Late Effects after a Transplant Using Your Own Cells (Autologous Transplant)

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Late Effects after a Transplant Using Your Own Cells (Autologous Transplant)

Saturday, April 17, 2021

Presenter: R. Greg Bociek, MD

Presentation is 51 minutes long with 7 minutes of Q & A.

Summary:  Autologous stem cell transplants use the patient’s own stem cells to rescue him or her from the effects of high-dose chemotherapy. This type of transplant is most often used to treat patients with multiple myeloma, non-Hodgkin lymphoma and Hodgkin lymphoma. This presentation discusses the transplant process, and common early and late complications.

Highlights: 

• Autologous stem cell transplants (using the patient’s own stem cells) are more common than allogeneic stem cell transplants (transplants that use donor stem cells) and continue to increase in number.
• Improvements in treatment, better patient selection, and better supportive care now enable  patients over 65 to undergo an autologous stem cell transplant.
• Several types of secondary cancers and other risks may follow an autologous transplant. It’s important for practitioners to monitor symptoms and provide effective treatments as these conditions arise.                    

Key Points:

(08:43) An autologous stem cell transplant is a more intensive therapy than standard chemotherapy, but may cure or extend the patient’s life.

(15:02) Short-term side effects of an autologous stem cell transplant are common, but temporary, and typically include nausea, vomiting, diarrhea and hair loss.

(15:21) After transplant, maintenance therapies are often used to prevent recurrence of the disease.

(19:51) Patients need to be re-vaccinated with childhood vaccines after transplant, and should consider the Shingrix vaccine to prevent shingles.

(31:02) Osteoporosis is a potential side effect of an autologous stem cell transplant.

(33:50) Breast health problems are uncommon after autologous stem cell transplant unless the patient received radiation to the chest.

(35:37) Problems with sexual health are common after an autologous stem cell transplant

(38:21) Infertility is likely after an autologous stem cell transplant but some people do regain fertility over time.

(41:35) There are wide variations in patients’ ability to return to work after transplant.

(42:55) Although uncommon, the risk of developing a secondary cancers such as myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and melanoma is increased after an autologous transplant.

Transcript of Presentation:

(00:01) [Daniel Gennari] Introduction.  Hello, my name is Daniel Gennari I would like to welcome you to the workshop: Late Effects after a Transplant Using Your Own Cells. It is my pleasure to introduce Dr. Greg Bociek. Dr. Bociek is a Professor of Medicine at the University of Nebraska Medical Center, where he has been on the faculty since 1998. His expertise is in the treatment of patients with lymphoma and chronic lymphocytic leukemia. Dr. Bociek is the Chair of the CAR T-Cell Toxicity Committee at Nebraska Medicine and the Chair of the Scientific Review Committee at the Fred & Pamela Buffett Cancer Center. Please join me in welcoming Dr. Bociek.

(00:49) [R. Greg Bociek] Overview of talk. Thank you, Dan. And good morning. Good lunch, good near lunch, everyone. Depending on where you are. Well, I'm coming to you from Omaha, Nebraska, this morning, and Omaha is windy, sunny, cold, hot, humid, wet, and that's just the last two hours of this morning. So we get a pretty changeable weather forecast here.

(01:08) I will go on and tell you I feel like there's sort of mini smorgasbord, or maybe I'm kind of the guy on the menu that's just the appetizer because nearly everything I touch on here is going to be a fairly dedicated talk. So things that I don't get into at a certain depth, you certainly can look through the program and probably find those topics elsewhere.

(01:27) So what I did not see in the talks was sort of a review of autotransplant, and we're just going to spend a little bit of time on that because I want to start with the conceptualization of some of the illnesses are we transplant and why we do this, and what the process is.

(01:42) And I think that'll set the stage for the things that I'm really going to touch on which are the complications. And you can see here immunologic and hematologic issues, infectious complications, how we deal with immunizations, our strategy, and some of the organ-specific things that frankly are not super common. And we're thankful about that, but they do affect some of our patients after autotransplant.

(02:03) Autologous transplants are the most common type of stem cell transplant and the numbers continue to increase. So these are just some numbers, by background, to show you what this is in terms of a growth industry, and not surprisingly, transplant continues to grow. We do have great new therapies, and we have other therapies other than transplant, but this is still kind of a growth industry. And you can see here from the Center for Bone Marrow Transplantation Research that autologous transplants are still the most commonly done, and that number continues to rise. And we're happy that we have this therapy available for the right patients in the right circumstance.

(02:31) Autologous transplants are most frequently offered to patients with multiple myeloma, non-Hodgkin lymphomas or Hodgkin lymphoma. This is just a sense of what kinds of illnesses we mostly transplant, and you can see the green are all the autotransplants. So it's not a surprise to us because we see so many of these. Myelomas, in what we call PCD which stands for plasma cell disorders, are probably the most common thing by a long shot that we transplant. And that's because virtually every patient with myeloma will be offered a transplant in first remission, which is different from many of the other illnesses you can see here.

(02:58) Lymphomas are the second most common, but there are very few lymphomas that we would recommend a transplant first remission. So these tend to be for people who have relapsed.

(03:07) And farther out in the middle of the green little thing that says HD is Hodgkin lymphoma, and then a little further to the right for there, the other malignancies probably is mostly things like germ cell cancer. So we would think like testicular cancers and things like that.

(03:20) Improvements in treatment, patient selection and supportive care now allow autologous transplants after age 65. This is a nice slide to see, also, as therapies get better, as supportive care gets better, as patient selection gets better, sometimes we actually find that we can broaden our patient selection. And you can see if you just follow the blue numbers along the top, that shows the proportion of patients that are over 65 years of age that we transplant. And you can see that number has gone up over time, and that reflects better medical care, better selection, better pre-transplant care, better awareness of how to look after complications. And that has given us confidence over time as we learn and refine the process to be able to offer this to patients over 65. And I would say at our center, off the top of my head, probably the oldest patient we have done an autotransplant on would be, I'm guessing, late 70s, maybe 77, 78 in that range. And obviously, we pick those people carefully, but in the right setting, it's still a decision in a reasonable discussion to have.

(04:14): Here are again trends, and you can see that the blue line is myeloma. And like I said earlier, it's a very common and increasingly common transplant. And so [until] we get data from large, large randomized trials that say that transplant is not the best thing to do, this will likely continue to be the trend for some time, at least in the United States, for sure.

(04:34) Survival for patients with certain types of lymphoma patients, following an autologous stem cell transplant  have improved in the last 16 years. Because you may or may not be used to what you are looking at, we call these Kaplan-Meier plots. They show, the line shows kind of a probability over time. And in this case, this is the probability of being alive after an autologous transplant for follicular lymphoma. And the point of this is just to show, as you see the numbers at the bottom 2005 and then 2006 to '10, et cetera, as we're getting from earlier to later on or from older to more recent, that it looks like the outcomes overall are better. So the dotted blue line at the top suggests that people are surviving longer overall after having this type of transplant in this era than they were decades ago. Again, that's a little bit more of the right patients, the right selection, the right pre-transplant care, the right post-transplant care, but it's nice to see that overall we're doing better.

