Donating Bone Marrow and Stem Cells to a Family Member: What You Need to Know.
April 4, 2017
Presenter: Dr. Michael Pulsipher, Medical Director of Children's Hospital of Los Angeles, and Co-Chair of the Donor Health and Safety Committee of the Center for International Blood and Marrow Transplant Research.
Presentation is 51 minutes long with 12 minutes of Q & A.
Summary: Bone marrow and peripheral blood stem cell transplants are a potential cure for many people with a life-threatening disease. Family members may be tested to determine if they can donate bone marrow or peripheral blood stem cells (PBSCs) to a relative who needs a transplant. This presentation reviews the procedures, risks, benefits and safety of donating bone marrow or PBSCs to a relative.
- There are three main reasons for a person may be asked to donate bone marrow or PBSCs to a relative: to treat the patient’s cancer, to replace dysfunctional bone marrow, or provide a form of gene therapy for a patient with an inherited disorder.
- Fully matched siblings are the ideal donors for bone marrow or stem cell transplantation but half-matched and even unrelated donors can lead to successful transplants as well.
- The side effects of donating bone marrow and PBSCs to a patient for transplant are typically quite minor, short-lived, and well controlled for most donors.
(00:08:57): Related donors minimize the risk of a patient developing graft-versus-host-disease after transplant, compared to unrelated donors.
(00:11:07): Donating bone marrow or peripheral blood stem cells is safe and involves minimal risks for donors.
(00:14:21): Bone marrow and PBSC donors are not required to share information about their own health with a patient who needs a transplant but may be asked to do so in certain circumstances.
(00:17:17): Proteins on the surface of a donor’s white blood cells, called HLA (human leukocyte antigens), must be similar to those on the patient’s white blood cells.
(00:21:57): There is a 25% chance that a brother and sister will be a complete HLA match for a patient.
(00:24:55): Younger bone marrow and peripheral blood stem cell donors are generally preferred over older donors.
(00:26:09): A donor’s blood type does not have to match the patient’s in order to donate bone marrow or peripheral blood stem cells.
(00:27:44): Even if a potential donor is a perfect HLA match for the patient, there may be reasons that preclude that person from donating.
(00:30:59): Bone marrow is collected or “harvested” from a donor through a surgical procedure under general anesthesia.
(00:31:52): Peripheral blood stem cells can be collected from a donor without surgery or anesthesia.
Transcript of Presentation:
(00:00:02): [Marla O’Keefe]: Introduction. Good evening, and welcome to BMT InfoNet's Webinar, Donating Bone Marrow and Stem Cells to a Family Member: What You Need to Know. My name is Marla O’Keefe , and I m the Director of Outreach for the Blood and Marrow Transplant Information Network or BMT InfoNet. And I'm happy to say I was an unrelated donor in 2002, so this webinar has particular interest to me.
(00:01:22): I would like to introduce our guest speaker, Dr. Michael Pulsipher. Dr. Pulsipher is the Medical Director of Children's Hospital of Los Angeles, and Co-Chair of the Donor Health and Safety Committee of the Center for International Blood and Marrow Transplant Research. Dr. Pulsipher is an internationally recognized expert on donor health and safety.
He is currently principal or co-principal investigator on six national multi-center studies and a co-investigator on multiple additional clinical trials. Dr. Pulsipher has authored more than 140 articles in peer-reviewed journals, including Journal of Clinical Investigation, Blood and Nature Genetics. He has written five book chapters and presented widely at national and international conferences. Please join me in welcoming Dr. Michael Pulsipher.
(00:02:21): [Dr. Michael Pulsipher]: Overview of Talk. Thank you very much. It's a real privilege to be able to spend some time today and talk to individuals who are considering doing a wonderful thing - donating either bone marrow or PBSCs to a family member. There may be some on this call who are unrelated donors in the National Marrow Donor Registry, and some of the information that I'll share today is relevant to that as well.
(00:03:09): So why do people donate either bone marrow or PBSCs? There are really three main reasons to do this, and I want to mention all of them so that you really have in mind what you're doing.
(00:03:27): There are three reasons someone may be asked to donate bone marrow or PBSCs to a relative: to a treat cancer; to replace dysfunctional marrow; and as a form of gene therapy for an inherited disorder. Most donors are donating to help their family member or, in an unrelated donor situation, help an individual whom they don't know, overcome cancer.
(00:03:42): What happens with the process of bone marrow [and stem cell] transplantation are two things: patients get very high-dose therapy to minimizes the risk of relapse that can occur with any cancer. And they get a “graft versus leukemia” effect in which the bone marrow [or PBSCs] see the cancer in the patient as “different”, and then fight and kill it.
(00:04:21): The second thing that happens is you can replace a dysfunctional marrow. Often, patients will have a problem with their immune system.
(00:04:36): The marrow is a wonderful organ, it happens to be my favorite organ. People don't really think of it as an organ, but it is, and it does three very important, essential things. It's your immune system that helps you fight infections and can help you fight cancer. It makes red cells that are important for carrying oxygen to the body. And it makes platelets that are very important for clotting.
So whenever the marrow doesn't work well, and there are a number of disorders where the marrow doesn't work very well, a bone marrow [or PBSC ]transplant can fix those disorders.
(00:05:11): The final thing that bone marrow is used for, in some cases, is gene therapy. There are a few disorders where children, especially, get an inherited disorder that's usually an enzyme defect that causes serious problems with their ability to live a normal life. A bone marrow [or PBSC] transplant can distribute white blood cells from the donor throughout the patient’s body and deliver an enzyme to different parts of the patient’s body. So, in other words, getting new bone marrow [or PBSC]allows us to deliver this enzyme to places in the body where it wouldn't otherwise be in a patient who has that gene defect.
