were randomized to receive 5 mg Revlimid on days 1 through 28, 10 mg Revlimid on days 1 through 21, or a placebo, all on a 28-day cycle. Response was assessed at 16 weeks, and responders continued treatment for up to 52 weeks.

Patients in the 5 mg Revlimid group and the placebo group who did not respond by week 16 were considered treatment failures and were given Revlimid at 10 mg or 5 mg, respectively, in an extension phase in which patients knew which treatment they were receiving. Patients who completed 52 weeks of treatment could also enter the open phase at their current dosage level.

Of the three groups, the 10 mg Revlimid group achieved the highest response rate of 41 percent. The 5 mg Revlimid group achieved a response rate of 17 percent, while the placebo group did not achieve any response.

The Revlimid groups also had a significantly higher rate of transfusion independence compared to the placebo group. Fifty-six percent of patients in the 10 mg Revlimid group no longer required blood transfusions as well as 41 percent of the 5 mg Revlimid group. Among the placebo group, 6 percent of patients achieved transfusion independence.

The most common side effects were severe neutropenia (low white blood cell count) and severe thrombocytopenia (low platelet count). Neutropenia was reported in 75 percent of the 10 mg Revlimid group, 74 percent of the 5 mg Revlimid group, and 15 percent of the placebo group. Thrombocytopenia was reported in 41 percent of the 10 mg Revlimid group, 33 percent of the 5 mg Revlimid group, and 2 percent of the placebo group.

Discontinuation of treatment due to adverse events within the first 52 weeks occurred in 16 percent of the 5 mg Revlimid group, 9 percent of the 10 mg Revlimid group, and 5 percent of the placebo group.

Researchers concluded that 10 mg was the ideal initial treatment dose of Revlimid, with dose reductions or discontinuation as needed. However, researchers also stated that Revlimid at both 10 mg and 5 mg was generally well-tolerated and achieved significant transfusion independence in transfusion-dependent low- or intermediate-1 risk MDS patients with the del-5q chromosomal abnormality.

For more information, see abstract 944 at the ASH Meeting Web site.

Vidaza is one of several newly approved drugs for the treatment of MDS. Clinical trial data indicates that Vidaza typically delays progression of MDS to acute myeloid leukemia and improves overall survival among MDS patients. The European Medicines Agency (EMEA) approved Vidaza for European markets in March 2009.

Researchers collected data from 147 MDS patients who were treated with Vidaza on different dosing regimens at hematology clinics in Spain. Vidaza was given to these patients on a compassionate use basis, before Vidaza was officially approved in Spain. The dosing schedule was determined by a patient’s disease status and scheduling availability.

Three different dosing schedules were studied, each on a 28-day cycle. Group A received Vidaza on days 1, 2, 3, 4, and 5. Group B received Vidaza on days 1, 2, 3, 4, 5, 8, and 9. Group C received Vidaza on days 1, 2, 3, 4, 5, 6, and 7, which is also the dosing schedule currently approved for Vidaza by the EMEA (and by the U.S. Food and Drug Administration).  The disease characteristics of patients in all three groups were similar, although there was a higher share of high- or Intermediate-2 risk MDS patients in group C.

Of the three groups, the overall response rate of group C was the highest at 74 percent. Group A showed a response rate of 58 percent, and group B showed a response rate of 65 percent.

Vidaza was generally well tolerated by patients in all three groups according to researchers. However, common drug-related side effects included severe neutropenia (temporarily lowered white blood cell levels) and severe thrombocytopenia (lowered platelet levels). The highest rate of these side effects were seen in groups A and B. In group A, 50 percent experienced neutropenia and 43 percent experienced thrombocytopenia, and in group B, 42 percent experienced neutropenia and 30 percent experienced thrombocytopenia. Group A also showed the highest rate of anemia at 29 percent. Group C showed the overall lowest rate of drug-related side effects, with 35 percent experiencing neutropenia and 22 percent experiencing thrombocytopenia.

The authors concluded that while different dosing schedules for Vidaza are possible, the dosing schedule currently approved by the EMEA received by group C has the greatest efficacy and safety in the treatment of MDS.

Since the data studied in the analysis represented a retrospective, non-random study, the researchers are awaiting further analyses for confirmation of their findings.

For more information, see abstract 2773 at the ASH Meeting Web site.

The article, which was published in the journal Expert Opinion on Investigational Drugs, summarized current developments in the study of Clolar, especially for elderly acute myeloid leukemia (AML) patients. Summaries of several studies involving the use of Clolar in MDS patients were also included.