(05:19) And the same data and the same observations would be true for people with diffuse large B-cell lymphoma. So the two most common lymphomas that we would transplant, and you can see the same theme and the same trend that the probability of being alive two or three or four or five years after this type of transplant is better in this current era than it was a decade or two ago. And those are always encouraging.

(05:42) Standard chemotherapy given to patients with lymphoma is designed to get the patient into remission. This is just to break now to the moment of what the whole purpose of the transplant is. And this is to show you that when someone is first diagnosed, for example, with the lymphoma, that where it says tumor visible, obviously at the beginning, they're going to have things that we can feel: big livers, spleens, usually lymph nodes, and they have a certain burden of tumor in the body.

(06:03) And as we give those cycles of therapy, for example, for a lymphoma, typically for a diffuse large B-cell lymphoma, that would be something like rituximab and CHOP. Every time we're treating that patient, we're dinging the malignant cells, and we're knocking them down. And I made the curve sort of sweep up a tiny bit between each cycle, and hypothetically, maybe things are trying to grow, but you get the point that we're sort of killing a constant proportion of cells each time we treat that patient. And by the time we get, in fairness, to two or three cycles, but the way I drew it here if you can go the end of five or six cycles, we have what we call a remission. And that simply means that we can't see tumor. The tumor is invisible.

 (06:39): So in the lymphoma world, that would mean a PET scan was normal. And if the patients had had disease in the bone marrow, we had done a bone marrow biopsy, and we can't see tumor.

(06:47) Remission does not mean cure but rather that the disease is not detectable. Now, I always tell patients, remission means you're kind of below the radar. You're under the water. There's not a test in the world today that can find one residual cancer cell in the lymphoma cell after treatments. But our treatments are good enough, and our scans are good enough to find fairly small amounts of residual disease. And in bone marrow, we could probably see if you have more than say one in a hundred thousand cells or something where lymphoma, we could probably see that.

(07:13) So the point here is that we can only give so much of these kinds of chemotherapy without dinging the body because all the drugs have side effects in places we wish they didn't. So we're talking about nausea and vomiting and sore mouth, and some drugs can eventually be hard on kidneys and heart and lungs. And so we can only do so much in terms of the intensity, but at the end, we hope we've gotten people to remission.

(07:34) Then, as I said, remission means the disease is not visible, but we don't know at the end of treatment that those people are cured. We can just say, you're in remission, your cancer is invisible, and we can't measure it. And so the way I put this on the slide, some of those people are invisible, but they're not yet cured, and the patient on the very bottom is cured. But as I said, we can't tell any of those apart. All we can say is you're under the radar, and we don't know what's going to happen.

(07:57) Patients who are in remission, but have a high risk of relapsing, may be a candidate for an autologous stem cell transplant. Now, knowing what kinds of lymphoma you have, knowing some of the other features of it, sometimes we can say, well, we know these certain people, even if they're in remission, are still pretty likely to relapse. And maybe those people deserve a discussion about transplants. For the rest, for those people, the idea is to take the disease that's invisible and squish it lower because, as you can see the way I've drawn this if we have people that have invisible disease, but that's still active in the body, eventually over time, those cells they're going to grow back and eventually lead to a recurrence.

(08:30) Now, these are the cells that we say are resistant. These are maybe only 1% of the original tumor that we couldn't kill, but they tend to grow back over time. And that's what leads to what we call a recurrence. And then the patient on the very bottom obviously was cured.

(08:43) An autologous stem cell transplant is a more intensive therapy than standard chemotherapy. So knowing that we have patients either in remission that have a high chance of their tumor coming back or patients that aren't quite in remission, and we know that we have to get them there to have any chance to cure, the idea of the autotransplant is to give more intense therapy then we can give with say, rituximab, and CHOP or bendamustine or drugs like that. And so what we're really doing is giving chemotherapy that's a little bit different and is beyond the capability of those five or six cycles of chemotherapy. And with the idea that for the little chemos, a little is good and a little more, a little better, and a whole lot more as a whole lot better then a whole lot more may take those residual 1% or one in a hundred thousand or one in a million cells and eradicate them and either lead to a cure for that patient or lengthen the time that they stay in remission.

(09:30) Outcomes include cure, prolonging remission, and extending patient’s life. So the idea here is that for some lymphomas and for multiple myeloma, for example, the idea is generally that we're prolonging remission, keeping the patient in remission longer. But if we do that well enough, we may also extend the patient's life. So the three outcomes could be that we cure out certain lymphomas or certain types of cancer. We prolong the time that the cancer stays invisible. And if we really do a good job of prolonging the time that cancer stays invisible, we may be able to extend that patient's life. And so these are the goals, and we always talk about these very specifically with the very specific different types of cancers we're talking about, whether it be germ cell cancer or lymphoma, myeloma, et cetera.

(10:09) Preparation and timeline for transplant. Timeline for transplant, you can see here. The first thing we do is obviously look at the patient's situation with respect to their illness. Is this a place in the lymphoma history of the myeloma history that we would want to do a transplant? And then we meet that patient, get their history, talk to them, look at their scans, evaluate them for fitness, which just generally means a little bit of blood work. Are your kidneys okay? Are your liver okay? Usually, a type of scan that we call an echocardiogram or an ultrasound picture of the heart to make sure the heart muscle squeezes good. And there aren't any unknown or anticipated problems. And then usually a set of lung function studies to make sure that we think that the lungs are reasonable.

(10:45) Salvage therapy may be used for relapsed patients. Then this is a model for a typical type of relapsed lymphoma, diffuse large B-cell lymphoma. We would give about two cycles, what we call salvage chemotherapy. And that's the chemotherapy we're giving after the tumor has either relapsed or perhaps not gone into remission. And then we restage them six or so weeks later. And we look at PET scans and maybe a bone marrow biopsy depending on where the tumor was, to see that this tumor responded. Does it still want to go away when we give modest doses of chemotherapy, because if it doesn't want to budge with those, an autotransplant is probably not going to be the right thing for that patient.

(11:17) Growth factors drugs are often used before harvesting a patient’s cells for later transplant. So we want to show that we can shrink the amount of tumor, but more than that, we want to show that it still wants to respond to these kinds of drugs. So we restage, and everything looks good. We put in some growth factor shots, and then the name for that would be Neupogen or G-CSF usually. And we give those daily for about four or five days. And then, we start to collect the cells on about the fifth day.

(11:44) We can collect cells in one to four days. It just depends. And we also have initial growth factor that we can use called Plerixafor if we have to, to help make more cells get into the blood. And we basically measure those on the first day of therapy to see how many of those, I'm just going to call them baby cells, peripheral blood progenitor cells are in the blood.

(12:03) After harvesting cells, chemotherapy (often BEAM) is used to prepare for transplant. Once we've collected enough cells, and we just know by counting every day what we collected and, as you know, they're frozen, stored away, we give the chemotherapy regimen. And there are many different ones, but the most common one we give for lymphomas is called BEAM. And that's a six-day regimen. And so we give those drugs over six days, and then we put the cells in the next day, and then we start to count forward, and that forward days is generally when patients start to feel most side effects in terms of whatever they're going to get, nausea, vomiting, diarrhea, et cetera. And that's really variable.