(00:05:58): So those are the three main reasons for donating bone marrow, and all very, very important for patients who are very, very ill.
(00:06:07): Using sibling donors usually results in the best outcome after transplant, but unrelated donors can provide a good outcome as well. So here is a slide that is very important to note. It mentions just part of the story, but the important thing to mention is this line right here. This is a sibling donor. Now you can see that the sibling donors - brothers and sisters - have the best outcomes, and it always has been the best.
(00:06:38): Now over time, unrelated donor outcomes have gotten a little bit better and that's a good thing because it gives you a little slack if [a sibling donor] can't donate, but sibling donors have always been the best donors, the ones that have allowed the best survival.
(00:06:56): Now this [graph] only goes to 2005. Right now, the difference between siblings and unrelated donors is very close, but because you get a lot more complications associated with unrelated donor transplantation, even though the survival is very similar, we always like to do a family or a sibling donor when we can.
(00:07:18): There are a number of different types of donors that are used in the United States for bone marrow [and PBSC ] transplantation, and this slide illustrates what we have done through the years. When bone marrow transplantation started, it was almost always [done] with sibling donors. Only later on did unrelated donors begin to increase very dramatically.
(00:07:47) There's this other category called “other relative”. There are a number of [related] donors who aren't a sibling match, and as you can see here toward the end [in later years], there's been a big increase in this type of donor. Now what type of donor is that?
(00:08:05): Mismatched or half matched donors for bone marrow [or PBSC] transplants are becoming more common. Originally most of these “other relative” donors were donors who weren't quite a full match. They had a single mismatch. But as time went on, we developed ways of doing transplants with mismatched donors and we have something called a half-matched or haploidentical donor. And over the last couple of years, we’ve developed simple and very important techniques to allow the use half-matched donors. That has allowed a lot more related donors to donate. So, the bottom line is that related donors contribute very significantly to the number of transplants that are done in America. Unrelated donors are more common right now, because not enough patients have a good matches with a relative.
(00:08:57): Related donors minimize the risk of graft-versus-host-disease when compared to unrelated donors. This next slide talks about the advantages of having a related donor. Now, when a recipient receives a bone marrow [or PBSC] [transplant], they have what I want to call a "your friend is your enemy" relationship with something called graft-versus-host disease (GVHD). The new [donor] bone marrow [or PBSCs] can go into [the patient] and restore the bone marrow after it's been treated with intensive therapy.
(00:09:39): The trouble is, many [patients] can get graft-versus-host disease [GVHD] where you can get a skin rash or severe diarrhea or liver dysfunction, and you can develop a chronic form of [GVHD], that can cause a lot of issues. It's a good thing, in a way, to get a little graft-versus-host disease because it may decrease the risk of relapse, but a lot of graft-versus-host disease is not good for anyone. Related donor bone marrow [and PBSCs] tend to give less graft-versus-host disease, which is good. The patients return to normal function earlier, they take less medications, and visit the hospital less often.
(00:10:19): Related donors are preferred in case a second infusion of donor cells is needed. The second advantage to having a related donor is that every once in a while, you need a second infusion of donor bone marrow or PBSCs. Sometimes [the patient’s] new bone marrow is a little bit weak and it's not doing quite what it needs [to do]. That can be because of infections or other complications that happen early on in the process.
Other times we see hints of the cancer coming back, and in that circumstance, if you treat it early with a second infusion of [bone marrow or PBSCs] from the donor, then you can bring it under control and often cure it. So, it's nice to have a related donor so that you can potentially use that related donor for second infusions.
(00:11:07): Donating bone marrow or PBSCs is safe and involves minimal risks for donors. Now here's a slide that really illustrates something that's important to understand. Whenever you do something in life, you want to know, "Well, does it give me any advantage?"
The most important thing to understand is that the biggest advantage you get from donating [bone marrow or PBSCs] is not for you. It's for the person who receives your donation. In other words, [the patients] are the ones who have a potentially lifesaving procedure that they otherwise couldn't have had, or a safer lifesaving procedure. They’re the ones who get the big benefit.
(00:11:44): But there are a couple of things that are actually advantageous to the donor. First, we can reassure you that this is a safe procedure. It does have [potential] complications associated with it. There are some things that seem scary but they're not. There are rare complications that can occur, but by and large, the vast majority of donors have a good experience, and the complications or discomfort associated with the donation process are very mild.
(00:12:33): In addition, it’s important to reassure people that there's really no long-term damage to [the donor’s] own bone marrow. We just finished a very large study of donors who donated a second time, and it showed no problems at all. You can donate bone marrow many, many times, you have plenty of it to go around, and it grows back very nicely.
(00:12:57): Donors often receive an emotional benefit from the privilege of helping to save the life of the patient. But I think one really important benefit that you can get from transplantation is an emotional benefit. Most of the people who donate feel that it's a privilege to be able to help out.
When you're a donor, you are providing something that many other people can't provide. It's a unique thing that you can provide, and to help save your family member's life is a real privilege. (You can tease them in the future and tell them things that they owe you, although I wouldn't recommend that necessarily.) But it is a real privilege to do that. And no matter what happens with the transplant, donors should have a strong sense that they've performed a very important service. No matter what happens in a transplant, whether it's successful or not in curing your family member, you've done a great thing, and you should keep that in mind.
(00:14:03): Now, there are a couple of other things that I want to talk about: you, as a donor, have the right to privacy, and you have the right to make your own decision and resist family pressure.
