Everything you ever wanted to know...
...about cord blood transplant, but were afraid to ask.
I had the benefit of a 12-hour drive recently with our medical editor, Kristen Hege, and I will now take my best shot at putting Bonnie’s treatment into perspective using layperson’s terms. With luck, it will read like a powerful story of good and evil along with the twists and turns that Spielberg presents in Star Wars. (Darth Vader is Luke’s father?) Or, it could be overwhelmingly boring. You decide.
First, some basic terms. Stem cells are cells that replicate themselves, but also create the basics of the immune system: white blood cells, red blood cells and platelets. White blood cells form a basic tenet of the immune system, red blood cells carry oxygen, and platelets allow clotting when you are cut or bruised. The real key here is “drilling down” into the component pieces of white blood cells: Neutrophils, the basic first line defense against everyday bacteria, lymphocytes, which are comprised of T-cells and B-cells - the soldiers who fight more heavy-duty infections -- and monocytes, the front-line infantry soldiers who signal t-cells to come to the rescue and serve as general garbage collectors in the blood.
Recall, that Bonnie has Acute Lymphoblastic Leukemia, which means that her lymphocytes have gotten out of control, creating a mass of infant lymphocytes in her system which fail to develop into infection-fighting cells, and replicate themselves over and over, essentially clogging up her system to the extent that she is overwhelmed with white blood cells that “crowd” the red blood cells and platelets, and no longer serve as an effective system. Recognize, too, that Bonnie’s immune system "sees" these renegade lymphocyte cells as “self” and thus does not attack them. This is what cancer is all about – renegade cells that grow and replicate themselves incredibly quickly but that the body’s immune system does not “see” as the enemy, thus the cells grow unchecked.
Two years ago, as a first step in irradicating her disease, Bonnie had aggressive chemotherapy which killed the fast-growing leukemia cells – the out of control “infant” lymphocytes. Eighteen months later, however, Bonnie relapsed which means there were still some remnant leukemia cells that managed to replicate themselves, and again, overwhelmed her system. With chemotherapy two months ago, she got back into remission, but at this point, without further treatment, it is a certainty that the leukemia cells will advance again, and this time it will happen in much less time than 18 months. Chemo alone is not an effective strategy for her leukemia cells anymore.
So, beginning tomorrow, Bonnie will have even more aggressive therapy, which is designed to eradicate the leukemia cells, but, as a side effect, will also eliminate her stem cells and the corresponding elements of her immune system. Hence the need for a bone marrow transplant-- she will receive a “new” immune system via transfusion of stem cells from the two new cord blood units. Beginning tomorrow, Bonnie will have total body irradiation, followed by very aggressive chemotherapy treatment. It will be much more aggressive treatment than her past two rounds of chemotherapy and the toxicity of the treatment will kill (almost) all of the leukemia cells (the infant lymphocytes who refused to develop into functioning cells) and (almost) all of her T-cells. (The “almost” phraseology is important to remember later.) The total body irradiation and high levels of chemotherapy will also create a toxic nightmare for Bonnie’s gut, liver and kidneys, as well as other organs, and the net effect is that Bonnie will be miserable – far worse than the last two rounds of chemotherapy.
This brings us to the cord blood transplant. The goal of this transplant is to get a few stem cells from the cord blood to Bonnie’s bone marrow, which will “trigger” replication of the stem cells, and creation of the white blood cells and their legion of functioning lymphocytes (T-cells and B-cells), neutrophils, red blood cells, and platelets. In a sense, this process is a lot like sperm cells finding an egg – it only takes a few stem cells to enter her bone marrow and kick-start the process of developing a new immune system. If this process works – the stem cells find the bone marrow -- you have engraftment, and four to five weeks out, you will see signals of this “new” immune system via blood tests that first show the presence of neutrophils, hence the constant focus on Bonnie’s “neut” counts. Eventually, at week four or five Bonnie’s neutrophil count should climb to 500 or so, which is the criterion for her leaving the hospital. At this point her neutrophils will provide a front line defense against basic bacteria and fungus infections.
Recognize, however, that during these four to five weeks post-transplant, Bonnie will have no immune system. So in this battle of good and evil, you have all sorts of normal bacteria, fungi, and viruses that our systems confront successfully everyday, but Bonnie’s system can not. Bonnie’s physicians in MN will not only manage the toxicity presented to her vital organs (gut, liver, kidneys) but will also be on the lookout for any infections. They will treat Bonnie prophylactically with many antibiotics, but will also add more to her regimen if any infections are discovered.