(12:30) Patients vary in how sick they become during and after transplant. I tell people, some people don't feel like they get very sick from the transplant. And some people feel like they get very sick, and age and gender and prior therapy and things like that don't necessarily matter or predict that very well. So we just tell patients to just be prepared, and we'll do everything we can to make you feel the best we can through that time.

(12:48) So if that's the course and what we're doing, of course, the two components, then will be the treatment. And we call that the preparative regimen generally it's chemotherapy, very possibly in some circumstances, radiation, but overall over time, we've learned, as I'll show you later, that adding radiation to the transplant regimens probably increases the risk of late secondary things called myelodysplastic syndromes. So generally, we're giving chemotherapy only.

(13:12) Believe it or not, we could give some of those regimens without stem cells, and people would be able to do that, but it would take three or four or five weeks for the blood cell counts to recover, and that's just not safe. And that's why we don't do it that way.

(13:24) So the graft source, in this case, we're saying autologous. We could use the word syngeneic would mean an identical twin. If someone has an identical twin, we will often have a discussion about whether that patient, whether that person is fit to be a donor for their siblings. And a long talk for different day would suggest that that might actually be a better source of cells than your own cells if you had an identical twin. And as I said, we're generally using peripheral blood stimulated by growth factor. We almost never have to use bone marrow now, once in a super rare while a patient, we just cannot get cells out of the blood, even with growth factor. And some of those people will need a bone marrow harvest to get the right number of cells for the transplant.

(14:04) In autologous transplants, stem cells function as a rescue product. So, as I said, we're trying to take the chemotherapy to a higher place than we can when we're giving drugs like CHOP and bendamustine. And so it's really a lot of chemotherapy followed by this thing that we call the peripheral blood stem cell infusion. And really, that's just a rescue product. And what I mean is the cells are not really part of the treatment per se. They're not what is helping cure the cancer. They are helping the blood counts recover in 10 or 12 or 14 days instead of 28 or 35 days. So essentially, the stem cells make this safe. They're kind of like a rescue.

(14:37) Temporary substantial bone marrow suppression means super low blood counts. Virtually all patients will need some red cells and some platelets. Virtually all patients will have white cell counts of 100 or so and yet recover in 10 or 12 or 14 days.

(14:50) The degree of immunosuppression, and by that, we'll get to that as I talk about the infections, I mean, what's really happening to the lymphocytes and what's happening to infection risk and viral infection risk, et cetera, is not anything more than really modest.

(15:02) Short-term side effects are common but temporary. The regimen-related side effects, again, what we mean is chemotherapy, nausea, vomiting, hair loss, and diarrhea can be quite significant, but they're temporary. And as I said, the high dose treatment is to support. So the chemotherapy is doing the heavy lifting, and the high dose therapy is making it feasible and safe, and shorter.

(15:21) After transplant, maintenance therapies are used to prevent recurrence. So after we get patients through transplant, the next thing, of course, we like to do is say, well, some of you may still have a chance of recurrence. And we would like to make that as minimal as possible. And here are just probably the most three common standard examples of maintenance therapies that we would do after lymphoma. So we have data from large studies that would support all of these. And so, for patients with mantle cell lymphoma, we were often giving rituximab every two months for up to three years based on one large randomized trial.

(15:47) For patients with myeloma, we're giving lenalidomide as maintenance therapy, and around the world people do this different durations. I think the theme here in the United States is probably you take that drug as long as you can. So it could be an indefinite medicine as long as you can tolerate it.

(16:02) And Brentuximab, there's a nice randomized trial saying that giving that for about 16 or 18 treatments after recurrence for Hodgkin lymphoma, that antibody therapy also prolongs the time that patients stay in remission.

(16:15) Radiation is used sparingly if at all. We would occasionally think about radiation, and I don't want to say it in unusual or disrespectful way, but we kind of think of radiation as a way to spot weld areas in patients that may have had a couple of places where there was a large tumor burden, and that might be three or four or five-inch tumor mass, or in centimeters of seven or eight or 10-centimeter mass. Sometimes we might give some radiation after transplant to try to say we did something extra for the biggest site where there might be the most resistance to cure.

(16:46) Patients need better education about their treatment from doctors. We move on to the sort of side effects and things now, and this is just an interesting survey I found. And this reflects on us. This doesn't reflect on the patients. This is how well are we educating you after transplant. So this is just an example that I found the literature that showed people within three to beyond 25 years of transplants, and they were asked questions about, well, what do you know about your transplant and what happened and what was to come? And you can see here that about four out of five knew exactly what their diagnosis was.

(17:13) Most people could say, "Well, I know what the components of the transplant were." Most people were aware of most of the possible late effects, but only maybe a third felt that they had actually had real discussions about those things. So that, again, that reflects on us the physicians, I think more than anything and not surprisingly younger people, maybe just feeling better, maybe brains working better, maybe more motivated, seemed to understood more about what the late side effects might be. People that got things that had extra risks that might've been extra prolonged discussions like radiation to the chest knew more. And obviously, people that actually had complications and were getting things done and were likely to know more.

(17:49): So let's just get a sense of what people knew. So fertility was probably the best understood and best known about late complications. And then fatigue would be kind of second and then secondary cancers you can kind of see as we go heart disease, hormonal changes. So this gives you a sense of what this particular group of patients knew. And again, I think it reflects on us that sometimes we don't have the proper discussion. Maybe we don't have time to spend in discussion because we're thinking more about the more recent things and how's work going and how your blood counts, and what antibiotics are we still on. So I think that as practitioners, we have to try to do a better job for that.

So after you get a transplant, I'm just titling this, the early post-hospital recovery periods. So recovering blood counts is pretty quick. All of you that have had an autotransplant would generally have probably said your cell counts recovered in 10 to 14 days. And so with growth factor help that we also give after the chemotherapy is done. Usually, people recover their cells. And as I said, 10 to 14 days after the start of the chemo.

(18:47) Other organ toxicity, it's not super common, but once in a while, someone gets sick, or they have low blood pressure, they get a bloodstream infection, the kidneys get dinged a bit, the liver get dinged a bit. Those are usually just things we're measuring by lab tests. And those usually get better within a very short time. We take out that double lumen catheter that we used to collect cells as soon as the platelet count recovers to about 50 in our institutions.

(19:09) So that comes up pretty quickly. We keep people on preventative antibiotics, and in our case, for an autotransplant, that's generally just meaning acyclovir. And we do that for about six months. We think that's a reasonable time. And I'll say a little bit more about that later.

(19:21) Nutritional and muscle mass recovery may take longer. Nutritional recovery, people generally do well on their own, and it just takes time to get tastes back and taste buds back. And we have nutritionists on faculty that are very good at helping people work on things that are easy to take and gradually reintroduce a more normal diet over time.