(00:14:21): Donors are patients, too, and are entitled to full privacy about their health. It’s very important to understand that you, as a donor, are also a patient, in a way. When you go through the process and learn how to be a donor, you are entitled to full privacy regarding all of your medical conditions, and that's very important. On occasion, you may have a condition that you don't want your family to know about. If that's the way you feel about it, it is your right, and you should stick to it. You can keep things private.
(00:15:04) In some circumstances, you may have medical conditions that your recipient doesn't need to know about. But there are a few [medical] conditions that can affect the health of the patient. In these circumstances, you will be asked, if you feel that it's appropriate, to reveal this information to the patient. Those conditions are ones where you could potentially give the patient a disease.
(00:15:41)For example, there are donors who have hepatitis B or hepatitis C. You can actually be a donor if you have hepatitis, and your recipient can receive medications that will minimize the chance of getting an infection. Sometimes it's better to do the donation from a related donor who has hepatitis than it is from another individual. But because you would potentially be giving the patient a disease, you would be asked to share that information with the patient.
(00:16:21): Many donors have no worries and are happy to share their information, but many donors don't want to share specific information about their health, and there's nothing wrong with that. If you feel that way, you have that right and privilege.
(00:16:36): Bone marrow [and PBSC] donors should have advocates to guide them through the process. One thing that's very important [to know], there is an accreditation process that all transplant centers go through. Accreditation is how transplant centers get a stamp of approval from a national organization that says they're doing transplants the way they should. And [one thing] that they are required to do is provide donor advocates. In other words, a donor should have someone to talk to at the transplant center who will be their advocate and will talk to them and give advice if they're feeling hesitant about the donation process. Someone who's on the donor’s side and team.
(00:17:17): Donating bone marrow [or PBSC] is a voluntary act and people should not feel pressured. Alternative donors are almost always available. Now that brings us to this issue. What if you just can't bring yourself to donate? There are a number of reasons why individuals might feel that way. One thing I want to state, and state very clearly, is that bone marrow or PBSC donation is a voluntary act. You should not do it unless you are willing to donate. There is a big and wonderful group called The World Marrow Donors' Association that is dedicated to doing donor studies. I'm running a national group through the Center for International Blood Marrow Transplant research that does donor safety studies. We support a donor's right to refuse. If you don't feel good about the donation, for whatever reason, you can refuse.
(00:18:08): It's important to understand that an alternative donor can be obtained in most cases. There are unrelated donors and cord blood donors who can donate, rather than you, in almost all cases. Now the risk profile [for the patient] will be different with a cord blood or an unrelated donor, but survival is very close. Very close. Especially if you have health conditions that may affect your ability to donate, you should not feel like you need to donate if your health is not good.
(00:18:49): If you're not feeling good about [being a donor], one thing that I would recommend is that you don't get your blood tested. When you're tested to be a donor, generally it's a one in four chance that you're going to be a donor. If you find out that you're a complete match, then all of a sudden, the pressure gets a little bit more intense from your family members. So, if you really feel that you don't want to donate, it's probably best just to say, "I don't feel good about being a donor and I'd rather not be tested." That way you won't have that extra pressure.
(00:19:26): Bone marrow donors should be good HLA matches for the patient. Now let's talk a little bit about the testing to find out whether a related donor is the right donor. What we are looking for in a donor is what we call an HLA match. Now, HLA stands for human leukocyte antigen, and those words mean human white cell protein. This is a protein that's on the surface of white cells. White cells are your immune cells that fight infection in your body, but they also are the guardians. They're the cells that keep foreign organs out. They can cause rejection of organs. The HLA proteins help you accept or reject organs.
(00:20:15): We test for a number of different HLA proteins. We do A and B, and now actually we do C and DRB1, and sometimes even DQB1. The donor’s proteins are then compared with those of the family member who needs a transplant.
(00:20:37) Full siblings can match at all of these antigens, and if they do match then that's great, they're the best donor. If [the sibling doesn’t] quite match, [they are] a single antigen mismatch donor. Every once in a while, these genes cross over and get mixed up, and so a sibling could be not quite a full match but just a one antigen mismatch. If that occurs you still could be the best donor for your family member.
(00:21:11): Nowadays, half-matched or haploidentical related donors are frequently used for transplant. Nowadays, we're [using] a lot of what we call half-matched donors., We look at A, B and maybe C and DR and DQ – you have two of each of these - which means you have 10 different things to match. Sometimes if you're only matched at half of these, at five of them, it's still good enough for you to be a donor as long as [the transplant team] use the haplo approaches.
(00:21:37): So, this is what the HLA genes kind of look like. This is a funny representation, but the bottom line is this is what a protein looks like. It goes on the surface of the white cell and feels around and tries to sense other proteins that are there.
(00:21:57): There is a 25% chance that a brother and sister will be a complete HLA match for a patient. Every brother or sister has a 25% chance, or one in four chance, of being a complete match because they get these genes from dad, and these genes from mom. Now, the other possibilities are the two blues going together, or the red going with the blue. So, the bottom line is there are four different possibilities. So, only a one in four chance that any given brother and sister will be a complete HLA match.
(00:22:33): How does the testing occur? The transplant center will have a way that they like to do the testing that they think is best and most efficient. Most centers do a blood test. Some centers will rather have you scrape [the inside of] your cheek. When you scrape it, scrape it good and hard because you actually have to collect some cells that line the surface of your cheek. You then send it to the lab, and you can know the results, usually, in four to seven days. You may also have to throw in a little mailing time in there if you're getting tested from a distance.
(00:23:13): What level of match matters? For standard transplantation, we're going to test either six or eight of those genes. Sometimes people test even more, nowadays, they'll test 10 or 12. But for related donors we oftentimes don't need to do elaborate testing of a lot of the extra matches. As I mentioned, you can have that crossover match where you've got a single mismatch, and you oftentimes can be used as a donor.