Now we get to the interesting part – the cord blood transplant. The downside of cord blood transplants is that the stem cells found in cord blood (v. adult stem cells) are very quiescent – it takes a lot more time for the process of replication to begin, and this replication takes much longer. Thus, the window for infection is four or five weeks v. two to three weeks via an adult stem cell transplant. On the positive side these stem cells are not as mature, and are therefore more “flexible” in reacting to a new host and therefore less likely to cause graft-vs-host-disease (more below). The net result is that the odds of engraftment are lower (~ 5-10% chance that the stem cells won't engraft), and the process takes longer, increasing the risk of infection.
So far we have a couple of issues: managing toxicity presented to Bonnie’s organs, watching carefully for signs of infections, and patiently waiting for engraftment to occur. There are a couple of other “battles” being fought, however. Earlier I stressed that (almost) all of Bonnie’s leukemia cells were eliminated, and (almost) all of her t-cells (the heavy duty infection fighters) were eliminated by radiation and chemotherapy.
There are a few remnants of leukemia cells and T-cells, however. The expectation is that T-cells from the cord blood transplant will “see” the leukemia cells, and unlike Bonnie’s current immune system, will clearly label these cells as the enemy, and eliminate them, so beyond “mopping up” these remnant leukemia cells with more aggressive chemotherapy and radiation, the “new” immune system will be the third approach to killing the renegade leukemia cells. Notice, too, that (almost) all of Bonnie’s T-cells were killed. The reality is that there are a few of Bonnie’s T-cells that will survive and they will be fighting the invasion of the new stem cells, as they are clearly foreign invaders. (Think of a last few guerilla fighters hiding behind stone walls taking potshots as the new army arrives.) If these T-cells are effective sharpshooters, there is a risk that none of the new stem cells will get through to the bone marrow and engraftment will not occur. The reason that there are two cord blood units being transplanted is to allow a high enough number of stem cells to hopefully overwhelm the T-cell sharphooters and increase the odds that a few brave stem cells will eventually find Bonnie’s bone marrow and begin the replication process.
The plot thickens when you think of two foreign armies arriving via two separate cord blood transplants. Not only are these two new armies fighting the remnant leukemia cells, fighting Bonnie’s last T-cell sharpshooters, but they are fighting each other, as well. Recall that not only was there a requirement that these two stem cells “match” Bonnie (to avoid total rejection) but they needed to have some degree of match with each other, which is intended to minimize the amount of “fighting” between these two separate “armies.”
This brings me to the last concept, which is called “graft v. host disease.” Simply put, this occurs when the new immune system takes hold and begins to “see” many elements of Bonnie’s body as “foreign” and thus begins an immune response trying to vanquish these seemingly foreign elements. To some degree, this phenomenon is wanted, as it fuels the “death” of the remnant leukemia cells and Bonnie’s remnant T-cells. But too much of this aggressive behavior provokes rashes, diarrhea, and liver damage, and again, makes Bonnie feel miserable. The expectation over time is that the new immune system retrains itself to see Bonnie as “self” but this “wiring” takes time. The net effect is that for at least six months after the transplant (and up to a few years if she actually gets significant graft-vs-host disease), Bonnie will be on immune suppressants that “tone down” this wayward immune response until the new immune system sufficiently retrains itself. Recognize that a positive side effect of cord blood transplant is that given that the new stem cells are relatively immature, they are more adaptable, which means that graft v. host disease is less prevalent with cord blood transplants.
If I dare to give an executive summary, this is it:
-Total body radiation and aggressive chemotherapy will do the best job possible to devastate Bonnie’s leukemia cells, but will also eliminate her stem cells and current immune system.
-Consequently, Bonnie needs a new immune system, which is delivered via stem cells from cord blood that hopefully will find her bone marrow, and will begin a replication process.
-For four to five weeks, Bonnie will have no immune system. Her physicians will monitor for infections carefully, and will do their best to manage the toxicity presented to her vital organs.
-At four to five weeks, Bonnie’s neutrophil count will go up, indicating the existence of a “new” immune system – engraftment will have occurred.
-Her physicians will carefully monitor graft v. host disease. To some degree this phenomenon is wanted as it will help eliminate the remnant leukemia cells. If her new system is overaggressive, however, it will fight other elements of Bonnie’s body and consequently, Bonnie will take immunosuppressants to “mellow” this affect. This will be managed for months to years until Bonnie’s new immune system sufficiently retrains itself to see Bonnie as “self.”
Ok, not as compelling as a Spielberg movie, but I hope you get the gist of this. Send me an email or post a comment below if you managed to get through all of this and found it helpful.
I had the benefit of a 12-hour drive recently with our medical editor, Kristen Hege, and I will now take my best shot at putting Bonnie’s treatment into perspective using layperson’s terms. With luck, it will read like a powerful story of good and evil along with the twists and turns that Spielberg presents in Star Wars. (Darth Vader is Luke’s father?) Or, it could be overwhelmingly boring. You decide.
