Understanding Leukemia

Understanding Leukemia with Charles A. Schiffer, MD, Chat Transcript
Monday, September 19, 2005, 2:00 – 3:00 PM ET
Moderator: On behalf of the American Society of Clinical Oncology (ASCO), welcome to the Cancer.Net Ask the ASCO Expert chat on Understanding Leukemia, a live question-and-answer session hosted by Charles A. Schiffer, MD.

During this hour, Dr. Schiffer will answer as many questions as possible. Due to an increasing number of chat participants and number of questions submitted for each chat event, time simply does not allow us to address all of your questions, and we encourage you to consult your doctor and cancer care team.

Some questions may be adapted so that Dr. Schiffer's answers can help as many people as possible.

Dr. Schiffer will take questions from 2:00 – 3:00 PM ET. As you prepare your questions, please keep in mind that Dr. Schiffer is unable to give individual medical advice in this setting, nor is he able to address questions that include information specific to one person's medical profile.

The information presented here is for informational and educational purposes only and is not intended to substitute the professional medical advice or treatment recommendations provided by your doctor.

This forum is neither intended nor appropriate to serve as a means of obtaining a second opinion on cancer diagnosis or treatment. In response to questions about specific drugs, Dr. Schiffer's comments will focus only on the state of current research and clinical trials.

It is advised that you do not delay seeking professional medical advice based on any information received during this chat event.

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Good afternoon and welcome. Thank you for joining us. Dr. Schiffer will now begin taking questions.

Charles A. Schiffer, MD, is currently Professor of Medicine and Oncology at the Karmanos Cancer Institute at Wayne State University School of Medicine.

Dr. Schiffer is a member of numerous professional societies including the American Society of Hematology and ASCO and sits on the editorial boards of several oncology journals. He is the editor of the Leukemia section in the journal, Current Opinion in Oncology.

Dr. Schiffer is a respected expert in leukemia and platelet transfusion therapy and has published numerous papers on these subjects.

Dr. Schiffer, thank you for taking the time to join us today.

Guest36: Is CLL or CML leukemia hereditary? What causes the majority of cases?

Dr. Schiffer: These are two entirely distinct diseases, and we'll address them separately. With regard to CML, there is no suggestion that this disease is hereditary or runs in families. We don't know the exact cause of CML, but there was an increase incidence of CML after the atom bomb exposures in Japan.

This had a peak in the decade or so after the bomb and no further increase after that. We also know that, in contrast to AML, there is no increase in the incidence of CML after exposure to chemotherapy or radiation treatment for other disorders.

With regard to CLL, we also do not know the cause of this disease. It is of interest that B lineage CLL is rare in Southeast Asia and Japan, whereas it is the most common type of leukemia in the western world. In general, CLL is not a familial disorder, but there are occasional families with multiple cases of CLL and other lymphoproliferative disorders.

There is, in fact, an NIH registry that is collecting information on such families. The hope is by studying this more carefully, it may be possible to identify a genetic marker that may be present in some circumstances.

To reassure people, in general, this is not a familial or hereditary disorder.

Guest22: Can you please talk about the relationship between myelodysplastic syndromes (MDS) and leukemia?

Dr. Schiffer: MDS, or myelodysplasia, is a common disorder that affects the myeloid stem cells, the immature cell that ordinarily matures into red blood cells, platelets, and white blood cells.

It has a variety of clinical problems associated with it, and probably includes a number of different disorders that are grouped under the name "MDS." Some of the subtypes of MDS have a tendency to progress to acute myeloid leukemia (AML).

If that occurs, it is generally more difficult to treat than patients whose leukemia does not have preceding MDS. But while leukemia is one problem associated with MDS, other problems that are more common include anemia, low blood platelets, and low white blood cell counts, which can predispose a person to infection.

Guest9: How does a patient figure out the options available for relapse treatment? Can you give specific steps to finding out all the possible options?

Dr. Schiffer: This is a complicated question because different leukemias relapse in different ways. Some require immediate treatment. This is usually the case in ALL or AML. Treatment can often be delayed in CML. Once a decision is made, though, that treatment is necessary. The choice of the type of treatment depends on a number of factors.