(19:37) Muscle mass, everyone leaves the hospital less well when they came in. Even if the transplant goes spectacularly well, even if they don't get much nausea, everyone comes out in sort of like a negative muscle and negative strength sense, and that can take weeks to months to get better.

(19:51) After transplant, patients need to be re-vaccinated. And then, we begin what we call our post-transplant vaccination series. So this is just an example of what we do. These are really hard to study by science. And so what I mean is the administration these vaccines is based on sort of expert opinion and measuring different antibody levels post-transplant and seeing what happens when they go up when you give a vaccine and things like that. It's hard. There's no study in the world that says, "If you give a pneumovax at this time versus that time, that there'll be less pneumococcal pneumonia." So they said these are kind of empiric expert opinion, but this gives you a sense of what we do.

(20:22) So at three months, we start to give vaccinations, and you can see that every one of these is a non-live vaccine with the exception of measles, mumps, rubella.

(20:32) Vaccines to prevent shingles. The one I want to really point out, which I think is important and a little bit important, maybe for the COVID era, and I'll tell you why in a second, is the use of the zoster vaccine. So the oldest Zoster vaccine was called Zostavax and was a live squashed version of the zoster vaccine. We did not give that. And I generally didn't even give it to any of my patients with hematologic malignancies because of the very, very tiny, but theoretical and at least reported once or twice in the literature possibility of that virus actually reactivating a lot and making the person sick. So we never gave that.

(21:05) The new vaccine, which has been out since probably off the top of my head 2017 or so, is called Shingrix. And many of you may know that, and that's sort of two shots, and you can see how we give that here. So the point of this slide is to show you that vaccines can work after transplant. So this is the Shingrix vaccine, and this shows you again. This is like a probability curve. So you can see over time the people that got vaccinated. This is what we call a randomized trial. Half the people are getting the vaccine. Half the people are getting a Shingrix shot. They don't know. Nobody knows it's the best way to keep all things pure in determining whether the treatment was good or not. And we've done the same thing with COVID vaccinations to prove that they work.

(21:45) This shows you that the people that got the vaccine had about a 10% versus a 20% incidence of shingles, and that's cutting the risk by half, and that's not trivial.

(21:55) So my point of this slide is to show you that vaccines can work. And of course, all our patients are asking us, and there's going to be a COVID section in this conference. Do we know if the COVID vaccine will work in the end? I think we can say to an individual patient, no, we may not know, but we know that the body can respond to vaccines in certain settings. And this is just an example where immunosuppressed patients can response. It'll take us a year to look at all the people with cancer and where they were in their journey that we vaccinated with COVID and measured antibodies on them six months or a year later to know actually know how many people are going to benefit. But I want to give you an example that the question is, can I even respond to a vaccine after a transplant after chemotherapy? Here's an example that says, yes, people can.

(22:41) Pneumonia sometimes occurs in patients several months after transplant. As we get a little bit longer maybe 70 ish, 100 days and a little bit beyond. Sometimes this thing shows up that's a little bit tricky and sometimes patients don't understand, and doctors aren't necessarily thinking about, and it's what we call idiopathic pneumonia syndrome, just meaning we don't know exactly what the cause is, but we know the people that are older have a higher risk of getting this.

(22:59) We know that people who have had radiation and certain drugs, like the BCNU is the drug that's in the BEAM regimen, bleomycin would be a drug that Hodgkin lymphoma patients might have had, brentuximab, another drug that Hodgkin lymphoma patients might've had. These probably make the risks a little bit higher. And the usual presentation is a patient that just has a cough and they're not bringing up spit or anything. They just have this dry cough. They feel like they can't do as much activity. Their exercise tolerance is down. And depending on how severe it is, and we listened to their lungs, you hear these little sounds that doctors call crackles or crepitations. And it literally sounds like squishing plastic wrap or something like that.

(23:35) Oxygen levels, when they put that little finger probe on your finger, might be normal. And so this is something that we have to think hard about, and doctors have to be aware of it. We always tell patients, "If you get that, you call us so that we know what to think about." Just because your family doctor, your oncologist, they just might not be as attuned to this. This is something that we want to know about.

(23:53) So this is what an X-ray might look like. This is a CT scan showing kind of a slice through the lungs. I didn't put a normal, but normally it would look obviously not so honeycomb is that. So you can see all the white little honeycomb-like stuff in there. There's all abnormal fluid and inflammation.

(24:08) Someone with heart failure might look the same as this. Someone with an infection like influenza or COVID might look the same as this. So we have to look and say, "What does the patient look like, feel like, does their exam suggest signs of heart failure? Do they have swelling in their lower extremities?" Things like that. And we would usually image them like this and do at least nasal washings for virus illnesses.

(24:29) Sometimes we might do the test called a bronchoscopy, where we slip a tube into someone through the mouth and down into the airways to get deeper samples, to look for infection. So the goal of those tests is to say this is not an infection, and super rarely, super, super rarely we might think about lung biopsy. I'm frankly not sure I've ever had to consider one for a patient in this setting.

(24:50) Pneumonia after transplant is often treated with steroids. So you kind of looked, and eventually, you know that things walk and talk and look a certain way. And people that don't have fevers and things like that that have this kind of thing, 10 or 14 or 20 weeks after transplant, more often than not, it's going to be this thing we call idiopathic pneumonia syndrome. We often treat those with steroids and drugs like prednisone or dexamethasone. There are not high-level trials to say those things work, but I can tell you we've had people sick enough. I mean, sick on ventilators from this that have gotten off, we know with a couple of weeks of steroids and people can at least in terms of how they feel get completely better over time.

(25:24) So that's an uncommon complication, but again, my point is sometimes overlooked, and sometimes people have six weeks of this before we hear about it. So those are the kinds of things that we really want to know about right away.

(25:35) Other lung problems after transplant. The drugs we give and, again, sometimes people who have had radiation can induce other kinds of lung toxicity, so this is separate from that thing. This is something that you might not even know you have. You probably aren't used to looking at what we call a flow-volume loop, but if you look at the blue thing on the left, the thing that starts over on the right at four and kind of goes down below the line, that would be where you take the breathing tube, and you're breathing in. And then the thing that goes above the line on the blue is when the patient's blowing out, and that's measuring kind of how fast the air is going out.

(26:05) So if that's a normal one on the left, you can see on the right where the red is. Everything has been squished down. And maybe the best way to think about that almost would be like if someone had a bunch of belts wrapped around your chest and you can only expand your chest so much. And this is something that we do see in our patients after transplant, sometimes. It could be five or 6% of people that don't have any symptoms and know they even have anything. We might only see it by doing these tests. So they don't even know. And a very sensitive way to measure this. There's a test that measures the gas transfer across the lungs. You may have heard before it's called the diffusing capacity. And the test basically just puts a tiny bit of carbon monoxide into the system and knowing what breathed into the patient and what the patient breathes out. You can basically measure how that gas is going across that lung membrane. And so up to 30 or 40% of patients would have impairment.

