Graft-Vs-Host Disease (GVHD)
Introduction
Graft-versus-host disease (GVHD) is often a much too frequent complication of allogeneic Bone Marrow Transplants (BMT). Bone marrow transplants are given to treat malignant and nonmalignant diseases such as leukemia, lymphoma, marrow failure also known as aplastic anemia, metabolic disorders, HIV, Inherited red cell disorders (Gratwohl, 2006). Bone marrow can be taken from umbilical cord blood, peripheral blood stem cells and from bone marrow itself from various donors. They can be obtained from either autologous which is from the recipient themselves or from an allogeneic donor which is from someone else either related or unrelated. GVHD, it is when the donor's bone marrow attacks the recipients organs and tissues, impairing …show more content…
the ability to function, thus increasing the recipients susceptibility to infection. About seventy percent of people who have had an allogeneic BMT with a related HLA-matched donor develop GVHD. HLA (human leukocyte antigen) is the body’s genetic markers and are used to determine the difference of “self” verses “not self” (John Hopkins Medicine, n.d.). When the body attacks these new cells it is called graft rejection. The greater the difference in the cells the faster the body attacks. To prevent rejection, total body irradiation and drugs are used to kill the cancer cells and suppress the bodies immune system. Many of the cases are mild, however severe cases can be life threatening (John Hopkins Medicine, n.d.). Most often GVHD is not a complication of autologous BMTs, but there have been some cases documented. GVHD is labeled as two separate diseases: acute GVHD and chronic GVHD. Patients may develop one or both. Acute and chronic GVHD have different symptoms, clinical signs and time of onset. GVHD can be a temporary inconvenience or a serious, life-threatening disease. The older one is to receives a BMT the more likelihood they are to develop GVHD. Keep in mind that incidence and severity of GVHD is also increased if a bone marrow donor is not unrelated or not perfectly HLA matched (John Hopkins Medicine, n.d.). GVHD symptoms are many and vary among patients, and the list is be overwhelming. Seventy to eighty percent of patients undergoing an allogeneic BMT with a related HLA-matched donor develop only a mild or moderate cases of GVHD, and about thirty percent not at all (Leukemia & Lymphoma Society, 2017). Although GVHD can be life- threatening or fatal, many patients do survive the disease some though with long-term debilitating side effects. With the advancements in technology the hope to improve engraftment which is the bodies ability to not reject the transplant.
Pathophysiology of Graft verses Host Disease
The disease usually involves the GI tract, skin, liver, lungs and mucosa. The donor’s marrow contains various components in particular T-Cells. When transplanted into the recipient the T-cells look at the HLA markers on the recipient’s cells and they in effect attach the patients tissues and organs. The patients immune system is suppressed prior to being transplanted, so it prevents to a degree, the counter attack for GVHD. The “graft” is the donated bone marrow and the “host” is the transplant recipient. In the acute GVHD there are four stages (mild, moderate, severe, and life-threatening.) These stages vary in degree which usually include the skin, liver, stomach, lungs and GI tract. Acute GVHD usually shows up in the first three months after a BMT (Gratwohl, 2006). In the early stages it will start out with skin irritation which resembles redness similar to a sunburn which includes peeling and blistering. When symptoms start to show in the stomach and intestines it can cause cramping, nausea, loose and bloody stools. Jaundice means it has effected the liver. When it has gone as far as the liver it is usually terminal. GVHD is graded according to the number of organs it has effected. In chronic GVHD usually develops after the third month post transplant (Leukemia & Lymphoma Society, 2017). This is believed to be caused from the “new” T-cells produced after the suppression and the new bone marrow has engrafted. Similar symptoms such as skin, liver and GI are effected as well as glands that secrete mucous (salivary, tears, saliva, vaginal and other tissues that have a mucosal lining) which give the symptoms of dry or burning sensation also affecting the body’s ability to properly absorb essential nutrients. Occasionally patients will have tightening of the tendons which makes movement of arms and legs difficult. When it attacks the lungs it usually brings on wheezing, pneumonia or bronchitis. Chronic GVHD usually is more prevalent in patients who are older or when the donor was unrelated or the HLA was not perfectly matched (Leukemia & Lymphoma Society, 2017). To decrease the risk of rejection allogenic transplant patients take immunosuppressive drugs (steroids, cyclosporin, and methotrexate) to try and prevent the disease to suppress the immune system. These drugs severely increase the risk of the patient getting an infection and having toxic side effects to the kidneys and neurologic system. Major precautions are taken to limit the exposure to harmful viruses, fungus and bacteria since the patient is immunocompromised they are at risk of contracting an infection. Some of these precautions include frequent hand-washing, masks, gloves (patient and visitors), eliminating fresh fruits, flowers, vegetables from the environment and diet to reduce harmful exposure. They are also advised to avoid live vaccinations, to avoid crowds, young children and sick family. Many patients recover from GVHD some symptoms remain indefinitely. Some residual effects are skin sensitivity, eye irritation, chronic diarrhea, and failure to properly absorb nutrients, lung and liver problems (Leukemia & Lymphoma Society, 2017). GVHD is very disabling many patients survive this sometimes fatal disease.