Clolar works by inhibiting DNA synthesis, which in turn interferes with the growth of tumor cells. It is currently approved in the United States for pediatric acute lymphoblastic leukemia (ALL) patients following at least two other failed treatments. The U.S. Food and Drug Administration recently declined approval for the use of Clolar in adult AML patients, citing the need for further clinical testing.

According to the authors, the most promising theme in recent Clolar studies is the efficacy of Clolar in treating elderly AML patients ages 60 years and above who are considered unlikely to benefit from standard chemotherapy.

It was also concluded that Clolar may be effective in the treatment of refractory and relapsed MDS, and its success in high-risk MDS patients has already been demonstrated. However, further studies are needed to establish the role of Clolar in MDS treatment.

The main MDS research detailed in the article was a Phase 2 study on the effects of Clolar as a single treatment agent in patients with high-risk MDS or one of several types of leukemia. In the MDS group, an overall response rate of 50 percent was observed, with 25 percent of patients achieving a complete response and 25 percent achieving a complete response with incomplete platelet recovery. Reversible liver toxicity was the most prominent side effect.

Combination treatments of Clolar with cytarabine (Cytosar-U) and idarubicin (Idamycin) in MDS patients were also examined.

In a Phase 1/2 study of Clolar given in combination with cytarabine to high-risk MDS patients as well as AML and ALL patients, an overall response rate of 38 percent was observed, with 22 percent achieving a complete response and 16 percent achieving a complete response with incomplete platelet recovery. Although both MDS and AML patients responded to the combination treatment, the exact response rate for the MDS group alone was not specified.

In a Phase 1 study, a combination of Clolar with both idarubicin and cytarabine was compared to a combination of Clolar with idarubicin alone in high-grade MDS and relapsed AML patients. A higher overall response rate was seen for the combination of Clolar with both idarubicin and cytarabine, with an overall response rate of 48 percent and 23 percent achieving a complete response. For the combination of Clolar with idarubicin alone, an overall response rate of 22 percent was observed.

One study compared the efficacy of oral Clolar with intravenous administration. The overall response rate was similar for both formulations, with an overall response rate of 37 percent for oral administration and 44 percent for intravenous administration.

In general, Clolar was tolerated well by patients in the studies. The most common side effects of Clolar and Clolar combination treatments were impaired liver function, swelling of hands and feet, and fevers and infections related to myelosuppression.

For more information, please see the study in the journal Expert Opinion on Investigational Drugs (abstract).

Velcade, a proteasome inhibitor, is an FDA-approved therapeutic agent for the treatment of multiple myeloma and mantle cell lymphoma. It is currently being studied for the treatment of MDS.

The study included 10 MDS patients with a median age of 64 years. Velcade was given at a dose of 1.3 mg/m² on days 1, 4, 8 and 11 every 28 days for a maximum of eight cycles. Six patients completed all eight cycles.

Of the six evaluable patients, three patients (50%) achieved a minor red blood cell response, and three patients (50%) achieved stable disease. Seven out of 10 patients survived to the median follow-up of 24 months.

Four patients experienced severe neutropenia (low white blood cell count), and six patients experienced severe thrombocytopenia (low platelet count). Seven patients experienced other non-blood cell-related side effects including diarrhea (one patient), fever (three patients), skin rash (two patients), and pneumonia (one patient).

The authors concluded that Velcade administered as a single agent has some efficacy in achieving hematological improvement in MDS patients; however, a larger sample of MDS patients is needed to confirm these results.

The authors added that a combination of Velcade with other drugs may increase its therapeutic activity.

For more information, see abstract 1777 at the ASH Meeting Web site.

In MDS, Revlimid is typically used as a treatment for Low- or Intermediate-1 risk patients, especially those who require red blood cell transfusions and have del-5q.  A del-5q mutation is a chromosomal abnormality characterized by a missing ‘q’ arm of chromosome 5. 

Revlimid is intended to help MDS patients achieve red blood cell transfusion independence, and is usually given at a standard dose of 10 mg daily during the first 21 days in repeated 28-day cycles.

Recent data indicate that, at its standard dose and for its target patient population, Revlimid can achieve transfusion independence in more than 60 percent of patients.  However, many patients treated with Revlimid also experience drug-related side effects, such as temporarily lowered white blood cell levels (neutropenia) and lowered platelet levels (thrombocytopenia).  In addition, treatment with Revlimid can be expensive.

