What is graft-versus-host-disease and who is most at risk?
Each year, thousands of patients with hematologic malignancies undergo allogeneic stem cell transplantation (that is, they receive a donor’s stem cells), offering them a chance at cure.
Graft-versus-host disease is a potentially deadly complication of this therapy and occurs in approximately 25 to 60 percent of patients.
Jonathan Cotliar, MD is here to discuss graft-versus-host-disease, why it occurs and it's treatment and symptoms.
Selected Podcast
Focus on Graft-versus-Host-Disease
Featured Speaker:
Jonathan Cotliar, MD
Jonathan Cotliar, MD Primary Specialties are Plastic Surgery. His Clinical Area / Sub-specialties are Dermatology and his Departments/Division/Program is Surgery/Dermatology. Transcription:
Focus on Graft-versus-Host-Disease
Melanie Cole (Host): Graft-versus-host disease is a complication that can occur after a stem cell or a bone marrow transplant With GVHD, the newly transplanted donor cells can attack the transplant recipient’s body. To learn more about this today, we’re talking with Dr. Jonathan Cotliar. He’s associate clinical professor within the division of dermatology at City of Hope. Welcome to the show, Dr. Cotliar. Explain a little bit about a stem cell or bone marrow transplant and what this complication called graft-versus-host disease is.
Dr. Jonathan Cotliar (Guest): Well, thanks for having me. Bone marrow transplantation is something that sort of developed or came to fruition in the ‘70s and ever since has been exponentially growing and is emerging as the treatment option for a lot of patients, primarily with hematologic diseases, whereby donors, either related or unrelated, are donating their stem cells to a recipient whose immune system is deficient and by accommodating these stem cells from a donor, it allows them to sort of reconstitute an immune system that can go on and fight cancer. Problem is that for a lot of patients, despite intensive immunosuppressive medications, they still develop something called graft-versus-host disease whereby cells that are originating from the donor recognize this new recipient as foreign and these white blood cells that are usually used to fighting infection sort of turn on this new recipient and say, “Hey, we don’t recognize this new body. We need to fight this off.” As a result, there are complications, primarily in the skin, the liver, and the gut, which we, as sort of proponents of graft-versus-host disease treatment providers struggle with from early after transplant, sometimes even years after transplant.
Melanie: What are the first signs and symptoms? If someone has had a bone marrow or stem cell transplant and they’ve been on these immunosuppressive medications, are there something you tell them specifically, “I want you to make sure to call right away if…”?
Dr. Cotliar: Yes. Well, the good thing is that early after transplant, while patients are hospitalized as their immune system sort of recovers, for those of us who take care of stem cell transplantation, we are very accessible because we know that in terms of rates of graft-versus-host disease, depending on the studies you read, it can be anywhere from one-third to two-thirds of patients who do get bone marrow transplant. Early on, one of the more common manifestations is diffuse skin rash and while the morphology or the characteristics of these skin lesions can be challenging for doctors, it’s usually up to a dermatologist who has experience in this area to make an assessment, a form of skin biopsy if needed, whereby we can confirm a suspicion of graft-versus-host disease. The skin tends to be one of the chief early presentation of acute graft-versus-host disease, and that can occur either in isolation or concurrently with diarrhea, which is a manifestation of intestinal acute graft-versus-host disease, and finally some inflammation of the liver that can be picked up on surveillance laboratory draws is also one of the key components. So, all of these features, either in isolation or in combination, makes us suspicious and allows us to make a diagnosis of graft-versus-host disease which can occur sometimes even a week after transplantation.
Melanie: Can it be prevented or are there certain people that are more at risk than others?
Dr. Cotliar: We know in terms of risk factors, there are few sort of chief key risk factors for developing graft-versus-host disease. That includes the older the patient, the degree of mismatch between donor and recipient, the new, I should say, host or recipient of the stem cell, depending on the amount of blood products they’ve received. All of these risk factors can confer to a given patient a higher risk of graft-versus-host disease. The sort of chief way we treat this is actually prevention, whereby patients receive prophylactic immunosuppressive medications usually a few days prior to infusion of the stem cells in the new recipient up until weeks to months thereafter to try to prevent either the occurrence of graft-versus-host disease or minimize the severity of graft-versus-host disease.