Literature Review Current research is largely directed at decreasing GVHD and toxicity at the same time increasing the pool of donors by advancing techniques to cross the HLA histocompatibility barriers more effectively.
Transplants are done with increasing measures of mismatch to reduce toxicity and transplant mortality by using nonmyeloblative therapy (produces minimal cytopenia) with increased suppression around the time of transplant and post transplant to obtain a partial graft followed by DLI to accomplish complete remission. DLI is also used in patients when relapse follows transplant. Gene therapy is type of stem cell in which the deficiency is corrected and then re-transplanted similarly to auto-BMT, therefore, smaller doses of chemotherapy are needed and risks of getting GVHD are abolished. While advancements are being made in gene transfer and expression research is expanding to include diseases such as HIV, betathalassemia, sickle cell, multiple sclerosis, lupus, and juvenile rheumatoid arthritis. Further research is also being made to de-differentiate cells into induced pluripotent stem cells, which allows the ability to correct the mutation in vitro, thus stimulating the cells to differentiate into stem cells for transplantation (Gratwohl, 2006). T-cell depletion is another method being researched and currently used in trials to reduce the severity of GVHD. T-cells in the body detect foreign antigens, and T-cells when removed decrease the incidence from 50% to about 15%. However, T-cells also are necessary for a successful engraftment of the new bone marrow in the recipient (Bader, et al., 2010). It is essentially a double edged sword. T-cell depletion reduces the risk of GVHD but relapse of the disease increased. The key challenge of allo-BMT is to prevent GVHD without losing the graft versus leukemia effect (GVL); which is the ability of the donors cells to eradicate the cancer with the “donated” T-cells to react against the leukemic cells further destroying
the cancer (Bader, Niethammer, Willasch, Kreyenberg, klingebiel, 2010). The risk of relapse is increased in patients without GVHD, therefore research is evolving in the direction of the timing of post transplant donor lymphocyte infusion (DLI) simply put a t-cell infusion. GVHD is a major complication of DLI therapy, however research is finding better processes to target the cancer cells and try and decrease the GVHD severity while increasing the GVL effect (Bader, et al.,2010). Monitoring of chimerism levels post transplant for interventional treatment to avoid graft rejection, to maintain engraftment, and/or to treat imminent relapse via pre-emptive immunotherapy is also effective (Bader, et al., 2010).
Summary of Interview A diagnosis of GVHD will affected patients’ emotional and psychological wellbeing as well as their health status, as did the case with the interview that was conducted. The side effects of the drugs used to treat the GVHD further put stress on the already delicate emotional state. Symptoms of anxiety, depression, confusion, mood swings, along with exaggerated feelings were very hard on him and his family. He had a strong family involvement which helped him cope in this trying time. During the recovery he was unable to socialize and interact with many of his friends and family and work was out of the question. His GVHD affected his skin and GI. He said he felt like a prisoner in his own home in the beginning. He then started with a support group for GVHD and he was then able to learn to cope with his disease. He would go to see movies during the day, shop during off-hours, eat out early to avoid crowds. His condition was critical for about one year post transplant and then the symptoms subsided for the next few years. He still has some debilitating symptoms but they are manageable. He was unable to return to his previous job and now works from home. His strength is slowly returning, but states that he is nowhere near 100%. He recalls the medical team bringing up the multiple side effects of transplant and at the time states he was so overwhelmed that he did not fully comprehend the severity of GVHD. He had to stop the medication to suppress his immune system due to the severity of the GVHD and his nutritional status. Because of the temporary ceasing of the medication he is now at risk to have a relapse of his leukemia. He goes for routine tests to see if he has had any signs of relapse. He is hopeful with all the ongoing research that new findings will be able to better help him when the relapse or transformation to another cancer occurs. Overall, he said he was one of the lucky ones who are surviving GVHD.
Conclusion
With the ever changing advancements (indications, techniques, and supportive therapy) the transplant field continues to be an advancing in the treatment of human disease especially GVHD. Since many patients undergoing an allogeneic BMT experience some degree of GVHD, physicians usually discuss GVHD with people in great detail prior to their transplant. Many people find this discussion frightening and overwhelming, especially if the risks of GVHD are not put into perspective. Patients find it hard to understand that a case of GVHD can be mild, moderate or severe, and that death, disfigurement or permanent disability is not the usual outcome only 20% of the cases end in fatality (Bader, et al., 2010).