In the recent Italian study, six transfusion-dependent MDS patients received Revlimid every other day during the first 21 days in repeated 28-day cycles.  Researchers hoped an alternating-day schedule would lower drug-related side effects as well as the overall cost of the treatment, while still maintaining the same level of efficacy.

This was the first study to examine the efficacy and possibly lower side effects of an alternating-day schedule for Revlimid, according to the researchers.

All six patients in the Italian study became independent of red blood cell transfusions, with three patients achieving independence in three months, and the other three in four months.

In terms of drug-related side effects, two patients experienced significant neutropenia, a rate of 33 percent, and one patient experienced significant thrombocytopenia, a rate of 17 percent.  No patients experienced fever or infection.

In comparison, recent data suggest that Revlimid given on a daily schedule produces significant neutropenia in 55 percent of patients, and significant thrombocytopenia in 44 percent of patients.

“I think dose reduction alone is responsible for this lowered toxicity,” Dr. Defina Marzia of the University of Siena in Italy, one of the authors of the report, told the Beacon.

The alternating-day schedule also reduced the cost of the drug by 50 percent.

Previous attempts to reduce Revlimid’s side effects included lowering the daily dose from 10 mg to 5 mg. This did decrease side effects, but it did not substantially reduce the overall price of the drug.

Although all six patients in the Italian study achieved transfusion independence with the alternating-day schedule, achieving independence took longer than with the standard daily schedule. Dr. Marzia pointed out that patients on a daily Revlimid dosing regimen typically achieve transfusion independence in four to six weeks.

The authors also pointed out that, due to the small number of patients and the short follow-up length of less than 14 months, the new alternate-day schedule needs to be explored in a larger study. Results based on at least 15 to 20 additional patients will be needed to confirm the study results, said Dr. Marzia.

For more details, please see the report in the British Journal of Hematology (subscription required).

The IJ sued the United States Attorney General Eric Holder over the National Organ Transplant Act of 1984, which makes human organ sales illegal, including financial compensation for bone marrow donations. An overturn of the ban could have a large impact on physicians, donors, and especially patients, including those with myelodysplastic syndromes (MDS).

Bone marrow transplants are an important part of treatment in various types of blood cancers. The stem cells, after being separated from the donated bone marrow and inserted into the recipient’s bloodstream, begin to repopulate the patient’s bone marrow with new blood cells.

For MDS patients, a bone marrow transplant is the only known treatment that can bring about long-term remission. However, a transplant is not an option for all MDS patients; it is generally most effective in younger, healthier patients.

The non-profit group MoreMarrowDonors.org recruited the IJ to file the lawsuit to overturn the ban and allow for compensation to be made to donors.

“We think that there is much folly in a government law standing between a patient and a potentially life-saving program,” said Shaka Mitchell, president of MoreMarrowDonors.org. “To that end, we decided this suit is of paramount importance.”

MoreMarrowDonors.org is proposing a pilot program that will compensate the most needed donors, especially minorities, with $3,000. The money would be in the form of a scholarship, housing grant, or donation to charity. Donors and patients would be matched anonymously through a national registry.

“Our hypothesis is that many people drop off the registry or fail to follow through once contacted because they cannot afford time away from work or other commitments. By providing small scholarships, housing allowances, and gifts to charity, we think we can prevent some of the attrition that eventually leads to patients unable to find marrow matches,” added Mitchell.

In the past, transplants required the removal of bone marrow directly from the pelvic bone. The procedure has become much less invasive and painful since the development of medications that prompt the donor’s stem cells to leave the bone and enter the bloodstream. A machine filters these mobilized stem cells from the circulating blood, and the stem cells are then frozen until transplantation.

But the donor and recipient must still be perfect matches in a bone marrow transplant – even more so than in a kidney transplant. This is where the problem arises – matches are hard to come by, and patients do not have the luxury of time to wait for a match.

An overturn of the current ban could result in more donors in bone marrow registries and a higher potential for matches among MDS patients seeking a bone marrow transplant.

The National Organ Transplant Act of 1984 was originally enacted to prevent the sale of kidneys and other organs that do not regenerate. But critics argue that the original law banning compensation for organs was not meant to pertain to bone marrow – unlike a kidney, bone marrow renews itself.

“Bone marrow got stuck in the statute – by mistake,” said Jeff Rowes, the IJ’s lead attorney on the case. He described bone marrow donation as an unusual form of blood donation. “No reason to treat them like kidneys or livers,” he added.

Criticism and ethical concerns over the proposed payment of bone marrow donors have also been raised (see The New York Times Opinion blog). Some wonder if compensation will negatively affect the number of altruistic donors on the registry.

