Guest Expert: The Treatment of Leukemia Peter Marks, MD Associate Professor of Hematology Director Yale Leukemia Program This is Healthline, a joint venture of WTIC NewsTalk 1080 and Yale Cancer Center. Yale Cancer Center is a resource for cancer programs throughout Connecticut, developing new advances in prevention, screening, diagnosis, and treatment. On Healthline, you will hear from some of the leading doctors in the country. Healthline is not intended to provide medical advice. Yale Cancer Center urges you to consult with a qualified physician in your community for diagnosis and for answers to your medical questions. And now, our co-hosts, oncologists, Ken Miller and Ed Chu. Miller Good morning and welcome to Healthline. My name is Dr. Ken Miller and I am the Director of the Survivorship Program at the Yale Cancer Center in New Haven. Healthline, with the Yale Cancer Center, is our way of providing you with the most up- to-date information on cancer care every Sunday morning at 8:30 a.m, here on WTIC NewsTalk 1080. Our Healthline program features some of the nation’s leading oncologists and cancer specialists who are in the forefront of the battle to fight cancer right here in Connecticut. Together, we discuss the latest information and treatment details for people with cancer. Our goal is to give you help by sharing this information, and to give you hope because there is a lot of hope in the battle against cancer. If you have questions for us, or for our guests, please e-mail us at firstname.lastname@example.org. If you are interested in listening to past editions of Healthline, or if you would like to learn more about a specific kind of cancer, all of our shows are now posted in audio and written format on the Yale Cancer Center website which is www.yalecancercenter.org. Today, our program focuses on leukemia treatment and our special guest is Dr. Peter Marks, Associate Professor of Hematology at Yale and head of the leukemia program. Peter, thank you so much for being with us today on Healthline. Marks Thank you very much for inviting me. Miller Let’s get right into it, what is leukemia? Marks Leukemia is a general term that describes a group of disorders. Cells that normally go on to form white cells become cancerous as they break free from the normal mechanisms that control their growth; they do not mature into normal functional blood cells. Miller Can you give us an example? Marks To understand the different types of leukemia it is helpful to understand a bit about the types of cells that make up the blood. In simple terms, the red blood cells carry oxygen, the platelets help in clotting, and the white blood cells protect the body from infection. The white blood cells can be further divided into cells that normally go on to protect the body directly from infection by making invaders; these are called myeloid cells and they destroy by engulfing. There are also cells called lymphoid cells that go on to form antibodies. With that in mind, leukemia is also divided into two broad categories; the myeloid leukemias and the lymphoid leukemias. Miller You described three types of cells in the blood, red cells, white cells and platelets. Are most leukemias coming from the white cells? Marks Many, but not all. There are leukemias that can arise from progenitor cells, which are early forms of cells and can actually be analogous to red blood cells or platelets, but all in all, the leukemias occur from cells that go on to become white blood cells with a few exceptions. Miller What are the most common types of leukemia that you see as a leukemia specialist? Marks The most common type of leukemia in the United States is acute myeloid leukemia, which affects about 12,000 people a year in the United States. The next most common is chronic lymphoid leukemia. Miller Do those have a lot in common or are they very different from each other? Marks They are quite different from one another. Acute myeloid leukemia is an acute illness that often requires hospitalization and aggressive or intensive treatment for younger individuals, and supportive care and very careful treatment in older individuals. Chronic lymphoid leukemia, however, is a leukemia that can often be observed in its early stages and many times it is treated as an outpatient with relatively mild chemotherapies or an outpatient chemotherapy regimen. So, they are quite different in how they present and how they are then treated. Miller If someone is told they have leukemia, the next question then would be what kind? Marks That’s exactly right. One needs to know what type of leukemia, whether it is an acute leukemia or chronic leukemia and then whether it is a myeloid or lymphoid leukemia. The different leukemias are treated very differently depending on the type of diagnosis. Miller For now let’s focus in on acute myeloid leukemia. This is obviously a very, very