Graft-versus-host disease (GVHD) is often a much too frequent complication of allogeneic Bone Marrow Transplants (BMT). Bone marrow transplants are given to treat malignant and nonmalignant diseases such as leukemia, lymphoma, marrow failure also known as aplastic anemia, metabolic disorders, HIV, Inherited red cell disorders (Gratwohl, 2006). Bone marrow can be taken from umbilical cord blood, peripheral blood stem cells and from bone marrow itself from various donors. They can be obtained from either autologous which is from the recipient themselves or from an allogeneic donor which is from someone else either related or unrelated. GVHD, it is when the donor's bone marrow attacks the recipients organs and tissues, impairing …show more content…
the ability to function, thus increasing the recipients susceptibility to infection. About seventy percent of people who have had an allogeneic BMT with a related HLA-matched donor develop GVHD. HLA (human leukocyte antigen) is the body’s genetic markers and are used to determine the difference of “self” verses “not self” (John Hopkins Medicine, n.d.). When the body attacks these new cells it is called graft rejection. The greater the difference in the cells the faster the body attacks. To prevent rejection, total body irradiation and drugs are used to kill the cancer cells and suppress the bodies immune system. Many of the cases are mild, however severe cases can be life threatening (John Hopkins Medicine, n.d.). Most often GVHD is not a complication of autologous BMTs, but there have been some cases documented. GVHD is labeled as two separate diseases: acute GVHD and chronic GVHD. Patients may develop one or both. Acute and chronic GVHD have different symptoms, clinical signs and time of onset. GVHD can be a temporary inconvenience or a serious, life-threatening disease. The older one is to receives a BMT the more likelihood they are to develop GVHD. Keep in mind that incidence and severity of GVHD is also increased if a bone marrow donor is not unrelated or not perfectly HLA matched (John Hopkins Medicine, n.d.). GVHD symptoms are many and vary among patients, and the list is be overwhelming. Seventy to eighty percent of patients undergoing an allogeneic BMT with a related HLA-matched donor develop only a mild or moderate cases of GVHD, and about thirty percent not at all (Leukemia & Lymphoma Society, 2017). Although GVHD can be life- threatening or fatal, many patients do survive the disease some though with long-term debilitating side effects. With the advancements in technology the hope to improve engraftment which is the bodies ability to not reject the transplant.
Pathophysiology of Graft verses Host Disease
The disease usually involves the GI tract, skin, liver, lungs and mucosa. The donor’s marrow contains various components in particular T-Cells. When transplanted into the recipient the T-cells look at the HLA markers on the recipient’s cells and they in effect attach the patients tissues and organs. The patients immune system is suppressed prior to being transplanted, so it prevents to a degree, the counter attack for GVHD. The “graft” is the donated bone marrow and the “host” is the transplant recipient. In the acute GVHD there are four stages (mild, moderate, severe, and life-threatening.) These stages vary in degree which usually include the skin, liver, stomach, lungs and GI tract. Acute GVHD usually shows up in the first three months after a BMT (Gratwohl, 2006). In the early stages it will start out with skin irritation which resembles redness similar to a sunburn which includes peeling and blistering. When symptoms start to show in the stomach and intestines it can cause cramping, nausea, loose and bloody stools. Jaundice means it has effected the liver. When it has gone as far as the liver it is usually terminal. GVHD is graded according to the number of organs it has effected. In chronic GVHD usually develops after the third month post transplant (Leukemia & Lymphoma Society, 2017). This is believed to be caused from the “new” T-cells produced after the suppression and the new bone marrow has engrafted. Similar symptoms such as skin, liver and GI are effected as well as glands that secrete mucous (salivary, tears, saliva, vaginal and other tissues that have a mucosal lining) which give the symptoms of dry or burning sensation also affecting the body’s ability to properly absorb essential nutrients. Occasionally patients will have tightening of the tendons which makes movement of arms and legs difficult. When it attacks the lungs it usually brings on wheezing, pneumonia or bronchitis. Chronic GVHD usually is more prevalent in patients who are older or when the donor was unrelated or the HLA was not perfectly matched (Leukemia & Lymphoma Society, 2017). To decrease the risk of rejection allogenic transplant patients take immunosuppressive drugs (steroids, cyclosporin, and methotrexate) to try and prevent the disease to suppress the immune system. These drugs severely increase the risk of the patient getting an infection and having toxic side effects to the kidneys and neurologic system. Major precautions are taken to limit the exposure to harmful viruses, fungus and bacteria since the patient is immunocompromised they are at risk of contracting an infection. Some of these precautions include frequent hand-washing, masks, gloves (patient and visitors), eliminating fresh fruits, flowers, vegetables from the environment and diet to reduce harmful exposure. They are also advised to avoid live vaccinations, to avoid crowds, young children and sick family. Many patients recover from GVHD some symptoms remain indefinitely. Some residual effects are skin sensitivity, eye irritation, chronic diarrhea, and failure to properly absorb nutrients, lung and liver problems (Leukemia & Lymphoma Society, 2017). GVHD is very disabling many patients survive this sometimes fatal disease.