There is also concern that payment will encourage individuals to conceal health conditions in order for donations to be accepted, leading some to worry about the affect an overturn may have on the quality of the donations.

The lawsuit may take a number of years to work its way through the federal court system. In the meantime, coverage of the lawsuit in the news media may raise awareness of the shortage of bone marrow donors and trigger an influx of donors to the registry.

“The goal is to make a serious dent in the shortage of bone marrow donors,” Rowes said. “Maybe save 1,000 lives a year.”

For more information, please see the IJ press release or Jeff Rowes’ blogging about the lawsuit on The Volokh Conspiracy.

About The H1N1 Flu

The H1N1 flu, also referred to as “swine flu,” has caused thousands of hospitalizations and more than 600 deaths in the United States since it was first detected in April 2009.

It is spread through person-to-person contact, often by sneezing or coughing, similar to transmission of the seasonal flu virus. Symptoms of the H1N1 flu and the seasonal flu both include a cough, sore throat, runny nose, body aches, headache, chills, tiredness, and sometimes fever, vomiting, and diarrhea.

About The H1N1 Vaccine

MDS patients are generally advised to get the seasonal and H1N1 vaccines as soon as they become available in their area. The seasonal flu vaccine will not protect against H1N1, so MDS patients are advised to get both vaccines.

Dr. Bart Scott, an MDS specialist at the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, explained, “I think of MDS as not only a disease of low peripheral blood counts, but also of impaired function. Therefore, there is a possibility that MDS patients with normal neutrophils have impaired immunity. For that reason, I recommend that all of my MDS patients receive the standard influenza vaccine.”

The H1N1 vaccine is available in two forms. The nasal spray contains a live but weakened (or attenuated) version of the virus, while the flu vaccine shot, which gets injected into the muscle, contains an inactivated (or dead) version of the virus. MDS patients should only get the flu vaccine shot, which contains H1N1 viruses that have been killed and which cannot make recipients sick with the flu.

In regard to the H1N1 vaccine, Dr. Scott said, “I would not recommend that patients with impaired immune function receive the intranasal version, nor their family members. However, they may benefit from receiving the dead virus vaccination administered as a subcutaneous shot.”

The H1N1 vaccine takes two weeks to create immunity within the body, but protection lasts up to a year. The flu season generally reaches its peak in December or January and can often last into April or May.

At this time, only one dose of the H1N1 flu vaccine is recommended to achieve immunity. However, the vaccine may have lower effectiveness in people 65 and older, as well as those with chronic medical conditions. Although it is considered generally safe for MDS patients, the H1N1 vaccine may not be as effective for them as it is for healthy individuals, since MDS affects the immune system. This is especially true for those MDS patients taking immunosuppressive drugs like anti-thymocyte globulin (ATG) or cyclosporine.

The H1N1 vaccine has no recorded negative interactions with MDS medications. However, it has been suggested by some doctors that patients wait until the end of treatment cycles of drugs such as Vidaza before receiving the H1N1 vaccine.

As long as patients are not currently suffering from other non-MDS illnesses, such as infections or other illnesses that produce fever, the inactivated H1N1 vaccine is considered safe for individuals with MDS. If a patient is experiencing a non-MDS illness, he or she should wait until symptoms, including fever, recede before receiving the vaccine.

The H1N1 vaccine, like any other medication or vaccine, carries risks. Serious complications, such as allergic reactions, are rare, but are distinguished by high fever or behavior changes after vaccination. Serious side effects such as these should be reported to a doctor or specialist right away. Mild reactions to the vaccination include soreness, redness, or swelling at the injection site, body aches, coughing, and fever.

The available 2009 H1N1 vaccine was created using the same processes and facilities used to make the currently licensed seasonal flu vaccine. Both have been tested for safety and effectiveness.

MDS patients are encouraged to speak with their doctors or specialists regarding specific concerns about the vaccine.

In many cases, availability of the H1N1 vaccine is limited, so certain groups have been given priority over others to receive it. Among those given priority are people ages 25 through 64 years of age with chronic health disorders or compromised immune systems, including MDS patients.

So far, families of MDS patients are not part of this priority group. However, family members are encouraged to get vaccinated with the inactivated version of the H1N1 vaccine, especially if circumstances prevent the MDS patient from getting vaccinated.

MDS patients and families who received the 1976 swine influenza vaccine are recommended to also receive the 2009 H1N1 vaccine. The difference between the two viruses is significant enough that the 1976 vaccine will not likely protect against H1N1.

