Acute Myelogenous Leukemia (AML): Emerging Treatment Approaches Judith Karp, MD April 15, :00pm ET

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1 Hello, everyone, and welcome to Acute Myelogenous Leukemia (AML):, a free telephone education program. It is my pleasure to introduce your moderator, Carson Jacobi. Thank you, Lindsey, and hello everyone. On behalf of The Leukemia & Lymphoma Society, thank you for choosing to spend this hour with us today. We welcome you to Acute Myelogenous Leukemia (AML): Emerging Treatment Approaches, featuring Dr. Judith Karp. We thank her so much for sharing her time and expertise with us today and for her ongoing dedication to serving families touched by cancer. We would also like to acknowledge and thank Cephalon Oncology and Eisai for their support of today s program and for their continuous support of patient education initiatives. You all should have received a packet of information in the mail including an agenda, a biography of Dr. Karp and an order form for The Leukemia & Lymphoma Society s materials. We encourage you to look through those materials at your leisure if you have not already done so. You will also find an evaluation form for you to fill out for today s program and for nurses and social workers, you can receive one hour of continuing education credit. All participants may visit our online evaluation center at to complete your evaluation online or mail it in an enclosed self-addressed envelope. I ll provide more information for nurses and social workers at the end of our program today. Now after Dr. Karp s presentation we will open up to questions from all of you, our telephone audience. We have over 1,300 individuals registered for our program today from across the United States and several international participants. They re from Barbados, Canada, Kenya, Lebanon, Mexico and Sweden. A special welcome to all of you. If we re not able to get to your questions today, you can call The Leukemia & Lymphoma Society s Information Resource Center, which we refer to as the IRC. The toll-free number, included in your packet, is This will connect you with an oncology professional, who can answer your questions, help you obtain information or order free materials specific to your needs. And the IRC s hours are 9 AM to 6 PM Eastern Standard Time, Monday through Friday. 1

2 We are also audiotaping and transcribing today s program for posting on the LLS Web site in several weeks, so you can watch out for that. This provides an opportunity to read or listen again to today s presentation, especially to follow up on any terminology or therapies that you may have missed. Now before I turn the program over to Dr. Karp, I would like to introduce the LLS President and CEO, John Walter, who s on the call today to welcome you and share a few words. John, thanks for joining us. JOHN WALTER: Thank you, Carson. I d like to add my welcome to all the patients, caregivers and healthcare professionals on the call today. We are fortunate to have as our presenter Dr. Judith Karp, a world-renowned physician and researcher in acute myelogenous leukemia and a long-time friend of LLS. We appreciate Dr. Karp s dedication to supporting the mission of The Leukemia & Lymphoma Society through her research, clinical practice and participation and leadership on The Leukemia & Lymphoma Society s Medical and Scientific Affairs Committee. I wish to thank her for taking the time out of her busy schedule to provide us today with an update on emerging treatment approaches for AML. The Leukemia & Lymphoma Society is committed to bringing you the most upto-date information about your blood cancer. We know it is important for you to stay current, so that you can work with your healthcare team to determine the best options for the best outcomes. Our vision is that one day the great majority of people who have been diagnosed with a blood cancer will be cured or they will manage their illness with good quality of life. Since its founding in 1949, LLS has invested more than $600 million for research, specifically targeting blood cancers. We will continue to invest in research for cures and programs and services that improve the quality of life for patients and their families. This teleconference is one step on the road of your journey to managing your life with AML. Thank you and I ll turn the program back over to Carson. Thanks, John. I now have the pleasure to introduce our speaker, Dr. Judith Karp. Dr. Karp is the Professor of Oncology and Medicine and Director of the Leukemia Program 2