serious disease and as you know my wife had AML about 8 years ago, and thankfully is doing well. What causes acute leukemia? Marks For the most part we don’t understand the inciting cause for the large number of cases of leukemia. Only very rarely are cases of leukemia genetic, that is somebody has a hereditary condition that leads to leukemia. There are very rare families with a rare genetic syndrome called Li-Fraumeni syndrome and other very rare genetic disorders. In terms of environmental exposure, we do know that certain chemicals such as benzine can increase one’s risk for developing leukemia, but most people would have to be exposed to reasonably high concentrations and generally that is prevented with our current environmental standards. People exposed to ionizing radiation that comes from nuclear power plants, and survivors from atomic blasts, are at an increased risk for leukemia. What that leaves us with is a majority of people where we don’t have an answer for what caused it. There is one exception to that; there are people who have conditions of the blood that are pre-leukemia called myelodysplastic syndromes. These individuals have a reasonably high rate of developing leukemia but it does not answer the question of why they developed the myelodysplastic syndrome in the first place. At least we can point to this as a reason why they develop leukemia. Miller Just a quick question related to that. Is it okay to have dental x-rays and mammograms? Marks Absolutely. We feel that the amount of radiation that goes with normal diagnostic procedures, and it has been studied quite extensively, is quite safe. Miller What are the warning signs that someone might be sick? Marks For acute leukemias the warning signs are often relatively nonspecific. They can include fatigue, easy bruising or bleeding, not just minor bleeding but excessive nose bleeding, a reddish rash over their arms and legs that does not go away and repeated infections that don’t go away with courses of antibiotics. If you have any one of these things it would be a reason to see a doctor. Miller How do you make the diagnosis? Marks The diagnosis today for leukemia is often times made using peripheral blood by obtaining a complete blood count. Our modern instruments can actually diagnosis many leukemias with the tests that are done on the peripheral blood. In some cases we have to look into the bone marrow by doing something called a bone marrow examination or bone marrow aspirate and biopsy. This allows us to look at the blood forming cells themselves and to see if there is leukemia in the bone marrow, which is where the blood cells normally form. Miller What happens after someone is diagnosed with acute leukemia? Marks When somebody has acute leukemia, first we have to understand whether they are a candidate for aggressive treatment or supportive care. This is based mainly on age and overall performance status. For younger individuals, say individuals less than 60 or 70 years of age, we generally would admit the patient to the hospital and speak with them about the benefits and risks of chemotherapy. We would start a relatively aggressive regimen of chemotherapy drugs that lead to hospitalization that lasts about a month, and that is followed by additional chemotherapy and sometimes even stem cell transplant. For older individuals, particularly those over 70 with acute leukemia, we tend to think more towards supportive care, low-dose chemotherapies, or clinical trials, because these patients are at risk for major complications when we give them standard chemotherapy that we would give to younger people. It is a little bit more complicated and complex and it really depends on the individual patient in older individuals. Miller We will be back to talk more about the treatment of acute leukemia and some advances being made. I would like to remind our listening audience to email questions to us at email@example.com. We are going to take a short break for a medical minute. Please stay tuned to learn more information about the treatment of leukemia with Dr. Peter Marks from the Yale Cancer Center. Medical Minute This is a medical minute brought to you as a public service by the Yale Cancer Center. There are over 10 million cancer survivors in the US and the number keeps growing. Completing treatment for cancer is a very exciting milestone but cancer and its treatment can be a life changing experience. Following treatment, the return to normal activities and relationships may be difficult and cancer survivors may face other long- term side effects of cancer including heart problems, osteoporosis, fertility issues, and an increased risk of second cancers. The Connecticut Challenge Survivorship Clinic at Yale Cancer Center provides a multidisciplinary approach to helping cancer survivors. The team includes a physician, a neuro specialist, nutritionist, exercise