First, some basic terms. Stem cells are cells that replicate themselves, but also create the basics of the immune system: white blood cells, red blood cells and platelets. White blood cells form a basic tenet of the immune system, red blood cells carry oxygen, and platelets allow clotting when you are cut or bruised. The real key here is “drilling down” into the component pieces of white blood cells: Neutrophils, the basic first line defense against everyday bacteria, lymphocytes, which are comprised of T-cells and B-cells - the soldiers who fight more heavy-duty infections -- and monocytes, the front-line infantry soldiers who signal t-cells to come to the rescue and serve as general garbage collectors in the blood.
Recall, that Bonnie has Acute Lymphoblastic Leukemia, which means that her lymphocytes have gotten out of control, creating a mass of infant lymphocytes in her system which fail to develop into infection-fighting cells, and replicate themselves over and over, essentially clogging up her system to the extent that she is overwhelmed with white blood cells that “crowd” the red blood cells and platelets, and no longer serve as an effective system. Recognize, too, that Bonnie’s immune system "sees" these renegade lymphocyte cells as “self” and thus does not attack them. This is what cancer is all about – renegade cells that grow and replicate themselves incredibly quickly but that the body’s immune system does not “see” as the enemy, thus the cells grow unchecked.
Two years ago, as a first step in irradicating her disease, Bonnie had aggressive chemotherapy which killed the fast-growing leukemia cells – the out of control “infant” lymphocytes. Eighteen months later, however, Bonnie relapsed which means there were still some remnant leukemia cells that managed to replicate themselves, and again, overwhelmed her system. With chemotherapy two months ago, she got back into remission, but at this point, without further treatment, it is a certainty that the leukemia cells will advance again, and this time it will happen in much less time than 18 months. Chemo alone is not an effective strategy for her leukemia cells anymore.
So, beginning tomorrow, Bonnie will have even more aggressive therapy, which is designed to eradicate the leukemia cells, but, as a side effect, will also eliminate her stem cells and the corresponding elements of her immune system. Hence the need for a bone marrow transplant-- she will receive a “new” immune system via transfusion of stem cells from the two new cord blood units. Beginning tomorrow, Bonnie will have total body irradiation, followed by very aggressive chemotherapy treatment. It will be much more aggressive treatment than her past two rounds of chemotherapy and the toxicity of the treatment will kill (almost) all of the leukemia cells (the infant lymphocytes who refused to develop into functioning cells) and (almost) all of her T-cells. (The “almost” phraseology is important to remember later.) The total body irradiation and high levels of chemotherapy will also create a toxic nightmare for Bonnie’s gut, liver and kidneys, as well as other organs, and the net effect is that Bonnie will be miserable – far worse than the last two rounds of chemotherapy.
This brings us to the cord blood transplant. The goal of this transplant is to get a few stem cells from the cord blood to Bonnie’s bone marrow, which will “trigger” replication of the stem cells, and creation of the white blood cells and their legion of functioning lymphocytes (T-cells and B-cells), neutrophils, red blood cells, and platelets. In a sense, this process is a lot like sperm cells finding an egg – it only takes a few stem cells to enter her bone marrow and kick-start the process of developing a new immune system. If this process works – the stem cells find the bone marrow -- you have engraftment, and four to five weeks out, you will see signals of this “new” immune system via blood tests that first show the presence of neutrophils, hence the constant focus on Bonnie’s “neut” counts. Eventually, at week four or five Bonnie’s neutrophil count should climb to 500 or so, which is the criterion for her leaving the hospital. At this point her neutrophils will provide a front line defense against basic bacteria and fungus infections.
Recognize, however, that during these four to five weeks post-transplant, Bonnie will have no immune system. So in this battle of good and evil, you have all sorts of normal bacteria, fungi, and viruses that our systems confront successfully everyday, but Bonnie’s system can not. Bonnie’s physicians in MN will not only manage the toxicity presented to her vital organs (gut, liver, kidneys) but will also be on the lookout for any infections. They will treat Bonnie prophylactically with many antibiotics, but will also add more to her regimen if any infections are discovered.
Now we get to the interesting part – the cord blood transplant. The downside of cord blood transplants is that the stem cells found in cord blood (v. adult stem cells) are very quiescent – it takes a lot more time for the process of replication to begin, and this replication takes much longer. Thus, the window for infection is four or five weeks v. two to three weeks via an adult stem cell transplant. On the positive side these stem cells are not as mature, and are therefore more “flexible” in reacting to a new host and therefore less likely to cause graft-vs-host-disease (more below). The net result is that the odds of engraftment are lower (~ 5-10% chance that the stem cells won't engraft), and the process takes longer, increasing the risk of infection.