(00:23:48): By definition, all parents are half matches for their children, and all children are half matches for their parents. Even if you're a half match, you can still be used. By definition, all parents are half matches for their children, and all children are half matches for their parents, and [using half-matched donors] is occurring now in many situations. I know of a situation where a grandchild was asked to be a donor for a grandparent, because patients are now undergoing transplantation at older ages.
(00:24:20): What happens if you have a big family? So, you've had sibling rivalry all of your life, and all of a sudden, you've now got more than one sibling who is a match for the patient. How do you decide who is the very best donor? There are a number of general principles, but what will usually happen is that your transplant center is going to think very carefully about it and come up with whom they think is the best donor, and it's going to be based on a number of things.
(00:24:55): Younger donors for bone marrow [or PBSC) transplants are generally preferred. The first thing that we think about is age. In general, younger donors are better. Once you're over a certain age, once you're over 40 or 50, then it doesn't matter. And sibling donors go until about age... Let's see, I think the oldest donor on a big study I just finished was 73, I believe. So, you can donate until you're well into your '70s. But in general, if the donor is younger, it works out a little bit better.
(00:25:32): Matching bone marrow [or PBSC) donors and recipients by gender is usually best. How about sex? Usually, it's best for the donor to be the same gender as the patient. The big risk is women who've had multiple pregnancies. That can increase the risk of more serious graft-versus-host disease. In general, what we try to do is give a male donor to males, and when we use female donors it's best to have donors who haven't had multiple pregnancies.
(00:26:09): Blood type matching isn't vital. You can actually be a donor if you don't have the same blood type [as the patient]. Eventually the new bone marrow will make blood and will replace [the patient’s] old blood type with [the donor’s] blood type. If [the donor] has a blood type that matches the patient’s blood type, it just makes things a little easier.
(00:26:30): If a patient has not had a CMV infection, then using a donor who has also not had a CMV infection preferred.
There's a virus in about 80% of us that is the result of CMV (cytomegalovirus) infection that we sometimes get in the first 10 to 20 years of our life. We have this virus living in our white cells. Generally, for the remainder of our life, it doesn't bother us unless we happen to be very immune suppressed. If a patient has not had a CMV infection, then having a donor that has not had it is preferred.
(00:27:10): Donor consent is necessary for bone marrow or PBSC transplants but adults can often consent for their children. Finally, we take into consideration whether the donor can consent. When children undergo a bone marrow [or PBCS] transplant, their brothers and sisters are almost always children as well. And donors younger than 18 absolutely can donate and have donated very safely through the years. But we tend to allow adults to consent [for children] if possible. Your transplant center is going to tell you who the best donor is.
(00:27:44): Even if a potential donor is a perfect HLA match for the patient, there may be reasons that preclude that person from donating. Even if the potential donor matches the patient, there may be reasons why that person won't be able to donate. Now what would that be? Here's the key: health of the donor. When we assess donors, we realize that a donor is doing something of their own free will. They don't have a health problem, they just happen to be a donor. Our first obligation is to minimize the chance of any harm occurring to the donor. So, the bottom line is, if you, as a donor, have some health issues, you might want to think twice about it.
(00:28:20): There are a number of reasons why we don't allow people to be donors. If you've had a history of recent invasive cancer, it doesn't make sense for you to be a donor.
(00:28:31): If you have an active serious disease, especially an autoimmune illness, we don't want you to go through the risk of being a donor, or potentially give that illness to your family member.
(00:28:43): If you have a blood disease, we don't want to give that blood disease to your relative. If you had sickle cell disease and you were a donor, you'd give that to your family member. You can transmit potential infections. So, we do our best to screen for infections like HIV, hepatitis, et cetera.
(00:29:02): We also do not like having women donate during pregnancy or while nursing, as it can cause issues, and we would not want to put the infant at risk. And finally, we like to avoid donors who are receiving experimental medications, so as not to cause any problems with the donation process.
(00:29:24): Older donors or those with serious reactions to anesthesia may donate peripheral blood stem cells rather than bone marrow. There are a couple of other reasons that are associated with the two types of donation, bone marrow and PBSCs. First, if you've had a history of serious reactions to anesthesia, we're not going to make you to donate bone marrow because you'd have to have general anesthesia to do that. If you have very severe lower back pain, it’s probably not a good idea to donate bone marrow because it might exacerbate your lower back pain. Now here it says older than 50. A number of older individuals do donate bone marrow, but the older you get, the more challenging the procedure is.
(00:29:58): A lot of centers prefer to have old individuals donate PBSCs. To donate PBSCs, you receive a medicine called G-CSF. If you have an allergy to G-CSF, of course we'd be careful about that. There are a couple of things, diseases of the eye that are known to be exacerbated by G-CSF, and so we tend to avoid that. Sometimes patients with a history of clots have been excluded, although we did publish a study showing that it doesn't necessarily increase your risk of clots.
(00:30:34): There are two ways to collect cells for a bone marrow or stem cell transplant: a bone marrow harvest and a peripheral blood stem cell collection. Now once you're known to be a match, what can you do? There are two major methods, and a third method that is a combination approach. The first approach is a bone marrow harvest, and the second is PBSC collection, and then there's a hybrid where you get G-CSF before a bone marrow harvest. So, let's talk a little bit about those first two.