Just to generalize, perhaps the most critical factor is the quality of the initial response. That is, if there was a very long remission, one would be more inclined to utilize the therapy that was associated with the long remission and to repeat that treatment.

On the other hand, if the remission was short, or the relapse occurred while treatment was being given, then it not advisable to use the same treatment. You may want to consider new drugs or different approaches.

Another important issue is to determine whether stem cell transplant should be considered as part of the treatment for relapse—either as treatment for the relapse itself, or commonly, as a consolidation treatment after a second response is obtained because it can take awhile to organize a transplant. It is advisable to think about whether it is appropriate at the time the relapse is detected.

For people relapsing after transplantation, this is an even more difficult question. The first consideration for those who receive allogeneic transplants would be the infusion of donor lymphocytes.

Guest174: In general, what do most patients with leukemia die from, opportunist diseases, etc.?

Dr. Schiffer: The usual cause of death in people with leukemia is infection, usually related to low neutrophil count. There have been major advances in supportive care, such that bleeding is an unusual cause of death. Bleeding, as a major side effect, is unusual. It is also important to emphasize that the symptoms of fatigue and weakness, which can be present in people with leukemia, can be helped with aggressive use of red blood cell transfusions.

Guest156: Can chemotherapy from leukemia treatment cause a person to lose motivation, drive, and personality? My daughter was a strong, viable person, but now it seems that is gone. She is in remission, but she has been left with some memory loss and lacks the "winning spirit" she had when she got sick.

Dr. Schiffer: Leukemia treatment is difficult, prolonged, and scary and requires a significant emotional and time investment on the part of patients and their families. It is common that many people feel quite bad and depressed with less energy once all the treatment is over; this comes at a time when one might expect them to feel great.

Some of this can be attributed to the fact that there is continued anxiety about whether the leukemia will come back, financial issues, or other stresses of the illness. Usually this is transient, and people gradually improve.

When depression is more prolonged, talking to one's caregivers, a therapist, or support group can be helpful. It is important to make sure that there are no specific medical causes that may be contributing to these problems.

Sometimes, there can be longer-term side effects from the chemotherapy, such as cardiac, pulmonary, or even subtle viral infections.

The patient should talk with his or her doctor about these possibilities.

Moderator: Transcripts of today's chat will be available September 20, 2005, on Cancer.Net by 12:00 PM ET. More information about receiving transcripts will be provided at the end of the chat.

jcc: How are the donor's stem cells matched to the patient's stem cells in allogeneic or syngeneic transplantation?

Dr. Schiffer: Matching is done by determining the tissue type of the donor and the recipient. These tissue types are inherited so that in general, parents and children are usually 50% different from each other. As a consequence, the first option is to look at siblings.

The chance of any one sibling being a match with another sibling is 25%. If there isn't a match within a family, a search for an unrelated donor begins. This begins with a computerized search of tissue types of millions of people around the world.

The chance of obtaining an unrelated match is a function of how common the tissue type of the patient is. For some people, you can readily identify dozens of donors, whereas for other people, often in minority ethnic groups, it can be considerably more difficult. In general, a donor can be found for most recipients.

Cord blood cells, which do not have to be as closely matched, are being used as another source of stem cells. An issue, however, with the cord blood cells, is that the dose of cells is not sufficient for adults. Most of the experience to date has been in the pediatric population.

Syngeneic transplants refer to transplants from identical twins.

Kara98: What risks are there for a bone marrow donor?

Dr. Schiffer: The risks to a donor are quite minimal. Most stem cell collections now are done using peripheral blood, rather than bone marrow. The donor receives a drug called G-CSF [filgrastim (Neupogen)], which increases the number of stem cells in the blood.

The donor then undergoes leukopheresis using a machine that can separate stem cells from the rest of the blood cells. The machine that is used is identical to the machine used to collect platelets from normal donors, which is done hundred of times daily in the United States.

The major discomfort with the procedure is the insertion of the needle. Some donors will also experience mild bony discomfort after the G-CSF. If bone marrow is used as a source of the stem cells, the procedure is more complicated.

The donor is anesthetized in the operating room and multiple bone marrow aspirates from the hip bone (both sides) are taken. The procedure is safe, but discomfort at the site of the bone marrow aspiration can last a few days.

