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«New York Forum Part 1 September 20, 2014 Page 1 of 30 Speakers: Virginia Klimek, MD Boglarka Gyurkocza, MD Simon Yeung, PharmD, MBA, Lac Jayshree ...»

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Boglarka Gyurkocza, MD: So, excellent question. Right now, I would like to say we published papers saying that transplants, allogeneic transplants, can be safely performed until the age of 75, but I have to say that we have transplanted older people than that and they had good outcomes. We just don’t have a large enough number of these people to say at this stage, but the oldest person I transplanted was 78 years old and he’s doing great and in terms of reduced intensity medications, yes we do use the same players, the same building blocks. We just give them at lower dose, lower doses

–  –  –

of chemotherapy and lower doses of radiation and just different combinations of graft versus host disease prevention.

Yes?

Q6: Can you kind of amplify the number of donor cells if you take the cord blood and put it in like a tissue culture or use re-competent DNA to stand the numbers?

Boglarka Gyurkocza, MD: Very, very good question. There are many centers that are using different approaches to kind of expand these cord units and one of them, I don’t know if you want to look it up, is a notch receptor stimulation. So, a notch like in they can expand these cells and more into the neutrophil development sort of to bridge that period. Here at the Sloan Kettering, we use a different strategy that we give cells from a sibling, haploidentical or half (inaudible 1:27:34) sibling, just T cells depleted cells from the sibling that will bridge that period before the cord units can engraft just provides some neutrophils and this will be rejected, but they will provide cells for that critical period of time when the cord units are still just trying to grow up in the bone marrow. Is that making any sense?

Q6: No.

Boglarka Gyurkocza, MD: There are many, many different strategies, many difference (inaudible 1:28:00) and that is a very active research to try to expand the cord cells. Yes. Anybody else?

Q7: Is the bone marrow harvest injected in the arm or is it…?

Boglarka Gyurkocza, MD: It’s an intravenous infusion. Our patients who undergo transplant have a central line inserted before they start conditioning. This is a large bore catheter with many lumens and it goes into one of the big neck ways, but it’s tunneled under the skin which protects it from infection and this can stay in for weeks and months and we use these large catheters and we infuse the stem cells through this catheter into the central line. So, not into the arm, but into a central line.

Q7: I see. Thank you.

Boglarka Gyurkocza, MD: Yes?

Q8: Sorry if I missed it, but the decision whether to use bone marrow cells or the peripherally mobilized cells. How often do you use either and what’s the impact on graft versus host versus graft versus tumor?

Boglarka Gyurkocza, MD: Very, very good question. So, we see that with that with bone marrow we see less graft versus host disease because there are less T cells in that graft and in the peripheral blood stem cell product there are more mature T cells and this works both ways. So if there is an aggressive disease and we want more pronounced graft versus tumor effect then we use the peripheral blood stem cells with T cells. We bite the bullet and say we will deal with graft versus MDSF2014-NYC-1 New York Forum Part 1 September 20, 2014 Page 22 of 30 host disease later or may use different preventions, but we really need to be aggressive here because the disease is bad. While if somebody has less aggressive disease and we know from these risk stratification that the risk of relapse is lower, we can try to spare them from graft versus host disease and that’s when we elect to do bone marrow as opposed to stem cells. So, this would be the simple way on our side and then we go to the donor and the donor has a choice. So in the end of the day the donor will say the final word. If the donor is willing to give either one, we can ask for either one, but if the donor says I cannot take GCSF because I have a disease that will be worse by that. I’m not going to take the growth factor, again, we just take whatever we get from the donor and work with it.

Q8: And is it the case that you always see GVHD when you have GVT or like are they…?