specialist, and a clinical social worker who work together to help care for cancer survivors. Please call (203) 785- CARE for more information or to make an appointment at the Connecticut Challenge Survivorship Clinic. Miller Welcome back to Healthline. We are here in the WTIC studios with my guest Dr. Peter Marks, the Director of the leukemia program at the Yale Cancer Center. Let me ask you, the feeling about acute leukemia in the past was that it was uniformly a fatal disease? Has the prognosis changed? Marks It really has. Acute leukemia in children, particularly acute lymphocytic leukemia, is now a relatively curable disease and about 85% of younger children who have acute lymphoid leukemia are cured with chemotherapy. Acute leukemia in adults is a more difficult disease. About 25 to 50% of adults with acute myeloid leukemia are cured with chemotherapy and/or hematopoietic stem cell transplant and probably about 15% to 25% of adults with acute lymphoid leukemia are cured with chemotherapy. Miller You were saying before the break that some people are admitted to the hospital for a one-month admission. Can you tell us more about what happens after that? Marks Usually they have to have some type of special catheter placed into one of their veins to allow us to give the chemotherapy medicines easily and to take blood, because many blood draws are performed and there are many drugs that will be given, not just chemotherapy medicines. After we give the chemotherapy medicines, which usually last about five to seven days, we then have to give antibiotics because often patients will develop fevers. We also have to give lots of hydrations because as the cancer cells break down they make waste products that need to be eliminated from the body. There are many things that need to happen during that initial month and we draw blood to monitor how patients are doing during the time. Usually for the first two weeks the blood counts go down and then we check to see whether the leukemia is gone by doing a bone marrow examination. Towards the last two weeks of the month the blood counts start to come back up and we are able to stop antibiotics and discharge the patient from the hospital. That is only the beginning of the treatment saga for someone with acute myeloid leukemia, or acute lymphoid leukemia for that matter, because they then need to go on additional chemotherapy called consolidation chemotherapy. The first cycle of chemotherapy that we just went over is called induction chemotherapy; consolidation chemotherapy is given to help make sure that the leukemia doesn’t come back. This is given with brief admissions to the hospital, only five or six days in the hospital, followed by several weeks as an outpatient. Now, in some cases, we can even give the entire regimen as an outpatient and many patients have been quite happy with that. Following several cycles of consolidation chemotherapy, some patients then receive maintenance chemotherapy. This is done for specific types of leukemia, acute promyelocytic leukemia or acute lymphoid leukemia for instance, and these maintenance regimens can last for two years. Miller When is stem cell transplant considered for a patient with leukemia? Marks Stem cell transplants are considered for patients who have particular prognostic features that would suggest that they won't do well with standard chemotherapy. Usually these are things like genetic abnormalities, whether they present with very, very high white blood cell counts, or if they present with involvement of their central nervous system at diagnosis. We might consider taking these individuals to stem cell transplant even when they are in their first remission. For patients who have good prognostic features to start, we would probably wait until they are in a second remission before considering a stem cell transplant. I should note, however, that there is still a lot of clinical investigation going on in regards to whether it is better to take people to transplant when they are in their first remission, or in a later remission. Miller Talking about certain subtypes of leukemia, my understanding is that with promyelocytic leukemia you can actually use a pill form of vitamin A. That is obviously very exciting and very different. Can you tell us about that? Marks Acute promyelocytic leukemia has always been known to be a little bit different from other leukemias in that it was originally known to be relatively sensitive to a particular drug called daunorubicin, which is a chemotherapy drug that is used in the other leukemias. A number of years ago there was a development from China where people realized that a drug called all-trans-retinoic acid could lead to remissions in this leukemia without the need for typical traditional chemotherapy. This was a major advance because individuals with acute promyelocytic leukemia often