(26:52) Now, again, normal sedentary life, not being a bicyclist, not being an Olympic athlete. You might never know that, but this is just showing you that things happen that are sort of under the radar. And certainly, current smokers would be more likely at risk for this. So everything that we can do to not smoke and stuff after transplant and pre-transplant is helpful.

(27:10) Getting out to a month to a year out. As I said, the white cells that we think of the neutrophils, those are the things that growth factors helping, they get better very quickly, 10 or 14 days. Platelets are a little bit longer, but within 14, 20, 30 days, those usually back up to pretty healthy numbers. Lymphocytes recover very slowly. And these are the cells B-cells and T-cells that are responsible for things like viral infections that I put here just examples, cold sores, and shingles. This is, in some ways, maybe some of the most common infections we see after transplant.

(27:42) Patients can have low antibody or immunoglobulin levels. And that generally makes them a little more susceptible to bacterial infections, not a super common problem after autotransplant, but once in a while, it happens. So the patient ends up 30 or 60 or 100 days after an autotransplant in the hospital with a bacterial pneumonia. The first thing I would do would be to check those levels and say, "If they're low, there might be a reason to give some immunoglobulin to that patient." But again, as I said, uncommon, much more common in other settings like patients with CLL, et cetera.

(28:14) Again, if you're unlucky enough, just to get a simple flu virus, they can be more severe in this setting. And people that normally would be sick might end up sick enough to be in the hospital on oxygen or even on a ventilator. So we see that the respiratory viruses are more severe often in this setting, but I want to make the point that this is pretty uncommon. Once people recover their white counts and get their catheter out, it's not super common that they end up with an infection. And if they do, I'd say again, probably the most common thing that we see after is zoster. And that's why we're so keen about the new zoster vaccine, Shingrix.

(28:46) Late low white blood cell counts are uncommon, but can occur after transplant.  Late neutropenia, also not common, but just wanted to point it out that it does happen. Sometimes people come after their six cycle of R-CHOP, and they're in remission, and they're six months after chemo, and their blood work is perfect, except the bacteria-fighting neutrophil count is literally zero. And we see that sometimes when we associate itself to be with the antibody rituximab and people are often getting this antibody close to the time that they're getting stem cell transplants. And so sometimes we see a post-transplant also.

(29:13) It can last a week, it'd be a long discussion to explain what it is, but the hypothesis is that it's actually a little bit of a self-generated antibody or autoantibody against those neutrophils because the drugs we're giving don't directly interact with those cells, certainly not at that time.

(29:31) Patients don't usually get sick with that it's usually just a lab number. And as I said, prior rituximab transplant and non-transplant setting, we certainly see once in a while, if the white count was really low if the neutrophil count was below, say 500 or 0.5 would be another way to say that we might want you on some antibiotics. And we might want to give you growth factor once or twice a week, just to kind of keep the count above that because that's the place above which important infections are unlikely. But again, not super common and usually transient. And usually, we don't have to do anything about it. And this doesn't last for a year or anything like that.

(30:04) Late bacterial infections are uncommon, but can occur after transplant. Late bacterial infections. Again, also uncommon, but I said anyone after transplant, that's been in the hospital, gone back home, and is on IV antibiotics and they think I have pneumococcal pneumonia. Who would absolutely want to know what their immunoglobulin levels were? If they were normal, we wouldn't know that we could do anything about it, but if they ended up being low, we would give IVIG or intravenous immune globulin potentially once a month for six to 12 months. And the idea there is worth thinking like, we're kind of if your gas tank's a little bit empty, we're filling it for you because you can't make the protein. And in other settings, in the transplant setting the data is limited, but in non-transplant setting, I would say definitely that the reasonable data that we cut the infection risk in about half by doing that for those patients.

(30:47) But as I said, evidence not super strong in the setting, but it would certainly be a discussion, and I would probably do it. If the immunoglobulins levels were 1% low, we probably wouldn't. But if they were really, really low, we would certainly think about it and probably try to do it.

(31:02) Osteoporosis is a potential side effect of an autologous stem cell transplant. Osteoporosis is a challenging one because as you can see here, there are lots of risks for osteoporosis that are outside of the cancer and the treatment. So getting older, female gender, certain ethnicities, people who smoke, people who continue to use alcohol all those things are important. The things that are related to treatment would be early menopause or gonadal failure. And or hormonal failure that could include testosterone for a male that might happen when we're doing transplants at an early age. So we might be reducing testosterone levels in a 40-year-old much quicker than we would if they hadn't had a transplant and same for a woman leading to premature ovarian failure. And so that time without those hormones is the additional risk.

(31:43) Autotransplants, don't usually on the right side of the column here, they don't usually need prolonged steroids for any particular reason. That's very uncommon, except as I said, maybe in the setting of that idiopathic lung disease. Myeloma is a special category because there are lots of steroids in the regimen, and of course, those patients start with problems in the bones, weakness in the bones because of the illness itself.

(32:03) Allogeneic transplant is also a whole separate category because the occurrence of graft versus host disease often leads to long-term need for steroids. And so I think the best summary way to think about this, especially for an auto, is the need to investigate and the time to start thinking about bone mineral, density, scans, et cetera, really depends on the person, the age of transplant, whether we made them infertile or not, whether we lowered those hormone levels and what all the other risk factors would be. So that's a complicated discussion for a primary care doc. It might be a discussion for an endocrinologist, frankly, at some point.

(32:37) Osteoporosis likely occurs for non-transplant reasons but transplant may increase future risks. Here's a little bit of data that would be, I think be reassuring, though, to show. So again, after autotransplant, this is a study of about 220 patients from Norway. And so this was looking at bone marrow density after autotransplant. These were adults that 18 age or older and the typical scan that we use in the United States, the standard, the machine is called the Lunar Prodigy DEXA scan. And so, if you look all the way to the right side column, where it says population osteoporosis, this would be about the expected numbers in males and females. You slide back to the middle column, this study population, you can see males had about 8%, which is about expected for population and the females had, if that's even real or important, one or 2% difference.

(33:17) The point is these are not people that are high, high risk for osteoporosis, and probably it's all the other non-transplant factors that relate in. Now, having said that, the degree of osteopenia being potentially at risk for future osteoporosis is not trivial. And so we still do scan these people once in a while, and you have to think about again, age and what else did we do? And do you smoke? And as I said, it's a bit of a complicated discussion, but it still has to be on our minds for patients even after autotransplant. It's 10 times more on our minds for patients after allogeneic stem cell transplant.

(33:50) Breast health risks are relatively uncommon after autologous transplant unless chest radiation was used. Breast health is another thing that, again, thankfully, uncommon, but for patients that in my world had lymphomas and increasingly we're getting better at not having to do this, but patients who had to have radiation, women, and men to be fair, who had to have radiation to the chest area at a young age are more at risk, probably for breast cancers. And again, I'm happy to say today that some of this data is 30 years old because we've learned over time how to limit chemo, how to use PET scans to limit chemo, how to use PET scans to limit radiation, and frankly, how to make those radiation doses smaller. So what we do today in 2021 is incredibly different than 20 years ago. And so thankfully, that risk is probably falling off over time, but still, meaningful radiation at a young age can increase the breast cancer risk.