(00:30:59): Bone marrow donation involves an operation under general anesthesia. What happens when you donate bone marrow is you go into the operating room and you get general anesthesia, so you're asleep through the whole thing. You don't feel anything at all. You might have a little discomfort when you get an IV placed. Then you're put on your stomach, and we do a bone marrow harvest in your posterior iliac crest. That's this little area right in the very back of your hip and the only purpose for it to be there is just to harvest bone marrow. I mean it really doesn't support anything. It's a great place to do a bone marrow harvest.
(00:31:30): We take a needle, go through the skin just in one place, so when you're done with this, you don't really have a scar or anything. And that needle then is inserted several times into the back of the hip, and bone marrow is removed. It looks like blood when it comes out of the body, and it's then collected and sent.
(00:31:52): Peripheral blood stem cells (PBSC) are collected without surgery and general anesthesia. The second method is PBSC collection. This very happy, smiling donor has had two IVs placed, one in one arm, one in the other arm. The blood [is withdrawn from one arm], is spun [in the machine where] white cells are removed, and the rest of the blood goes right back [to the patient through the iv in the other arm.]
(00:32:09): This donor has been primed with Neupogen or G-CSF for five days by a subcutaneous shot. That priming of G-CSF causes his bone marrow stem cells to go out of the bone marrow and migrate through his body so they’re circulating all through his blood, and that allows the donor cells to be collected through the apheresis procedure. You're hooked up to the machine for about four hours. Most of the time it just takes a single day, but many times it takes more than one day.
(00:32:39): So, what are you more likely to get, a bone marrow or a PBSC harvest? That really depends on how old your recipient is.
(00:32:49): Bone marrow is the preferred source of cells for children needing a transplant. Peripheral blood stem cells are almost always used for adults who need a transplant. As we've gotten better and better data on the pediatric side, we know they do better with bone marrow, and so bone marrow is usually the preferred source [of cells]. On the adult side, peripheral blood or PBSC is collected [from the donor] almost all of the time. It's rare that bone marrow is used for adult patients. This is mainly because the diseases are different, and the approaches are different between adult and pediatric transplants.
(00:33:22): Now I mentioned a little bit about haploidentical. Here it's 50/50. The haploidentical are half-matched patients. [Transplant teams] started doing mainly bone marrow transplants with haploidentical donors, but very quickly people did PBSC transplants as well, because they were using an approach where they depleted T-cells. And when a newer approach, using post-transplant Cytoxan came along, all of a sudden both of them increased pretty significantly. So, if you're a half-matched donor, whether they're going to ask you to [donate] bone marrow or PBSCs will depend on the transplant center and the disease.
(00:34:04): What are the side effects of donating bone marrow? This is an overview. This lists all sorts of possibilities. I'm going to go into a lot more detail about the more common potential side effects that can occur.
(00:34:21): Bone marrow donation usually causes fatigue and back discomfort, and occasionally, bleeding. Other complications are rare. These [on the slide] are the common side effects that occur in a majority of patients: a little bit of fatigue, maybe some back discomfort, et cetera. Less common, you can have a little bleeding. And just like when you donate blood, you've got to be careful when you stand up quickly, we don't want donors to faint. These other things that can occur sometimes happen with different types of anesthesia.
(00:34:45): You can see, here, very rare complication. When it says 1%, these are way less than 1%. But when you add them all together, then usually about 0.3 to 0.4% of patients will have something like an infection, some a numbness, stay in the hospital because maybe they fainted or something like that. Life-threatening or incapacitating complications, almost never. But on occasion, in a patient who may start the process with bad heart disease (this is why we try to avoid doing any patients like this) you could have other things that can occur.
(00:35:26): Peripheral blood stem cell donors may experience bone discomfort from G-CSF given prior to collecting their stem cells. How about PBSC collection? The most common side effects are discomfort associated with the bones. The medicine that we give, G-CSF, causes those bone marrow stem cells to circulate which can cause back pain, bone pain, a little bit of headache, IV site pain. Now the thing to keep in mind is that it's hard to call this pain. It’s more like discomfort. You feel like you're coming down with a cold or something, so it's usually not too bad. Less common side effects you can see here, and more serious things that can happen as well. There's this very rare side effect of splenic rupture. It occurs in one in 10,000 or less. Don't go play football right after you donate your PBSCs.
(00:36:17): Now how is donation going to affect you day by day? First, you need to get cleared. In other words, you need a physical examination and blood test at least a week prior to the transplant, and sometimes this will happen up to a month prior to transplant. Then, as long as you're cleared and everything is good, you'll move forward with the procedure.
(00:36:39): Bone marrow donors should avoid vigorous physical activity for a few days after donating. The bone marrow donation. Once you get that clearance done, your relative is going to start receiving preparative chemotherapy that lasts somewhere between five to 10 days, sometimes a little bit longer. On the day of, or the day before, they plan to infuse the bone marrow, they will have you go to the operating room to have your bone marrow harvest done.
(00:37:01): We generally recommend that after the harvest you avoid vigorous physical activity. Don't schedule a soccer game for a couple of days after the harvest. Take it easy for a few days. You're generally able to go back to work within a few days after the bone marrow harvest.
(00:37:16): The PBSC collection. The donor clearance takes about seven to 10 days [from the first exam]. The patient starts getting your chemo, and on the last five to six days of the chemo, you'll start daily G-CSF shots. That sometimes will be done at the center where the cells are going to be collected, or sometimes at home. if insurance allows it and if you're willing and able to give yourself a shot or have someone else give you a shot. This is a simple shot under the skin like an insulin shot. It doesn't have to go in your muscle so it doesn't hurt too much.
(00:37:49): The PBSC collection starts on either day four or five after the G-CSF is given, usually through a standard IV. But on occasion, people don't have good veins. They may need to put in a bigger catheter, and sometimes you must have anesthesia in order to get that catheter.