3 at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital in Baltimore, Maryland. Her research interests focus on the experimental therapeutics of acute leukemias including the development of timed sequential therapy, new biologic agents for older adults with acute leukemias and new approaches to the treatment of refractory acute leukemias, including secondary leukemias that evolve from myelodysplasia or from prior cytotoxic chemotherapies. You can read further about Dr. Karp from her biography that s included in the packet. Dr. Karp, we re so privileged to have you with us. I ll turn the program over to you. Carson and John, thank you very much. And it is my privilege to be here today to talk about AML with everyone. I suspect that this is a very well-versed audience, a very sophisticated audience, so what I would like to do is just spend a brief moment talking about the demographics of AML and then go into some of the newer drugs and treatment concepts and actually end up with genetics. I thought I would do the genetics first and then I thought about it and I thought maybe it would be better to do that last. So if you re all ready, let s get going. Everyone says that AML is a rare disease and, of course, in my estimation it s not a rare disease because that s what I do. But the truth is, is that there will be at least 14,000 to 15,000 new cases of AML this year and that does not include the so-called 6,000 unclassified leukemias, 90 percent of which are AML. The other thing is that people think of AML as a disease of children, much like ALL. The median age for patients developing AML is 70 and, the last time I looked, that might not be old, but it certainly isn t childhood. The other thing is that there are about 11,000 to 12,000 new cases of myelodysplasia a year, many of which will evolve to AML or may already be AML in disguise. And we have a lot of work to do here. If you re under the age of 55, your chances of getting a remission with traditional cytotoxic or cell-killing chemotherapy is 70 or 80 percent, with a remission duration that s a year and a half to two and a 30, perhaps 40 percent chance of being cured either with chemotherapy or bone marrow transplant, depending on certain features of your leukemia. 3

4 If you re over the age of 55 to 60, there s a dramatic change. The chance with traditional chemotherapy of getting a reasonable complete remission is less than 40 percent. The duration of those remissions is only seven or eight months. And the chances of being cured drop remarkably. So we ve got a lot to do. We ve made some major progress. I think that alltrans retinoic acid, a Vitamin A derivative for acute promyelocytic leukemia, has changed that disease dramatically and in fact is part of a true standard of care for that disease. Drugs like Vidaza and Dacogen and Revlimid for myelodysplasia are very exciting. Gleevec and Sprycel for chronic myelogenous leukemia or Rituxan for chronic lymphocytic leukemia, all of these things are incredibly important, they re all derived from a molecular understanding of the diseases. But the job is nowhere near done and won t be done until we can either cure 100 percent of people or turn this very terroristic disease into just something like a nuisance. So what do we need to do to cure the disease? Well, we need to obviously continue with our basic science investigations, to understand the obstacles that we now face to curing leukemia. And these obstacles relate both to the patient and to the disease and to understanding which pathways in the cell are the most critical and how the cell also can develop a resistance, by recruiting new pathways. And I think we have done that and I think that as a result of that, we actually have a number of new drugs that are in the clinic and those that are coming up to the clinical testing point, that I think provide significant excitement for now and for the future. One of the big challenges that we face is the notion of targeted therapy. It s a marvelous idea, but the fact is that leukemia does not live by one lesion alone, it doesn t sustain itself by one lesion alone and it s very unlikely that we re going to cure it with one drug alone. But with the understanding of what pathways are important, we may be able to combine some of these targeted therapies and combine them with regular chemotherapy, to improve the outlook. So I think what I would like to do at this point is just review with you some of the new drugs and new treatment concepts that are moving to the foreground. 4

5 I think one point that I want to make now and repeatedly is that the only way that we re going to get better is by doing clinical trials, at all stages of the disease, from new diagnosis to most refractory, from induction therapy to remission consolidation and maintenance therapy. The only way we re going to learn is through clinical trials and it really offers a chance that you don t have otherwise. I think it s important to understand that until we re curing 90 or 100 percent of people with these horrible diseases, we do not have a standard of care. People may say well, this is a standard therapy, don t make the mistake of thinking that it s a standard of care because it isn t. We re not there yet and the only way we re going to get there is with clinical trials. And what we learn from today s clinical trials will be the basis for what we do tomorrow. I think that s a very important point. The other thing about clinical trials is that in people who are older, (I have a lot of folks now who I care for who are over the age of 80), we may need some different endpoints. We keep thinking about complete remissions for these folks, but maybe we need to change our goals and instead work to turn the leukemia into a chronic niggling little problem that is easily dealt with rather than trying to cure the leukemia with drastic measures. So on to some new drugs. I think there are four categories of drugs and treatment concepts that are currently in play. First of all there are new cytotoxic drugs. These drugs are aimed at killing cells, just like the old ones, but the new drugs trigger new pathways that lead to cell death and thereby overcome resistance and are being combined with the traditional agents like Ara-C and daunorubicin or idarubicin. For example, clofarabine is a relatively new drug that by itself has some very impressive activity in older folks. And when combined with Ara-C, has impressive activity in patients whose leukemia has relapsed. There is a drug called Cloretazine or laromustine, it s a little bit like the well-known drug Cytoxan, in the same class but actually quite different. And it, too, has impressive activity in acute leukemia in patients who are in their 60s, both in patients with full-blown leukemia and patients with leukemias that evolved from myelodysplastic syndromes. New drugs such as voreloxin and flavopiridol work on the mechanics of the cell cycle, preventing cells from actually completing the division cycle by blocking the progress at different stages of that cycle. These are showing tremendous progress up front for patients with AML who are newly diagnosed, who are over the age of 50, and also in patients with relapsed or even refractory disease. 5