(34:36) So these are just some guidelines. After about age 25, and after you're about eight years or so after radiation therapy, clinical breast exams by physicians and patients are certainly worth something doing they're easy, and they're cheap, and they don't cost anything, and they make people feel empowered, and we're educating our patients. Mammograms starting annually again, about eight years after transplant, would be reasonable if you had radiation, but generally, we wait until you're in your 30s. And breast MRI. This is something that we do overlook in that I can tell you I do not believe I've ever diagnosed a breast cancer with an MRI in a patient after an autotransplant, but we do have some people that we screen this way, and the guideline would be to think about that about eight years after radiation. Again, not until you're a little bit later.

(35:19) Generally, for us to get MRI covered for this setting, we'd have to say that we think the patient's lifetime risk is probably over 30% for that to get covered by insurance. So that number may not be real, but I'm saying that's kind of the threshold at which insurance will say, "Okay, this is a reasonable thing."

(35:37) Problems with sexual health are common after transplant. Sexual health is something that we really probably don't do a great job of in clinic because we're spending so much time on other things, but here's just a couple of surveys of women. And the next slide will be about men. Female lymphoma subjects within average or middle-age in this group of patients is about middle 50s, 53, and compared to a control group. So people that are similar age and similar health problems that didn't have a transplant, the transplant group definitely reported more sexual problems compared to the controls and more sexual related discomfort, reduced frequency of sexual activity, more sex-related fatigue. Increased sexual activity being associated in this particular study with people that were older and maybe not surprising being at a consistent relationship.

(36:22) Sexually related fatigue was related to people being younger and already having chronic fatigue and having other ongoing emotional issues and distress. And life, even after a transplant like this, when things feel like they're getting back together are still complicated and there are a lot of things that sort of co-influenced other things in our life. And I think this is a good example where probably multiple factors point to and increase these types of problems that we're just sometimes not good at dissecting. And sometimes we don't have enough time in clinic to do a good job of dissecting it, but we are doing our best, obviously.

(36:55) Similar survey for men. And so this is a middle-age of about 55. And again, compared to a control group of similar age and similar health problems, but who had not had a transplant. About four to 10, 39% reported sexual satisfaction overall, about a third said, "I only have a normal or, a reasonable sexual drive a couple of days a month." And that's obviously discouraging and can't be normal for youngest people. And only four to 10 patients saying they had erections that were firm enough for sexual activity. And that might only happen a couple of times a month.

(37:27) So you can get the message here that this is also something that's real and is important and something that we have to spend time on and something that primary care doctors have to think about because we're not seeing these patients every month and we may be seeing them only once a year after they go home after transplant.

(37:42) Some of the things we have to think about. And as we all get older cardiovascular, small vessel microvascular disease, disease is probably the reason that men have impairment with erections as they get older. And so that's something that obviously plays into this. And in this particular study, again, being older, having chronic fatigue, things you can sort of see the themes over and over physical inactivity. These are things that did not sort of correlate with better sexual functioning, but again, three or four or five different things are all conspiring in our lives to potentially contribute to that. It's hard to just dissect out exactly the one thing that we can fix.

(38:21) Infertility is common after a stem cell transplant but some people regain fertility over time. Fertility is a really important discussion for our young people after transplant. So it's hard to study because it's hard to know exactly who tried. And it's hard to know whether we knew whether the spouse had fertility issues. So you can get a sense that even when you try to write papers about this, they're very limited. But we do know that people certainly can regain fertility after treatment. They can regain fertility even after getting radiation as part of their transplant. And it shouldn't be a surprise that if you're in your 20s or 30s, that's way more likely to happen than if your 40s, and to be fair about all we can tell people is in your 20s and 30s is more likely to happen.

(38:59) I usually counsel patients to wait a certain period, and I'm just saying two years is a reasonable number for two reasons. One to get back in a groove of life, two to have a reasonable sense that the lymphoma is not coming back. The thing I treat most often. But I can tell you that I've had doctors tell their patients and even oncologists tell the patients, "No periods, you're not fertile, you can have a baby. Don't worry about it." And we have had people have babies without having a single return to the menstrual cycle.

(39:27) Successful pregnancies are possible after transplant. So presumably, the first cycle that ovulated was the one that got pregnant. So I always tell people, lack of menstrual cycles does not mean anything. You've got to do everything that you would normally do to not get pregnant if you don't want to get pregnant. So assume that you could be fertile because the next time can be the first time that you had an ovulatory cycle. And almost with shame I tell you this, but once in the history of the world, I know of a pregnancy that got diagnosed on a CAT scan as a routine follow-up CAT scan, and you can only imagine how horrifying that is. So we can't overstate enough this whole concept of fertility after transplant.

(40:07) Thankfully pregnancy risks, probably aren't very different. And again, you can understand these are hard to measure because they're surveys, and they're hard to get perfect complete data. But from what we can tell, I can tell you that the miscarriage rate, which in the population is probably around seven or eight or 10%, does not seem to be spectacularly different. Requirements for caesarean section might be a little higher. 30% is probably high to compare to a population that hadn't had transplant.

(40:32) The need for assisted fertility techniques, 20%, is probably about double what the population expectation would be. But thankfully, when people do get pregnant, the risk of pregnancy complication is similar, pre-term delivery similar, and I can tell you, even for patients that we have once in a while, a patient will show up with Hodgkin lymphoma and pregnant. And I can tell you that beyond the first trimester, once all the organs are formed in the baby, all that stuff is done. If we have to, we can actually give those people chemotherapy and put them in remission and sometimes cure them with their baby on board. And studies of that also suggest that those babies are not different than the important way.

(41:10) So I'm not trying to overstate that or be dramatic, but we spend all this time saying, "Well, don't have this thing when you're pregnant, don't do that thing when you're pregnant," people that need chemotherapy in the second and third trimester for things like Hodgkin lymphoma, young female, we can do this, and we can do this safely. And I've treated at least a handful of people like that in my life, very successful and had spectacular pregnancy outcomes.

(41:35) There are wide variations in patients’ ability to return to work after transplant. Working after transplant is important thing too. So again, everyone is different. I have people that go back to full-time work a month after transplant. And I have people that feel like they can't go back to work 12 months after transplant, and obviously physical health, financial concerns, type of work, how hard is your job, how intense it all matters. And again, not surprising, these are fairly common sense things. People that have the energy and ability to work pre-transplant, as you can see here, the study of about 275 patients, 77 people working pre-transplant, they were in pretty good health. Almost that number were working at the time of survey and being well enough to work before transplant obviously predicted for being well off to work after transplant, but people's work hours do drop.

(42:20) So what we usually tell people is, first of all, every patient I've ever transplanted, I think in my life that I can remember, has said, "My boss has been very good and very understanding about this," number one. Number two, we say, "Whatever you need from us, we will give you any letter, any explanation, anything you want us to tell your employer," and almost without fail people come back and say, "My boss said I could start two hours a day, three days a week, and just sort of gradually work up." And so that usually works out well with good communication between an employer and an employee. And we just kind of help guide that where we need to.