(00:38:11): The collection continues for one to two days, on occasion a third, and the aches and discomfort are generally gone within one to two days. So that's how the PBSC collection works.
(00:38:23): What about children? Children as young as three months, and younger, have been donors, and can safely do that. They've donated bone marrow, PBSCs, and the third option: getting Neupogen prior to a bone marrow harvest.
(00:38:42): Some states and countries require that pediatric donors have an independent advocate or a court advocate, because they're children and they can't give true consent. Studies have shown that children tend to do a little bit better than adult donors. They can also, on occasion, have serious complications way less than 1% of the time. Children tend to report less pain and recover more quickly than adults.
(00:39:15): Peripheral blood stem cells donors tend to fully recover from the process within two weeks. Bone marrow donors may take a little longer to recover. This is a map of recovery. So, these are patients who donated PBSCs and bone marrow. What you can see on the slide is when the donor says, "I'm 100 percent back to normal." So what that means is, on occasion people may feel like, "Oh, gosh, am I a little stiffer than I was before I did the bone marrow harvest? Or do I feel a little bit of local tenderness there?"
(00:39:39): And what you can see here is for PBSCs, 90% of donors feel back to normal within two weeks. By the time you get out to 90 days, 99% feel back to normal, and then at 180 days you're a little bit better. Bone marrow, it takes just a little bit longer and that's mainly because if someone taps the donor on back where their bone is healing, they might feel a minor amount of tenderness.
(00:40:22): What should you do to make sure your bone marrow or PBSC donation goes well? Be careful about having too much alcohol during the process because it can increase your liver function test, and then everyone's going to be all worried about you, and you're going to get a bunch of extra tests and all sorts of stuff, so it's nice to avoid that. The same goes for unnecessary medications and herbal supplements. The bottom line is you just don't want to do things that are going to be tweaking your blood tests or your liver tests.
(00:40:51): Also, you want to try to do what you can to avoid getting sick because the last thing you want to do is get a terrible infection and be at increased risk when you undergo your anesthesia if you're going to do a bone marrow harvest.
(00:41:04): The patient’s insurance pays for the donor’s medical bills for collecting bone marrow or PBSCs. It's important to tell you who pays and what happens if there are complications. The patient's insurance will pay. Essentially people when [the transplant team] gets approval [from the insurance company to do the transplant], the patient’s insurance is lined up to take care of everything.
Now what if there are long-term issues? The patient’s insurance pays for the initial issues, but then, if you have some sort of a chronic ache or something that you think is associated with the donation, your own insurance will eventually pick that up and take care of it.
(00:41:45): Bone marrow and peripheral blood stem cell donors are encouraged to participate in studies so more can be learned about the process. So how about studies, should you participate in studies? I highly suggest that. There are a lot of things we would like to know about donors. There's not enough known about safety and psychological well-being of related donors, so I encourage it.
(00:42:03): Donor studies usually don't change anything that you do as a donor. What they usually do is just follow you and see if you're going to have any complications. Sometimes if the recipient is going to require more PBSCs or bone marrow donated than would usually be donated, they have to ask your permission for that, and they'll let you know. But in general, the studies that you'd participate in won't cause a lot of harm.
(00:42:30): Studies of bone marrow and peripheral blood stem cell donors have shown it is a very safe process with minimal side effects. Now, in the last two minutes, I want to talk about a related donor safety study, a big one that we did. We've already published two papers on psychosocial health associated with donors. This study was done at 54 different centers, from 2010 to about 2015. And we looked at the way the donors felt during the process, and how they recovered. And let me just show you quickly what things look like here.
(00:43:07): Again, only very severe pain, which occurs in a very small percentage, would you really call pain. Most of what [donors] experience during the donation process is something that I prefer to call discomfort, and you can feel it in all different areas. You get a little bone discomfort when you take the G-CSF, it makes you feel like you're coming down with a cold or flu.
(00:43:31): This is self-reported, you basically say, "How bad is your pain?" It's usually none or mild. In other words, "I feel something but it hardly is bothering me." If it's moderate, it's making you feel like you ought to take something. Severe means you don't feel good enough to go to work. And disabling, which almost never happens, would mean that you'd really need serious pain medications.
(00:43:55): We also looked at a whole bunch of other things that can occur. You can experience fever, get a little tired, you can have a local reaction, nausea. These are mainly complications that occur with anesthesia, and sometimes with Neupogen.
(00:44:13): Older bone marrow and peripheral blood stem cell donors may experience side that are slightly more severe than younger patients. First I want to talk about older donors. Many older people are now donating bone marrow or PBSCs because we figured out ways to treat patients who are over age 60 and 70 with reduced intensity or reduced toxicity approaches. This is the experience of about 250 donors who were over age 60. What you can see from this experience is that the majority of the donations occur at the age of 60, but we had 10% of those donations occurring from 70-year-olds.
(00:44:57): What you can see here is that more women than men needed a central line placed, and if you had to have apheresis or a collection over many days, then almost everyone needed a central line. As you get older, you're more likely to need more than a single day of PBSC collection to get enough cells to do a safe count.
(00:45:23): Your platelets can fall over time, so we watch people very carefully and make sure they don't have any bleeding. Sometimes patients' platelet counts can go down to less than 50,000, putting them at a little bit of an increased risk for bleeding.
(00:45:46): These are grades of skeletal discomfort, or the common symptoms that I mentioned. An important thing to understand is that about 30% of people above age 60 have some baseline discomfort to begin with. And when you get your G-CSF, that goes up to close to 70%, and then it gets better over that month after.
