About this course:
This course will assist nurses working in various settings in understanding how to care for patients who have undergone hematopoietic cell transplantation (HCT) and the indications, criteria, types, risks, and patient education associated with participating in HCT.
This course will assist nurses working in various settings in understanding how to care for patients who have undergone hematopoietic cell transplantation (HCT) and the indications, criteria, types, risks, and patient education associated with participating in HCT.
This learning activity is designed to allow learners to:
- discuss healthy versus abnormal physiology of the bone marrow and factors that lead to HCTs
- identify characteristics of a suitable donor
- describe the various types of transplants available for patients with hematologic disorders
- discuss the diagnostic testing utilized to match a donor and a recipient
- explain the various procedures to harvest stem cells and the transplant processes
- identify the complications associated with HCTs for both donors and recipients
The hematopoietic system is responsible for the production of blood cells. This system consists of blood cells, precursors, bone marrow, and lymphoid cells. A typical person requires 100 billion new blood cells per day. Hematopoiesis is the process of creating these new blood cells. During the fifth week of gestation in a developing fetus, hematopoiesis begins in the developing blood vessels within the endothelial cells and continues in the liver and spleen. After birth, this production becomes the responsibility of the bone marrow. Extramedullary hematopoiesis describes when blood cell formation occurs in an adult's tissues other than bone marrow, including the spleen, liver, lymph nodes, adrenal glands, cartilage, adipose tissues, and kidneys. Although extramedullary hematopoiesis can lead to normal blood cells, it often suggests the presence of diseases in an adult, such as pernicious anemia (i.e., a type of vitamin B12 anemia), sickle cell anemia, thalassemia (i.e., low hemoglobin levels), hereditary spherocytosis (i.e., a disorder that affects red blood cells leading to hemolytic anemia), and some types of leukemia. Actual bone marrow consists of connective tissue that holds the immature blood cells (Ignatavicius et al., 2018; McCance & Huether, 2019).
Two types of bone marrow are found in adults: red bone marrow (active or hematopoietic marrow) and yellow bone marrow (inactive marrow). The red bone marrow’s color is due to the high production of erythrocytes. Yellow marrow contains many adipose cells, which give the marrow its color. As the skeletal system grows, red marrow is gradually replaced by yellow marrow within the long bones, such as the femur and humerus. As adulthood is reached, red marrow remains most prevalent in the flat bones of the pelvis, vertebrae, cranium, mandible, sternum, and ribs (Ignatavicius et al., 2018; McCance & Huether, 2019).
Bone marrow is located inside the ilium, sternum, cranium, ribs, vertebrae, and scapula and in the cancellous material at the proximal ends of the femur and humerus. The bone marrow produces approximately 2.5 billion erythrocytes, 2.5 billion thrombocytes, and nearly 1 billion leukocytes per kilogram of body weight daily. When the bone marrow initially produces cells, they are undifferentiated and referred to as hematopoietic stem cells. As the body determines how many and what type of cells are needed, the cells become committed stem cells or precursor cells. When the cells are committed, they become either lymphoid or myeloid progenitors. Facilitated by growth factors specific to the cell type, they continue to grow and divide. Lymphoid progenitor cells will differentiate into T lymphocytes, natural killer (NK) cells, or B lymphocytes. As they mature, the myeloid progenitor cells will differentiate into basophils, eosinophils, monocytes and macrophages, neutrophils, platelets, and erythrocytes. This process continues daily in the same manner, apart from a disease process or aging (Ignatavicius et al., 2018; McCance & Huether, 2019).
Changes in Bone Marrow
Bone marrow function is impacted by aging, resulting in decreased blood volume and lower levels of plasma proteins. Some of the etiology for this reduction of plasma proteins may be related to reduced dietary protein intake. With the aging process, there is a reduction of blood cells, especially red and white blood cells (WBCs), but not a decrease in platelets. The aging process also impacts lymphocytes as they become less reactive to antigens throughout their lifespan, provoking a decline in immune function. Actual antibody production and levels of available antibodies lessen with age, and the response time is slower. In younger adults, the WBC count usually rises during an active infection proportional to the degree of disease; however, this is not true for older adults. The elevation in WBCs in an older adult will not be as high as in a younger adult. Hemoglobin levels also decline in approximately the fourth decade of life, a process that continues into older adulthood. This may lead to iron-deficiency anemia related to aging and a decreased intake of iron-rich food (Ignatavicius et al., 2018; Norris, 2019).
At times, the bone marrow does not function appropriately, leading to a significant reduction in the production of one or more cell types. Patients may develop anemia, thrombocytopenia, or granulocytopenia based on the decreased cell type. These disorders are referred to as underproliferation, while myeloproliferative diseases involve an overproduction of cells resulting in an elevation of peripheral blood counts. The overproduction of RBCs in the bone marrow is called polycythemia, and excess platelet production is known as thrombocytosis. Patients may have leukemia if there is an abnormal proliferation of WBCs. These disorders are treated with a hematopoietic cell transplant (HCT; Norris, 2019).