6 So this is a very exciting possibility and these drugs are being combined safely and effectively with other drugs such as Ara-C and anthracyclines like daunorubicin or mitoxantrone. There s another completely different class of drugs called antisense molecules. These molecules are designed to attach to and inhibit messenger RNA. These have been developed for key molecules that make cells survive. By being able to silence or neutralize those survival molecules, it may be that the drugs that we use to kill cells to begin with, like Ara-C and daunorubicin, actually will have much more effect. There are some very interesting clinical trials that are going on with this approach, again, in patients whose leukemias are associated with poor risk factors or are in the refractory state and the results of these are again encouraging. So those are some of the new cytotoxic drugs: they kill cells by attacking phases of the cell cycle or specific molecules that make the cell survive when it s been damaged. There s a new concept called epigenetics, based on the finding that, in the malignant state, certain genes are turned off and that the processes of turning those genes off contribute to making or maintaining the malignant state. There are drugs that can reverse the silencing process, and these drugs are being studied very intensively in both the laboratory and the clinic. In fact, there are now many clinical trials, using these very interesting agents, either alone or in combination to try to open up genes that will drive the cell to look normal. The problem in leukemia is that the malignant cells remain immature, and as such do not function but rather suppress the normal stem cell. If we could get leukemic cells mature, perhaps they wouldn t be such sociopaths and maybe the cell would look and act normal. There are two processes that lead to gene silencing. One is caused by methylation, and there are two drugs that inhibit the process; 5-azacytidine or Vidaza, and Dacogen. Another mechanism of gene silencing is called histone deacetylase inhibition. Histone deacetylases attack different parts of the genomic structure and silence genes in a way that is different from methylation. There are several histone deacetylase inhibitors in clinical trials for example valproic acid, SAHA, entinostat and these drugs are now being combined with Vidaza or Dacogen. They appear to have their greatest benefit with patients whose cells have some ability to differentiate already, for instance, in the setting of myelodysplasia. There may be positive effects in some in older patients with leukemia, as well. 6

7 Thirdly, and the model for this is acute progranulocytic leukemia (or APL), there is so-called differentiation therapy. APL is the most curable of the acute myeloid leukemias. And for this disease I think we have a true standard of care. Dr. Martin Tallman in this country and the French investigators really pioneered the use of the Vitamin A derivative all-trans retinoic acid. This is a very interesting story. The Chinese knew for 1,000 years that retinoids were good for APL. And in 1990 the molecular lesion for APL was characterized and it was found that it was an abnormal retinoic acid receptor. All-trans retinoic acid overcame the effects of that abnormal receptor and so, when added to chemotherapy, the cure rate for APL goes up to 75 percent. The concept of differentiation therapy is being translated to other leukemias by testing all-trans retinoic acid and some of the histone deacetylase inhibitors that we mentioned earlier, sometimes combining the drugs with growth factors to push the growth and differentiation, of those leukemic cells. Finally, what I would like to discuss with you is immunologic therapy or immunotherapy. This is not a new concept. Bone marrow transplantation exerts its effects on the immune system. The problem is that we need harness that immune reaction, and so there is a lot of work going on, trying to understand how graft-versus-host disease evolves, which subsets of immune cells are responsible and if those subsets can be tamed by giving Cytoxan after a transplant, which is being done here and in Seattle. The concept of donor lymphocyte infusion after the transplant, i.e., removing some of the more toxic immune cells before the transplant and then giving them back when the patient is healthier, is also an exciting concept. Finally, having a vaccine that could target the fundamental leukemic cell, hopefully exclusively, and not target the normal stem cell, and cause an immune reaction against that leukemic cell. This is a concept that is being tested across the country and around the world. Finally, I want to talk briefly about our rapidly increasing knowledge base regarding the biology of leukemia, especially with regard to understanding which genes are involved and what that involvement means. I suspect that many people in the audience are quite familiar with FLT-3. The FLT-3 molecule is one of the natural molecules on a normal cell. It acts as a receptor for a growth factor and is essential to the development of normal stem cells. But when the gene for FLT-3 is mutated, it is continuously active, which means that the cell keeps growing without any control. It does not cause AML per se, but it makes the leukemia very resistant to chemotherapy. 7