Boglarka Gyurkocza, MD: Very good question and the field has been working on this to separate graft versus leukemia effects from graft versus host disease. They don’t always come together. There can be some clinical graft versus host disease that it does not really manifest as severely and very strong graft versus leukemia or graft versus tumor effects. Sometimes we see graft versus host disease and relapse of the disease. So, some people do get the worse of both worlds that it’s not working on the leukemia or the cell gives them this complication. So, we do see some dissociation of the two, but most of the time they go hand in hand. Not all people develop graft versus host disease, but I would say about 40 percent of the patients do develop some form of acute graft versus host disease and somewhere between 40 to 60 percent of people chronic versus host disease. The field evolved in recent years and we are able to treat graft versus host disease much better. So, it’s, again, not the end of the world, but there is some work to be done there.

Q9: What’s the timeframe that a patient needs that Dr. Klimek decides that you know what, I think this person may need transplant of a patient with you till the time that they actually go for a transplant. Give me a… Boglarka Gyurkocza, MD: So usually, we can transplant. So if Dr. Klimek refers a patient to us, we can usually transplant that patient within the month if we think that it’s important that the disease is aggressive and we are running out of time we usually are able to perform like get going in a month.





So, it’s… Yeah. I think this is a very dynamic field and we are able to do things faster and better these days. It’s not perfect yet, but hopefully we… Virginia Klimek, MD: I’ll just comment that it is very impressive that they’re able to identify and screen and get these donors in quickly, but one of the factors, one of the big factors that affects the length of time between when we say that somebody should be considered for transplant and when they actually have transplant is in addition to finding a donor sometimes people need to undergo some MDS chemotherapy to prepare them for transplant. So, they might need two to four months of chemotherapy to get their disease under control, under better control, before they go onto transplant.

So, there’s additional factors in addition to the donor situation, but especially now with these cord blood units, they’re sitting in a freezer somewhere. We don’t have to find somebody in Holland or wherever they are and get them in and screen them. So actually, the cord blood unit now mean that we can get people to transplant much faster.

–  –  –

Boglarka Gyurkocza, MD: Thank you.

(Applause) Virginia Klimek, MD: While they’re getting lunch brought in and you’re working up your appetite for lunch, I’d like introduce Dr. Simon Yeung. He’s a member of our integrative medicine services here at Sloan Kettering. We value their input and consultation and expertise in the use of vitamins, botanicals, any kind of nonprescription supplement, how we work those drugs, if you will, into the regimen that we’re giving people with MDS and I asked him to come and talk to us a little bit about his experience and maybe some recommendations for how these drugs in MDS.

Simon Yeung: Thank you for having me here today and thanks for the kind introduction. So, my name is Simon Yeung and today I’m going to talk about herbal supplements in terms of care with the focus on MDS.

First of all, I wanted to let you know about the (inaudible 1:35:09) cancer center integrated medicine department. Many of you have been (inaudible 1:35:15). We use rationale and (inaudible 1:35:18) without the… to treat both inpatient and outpatients.

The type of therapy we provide include massage therapy, mind/body therapy, music therapy, acupuncture, exercise centers, diet, nutritional counseling and also (inaudible 1:35:42) supplements.

We do not actually use (inaudible 1:35:44) to treat patients though, but we do provide information and those products. So to that end, we have the (inaudible 1:35:51) website. This is the address and this is also a free app you can download if you have an Apple iPhone, iPad. We provide free information on supplements, vitamins and proven treatments that a cancer patient use. (inaudible 1:36:11) of this website.

So, I want to talk who’ll use dietary supplements. The natural product that are most commonly used can be (inaudible 1:36:19) alternative medicine methodology and more than 70 percent of cancer survivor use dietary supplements. If you do use herb and things like that actually you’re in the majority and the user tend to be female with high education level and physical activities. Many people think that people use herb because of ignorance. Actually, it’s the smart people that use a product because of a personal choice and some study indicated that four out of five user use more than one supplements in a (inaudible 1:36:51) cancer patient survivors, many of you also using a lot of prescription drugs and this increase the risk of (inaudible 1:37:58) pharmacy (inaudible 1:37:00).