(00:46:16): These are the different things that can occur. A few patients are going to have some back discomfort, headache. These are different areas of the bones that are uncomfortable. You can have a little bit of discomfort in the neck, et cetera. I did this donation myself, and I felt a little bit of discomfort right in the back of my neck, mainly on day four.
(00:46:39): On occasion you can feel really fatigued. About a third of patients feel fatigued, sometimes they have trouble sleeping. I always recommend a little Tylenol before bed.
(00:46:50): We noticed that females were less likely to return to normal rapidly, and if you had some discomfort when you started, you were more likely to have higher levels of discomfort, and that makes sense.
(00:47:05): Bone marrow donation occurred in nine patients above age 60, and they had had less pain than the younger donors.
(00:47:15): So, in conclusion, patients older than 60 do okay. They do surprisingly well. In fact, they have a better attitude. Our quality-of-life studies show that they did better psychologically than younger donors.
(00:47:34): How do younger related donors compare to unrelated donors? Well, we looked at a large population of about 920 of PBSC related donors and 120 related bone marrow donors, and all sorts of unrelated donors. And we did some direct comparisons, and here's what it looks like.
(00:47:54): The related donors don't have quite as much overall discomfort. Remember this is grade one, you hardly feel it. This is grade two, maybe I'm going to take something. Grade three, for sure I'm going to take something. And you can see that the related donors who are, in general, a little bit older had just a little more discomfort during the procedure compared to the unrelated donors who are generally a little bit younger.
(00:48:22): The same thing with the symptoms associated with bone marrow donation. The PBSC donation, the same thing as the bone marrow donation. The related donors, who are a little bit older in general, [than unrelated donors] feel a little more discomfort. More of them might need to take some Tylenol or take some other pain medicine at their peak, and then they begin to recover.
(00:48:50): And these are symptoms in the PBSC donors.
(00:48:52): Related bone marrow or peripheral blood stem cell donors who have health problems prior to donating may experience more discomfort or symptoms from the donation process. Now one thing that's important to understand is that related donors can have comorbidities or health issues. And I just want to show you what can occur with the different types of health issues. The bottom line is that the presence of a comorbidity means the donor is more likely to have a little discomfort or symptoms. And that makes sense, if you have a chronic health problem, then it's more likely that you're going to be a little more uncomfortable during the procedure.
(00:49:32): Now for pediatrics, we had about 300 donors who were pediatric, and we show almost the same thing. This is youngest, age zero to six, a little bit older, and the oldest ones. Now interestingly, the oldest, the group that was affected more than any of the other group, was teenage girls who tended to have more discomfort and a little bit less fully recovered, compared to younger donors. And that was true for pain, and symptoms actually weren't all that different. Not quite as different as the pediatric donors got a little bit older. (00:50:18): So, the conclusion from that study basically is that, younger donors have similar pain and symptoms.
(00:50:27) Adult donors have more discomfort at baseline, and they recover just a little more slowly, but still the vast majority of them recover and do well and are very happy to donate again if they're asked. A little more persistence in symptoms, comorbidities can increase your risk a little bit.
(00:50:48): So, in summary of the whole talk, I want to emphasize that related bone marrow and PBSC donation is generally safe. The most common symptoms are very mild to moderate, short-term discomfort and fatigue.
(00:51:03): No long-term problems have been noted with bone marrow function [in donors]. Women, older, and heavier donors have a slight increased risk of discomfort or some of the other symptoms. The act [of donating] is voluntary, and you have the right to refuse. Donor studies can help us learn and may benefit future donors. So, my bottom line here is if you choose to donate, thank you so much for your generous gift, and I'd be more than happy to take any questions.
Question and Answer Session
(00:51:39): [Marla O’Keefe]: Thank you, Dr. Pulsipher, that was an excellent presentation that covered a lot of ground, and I certainly learned a lot, and I hope that those on the call did as well. There are some questions I think that we can answer here. Pauline asks, she said she had read there were a handful of cases where donors have developed blood cancers after receiving Neupogen injections in preparation to donate stem cells. Has the ongoing study shown whether there is in fact a risk?
(00:52:14): [Dr. Michael Pulsipher]: So, this is a great thing that I am very happy to answer because I published a study of over 10,000 PBSC donors a couple of years ago, and we did a very careful comparison. One of the challenges you have is that a certain number of individuals will get blood cancers, no matter what. So, what you need to do when you're trying to sort this out is figure out whether you've caused an increase in the risk by using the G-CSF, or whether that individual was just going to get cancer anyway.
So, we did a very detailed study, and interestingly we showed that for unrelated donors, their risk for getting cancer was actually lower than the general population. And with this huge study it was a great relief to all of us. So currently we do not believe that normal donors have an increased risk of getting blood cancers associated with G-CSF treatment.
(00:53:24): [Marla O’Keefe]: Thank you. The next question is from Colleen. She says, "I am a potential donor for my sister through a clinical trial at the NIH. Their donors get injections of filgrastim for five days prior to donation. Is this a different medication than what you were describing for the stem cell procedure?"
(00:53:45): [Dr. Michael Pulsipher]: It is not. Filgrastim is a long, complicated name, and it's the same as G-CSF.
(00:53:54): [Marla O’Keefe]: Another question from Jane. "My sister lives in another state and it would be a hardship to travel to her hospital. Can the bone marrow or stem cells be collected where I live and shipped to her hospital?"
(00:54:10): [Dr. Michael Pulsipher]: This has happened in some cases. The National Marrow Donor Program that coordinates unrelated donors has, in some cases been able to arrange to do a bone marrow collection and have that shipped. That would, however, have to have insurance approval in order to do it. I've also had instances where a local transplant center has been willing to do the harvest outside of the National Marrow Program. In other words, they can go to a bone marrow transplant program close by and have that occur as well.