8 There are inhibitors of the mutated FLT-3 molecule that are in clinical testing in some newly diagnosed patients or in the relapse setting. We know that these inhibitors truly do target the mutant FLT-3 molecule quite selectively. By itself in the face of full-blown leukemia, those drugs don t do much, but when they are combined and sequenced with traditional chemotherapy, the effects appear to be very promising so far. We continue to learn that there are a number of molecules that have been identified that can determine the prognosis. This is a very important thing because it will help us to more accurately determine who is at risk of relapse, who needs more therapy versus who needs less. You don t want to do a bone marrow transplant on someone who doesn t need it, but you do want to do it if the patient is going to benefit from it. This area of genetic risk assessment, if you will, is just beginning. We re learning that there are many combinations of abnormalities in these different molecules and these molecules extend from the cell surface right into the nucleus. And depending on how they re combined, the prognosis can either be more or less positive. I think that the real future of these types of studies is that eventually we will be able to develop selective therapies based on the genetic features of the disease, both during induction and in remission. This is an area where there have not as yet been many fruitful studies. In this regard, one area where we need to focus our interest is in treating patients when they re in remission, especially patients who are older, where we have learned that traditional consolidation therapies don t help us. What we do know is that there are several drugs or drug classes that can target some of these critical molecules. In addition to FLT-3 there is a gene called Nucleophosmin 1 that can be mutated and the mutated gene is sensitive to regulation by the histone deacetylase inhibitors. Mutations in a differentiation gene called C/EBP alpha can be corrected, functionally by all-trans retinoic acid. Vascular endothelial growth factor, a very important growth factor in making cells survive and be resistant to chemotherapy, can be suppressed by an antibody called Avastin, which is approved for renal cell cancer and may have some promise in our blood cancers as well. So just to sum up, we are making progress and that s a good thing, because we have a lot of progress to be made. Clinical trials are the way we re going to do it. We have lots of ideas. We have lots of new drugs. It takes a long time to learn how to use those things best, but we might as well get started. 8

9 And I think we have gotten started. The Leukemia & Lymphoma Society has provided major support, both to the laboratory studies and the very innovative clinical trials of some very new agents. That s what we need to do. And one of these days we ll have a true standard of care and these diseases will just be nuisances and that s my hope for the future. And I m ready to take questions, Carson. Very good. Thank you so much, Dr. Karp, exciting news and information about these emerging treatment approaches. It is now time for the question and answer session. So before Lindsey gives instructions for you to enter the question and answer queue, I would like to remind you that because we have many participants on the line, for everyone to benefit, if you can please keep your questions general in nature and brief, and Dr. Karp will provide an answer general in nature. Your phone line will be muted after you ask your question, so Dr. Karp can respond. So Lindsey, please give instructions, so our audience can queue themselves to ask a question. LAURA: To participate in the call by asking a question, please dial star-1 on your keypad. We will take questions in the order they are received. Be aware that due to time constraints, we can only take one question per person. Once your initial question has been voiced, the operator will transfer you back into the audience line. Again, to participate in the call by asking a question, please dial star-1 on your keypad. Great. We ll take our first question, please. Our first question comes from Laura from North Carolina. Yes, Dr. Karp, my question is you say the median age is 70. I happen to have two children diagnosed with AML three years apart. One went through a bone marrow transplant, donor leukocyte infusions, did great for two years, relapsed and passed away a little over a year ago. My other daughter, of course, worried to death that it might come back. My question is, do you recommend me looking into the vaccine? Because every time I ve talked to her doctors, they say we don t know enough about it. 9