present with a hematologic complication where their blood essentially clots out of control so they can bleed quite terribly, but with the introduction of this new medicine, it has helped us to bring people into remission without that complication. It has become integral now in our current treatment regimens for acute promyelocytic leukemia. Miller The other thing that I have read about is arsenic. Is arsenic used in treatment? Marks Arsenic has found a role in treatment; again in acute promyelocytic leukemia. This is one of those things that came out of perhaps a more homeopathic type regimen, but there are some signs of benefit behind it now and arsenic trioxide is given to people with relapsed acute promyelocytic leukemia and it is quite effective. In addition, it is now being used in patients who are in first remission as part of the maintenance regimen. So, it has found its way into mainstream treatment. Miller We have an e-mail question from Bob who lives in Wethersfield. He says, My mother was recently diagnosed with acute myelogenous leukemia. Does the medication Gleevec have a role in her treatment? Marks Acute myelogenous leukemia is due to a variety of different genetic abnormalities that are quite heterogenous. There are lots of different ones and unfortunately the particular genetic abnormality that makes another type of leukemia chronic myeloid leukemia very sensitive to Gleevec is not present. So, although this medicine imatinib, also known as Gleevec, is wonderfully effective in chronic myeloid leukemia, in acute myelogenous or acute myeloid leukemia, it generally does not have a role. Miller How well does it work in chronic myelogenous leukemia? Marks For chronic myeloid leukemia, or chronic myelogenous leukemia, they are the same thing, it is one of the most remarkable advances over the past decade in cancer. It has transformed how we as oncologists care for patients. Back in the 1980s and 1990s, patients who had chronic myeloid leukemia and could not undergo bone marrow transplant within four to five years, would develop very aggressive forms of disease and eventually die. Since 2000, when Gleevec was first introduced, patients have been treated with an oral medication once daily. They then go into remissions and 85% of people that go into remissions appear to stay in them for very long periods of time. The most recent data that was published late last year said that people are staying in remission for five years or longer and are doing quite well. It has transformed the management of this particular cancer, and has served as a paradigm for what we hope to achieve in other cancers. Miller I would like to remind you that you can e-mail your questions to us at firstname.lastname@example.org. We are going to take a short break to listen to a survivor story. Please stay tuned to learn more information about leukemia with Dr. Peter Marks. Survivor Story A few years ago the diagnosis of cancer was a death sentence for many patients, but today, thanks to advances in clinical research we are turning the corner in the battle against cancer. There are over 10 million cancer survivors now living in the U.S. They are the true heroes in the war against cancer. Here is the story of a hero from Fairfield. I visited a walk-in clinic on Christmas Eve in 1999, because I thought I had the flu. The doctor there suspected that it was something more serious, and as he examined my belly, he found a mass. I was referred to Dr. Tom Rutherford, a gynecologic oncologist and researcher at Yale Cancer Center, where I had surgery and received chemotherapy for stage II ovarian cancer. Because of early detection, excellent treatment, and the benefit of the latest research, I recently celebrated 6 years as a cancer survivor. Today, I am a fervent believer that women should pay attention to changes in their bodies and should not be reluctant to tell their physicians any concerns they have, even those they feel might sound trivial. Early detection is the best way to cure cancer. This survivor’s story has been brought to you by Yale Cancer Center. Miller Welcome back to Healthline. This is Dr. Ken Miller, and I am in the WTIC studios with our guest Dr. Peter Marks from the Yale Cancer Center. We are discussing some very exciting breakthroughs made in the treatment of leukemia. Peter, treatment for leukemia is very individualized, how does the care team at Yale create a treatment plan for patients with leukemia? Marks The optimal treatment of leukemia involves a treatment theme that includes expert laboratories and pathologists who facilitate making the correct diagnosis. It includes hematologists/oncologists who develop the treatment plan, nurses and other staff such as nutritionists and social workers who provide expert day to day care, and it involves our consultation with specialists such as infectious diseases experts and radiation