It takes a lot of coordination on the part of both centers, because it's a lot easier to get insurance approval when the donor is at the center where the transplant is taking place. But believe me, most centers will work hard to try to find a place to get that done, if you simply can't go to the local center. So it's a little bit more work for them, but if you simply can't do it, then ask about those options. And if life is good and insurance approves and you can find a local center willing to do the procedure, you can do that.
(00:55:23): [Marla O’Keefe]: Great, thank you. Joe asks, "Can I choose whether to donate bone marrow or stem cells?"
(00:55:30): [Dr. Michael Pulsipher]: You absolutely can. In fact, what happens is, when you are asked to donate, you generally will have someone tell you what they would prefer, but you should at the same time say, "Please tell me about both methods of donation," and if you prefer one over the other, you can make that choice. Now, they will also inform you of the risks. So for example, there is a disease called aplastic anemia, which is a bone marrow problem where your bone marrow has failed, it doesn't work very well.
There was a very nicely done study that shows that bone marrow is superior to PBSCs because it causes less graft-versus-host disease and better overall survival. So under that circumstance, you still could choose to give PBSCs, and in fact, sometimes your bone marrow center would say, "We don't want you to give bone marrow because it's not going to be good for your health, because of maybe a condition that you might have." But if you can give bone marrow, it is better for the recipient.
So what you're going to have to do is take your preference into consideration, and realize that in certain cases it does matter whether you offer bone marrow or PBSCs. In some cases the outcomes are the same either way, but do take that into consideration as you make your decision. But you are the ultimate decider. If you decide that you only want to give peripheral stems cells, or that you only want to give bone marrow, then that's something that generally people will respect.
(00:57:14): [Marla O’Keefe]: Another question is, "Does my employer have to give me time off work to be a donor?"
(00:57:21): [Dr. Michael Pulsipher]: So that's a good question. Usually, have to, is a difficult situation. Most employers are reasonable and will work with you, but there are certain circumstances where you may have a situation where your employer doesn't want to give you that time off. In that circumstance, you might ask for FMLA, which is the Family Medical Leave Act, because your donation can be absolutely considered essential caregiving to an individual in your family.
Now when you get FMLA, you won't have the ability to get paid for that, but at least you can, in many circumstances, your employer is obligated to give you some time off to go deliver it. But like I mentioned, hopefully you can reason with your employer, because you can generally limit it, if you're only going to be there for the donation process, you can generally limit the time.
(00:58:26): [Marla O’Keefe]: Thank you. And another question from Pauline. She says, "I have chronic migraines. I have read that I cannot take NSAIDs. Is this just a week prior to the transplant, or does this continue afterwards? And if so, for how long?" And then the second part of the question is, "What painkillers are safe to take, excluding Tylenol, which does not work for my migraines. I also take triptans, is this safe?"
(00:58:54): [Dr. Michael Pulsipher]: Ah. Okay. Well, so this, what I would recommend you would do is speak to your transplant center about specifically. If the transplant center is telling you not to take NSAIDs, they're concerned about an increased risk of bleeding that can be associated when you take something like Motrin and it's still onboard. Aspirin, if you ever take it affects your platelets for a long time, and you have to be off aspirin for at least seven days.
Medicines like Motrin, which is ibuprofen, or other NSAIDs, they affect your platelets, only when they're in your system. So you might be able to work out with them that you can continue to take Motrin, et cetera, early on, but then you'll need to stop right before your collection. If your pain is more significant during your collection, there are other medications they can substitute that won't increase your risk of bleeding. But do talk to your transplant center about that so they can know your concern.
(01:00:09): [Marla O’Keefe]: George asked, "If I donate bone marrow for my brother, does that guarantee he will be cured?"
(01:00:15): [Dr. Michael Pulsipher]: Absolutely, no. It guarantees that you're a wonderful brother. But one thing that I should make sure that you and all donors should understand, when you donate, you've done all you can. Once you've donated, then it's all up to the combination of good luck, whatever the disease that your sibling has, whether they end up developing complications, et cetera. In other words, when patients go through transplant, they're there for a real reason, and that is they either have cancer or a life-threatening disorder. No transplant is 100 percent successful.
There is a chance that a bone marrow donation can result in the bone marrow working just fine, but then the patient relapses, and that's not your fault. In fact, nothing that happens during the procedure is your fault. You're just the good guy who does the right thing, and you should never feel guilty about the outcome, because that outcome's not up to you. That outcome is up to the disease that the patient is facing and the many potential challenges that could occur.
(01:01:43): [Marla O’Keefe]: Another question from Colleen. "How long is the procedure or surgery for donors that donate bone marrow?"
(01:01:50): [Dr. Michael Pulsipher]: So this depends totally on the volume that's being taken. If you are an adult donating to an adult, then generally they will remove somewhere between two to four cups of your bone marrow. That can take a couple of hours. And then of course there's time to get the anesthesia and recover from the anesthesia. So the longest harvests from you going into the operating room until you're out of recovery can be up to four hours.
If you're a younger patient or if you're an adult donating to a very young patient, the volume that they take is very small, maybe a cup or two cups at most. And oftentimes that can be done in an hour of operating time. But somewhere between one to four hours, again, depending on the volume that has to be harvested.
(01:02:48): [Marla O’Keefe]: Closing. Okay. Thank you Dr. Pulsipher, it looks like we've answered all of our questions. So, we appreciate your time and this wonderful presentation. And thank you to everyone for listening and for posing your questions and enjoy the rest of your evening.
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