10 BARBARA: You know, that s a very aggravating, but very, very accurate statement. And we don t know enough about it. In fact, we know very little; most of the vaccine trials are for adults and we are very early in the testing process. I don t think it s unreasonable to call some of the places. Actually the National Cancer Institute has a central line that could help you find out where the clinical trials are taking place so that you could talk to someone and find out if this would be feasible. As I said, most of the vaccine trials are for adults. Some day in the future it ll be something that we hopefully can give to everybody. Thank you, Laura, for being on, and we are sorry for your loss. We ll take our next question, please. The next question comes from Barbara from California. Dr. Karp, my husband Peter is 71 and has AML. He s now being treated for MDS with Dacogen and it s the first time in a year that he s actually feeling better. What I d like to understand is does a person who has AML automatically have MDS as well? Because we just found out about the MDS fairly recently. Or can you have MDS without having AML? Excellent question. Yes, you can have MDS that has not evolved to AML and there are some types of MDS that never become AML. In fact, probably only a third to a half of all MDS does become AML, but that percentage in older patients goes up. Sometimes when you make the diagnosis of AML, you don t realize that somebody had MDS. They were hail and hearty, they were tired, but they didn t go to the doctor, they don t have a history of transfusions or anemia or problems with platelets, and so the diagnosis of MDS underlying the AML can t be made until perhaps you see which way things have evolved. And sometimes you can see from treatment that you put somebody back to an MDS state, you don t cure the leukemia, but you get a remission that has a little bit of that MDS in it. Sometimes the chromosome abnormalities will be very suggestive of a prior MDS or other type of disorder. I m very excited to hear that your husband is doing well with the Dacogen and that s really where Dacogen is showing its stuff, is in the patients who have MDS that is complex or has already evolved to AML. So I hope that his good health continues for many years. Barbara, thank you for the question. Let s take another question, please. 10

11 JANE: The next question comes from Jane from New York. Yes, Dr. Karp, my husband has AML. He s 64. And he has just started ON1910. I wondered if you had any information you might be able to share with me about that. If I only knew what ON1910 was, I would be delighted. I don t know what it is, I m sorry. I have no idea. There are many new agents out there and all of us are patting one piece of the elephant, as it were. And so I m sorry, I don t know that particular agent. If you know what its mechanism of action is or whatever, I would be happy to talk about it. But I don t want to give you any fake information. I will tell you, though, that no matter what it is, if he s in a clinical trial with people who literally do leukemia for a living and are passionate about it, then he s in the right place and he s getting the right thing. Jane, thank you for the question. And you can always follow up with our Information Resource Center and one of the specialists can help you with a search and can possibly answer that question for you. And also back to Laura s question about the vaccines and her child, we also can help you with a trial search if you have any interest, based on your child s age and location. So please know that the IRC can do that for you. Let s take our next question, please. EVELYN: The next question comes from Evelyn from Missouri. Hi. I m in Montana. I was treated at University of Washington Hospital in September, 2007 with induction and consolidation treatments and I was in Seattle for seven months. And you were talking about clinical trials and I was on Ara-C and Idamycin. And so I am 67 right now. Is there any benefit for myself to do clinical trials? I think this is an important discussion that you should have with your physician. There are many things that go into whether or not you need more therapy at this time. If your leukemia were to come back or there was some evidence that it in fact was going to blossom, then that would trigger a search for an appropriate clinical trial. And certainly the folks in Seattle are among the best in the world and they do wonderful clinical trials. And as long as you re followed closely, I think you ll be in good shape. But I think if the leukemia were to come back, definitely a clinical trial would be something to pursue vigorously. 11