Melanie: If you determine that they do have GVHD, what then is the treatment? What do you do for them?
Dr. Cotliar: In order to answer that question, we need to make a distinction between acute and chronic graft-versus-host disease. Formerly, acute graft-versus-host disease is only differentiated from the chronic from by this sort of arbitrary delineation of a hundred days. We now know that the pathophysiology of GVHD is far more complex and with the advent of what we call mini transplantation or stem cell transplant that don’t require full ablation of one’s own bone marrow to allow for donor stem cells to take hold, we know that relative levels of immunosuppression can alter somebody’s likelihood of developing graft-versus-host disease. So, the distinction is less of one chronologically and more of clinical presentation. I already alluded to the fact that acute graft-versus-host disease does tend to occur earlier after transplant. It’s characterized by inflammation in the gut and then the liver and has very non-specific findings in the skin. We contrast that with chronic graft-versus-host disease where patients may develop sclerotic skin lesions that may sort of limit their range of motion that may lead them to profound weakness. It may lead to ulcerations of the skin. It may lead to problems with the eyes or the oral mucosa, some of the deeper skin structures such as the fascia or even the muscle. So, those are the distinctions we make.
Melanie: If it’s chronic and you’re treating them with something that suppresses the immune system, even something like prednisone, Dr. Cotliar, you know there are always side effects, and so do they then have to worry about the side effects for something you’re really trying to treat them for to help with what you originally did? I mean, how do you, as a doctor, balance all of these different things?
Dr. Cotliar: That’s a great question, and again, I wanted to answer your previous question as well. Systemic steroids are typically first-line therapies for both acute and chronic graft-versus-host disease. Systemic steroids are great for short periods of time especially in high doses because they provide a level of anti-inflammation that is unparalleled. The problem is if they are chronically administered, they lead to things such as diabetes, osteoporosis, cataracts, among others, and so the sort of the push has been to try to find steroid-sparing agents both for the treatment of acute and chronic graft-versus-host disease. The problem is that if you look at their literature, if somebody is either dependent on systemic steroids, meaning we cannot sort of effectively taper down a given effective dose, or if they are resistant to treatment with systemic steroids, no single line second agent has been shown to be more effective than any other. What this leads us, both in the acute and chronic forms and we’re trying to treat either one of those, is that a lot of it is trial and error and that may be based on a given institution’s sort of protocol with respect to how they like to treat graft-versus-host disease with second line agents that may be related to a patient’s underlying comorbidities, whereby they may not be candidates for treatment with one immunosuppressive medication over another, that may be a function of a patient’s ability to get to the medical center in a timely fashion or with the type of frequency that may be required for certain systemic treatments that we can’t otherwise give if they live quite a distance away. All of these are major factors, and unfortunately, there is not one formula that fits all.
Melanie: Tell us what’s on the horizon. We don’t have a lot of time, so in just the last few minutes, what’s on the horizon for graft-versus-host disease research and treatment and what advice would you have for listeners why they should come to City of Hope for their treatment and care?
Dr. Cotliar: Well, I think anytime that a patient is able to be seen by a team of multidisciplinary doctors or be seen in the context of a multidisciplinary clinic where there is cross-collaboration among different specialties, meaning I, as a dermatologist, can share clinical space with the transplant doctor and I may have really good access to an ophthalmologist or a medicine person or a physical therapist, anytime you can see all these people under one roof like we’re fortunate enough to have at City of Hope, and certainly this type of setup exists elsewhere, this kind of a setup certainly benefits patients. Specifically at City of Hope, we are offering a multidisciplinary chronic graft-versus-host disease clinic, which we do once a week and the benefit of that is we’re able to assess patients in a room together, both the dermatologist and the transplant oncologist.In terms of what’s on the horizon, there was a groundbreaking paper on the New England Journal of Medicine last year showing that low-dose interleukin-2, which is the chemical that our bodies make naturally but given in low doses, may provide extreme benefit to patients specifically with the most severe form of chronic graft-versus-host disease which is the sclerotic form. In addition, there are a number of emerging biologic therapies such as agents that target interleukin-6 and interleukin-17 that may very well play a role in not just effectively treating graft-versus-host disease, but perhaps even as part of a prophylactic regimen to try to preempt the development of graft-versus-host disease.