DaveL: Can you please discuss how leukemia is different in children than it is in adults?

Dr. Schiffer: Leukemia in adults has many differences but also many similarities. For example, in AML, the disease is quite similar in children and adults, although it is uncommon in children who had prior MDS. In addition, certain cytogenetic subtypes of AML occur more frequently in children.

In general, it is the more favorable subtypes that are more common in children and younger adults. The principles of therapy are very similar. There are more differences between adults and children with ALL.

For example, about one-third of adults have ALL associated with the Philadelphia chromosome. This is quite resistant to treatment in adults, but it quite uncommon in children with ALL.

There are differences in the frequency of other molecular subtypes of ALL in adults and children, and it is largely because of these differences that the outcome of treatment is much better in children than in adults.

In addition, children tolerate more intense treatments more easily than adults. This is a particular issue in people with AML because the median age of adults with AML is around 65.

Guest106: I am a 41-year-old female and was diagnosed with CLL three years ago. I did 12 rituximab (Rituxan) treatments last year. They were effective for a couple of months. My white blood count is steadily increasing and my dilemma is what kind of treatment should I do next. Do you suggest aggressive treatment through a clinical trial or just keep doing rituximab for as long as I can? Should I seek a second opinion?

Dr. Schiffer: I can't answer the question specifically, but I can make general comments about CLL. In general, treatment for CLL controls but does not eliminate disease, so patients have to face this particular question frequently.

There are a number of different options at the moment, including the use of fludarabine (Fludara), either alone or in combination with (Cytoxan). Some people would consider three drugs: fludarabine, cyclophosphamide, and rituximab. These are options that should be discussed with your doctor.

In addition, because treatment can control but does not cure the disease, many doctors also discuss the use of stem cell transplant in younger patients with CLL.

Also, there may be clinical trials that would be suitable for this situation.

Beth67: How can a person with leukemia best manage anemia and low platelet counts? These can be very debilitating side effects.

Dr. Schiffer: With regard to anemia, the major recourse is through red blood cell transfusion. Part of the answer depends on what type of leukemia, whether treatment is being given continuously or episodic, but red blood cell transfusions remain the standard and should be used liberally.

Erythropoietin can help in certain circumstances, but it is difficult to be more specific without further details.

Platelet transfusion can be used both to treat and prevent hemorrhage. Using platelet transfusions are highly dependant on the patient's circumstances. It is important to emphasize, however, that the decision to administer platelets should take into consideration any clinical factors in addition to the platelet count itself.

For example, there are many patients that have stable, low platelet counts, even less than 10,000, who do not have any bleeding and who, therefore, do not need any platelet transfusion. On the other hand, there are people who have bleeding at higher platelet counts and need transfusion. This is highly variable from individual to individual.

Other clinical factors have to be considered by the patient's physician when deciding about whether to administer platelet transfusion.

Guest215: What are the new treatments on the horizon (or in trials) for MDS?

Dr. Schiffer: There have been a number of new treatments recently for MDS. A drug called azacitidine (Vidaza) was recently approved by the FDA and produced benefit in approximately one-third of those who received it. A drug that is similar to this, called, decitabine, has also undergone extensive clinical trials and is being reviewed by the FDA with results that are in the same range.

Lastly, just last week, the FDA reviewed a drug called lenalidomide (Revlimid), which produced extremely high response rates in people with a certain subtype of MDS called 5q- syndrome. Lenalidomide is given orally and the others are currently given by injection. What is particularly exciting is that specific therapy for a specific subtype seems to have been identified.

Still, there is an enormous need for improvement and patients are encouraged to participate in clinical trials with these and other new agents in order to improve outcomes further.

Moderator: The chat is now ending. Thank you for your thoughtful questions.

We hope this discussion has been valuable, and we regret not being able to answer every question. We want to thank Dr. Schiffer for lending us his time and expertise.

TRANSCRIPTS: The full text of today's chat will be available on Cancer.Net (www.cancer.net) September 20, 2005, by 12:00 PM ET. To receive a copy of the transcript by e-mail, please send a message to chats@asco.org.

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The featured expert is Lori Goldstein, MD, of Fox Chase Cancer Center.

The chat room is now closed. Thanks again for joining us.

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Last Updated: September 20, 2005