12 PAUL: CAITLIN: Evelyn, thank you for the question. Let s take our next question, please. The next question comes from Paul from Ohio. Hi, Dr. Karp. If someone has AML and they have shown no evidence of leukemia during a recent bone marrow aspiration, but counts remain low, all counts remain low, is Atgam ever appropriate to use? And if so, what are the risks for using Atgam in a situation like that? That s a very good question. Atgam is an immunologic reagent that has found a very important place in the treatment of aplastic anemia and in some types of myelodysplasias, particularly those myelodysplasias that may relate to immune suppression of the bone marrow. In AML, however, there is no good evidence that Atgam would be helpful. And as with everything else, you know, for every action there is a reaction, every drug has its good points and its bad points. Immune suppression is not for the faint of heart. And now there may be a very good reason that your physician thinks that Atgam would work and so I don t want to say oh, it would never work. There may be selected situations where in fact this is exactly right. But as a generalized statement, the use of immunosuppressants to make counts come back quickly has, sadly, never been shown to be helpful in general. I hope I ve answered your question. Paul, thank you for the question. Another question, please? The next question comes from Caitlin from Connecticut. I received a bone marrow transplant in Seattle almost two years ago and I was told if I got to two years my odds of a cure were 89 percent. I m two and a half years out from diagnosis and two years from transplant and I was just wondering, because I think it was quoted in the beginning the odds of a cure are 30 to 40 percent, and that s very different than what I had been told in Seattle. Thank you. Well, the odds of cure in you were 100 or zero. And I don t know your age. If you take all people under the age of 50 or 60, you will find that the cure rate is 30 to 40 percent for all of those people. Probably 20 percent of those people will have what s called primary refractory leukemia, which means they won t ever get a remission. Another group of those patients will have a myelodysplastic syndrome underlying their leukemia and either may never get a remission or will have a short remission. There will be a very small proportion of people whose chromosomes are, quote, favorable (I always consider that an oxymoron). 12

13 But people with normal cytogenetics may have a FLT-3 abnormality, which carries with it a poor prognosis. So you are looking at yourself, which is great, I wouldn t want you to look at anybody else, but when you look at all-comers, then you see an overall cure rate of 30 to 40 percent. Now the fact that you have gone as long as you have puts you in a very select and wonderful group. We are not able to do that, tragically, for most patients. So I m thrilled for you, as your physician should be, and I hope I ve answered your question. MARTA: MARY: Caitlin, thank you for the question. Let s take our next question, please. The next question comes from Marta from Florida. I am an AML survivor. I was diagnosed in 2003 and my blood counts are also low, abnormally low, but I have high energy and feel fantastic. Are there some genetic paths I should explore in terms of risk assessment? Or just go on enjoying life? Oh, I think going on and enjoying life is exactly what you should do. You are obviously doing great. If you are not requiring transfusions, you re not getting infections, and your counts are only mildly low, there s nothing that we know how to do that s going to make the bone marrow look prettier. But if it s acting pretty and you don t have any blasts and your leukemia has not come back, I would probably get off this conference call and go out and play golf. Thank you, Marta, for the question. Let s take our next question, please. The next question comes from Mary from Alabama. I have been diagnosed with AML with APL subtype. And I had arsenic trioxide as my infusion therapy. I did well with the arsenic and they gave me the daunorubicin and I was wondering if my chances are better for a cure with the arsenic trioxide. That s an excellent question. APL is among the most curable subtypes of AML. I think we have a great understanding of APL on a molecular level. And we ve learned how to take care of some of the problems that commonly complicate the leukemia, for instance, the potential bleeding problems which used to be lethel. Arsenic is a very interesting drug. Again, the Chinese have led the way in this. And the use of arsenic has been very successful in those few people who do relapse. 13