Melanie: That’s very exciting and it’s a great multidisciplinary approach that you have, Dr. Cotliar. Thank you so much for joining us. You are listening to City of Hope Radio. For more information, you can go to cityofhope.org. That’s cityofhope.org. This is Melanie Cole. Thanks so much for listening.
Focus on Graft-versus-Host-Disease
Melanie Cole (Host): Graft-versus-host disease is a complication that can occur after a stem cell or a bone marrow transplant With GVHD, the newly transplanted donor cells can attack the transplant recipient’s body. To learn more about this today, we’re talking with Dr. Jonathan Cotliar. He’s associate clinical professor within the division of dermatology at City of Hope. Welcome to the show, Dr. Cotliar. Explain a little bit about a stem cell or bone marrow transplant and what this complication called graft-versus-host disease is.
Dr. Jonathan Cotliar (Guest): Well, thanks for having me. Bone marrow transplantation is something that sort of developed or came to fruition in the ‘70s and ever since has been exponentially growing and is emerging as the treatment option for a lot of patients, primarily with hematologic diseases, whereby donors, either related or unrelated, are donating their stem cells to a recipient whose immune system is deficient and by accommodating these stem cells from a donor, it allows them to sort of reconstitute an immune system that can go on and fight cancer. Problem is that for a lot of patients, despite intensive immunosuppressive medications, they still develop something called graft-versus-host disease whereby cells that are originating from the donor recognize this new recipient as foreign and these white blood cells that are usually used to fighting infection sort of turn on this new recipient and say, “Hey, we don’t recognize this new body. We need to fight this off.” As a result, there are complications, primarily in the skin, the liver, and the gut, which we, as sort of proponents of graft-versus-host disease treatment providers struggle with from early after transplant, sometimes even years after transplant.
Melanie: What are the first signs and symptoms? If someone has had a bone marrow or stem cell transplant and they’ve been on these immunosuppressive medications, are there something you tell them specifically, “I want you to make sure to call right away if…”?
Dr. Cotliar: Yes. Well, the good thing is that early after transplant, while patients are hospitalized as their immune system sort of recovers, for those of us who take care of stem cell transplantation, we are very accessible because we know that in terms of rates of graft-versus-host disease, depending on the studies you read, it can be anywhere from one-third to two-thirds of patients who do get bone marrow transplant. Early on, one of the more common manifestations is diffuse skin rash and while the morphology or the characteristics of these skin lesions can be challenging for doctors, it’s usually up to a dermatologist who has experience in this area to make an assessment, a form of skin biopsy if needed, whereby we can confirm a suspicion of graft-versus-host disease. The skin tends to be one of the chief early presentation of acute graft-versus-host disease, and that can occur either in isolation or concurrently with diarrhea, which is a manifestation of intestinal acute graft-versus-host disease, and finally some inflammation of the liver that can be picked up on surveillance laboratory draws is also one of the key components. So, all of these features, either in isolation or in combination, makes us suspicious and allows us to make a diagnosis of graft-versus-host disease which can occur sometimes even a week after transplantation.
Melanie: Can it be prevented or are there certain people that are more at risk than others?
Dr. Cotliar: We know in terms of risk factors, there are few sort of chief key risk factors for developing graft-versus-host disease. That includes the older the patient, the degree of mismatch between donor and recipient, the new, I should say, host or recipient of the stem cell, depending on the amount of blood products they’ve received. All of these risk factors can confer to a given patient a higher risk of graft-versus-host disease. The sort of chief way we treat this is actually prevention, whereby patients receive prophylactic immunosuppressive medications usually a few days prior to infusion of the stem cells in the new recipient up until weeks to months thereafter to try to prevent either the occurrence of graft-versus-host disease or minimize the severity of graft-versus-host disease.
Melanie: If you determine that they do have GVHD, what then is the treatment? What do you do for them?