(42:55) Although uncommon, the risk of secondary cancers such as myelodysplastic syndrome, acute myeloid leukemia and melanoma is increased after an autologous transplant. Secondary cancers are obviously a concern. And again, thankfully, in the setting of autotransplant, not super common, but you can imagine, I mean, just being a certain age and gender and the prior smoker and prior alcohol, all those things are pre-existing risks that are outside of what we did for the treatment. Post-transplant maintenance therapy, lenalidomide is probably the most important example. This medicine does have some risk of secondary cancers happening. And so those things have to be watched for very carefully.

(43:23) These other statements are a little bit hard. They're hard to make with great certainty, but males might be a little bit more at risk for secondary cancers. Being transplanted at an earlier age might be a little bit more of a risk for a second cancer, and early-era transplant means, for the most part, in the setting of autotransplant that 20 years ago, we were giving chemotherapy and sometimes total body radiation to our patients with certain lymphomas. And it turned out that that was not so good for secondary cancers. And I'll show you. I think a slide on that in a second.

(43:52) The most important thing from our standpoint, that we really have a sense is probably related to the prior therapy, would be the bone marrow disorders like we call them myelodysplastic syndrome, which is kind of like a pre-leukemia and acute myelogenous leukemia or AML. These are the most common things that we think about. And not surprisingly, as I said, the initial chemotherapy you got, the drugs you got, how many times your lymphoma might've been treated to get it in remission, all those things are going to count before the transplant even happened, but being younger might increase that risk. Use of radiation, you can see here, why we abandoned it because many studies said essentially the same thing, three-ish, four-ish us, or 5% risk of a secondary bone marrow disorder at 10 years if you didn't have radiation versus up to about 10% if you had radiation as part of your transplant regimen. So that helped us learn to abandon it.

(44:40) Alkylating agents or drugs like cyclophosphamide, those are things that are risks. There's a drug called etoposide that we would use in some lymphomas that would be a risk. So overall, there might be a five or 10 fold increase, over a person that never had to have the transplant. Well, that sounds scary because that's 10 times, but these are still uncommon in the population. So a 10 times risk of a super rare thing is still pretty rare.

(45:02) Types of secondary cancers that may occur. Melanoma risk may be increased, and we always have people see a dermatologist once a year, make sure someone is doing a good sun checks.

(45:09) And lymphomas, believe it or not, you could be transplanted for one type of illness and end up with lymphoma. Three-fold increase, also sound high, but if you think of a lifetime risk in an average person that's 1% of, say, developing and non-Hodgkin lymphoma, three times that is still only 3%. So the number sounds scary, but in context, they're still relatively uncommon.

(45:30) Here's an example of secondary cancers after transplants. So the top line up here, the dotted line, shows the risk of all cancers. The line looks like it's going up, but if you look on the side, we're only talking about six or seven or 8% risks. And again, the solid tumors is the black straight, the non-dotted black line, that looks like an important number, and it's going up over time. But remember that people are getting malignancies as they age for reasons outside. It's really hard to circle in and say, "Well, we know this lung cancer is because of prior therapy," for example.

(46:04) On the bottom, the hematologic malignancies. That is something that I think we do have a good sense that the drugs we use are impairing those cells and probably increasing that risk. But you can see in this particular study that risk was low. That's in about seven of nearly 8,000 patients.

(46:21) Heart health. All we can tell people is, "Do your best to do the things that will keep you healthy." So we know that there, again, people will get ischemic heart disease, even if they weren't going to have a transplant, but there does seem to be some extra risk of heart disease and vascular disease. And that has to do with things like prior radiation, that has to do with drugs, like Adriamycin that we give to a lot of lymphoma patients. And there was a little bit of a stroke risk that might be a little bit more than population average.

(46:47) How to reduce the risk of secondary cancers. So, what can we do? Well, we pick the safest medicines we can, we try to never use radiation when we don't have to. We try to help people with smoking. And we say that very aggressive attention after treatment and transplant to cholesterol levels and blood pressure and blood sugars, if you're diabetic, and stopping smoking, those are all the things that really are 90 or 95% of the impact. Those are the things that we can do. And here's one study. I just put here that persistent blood pressure and blood fat issues a year after transplant are associated with an increased risk of vascular disease.

(47:23) These are really hard to measure in large populations because there's so many other factors that relate to getting these disorders, but we tell people aggressively, aggressively try to, don't be lazy about your diabetes be very on top of these things, be very motivated. These are things that do matter.

(47:38) Thyroid problems can occur after an autologous stem cell transplant. So, in some ways, these are things that we look at, and I didn't talk about every one of these, but here I list by organ system what we measure and what we do. And you can see thyroid is a simple thing I didn't talk about, but chemotherapy and obviously radiation to the neck area can increase that. Simple blood test and a simple medicine that you have to take for life, but simple fix.

(47:58) Cataracts can occur after transplant and are easy to treat. Cataracts are something that are not uncommon. And again, radiation is important for that. Thankfully, a pretty simple fix surgically. People almost never get infections or have problems with that type of surgery.

(48:07) Bone health, we talked about, I think there's a whole talk about that in this conference. And that's sort of assessing well, 'What is the underlying other reasons for fracture risk?' And do we need you to see an endocrinologist? And when should we start a DEXA scan? And there are scores that come from those DEXA scans that you have to think about and interpret carefully. For people at relatively low risk that might just have some thinning of the bones, osteopenia, we're going to say calcium vitamin D. For people that actually have frank osteoporosis, that's a discussion with a primary care doctor or an endocrinologist.

(48:38) Breast health we talked about. Oral again, thankfully, autotransplants don't seem to impair saliva and stuff for more than weeks, but just keeping up with those things is important.

(48:49) Then heart health, again, we just sort of talked about this. Skin health, it's nice to see someone once a year, one person should be looking at your skin once a year, and ideally, that's a dermatologist.

(49:01) Secondary cancers. We just watch for symptoms. We're not doing CAT scans and bone marrow biopsies and things. We're basically seeing people saying, "How do you feel? What does your blood work look like? How's your exam." And we just spend time as much as we can on, as I said, blood lipids, blood pressure, things like that.

(49:18) Fertility we've talked about, but measuring hormone levels and people is important because it gives us a sense that for a male, for example, that has a low testosterone level, that's at least a discussion about, should we be thinking about replacement.

(49:32) Now, testosterone replacement has some risks and actually has some vascular risk. So that's a very cautious discussion and often help with an endocrinologist.

(49:41) The immune system recovers over time.  Immune system, as I told you, most things recover over time. Basically, stay on the right preventative drugs, which for us is really mainly acyclovir for about six months after transplants to reduce herpetic infections like cold sores and shingles. Get your vaccines on time. And occasionally, we go into that discussion of IVIG.

(50:00) Few people have major life-altering complications after an autologous stem cell transplant. So thankfully, most of our people come and see me a year or more later, and they say, "I'm probably 90 or 95% of what I was." And few are left with major life-altering medical issues after this type of transplant, which we're very thankful for. Fertility, super important discussion, as I said, certainly can come back in young people and can come back before you even know it.