14 RITA: Whether or not arsenic is better than all-trans retinoic acid we don t know. The effort is going to be to combine the two drugs up front. Your chances of having a very long and wonderful response are excellent with the arsenic and the daunorubicin and so I think you ve been treated perfectly well. And good luck to you. Mary, thank you for the question. Another question, please, Lindsey. The next question comes from Rita from Pennsylvania. Dr. Karp, thank you so much for the enlightening conference. I wanted to hear your opinion on the tandem transplant. I know they re not done frequently and the University of Arkansas has been one of the pioneers and continue to do that. I just wanted your general feeling and especially about the haplo if there s not able to be a good donor found after an auto-bone marrow, when you re repeating with the allogeneic. Excellent questions. Let me preface this by saying that I m a leukemia girl and I m really not a transplant girl. That said, you can t do leukemia and not know a little bit about transplant. The tandem transplants have applied predominantly to multiple myeloma and I think that the debate as to whether they should be done, whether they re better than other forms, will probably go on well into the middle of this millennium. It s an area of controversy. Suffice it to say that I think Bart Barlogie and his team have demonstrated some remarkable long remission rates/cure rates in patients with myeloma who have gotten tandem transplants. And these are autologous transplants, meaning your own bone marrow. Tandem transplants really don t apply to the allogeneic bone marrow transplant. Allogeneic just means from somebody else and those can either be what s called a full transplant or a so-called mini-transplant. They can be matched or half-matched, i.e. haplo. I think that the mini-transplant, you know, is it as good as a full transplant? This is a research question that s being determined. If you re 50 or 55 and under, then I think that the urge in general is to do a full intensity transplant from a matched donor, preferably if you have a sibling, otherwise a donor from the registry. That s preferred because that s what s been done for the last 40, 45 years. The mini-transplant is something that has come into vogue for older patients. And the haplo-identical transplant is one that should be done only in a research setting. The graft-versus-host disease and its management are very, very intricate and sophisticated, and require a well-educated hand. 14

15 ANNE: ANNE: I don t know that there s a good way to compare all of these things because, first, they are investigational. And second, there are not huge studies comparing one to the other. Much of it depends on what type of donor is available for an allogeneic transplant. If you don t have a sibling or you don t have a sibling who s matched, you can t have a matched sibling transplant, it s just that simple. So I think, though, that the various and sundry types of transplants and the different preparative regimens and the different anti-gvh regimens are all major improvements on what we used to do 40 years ago. This is an area where clinical trials are very important and many of them are being done. So I hope I ve answered your question. Rita, thank you for the question. Let s take another question, please. The next question comes from Anne from Florida. I m 64, I ve had two rounds of chemo, but it s returned. And one of my neighbors had given me something through I don t have a computer so she had given me something, I think it was off of Yahoo, which was from Johns Hopkins. And it was saying that they have come up with finally a dietary alternative that would help you kind of keep it in check. It tells how sugar is one of the main sources that cancer cells like to feed on. And also mucus, you know, if you have some dairy products and things like that. And it was very enlightening to me. It explained why I get some side effects sometimes on it. So I was wondering, is there a more detailed issue of this report that actually would list more things that I could be more conscious of and be aware of, so that I could at least maintain more control of the inflammation on the cancer cells. Because I found when I do eat or avoid certain things, that my results are better on my labs. And I think it s kind of more than a coincidence, so I d like to kind of continue with it as possible. But are you aware of that study or what was put out? Actually, no, I m not. Oh, darn. But let me say this. Number one, if you have found that how do I want to say this? There is so much that we don t know, regarding the whole area of alternative approaches and vitamins, dietary manipulation. I believe that they are very important, but I don t know how we re going to study them and we certainly haven t studied them well in the past. 15

16 Again, I would encourage you to either contact the National Cancer Institute or The Leukemia & Lymphoma Society, where there may actually be a good backlog of information on this area. One of the problems of the dietary approach is that it always works in the laboratory. (It s also a problem when we re studying drugs and other chemicals in the laboratory) You ve got these cultured cells that may or may not relate to human life and it always works in the laboratory. But when you go to take it into people, it s not quite so smooth. Again, this is one of the reasons that clinical research is so important. You can t simply derive something from the laboratory and say it s going to work. So that s a little bit of a sidelight, but I d actually like to learn more about this study. Are you sure it came from Hopkins? Anyway, thank you for your question and I hope I ve answered your question. JOAN: JOAN: Thank you, Anne, for the question. Let s take another one, please. The next question comes from Joan from Texas. Hello and thank you very much. You ve given me lots of things to think about. I have not had a whole lot of studying on my condition. I had cancer a precancer of leukemia when I was a child. I m 76. I had marvelous treatment from two doctors and a compounding pharmacist and I got alright, but it showed up again as MDS in And I had a biopsy six months later, showing that I did have MDS. And I ve been just trolling along. I have many other health problems. And I stay balanced with sometimes without a fight. But when I did go down to very serious lows, maybe having a transfusion, I found a kidney doctor who realized I had renal anemia also and gave me Aranesp. I took five shots over a six and a half month period and I went up to high altitude, that s 9,000 feet, and it seemed to be the thing. And I have been making cells, so they are immature. Joan what s your question for Dr. Karp, so she can answer? I was just giving her background. What should I do now? I think you ought to keep doing what you re doing. What should you do now? I would keep doing what you re doing. I think that your myelodysplasia is of the nature that does not compromise your bone marrow function completely. You still obviously have some. And it responds to the Aranesp. And it sounds to me like you ve got another 76 years left. 16