oncologists in order to provide integrated care for the patient. Miller I know you have very strong feelings about patient focused care. Can you tell us about your own outlook? Marks The treatment plan for any leukemia needs to be individualized to the patient and that comes from a partnership that is developed between the patient and their physician. Every person reacts somewhat differently to the diagnosis of leukemia and our goal is to help each patient understand the treatment options available. This includes understanding the potential risks and benefits associated with the treatments, and then agreeing upon a course of action that make sense medically in the context of the individual's preferences for treatment. As things progress, we reassess the course of action that we have chosen to be sure it continues to meet the patient’s needs. In summary, rather than treating the disease leukemia, what we are ultimately hoping to achieve is care that is focused on the individual person who happens to have leukemia. Miller Coming from a non-leukemia doctor's point of view, there is a feeling that at the Yale Cancer Center people being treated for leukemia are being treated holistically as a person with the disease, rather than just the disease. That is greatly appreciated by everyone. For someone who is diagnosed with leukemia, what research initiatives are underway at the Cancer Center as part of your program? Marks In terms of both laboratory and clinical research, Yale has established strong programs in the investigation of cutaneous T-cell lymphoma that may transition into leukemia. My group’s particular clinical research focus at the moment is on the treatment of older individuals with acute leukemia and the treatment of patients with relapse disease; particularly those with acute myeloid leukemias or those who have relapsed acute myeloid leukemia. Miller Are there any clinical trials currently available that you can tell us about? Marks There are several clinical trials currently available at Yale for appropriate patients with cancers of the blood. At the moment, these are largely focused on patients who are candidates for hematopoietic stem cell transplantation, but we're currently in the process of activating several multicenter clinical trials that will investigate novel agents, or novel combinations of agents, for the treatment of acute leukemia and also for the treatment of chronic myeloid leukemia. Our hope is to offer eligible patients in the community the opportunity to have access to what are thought to be the latest advances in the field through participation in these clinical trials. Miller If a patient wants access to these clinical trials, or another type of treatment for leukemia at Yale, who should they contact? Marks They can access information on clinical trials that are available at the Yale Cancer Center at www.yalecancercenter.org. For patients who are interested in clinical trials in general, they can look on government websites sponsored by the NIH at www.clinicaltrials.gov. Miller I understand you are about to give a talk on leukemia for the public, can you tell us a little about it? Marks The Leukemia & Lymphoma Society is a not for profit organization that sponsors a range of programs from educational information sessions to financial assistance for patients in need. The Society is sponsoring an introductory talk on leukemia for patients and their families. It will be held on March 26, 2007, from 5:30 p.m. to 7:30 p.m. at Yale-New Haven Hospital. For more information, and if you like to register for this free talk, you can contact Shelley Carpenter at the Leukemia & Lymphoma Society at 203-427-2049 or e-mail her at email@example.com. Miller Terrific. That'll be coming up in a few weeks and we'd love to have people go and learn more about acute leukemia. If you have questions for Dr. Peter Marks, or for Healthline, I encourage you to go to our website www.yalecancercenter.org for more information about cancer and the resources available to you. Peter, I would like to share personally, as a person whose wife is a leukemia survivor, it is really wonderful to hear about all of these advances. The prognosis continues to get better for people with these types of diseases. I would like to thank Peter for joining us. Marks Thank you very much for having me. Miller Remember, tune into WTIC NewsTalk 1080 every Sunday morning at 8:30 a.m. for Healthline with the Yale Cancer Center. Our next program will focus on the treatment of colorectal cancer, and our guest will be my co-host Dr. Ed Chu. Until then, this is Dr. Ken Miller from the Yale Cancer Center wishing you a safe and healthy week. You have been listening to Healthline, a joint adventure of Yale Cancer Center and WTIC NewsTalk 1080. Join us next Sunday morning from 8:30 to 9:00 am for another edition of Healthline on WTIC NewsTalk 1080.