MDS patients and families who have experienced flu-like symptoms since the spring of 2009 should still be vaccinated against H1N1.

Preventing H1N1 Infection

Even if an MDS patient gets the H1N1 vaccine, he or she should continue taking all necessary precautions to prevent infection, since the vaccine may not be as effective in people with compromised immune systems.

Patients and families should wash their hands with soap and water, or alcohol-based hand cleansers, after sneezing or coughing. They should also avoid touching their eyes, nose, or mouth, as well as avoid others who are experiencing H1N1 symptoms. MDS patients should also consider wearing a face mask when in crowded public places or while traveling.

Treating H1N1 Infection

A specific test is needed to determine H1N1 infection. If an MDS patient develops H1N1 or the seasonal flu, their doctor may advise the patient to take an antiviral drug, either Relenza (zanamivir) or Tamiflu (oseltamivir).

Antiviral drugs are prescription medications such as pills, liquid, or inhaled powder that stop flu viruses from reproducing inside the body. These drugs can make illness milder, lead to quicker recovery, and may prevent serious flu complications. Antiviral drugs should be taken within 48 hours or as soon as possible after symptoms begin for maximum effectiveness.

For more information about the H1N1 vaccine, please visit the CDC Web site, the Aplastic Anemia and MDS International Foundation Web site, and previous MDS Beacon coverage of the H1N1 vaccine.

Valproic acid is commonly used to reduce seizures in epilepsy patients and to treat bipolar disorder. It has recently become of interest as a possible treatment for blood- and bone marrow-related cancers like MDS.

Previous studies have shown that two classes of drugs, hypomethylating agents, which include Vidaza, and histone deacetylase inhibitors, which include valproic acid, used together can suppress cancer. This is done by inhibiting methylation of DNA, a process that at normal levels prevents genetic abnormalities but at higher levels can lead to MDS.

This Phase 2 study included 62 patients with either intermediate-2 or high-risk MDS and was conducted at several Italian hematology centers.

Valproic acid was given orally from the start of treatment to reach a desired plasma concentration of more than 50 μg/mL, at which point Vidaza was administered using standard dosing. Patients were allowed supportive care but not growth factors.

Additionally, tretinoin (all-trans retinoic acid, Vesanoid), a chemotherapy drug used to treat acute promyelocytic leukemia, was given in cases of little response, disease stability, or failure after four cycles of Vidaza and valproic acid.

The study evaluated response to treatment, transformation to acute myeloid leukemia (AML), survival, and side effects.

Forty-one patients completed four cycles of treatment, and 26 of those patients continued to complete the full eight cycles.

Of the patients that completed eight cycles of valproic acid and Vidaza, 31 percent achieved complete or partial remission. Hematologic improvement was reported in 15 percent, and the disease was stable in 39 percent. The Vidaza and valproic acid regimen also reduced the need for red blood cell transfusions.

However, the addition of tretinoin had no significant clinical benefit.

Patients’ prognostic factors had a significant impact on outcome. At 10 months, disease progression or transformation to AML was observed in 45 percent of high-risk patients compared to 10 percent of lower-risk Intermediate-2 patients. Likewise, survival was also negatively impacted by higher risk. Median survival was 8.9 months for high-risk patients and 18.7 months for Intermediate-2 patients.

Higher response rates were seen in patients who reached higher valproic acid concentrations in their blood, indicating that valproic acid enhances the efficacy of Vidaza.

The most common side effect was low blood cell counts. Twelve patients discontinued treatment due to infections, cardiovascular complications, and neurological toxicity. The mild neurological toxicity seen during treatment was most often linked to Vidaza, while toxicity linked to valproic acid was usually temporary and reversible, said Dr. Maria Teresa Voso of the Hematology Institute in Rome and principle investigator of the study.

“Side effects were mild, and I think that this combination is feasible in higher risk MDS patients,” said Voso.

According to Voso, the research group has plans for a randomized study involving a control group along with the combination therapy group.

For more information, please the study in Clinical Cancer Research (abstract).

MDS U.S. Patient And Family Forum – The Myelodysplastic Syndromes Foundation will be holding a Patient and Family Forum in Pittsburgh, PA on October 21. Guest speaker Dr. James Rossetti of the Western Pennsylvania Cancer Institute will provide important information for MDS patients and their families. The event is free, but registration is required. For more information about registering for the event or for a detailed listing of upcoming U.S. or international forums, please see the MDS Foundation Web site.

For a more detailed listing of MDS-related events, please check the MDS Beacon Events Calendar.