So why do cancer survivors use herbs? First off, it’s a sense of control that their health after cancer diagnosis, MDS diagnosis if they didn’t do enough for yourself and now you want to do something proactive. So, you resort to herbal supplement for your own health and they’re perceived as natural and safe. I can show you that natural is not always equal to safe. Some of (inaudible 1:37:26) specify with the mainstream medicine. (Inaudible 1:37:30) poison then you think there must be a secret miracle herbal treatment that the mainstream medicine may have missed it or the pharmaceutical company may have suppressed its use. Actually, those are not true and also herbal medicine or (inaudible 1:37:45) holistic approach. They don’t look at you as having disease in the blood and the

–  –  –

bone marrow. They look at you as a person and harmonize you. So, this is very appealing to many people and also most of you would use a product called prevention treatment as well as central relief.

So, I wanted to discuss some of the herbal product use of MDS. I think there are very few herbal supplement have been studied in cancer patients and they don’t feel it has been studied in MDS patients, but I’m going to mention a few of them. The first one is this maitake mushroom. The maitake mushroom is just one of the medicinal mushroom used in Asia. It is very popular over there and the (inaudible 1:38:27) is its Japanese name means dancing. The reason is is that in (inaudible 1:38:31) people recognize the benefit of this mushroom. If they find it in the wilderness they will start dancing because it’s happy there and they find a product like this. More (inaudible 1:38:42) find that it contained beta (inaudible) that has even a modulating activities and also there’s some studies suggesting that it can reduce tumor toxicity by improving the white cell count and function and in Japan they also see where it’s the case so they’re suggesting that it can leap to tumor repression in cancer patients. Now, we did a study over here at Sloan on breast cancer patient trying to look for to see if there’s (inaudible 1:39:10) activities and also to see what dose we can use in patients and related post-menopausal breast cancer patient and we defined that this product has (inaudible 1:39:20) activities. Now, we have to use this term very careful because (inaudible 1:39:25) activities not many people mechanism halfway, but we do find out that in some cases if you give too much of this product you would actually suppress the immuno-activities and they find out from this the study in breast cancer patient the dose, the optimal dose of use is 6 milligram (inaudible 1:39:34) per day and we use those information to get in our study in MDS patients which are (inaudible 1:39:50) investigate and we find out that (inaudible 1:39:55) patient that it can increase the neutrophil and monocyte function in MDS patients. Now this in (inaudible 1:40:04) we didn’t find any good (inaudible 1:40:06) in the count but we found that the function itself sometimes is more important for example in better for reducing infection risk, but there are also some report suggesting that maitake mushroom may have some (inaudible 1:40:20) fact with high (inaudible 1:40:23) agent because it can actually lower blood sugar and also it can interfere with some anticoagulant drug and the result that we have is this, again, from a very small study and we plan to carry on to some even larger number of patients and maybe in Asia where there are more people have MDS and then include that we do not recommend people will use it as a treatment for MDS.

The second one is ginger and cacumen. This is also a small study on this one, but Gingerall is actually derived from ginger. Some of them we use as a spice in cooking and the other one is this cacumen. Cacumen is derived from turmeric that cacumen the turmeric has to been used in many clinical trial intensive patients. This is probably one of the more promising natural product than (inaudible 1:41:15) in cancer treatment. If you don’t know what turmeric is and if you had (inaudible 1:41:21) the current common use in India in sort of major (inaudible 1:41:25) is actually turmeric and scientific study shown that they have (inaudible 1:41:31) and also anti-cancer activity and Gingerall somebody made a study also shown (inaudible 1:41:35) activities and in one of the small study reported one of the meeting they use eight gram per day of the cacumen just (inaudible) has this really low (inaudible 1:41:52) and also (inaudible) 12 gram of Gingerall and they give it to patients, a small number, like nine patients for four to 18 months and they find out that this product in combination is well tolerated and can have some potential benefit for patient who are not transfusion

–  –  –

dependent and we do not get a lot of information on this study because it’s not actually published in the journal but rather say it’s a big part in (inaudible) in 2008.



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