17 IMOGENE: Thanks so much, Joan, for the question. We ll take our next question, please. The next question comes from Imogene from North Carolina. Hi, Dr. Karp. I ve been in remission since August of 2006 and I ve made friends with a person in Texas, who has gone through consolidation and induction and has had an almost immediate relapse and they re getting ready to do a bone marrow transplant on her. We back and forth and she s anxiously and fearfully awaiting this procedure, which is the only option left. But what concerns me is that she s under the impression that she s going to have this transplant of marrow and that she s going to go to the hospital each day to get treatment while she s being processed with this treatment. And it was my understanding, now mind you I know I m four years behind, but it was my understanding that whenever you get a transplant, that you have to go into total isolation because you just have no immunity at all. And I m fearful for this friend that if they re going to treat her as an outpatient, that she doesn t stand a chance. I want to know how you feel about that. Well, with prophylactic antibiotics and what we call N95 masks and continuous hand washing and very careful monitoring, many places are allowing patients to go home after the acute part of the transplant. And come back and forth. Once neutrophils recover, our transplant unit has patients go home, but they come back every single day to the outpatient department. This is done in Seattle, this is done at the M.D. Anderson, it s done at the Dana-Farber, it s really done everywhere. As long as you re seen every single day and your environment is somewhat controlled. In general, people just do better when they re home. And so I think that it s not unheard of to be allowed to be home, with certain restrictions. But sleeping in your own bed is a real privilege and it s probably good mental health, if nothing else. So don t be fearful. I think it s probably okay. TERESA: Imogene, thanks for the question on behalf of your friend. Let s take another question, please. The next question comes from Teresa from Ohio. Dr. Karp, I am close to 70 years old. I was diagnosed one year ago this month with AML. My bone marrow has been clean since my induction and I m on Zarnestra. I had some questions, like can you tell me how is this progressing and what the results and what s the longest someone has been on it. I m on the 100. I did not tolerate well the 300 and

18 Let me tell you, the study in the Eastern Cooperative Group, in the ECOG, has been going slowly. There have been lots of readjustments and whatever. We actually did the original trial and we only gave Zarnestra for a year. We gave it for two out of every three weeks for a total of 16 cycles. We started that study in 2002, we completed the study in late 2005, early 2006 and there are still several people who are frisky and kicking their heels in It is always my joy to see these folks in clinic. Certainly we didn t get 100 percent of what we wanted, but it was well tolerated and a substantial number of folks, especially people whose leukemias were really nasty (the people who really needed it) truly seemed to benefit. I m very glad to hear that you re on this trial. I think that s a wonderful thing. I commend you; I commend your doctor, because this is what we need to do. You got into remission. Let s keep you there. And hopefully we will learn that five years from now you ll be calling in and saying, Hey, I m just fine. So good luck to you. Thank you, Teresa, for the question, and actually thank you all for your questions. Our program has come to an end. The hour went by very quickly. If you can please help me thank, in your own way, Dr. Karp. We are so grateful that she has donated her time to us today and we thank her for all the work that she does every day in supporting families touched by cancer. We also would like to thank again Cephalon Oncology and Eisai for their support. We hope that many of your questions were answered and that the information will assist you and your family in your next steps. A reminder to all to please fill out your evaluation forms. We encourage you to complete your evaluations online, to save some trees, by visiting or you can mail your evaluation in the envelope provided. If you are a nurse or social worker filling out your continuing education credit form, you must enter the code AML 892. Our Information Resource Center is open. The number is and our specialists are ready and available to speak with you or to answer questions you may have. 18

19 On behalf of The Leukemia & Lymphoma Society, Dr. Karp and I would like to thank you for sharing this time with us. Good-bye and we wish you well. Thank you. This concludes today s conference call. You may now disconnect. END 19