Dr. Cotliar: In order to answer that question, we need to make a distinction between acute and chronic graft-versus-host disease. Formerly, acute graft-versus-host disease is only differentiated from the chronic from by this sort of arbitrary delineation of a hundred days. We now know that the pathophysiology of GVHD is far more complex and with the advent of what we call mini transplantation or stem cell transplant that don’t require full ablation of one’s own bone marrow to allow for donor stem cells to take hold, we know that relative levels of immunosuppression can alter somebody’s likelihood of developing graft-versus-host disease. So, the distinction is less of one chronologically and more of clinical presentation. I already alluded to the fact that acute graft-versus-host disease does tend to occur earlier after transplant. It’s characterized by inflammation in the gut and then the liver and has very non-specific findings in the skin. We contrast that with chronic graft-versus-host disease where patients may develop sclerotic skin lesions that may sort of limit their range of motion that may lead them to profound weakness. It may lead to ulcerations of the skin. It may lead to problems with the eyes or the oral mucosa, some of the deeper skin structures such as the fascia or even the muscle. So, those are the distinctions we make.
Melanie: If it’s chronic and you’re treating them with something that suppresses the immune system, even something like prednisone, Dr. Cotliar, you know there are always side effects, and so do they then have to worry about the side effects for something you’re really trying to treat them for to help with what you originally did? I mean, how do you, as a doctor, balance all of these different things?
Dr. Cotliar: That’s a great question, and again, I wanted to answer your previous question as well. Systemic steroids are typically first-line therapies for both acute and chronic graft-versus-host disease. Systemic steroids are great for short periods of time especially in high doses because they provide a level of anti-inflammation that is unparalleled. The problem is if they are chronically administered, they lead to things such as diabetes, osteoporosis, cataracts, among others, and so the sort of the push has been to try to find steroid-sparing agents both for the treatment of acute and chronic graft-versus-host disease. The problem is that if you look at their literature, if somebody is either dependent on systemic steroids, meaning we cannot sort of effectively taper down a given effective dose, or if they are resistant to treatment with systemic steroids, no single line second agent has been shown to be more effective than any other. What this leads us, both in the acute and chronic forms and we’re trying to treat either one of those, is that a lot of it is trial and error and that may be based on a given institution’s sort of protocol with respect to how they like to treat graft-versus-host disease with second line agents that may be related to a patient’s underlying comorbidities, whereby they may not be candidates for treatment with one immunosuppressive medication over another, that may be a function of a patient’s ability to get to the medical center in a timely fashion or with the type of frequency that may be required for certain systemic treatments that we can’t otherwise give if they live quite a distance away. All of these are major factors, and unfortunately, there is not one formula that fits all.
Melanie: Tell us what’s on the horizon. We don’t have a lot of time, so in just the last few minutes, what’s on the horizon for graft-versus-host disease research and treatment and what advice would you have for listeners why they should come to City of Hope for their treatment and care?
Dr. Cotliar: Well, I think anytime that a patient is able to be seen by a team of multidisciplinary doctors or be seen in the context of a multidisciplinary clinic where there is cross-collaboration among different specialties, meaning I, as a dermatologist, can share clinical space with the transplant doctor and I may have really good access to an ophthalmologist or a medicine person or a physical therapist, anytime you can see all these people under one roof like we’re fortunate enough to have at City of Hope, and certainly this type of setup exists elsewhere, this kind of a setup certainly benefits patients. Specifically at City of Hope, we are offering a multidisciplinary chronic graft-versus-host disease clinic, which we do once a week and the benefit of that is we’re able to assess patients in a room together, both the dermatologist and the transplant oncologist.In terms of what’s on the horizon, there was a groundbreaking paper on the New England Journal of Medicine last year showing that low-dose interleukin-2, which is the chemical that our bodies make naturally but given in low doses, may provide extreme benefit to patients specifically with the most severe form of chronic graft-versus-host disease which is the sclerotic form. In addition, there are a number of emerging biologic therapies such as agents that target interleukin-6 and interleukin-17 that may very well play a role in not just effectively treating graft-versus-host disease, but perhaps even as part of a prophylactic regimen to try to preempt the development of graft-versus-host disease.
Melanie: That’s very exciting and it’s a great multidisciplinary approach that you have, Dr. Cotliar. Thank you so much for joining us. You are listening to City of Hope Radio. For more information, you can go to cityofhope.org. That’s cityofhope.org. This is Melanie Cole. Thanks so much for listening.