Literature Review Current research is largely directed at decreasing GVHD and toxicity at the same time increasing the pool of donors by advancing techniques to cross the HLA histocompatibility barriers more effectively.
Transplants are done with increasing measures of mismatch to reduce toxicity and transplant mortality by using nonmyeloblative therapy (produces minimal cytopenia) with increased suppression around the time of transplant and post transplant to obtain a partial graft followed by DLI to accomplish complete remission. DLI is also used in patients when relapse follows transplant. Gene therapy is type of stem cell in which the deficiency is corrected and then re-transplanted similarly to auto-BMT, therefore, smaller doses of chemotherapy are needed and risks of getting GVHD are abolished. While advancements are being made in gene transfer and expression research is expanding to include diseases such as HIV, betathalassemia, sickle cell, multiple sclerosis, lupus, and juvenile rheumatoid arthritis. Further research is also being made to de-differentiate cells into induced pluripotent stem cells, which allows the ability to correct the mutation in vitro, thus stimulating the cells to differentiate into stem cells for transplantation (Gratwohl, 2006). T-cell depletion is another method being researched and currently used in trials to reduce the severity of GVHD. T-cells in the body detect foreign antigens, and T-cells when removed decrease the incidence from 50% to about 15%. However, T-cells also are necessary for a successful engraftment of the new bone marrow in the recipient (Bader, et al., 2010). It is essentially a double edged sword. T-cell depletion reduces the risk of GVHD but relapse of the disease increased. The key challenge of allo-BMT is to prevent GVHD without losing the graft versus leukemia effect (GVL); which is the ability of the donors cells to eradicate the cancer with the “donated” T-cells to react against the leukemic cells further destroying
the cancer (Bader, Niethammer, Willasch, Kreyenberg, klingebiel, 2010). The risk of relapse is increased in patients without GVHD, therefore research is evolving in the direction of the timing of post transplant donor lymphocyte infusion (DLI) simply put a t-cell infusion. GVHD is a major complication of DLI therapy, however research is finding better processes to target the cancer cells and try and decrease the GVHD severity while increasing the GVL effect (Bader, et al.,2010). Monitoring of chimerism levels post transplant for interventional treatment to avoid graft rejection, to maintain engraftment, and/or to treat imminent relapse via pre-emptive immunotherapy is also effective (Bader, et al., 2010).
Summary of Interview A diagnosis of GVHD will affected patients’ emotional and psychological wellbeing as well as their health status, as did the case with the interview that was conducted. The side effects of the drugs used to treat the GVHD further put stress on the already delicate emotional state. Symptoms of anxiety, depression, confusion, mood swings, along with exaggerated feelings were very hard on him and his family. He had a strong family involvement which helped him cope in this trying time. During the recovery he was unable to socialize and interact with many of his friends and family and work was out of the question. His GVHD affected his skin and GI. He said he felt like a prisoner in his own home in the beginning. He then started with a support group for GVHD and he was then able to learn to cope with his disease. He would go to see movies during the day, shop during off-hours, eat out early to avoid crowds. His condition was critical for about one year post transplant and then the symptoms subsided for the next few years. He still has some debilitating symptoms but they are manageable. He was unable to return to his previous job and now works from home. His strength is slowly returning, but states that he is nowhere near 100%. He recalls the medical team bringing up the multiple side effects of transplant and at the time states he was so overwhelmed that he did not fully comprehend the severity of GVHD. He had to stop the medication to suppress his immune system due to the severity of the GVHD and his nutritional status. Because of the temporary ceasing of the medication he is now at risk to have a relapse of his leukemia. He goes for routine tests to see if he has had any signs of relapse. He is hopeful with all the ongoing research that new findings will be able to better help him when the relapse or transformation to another cancer occurs. Overall, he said he was one of the lucky ones who are surviving GVHD.
Conclusion
With the ever changing advancements (indications, techniques, and supportive therapy) the transplant field continues to be an advancing in the treatment of human disease especially GVHD. Since many patients undergoing an allogeneic BMT experience some degree of GVHD, physicians usually discuss GVHD with people in great detail prior to their transplant. Many people find this discussion frightening and overwhelming, especially if the risks of GVHD are not put into perspective. Patients find it hard to understand that a case of GVHD can be mild, moderate or severe, and that death, disfigurement or permanent disability is not the usual outcome only 20% of the cases end in fatality (Bader, et al., 2010).