(50:21) Psychological health is important. Normal life and normal work-life can resume. Psychological health is important. There are things that are hard for us to touch on, it's not very easy for doctors to talk about, when your scan looks good and your blood work looks good. It's very hard to get in deeper and say, "Well, how are you coping? And are you thinking about your illness every day? And you're waking up every day, opening your eyes, looking at your ceilings, saying I had lymphoma yesterday?" Those are things that are hard for us to help counsel on.

(50:43) And most people, I think, get sort of a contextual understanding over time that the risk is lower, I'm five years out now, and the chance that my lymphoma's coming back is much lower. People do a lot of that on their own, but I think we have to pay attention to that and then refer and have psychologists and where necessary psychiatrist to help manage some of these things.

(51:03) The usual age-appropriate health screenings are important for those who have had an autologous stem cell transplant.. Never forget about age-appropriate health screenings, colonoscopies, mammograms, pap smears, sun safety, and any kind of transplant-related things like we talked about, pulmonary disorders and things like that, having that follow-up done.

(51:15) So that's where I'm going to end. I actually didn't look at where I was for time, but I will now see kind of what questions we have here.

Question and Answer Session.

(51:28) [Daniel Gennari]  Thank you, Dr. Bociek. That was a great presentation. We're definitely going to take some questions. We have a lot of them. As a reminder, if you have a question, please type it into the chatbox on the lower left-hand corner of your screen.

(51:44) And the first question we're going to give to Dr. Bociek is in regard to a relationship between lymphoma and an autoimmune disease known as, I believe it's IgG4 disease. Are you aware of any connection or links between IgG4 disease and lymphoma after transplants?

(52:12) [R. Greg Bociek]      Well, so I guess I would say that, I mean, so there are some things that would suggest that patients with autoimmune disorders might have a high risk of lymphoma. And then the more common things would be things like rheumatoid arthritis and lupus. And so it's always hard to know the chicken or the egg. So if the question is, does someone with lymphoma have a higher chance of getting IgG4 disease? The answer is that might be, but again, we're not sure if the underlying thing was an underlying immune deficiency in that person that made them more at risk for autoimmune diseases in general. And that one of those things was why the lymphoma came about. So I guess my answer is, it's just hard to say chicken or the egg in that circumstance.

(52:59) In other words, which led to which risk, if that makes sense.

(53:03) [Daniel Gennari]     Right. Our second question, I'm going to go through these kinds of quickly because there are quite a few of them. Can you get trigeminal neuralgia years after a stem cell transplant?

(53:20) [R. Greg Bociek]      Yeah, again, I would say without someone writing a paper, so we looked, and we found that 13% of people got this. It's hard for me to think from the standpoint of a mechanism, why that might be true, but I never say never about any kinds of these things. I would not generally say to someone, gee we see that in 15% of people. So I would say that would be uncommon, in my mind, to think that that might be related to transplant.

(53:49) [Daniel Gennari]      One of the viewers would like to know if there is a maintenance therapy for non-Hodgkin's lymphoma?

(54:01) [R. Greg Bociek]      I just want to touch for two seconds on, I'm just, this is, I shouldn't say this, but I'm going to. So, the IgG4 question someone was from Montreal. I just want to say hi, because I'm from Ottawa originally. So I just couldn't overlook that, and maybe I'll have to have a Montreal smoked meat sandwich this afternoon for that.

(54:17) So sort of the question next was about maintenance therapy. So as I said, as many of you know, non-Hodgkin lymphoma is one word for 70 or 80 different disorders, and it would be hard to go line by line by line, but we do often offer maintenance therapies for patients with follicular lymphoma. And so this is separate of transplant. Follicular lymphomas, sometimes mantle cell lymphomas, a lot of our therapies for CLL, chronic lymphocytic leukemia, which is really a lymphoma that happens to circulate cells in the blood, a lot of patients go on medicines today that are chronic and oral, and you take until you can't anymore. So in a way, you could think of that as a maintenance therapy. So there are a number of maintenance therapies.

(54:59) For Hodgkin lymphoma, I mentioned very briefly, the medicine called brentuximab, which is an antibody very specific to one of the proteins that sit on that Hodgkin cell we call a Hodgkin Reed-Sternberg cells. So there definitely are maintenance therapies. For the most part maintenance therapies in lymphoma seem to keep the illness in remission longer for an illness that we don't think we're necessarily going to cure, like a follicular lymphoma, but they don't tend to allow us to conclude things like you're going to live longer. So what I generally say is longer in remission, but maintenance therapies, like we talked about, have some risks. They increase infection risk a little bit. As I said, sometimes people show up with low blood counts.

(55:38) There's still a bit of a trade-off, and that's a pretty complex discussion to have with a doctor. Although on average, I think more oncologists are in favor of maintenance therapies. To me, it's a more nuanced discussion that is very specific to that person and their risk. And because the alternative, then I could explain, is that saving a medicine like rituximab for use in the future, it might have some value too. So it's almost like if you spend the money now if you use the drug now, it might be less helpful in the future. And so there's a lot of complex trade-offs there, but there are a number of lymphomas for which we would at least have a discussion about maintenance therapy. Yes.

(56:22) [Daniel Gennari]     One of the caregivers viewing the presentation would like to know, "My husband had a stem cell transplant and is day plus 30. Although his neutrophils were at 1.99 when leaving the hospital, they have now dropped below 0.5. Is this an indication of a failed stem cell transplant?"

(56:43) [R. Greg Bociek]      No. That's a great question. So the answer to that is pretty much 0%. So, no, it's not an indication of a failed transplant. So remember two things. One is we're giving growth factors for a while after cells and cells recover. And I always tell patient, after we stopped your growth factors, day 14, whenever it is, there's going to be a little bit of a dip. And sometimes that dip is pretty significant and generally, again is really hard because it's hard for me to give specific advice, but I would just tell you that generally, I'm not panicking and hopping back and putting those people back on growth factors. Usually, we try to give them time.

(57:19) And so yes, once in a while, we will see a cell count at day 30 or so dropped to 400. And depending on health, other things, COPD, how important the fever, if you get it. How far do you live from a good hospital? All of those things weigh into whether or not we would do something or just watch it. But remember that the longer we help it with growth factor shots, the less of your body's bone marrow cells are figuring out we got to make the growth factor to make the cells get better. So it's kind of like we're giving them a crutch and a reason to not do it on their own.

(57:51) So not a concern about relapse, not a concern that the transplant didn't work. Just something that again, between a patient and doctor, how are we going to manage this? Are we going to watch this? Are we going to give a tiny bit of growth factor once a week? All of those would be appropriate, but 0% panic. So I'm glad you asked that because I would want to get that off your chest.

(58:12) [Daniel Gennari]     Closing. Okay. I think we have reached the end of our available time. Doctor, I really appreciate everything you've done. And on behalf of BMT InfoNet and our partners, thank you very much for your helpful remarks or answers to the questions. Thank you, audience, for your excellent questions.