So far we have a couple of issues: managing toxicity presented to Bonnie’s organs, watching carefully for signs of infections, and patiently waiting for engraftment to occur. There are a couple of other “battles” being fought, however. Earlier I stressed that (almost) all of Bonnie’s leukemia cells were eliminated, and (almost) all of her t-cells (the heavy duty infection fighters) were eliminated by radiation and chemotherapy.
There are a few remnants of leukemia cells and T-cells, however. The expectation is that T-cells from the cord blood transplant will “see” the leukemia cells, and unlike Bonnie’s current immune system, will clearly label these cells as the enemy, and eliminate them, so beyond “mopping up” these remnant leukemia cells with more aggressive chemotherapy and radiation, the “new” immune system will be the third approach to killing the renegade leukemia cells. Notice, too, that (almost) all of Bonnie’s T-cells were killed. The reality is that there are a few of Bonnie’s T-cells that will survive and they will be fighting the invasion of the new stem cells, as they are clearly foreign invaders. (Think of a last few guerilla fighters hiding behind stone walls taking potshots as the new army arrives.) If these T-cells are effective sharpshooters, there is a risk that none of the new stem cells will get through to the bone marrow and engraftment will not occur. The reason that there are two cord blood units being transplanted is to allow a high enough number of stem cells to hopefully overwhelm the T-cell sharphooters and increase the odds that a few brave stem cells will eventually find Bonnie’s bone marrow and begin the replication process.
The plot thickens when you think of two foreign armies arriving via two separate cord blood transplants. Not only are these two new armies fighting the remnant leukemia cells, fighting Bonnie’s last T-cell sharpshooters, but they are fighting each other, as well. Recall that not only was there a requirement that these two stem cells “match” Bonnie (to avoid total rejection) but they needed to have some degree of match with each other, which is intended to minimize the amount of “fighting” between these two separate “armies.”
This brings me to the last concept, which is called “graft v. host disease.” Simply put, this occurs when the new immune system takes hold and begins to “see” many elements of Bonnie’s body as “foreign” and thus begins an immune response trying to vanquish these seemingly foreign elements. To some degree, this phenomenon is wanted, as it fuels the “death” of the remnant leukemia cells and Bonnie’s remnant T-cells. But too much of this aggressive behavior provokes rashes, diarrhea, and liver damage, and again, makes Bonnie feel miserable. The expectation over time is that the new immune system retrains itself to see Bonnie as “self” but this “wiring” takes time. The net effect is that for at least six months after the transplant (and up to a few years if she actually gets significant graft-vs-host disease), Bonnie will be on immune suppressants that “tone down” this wayward immune response until the new immune system sufficiently retrains itself. Recognize that a positive side effect of cord blood transplant is that given that the new stem cells are relatively immature, they are more adaptable, which means that graft v. host disease is less prevalent with cord blood transplants.
If I dare to give an executive summary, this is it:
-Total body radiation and aggressive chemotherapy will do the best job possible to devastate Bonnie’s leukemia cells, but will also eliminate her stem cells and current immune system.
-Consequently, Bonnie needs a new immune system, which is delivered via stem cells from cord blood that hopefully will find her bone marrow, and will begin a replication process.
-For four to five weeks, Bonnie will have no immune system. Her physicians will monitor for infections carefully, and will do their best to manage the toxicity presented to her vital organs.
-At four to five weeks, Bonnie’s neutrophil count will go up, indicating the existence of a “new” immune system – engraftment will have occurred.
-Her physicians will carefully monitor graft v. host disease. To some degree this phenomenon is wanted as it will help eliminate the remnant leukemia cells. If her new system is overaggressive, however, it will fight other elements of Bonnie’s body and consequently, Bonnie will take immunosuppressants to “mellow” this affect. This will be managed for months to years until Bonnie’s new immune system sufficiently retrains itself to see Bonnie as “self.”
Ok, not as compelling as a Spielberg movie, but I hope you get the gist of this. Send me an email or post a comment below if you managed to get through all of this and found it helpful.
posted by gbiddle616 at Tuesday, July 26, 2005
5 Comments:
Gib: Very helpful - thanks for translating! Jeff
Hi Gib - You've outdone yourself! Thanks for keeping the rest of us so well informed. How goes the new job? Blogger Blodge
Thank you so much for keeping us all in the loop and even, informed. How lucky to have such a great support network of friends/family on your side. Go Bonnie!
Gib, your communication skills are outstanding! You succeeded in laymans terms...thanks for the info. Go Bonnie!!
D.
Hi, thanks all for your comments. Kristen did some last-minute edits, so I now have a high degree of confidence that this is accurate.
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