HCT is also commonly referred to as a hematopoietic stem cell transplant (HSCT) or a bone marrow transplant (BMT); however, the terms HCT or HSCT include other methods of donating and receiving stem cells. An HCT involves infusing healthy stem cells into a patient to replace damaged or diseased bone marrow. Initially, the only type of HCT was allogeneic. Now, transplants may be allogeneic, autologous, or syngeneic. An allogeneic transplant uses bone marrow harvested from a patient's sibling or an unrelated donor with a similar genetic makeup. With research and advances in medicine, allogeneic HCT has evolved into utilizing human leukocyte antigen (HLA) stem cells that have been matched explicitly to an individual patient. An autologous HCT involves harvesting cells from the patient’s body. Before beginning treatment (i.e., high-dose radiation or chemotherapy), a patient's hematopoietic stem cells are collected. After collection, the cells are preserved while the patient undergoes treatment, and then the cells are reinfused back into the patient. A syngeneic transplant is extremely rare and consists of receiving a donation from a recipient's identical twin (Ignatavicius et al., 2018; Negrin, 2022).
Various cells are used in HCTs, including hematopoietic stem cells. These cells can be obtained directly from an individual's bone marrow or bloodstream. When obtained from the bloodstream, hematopoietic stem cells are referred to as peripheral blood stem cells (PBSCs). Another source for hematopoietic stem cells is the umbilical cord after delivery. For children, matched stem cells from umbilical cord blood involve less risk of graft-versus-host disease (GVHD). Healthcare providers (HCPs) will decide the best type of transplant for each patient based on their diagnosis, age, overall physical health, and diagnostic test results. HCPs will determine whether a BMT, a peripheral blood stem cell transplant (PBSCT), or a transplant using stem cells from cord blood is the best option (Norris, 2019; S
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Indications for HCT are the presence of dysfunctional or depleted bone marrow. The application of HCT has expanded, with over 22,000 HCTs performed in the US and 60,000 performed worldwide in 2018. Of these, approximately 9,028 were allogeneic transplants, and 14,709 were autologous transplants. An HCT is used as a treatment for some types of cancers, particularly malignancies of the blood or blood disorders. When patients with cancer undergo extensive chemotherapy or radiation, healthy cells and malignant cells are destroyed. The higher the dose of chemotherapy or radiation is, the more detrimental the effects on the bone marrow cells will be. These treatment options target cells that divide quickly to eliminate the cancerous cells, but healthy cells in the bone marrow also divide rapidly. Therefore, patients experience the destruction of both healthy and unhealthy cells, leaving them at risk of infection and bleeding. Unfortunately, higher doses of radiation and chemotherapy may be needed to eradicate more resistant cancer cells, causing even more damage to the body's healthy cells. Utilizing HCT following chemotherapy or radiation allows healthy cells to be infused to assist the bone marrow in producing healthy cell types (Kanate et al., 2020; Khaddour et al., 2022; Negrin, 2022; Saad et al., 2020).
The most common types of malignant diseases treated with HCT include multiple myeloma, Hodgkin and non-Hodgkin lymphoma, acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndrome, chronic myeloid leukemia or chronic lymphocytic leukemia, myelofibrosis, essential thrombocytosis, polycythemia vera, and solid tumors. For patients diagnosed with leukemia, receiving an HCT can lead to remission. Allogeneic HCT is indicated when malignant or defective hematopoietic stem cells need to be replaced. The most common malignancies treated with allogeneic HCT include acute myeloid leukemia, acute lymphocytic leukemia, and myelodysplastic syndrome. Autologous HCT is indicated when a patient's hematopoietic stem cells become damaged due to high-dose chemotherapy or radiation treatment. Malignant diseases most commonly treated with autologous HCT include multiple myeloma and Hodgkin and non-Hodgkin lymphoma. Non-malignant conditions that HCT can treat consist of aplastic anemia, severe combined immune deficiency syndrome, thalassemia, sickle cell anemia, Chediak-Higashi syndrome (rare immunodeficiency disorder), Kostman syndrome (severe congenital neutropenia), and enzymatic disorders. Since bone marrow is part of the immune system, research is being completed to determine if HCT can be utilized as an effective treatment for autoimmune diseases, including systemic lupus erythematosus and relapsing-remitting multiple sclerosis (Khaddour et al., 2022; Saad et al., 2020).
Before deciding whether a patient is a candidate for an HCT, the provider will order multiple diagnostic tests to characterize the candidate's health and confirm their medical diagnosis. The provider must ensure that the potential candidate is physically capable of undergoing the transplant. Testing and evaluation results indicate the patient's risk of disease relapse and mortality following HCT. Factors considered include overall health, prior treatments, age, current diagnosis, disease stage, and prognosis. Instead of chronologic age, potential transplant candidates are evaluated based on physiologic age, considering comorbidities and functional status. Other tests and tools used to evaluate the patient's health and performance status include the Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status scales, which are used to determine functional status; left ventricular ejection fraction; pulmonary function testing, including forced vital capacity measurement; laboratory testing of kidney and liver function; and the HCT-comorbidity index (HCT-Cl), which predicts the rate of survival. HCT-Cl is especially helpful in determining each patient's risk of non-relapse mortality following an allogeneic transplant. Non-relapse mortality is often related to pre-existing comorbidities. The patient's psychological status is also assessed to determine eligibility. Due to the length of recovery and potential risks, patients must be psychologically able to undergo the treatment, adhere to aftercare, and have a support system to assist them. Ongoing studies are being conducted to determine the most reliable evaluation tools to predict outcomes of HCT for elderly patients (National Marrow Donor Program [NMDP], n.d.-d; Saad et al., 2020).
There is a significant need for community members to become donors, as many transplants come from unrelated individuals whose generous donations have saved lives. The NMDP is a nonprofit organization that operates the most extensive registry, managing over 11 million donors and cord blood units. They are responsible for the Be the Match campaign, which assists clinicians in finding matching donors for their patients. Many people worry about donating bone marrow, stem cells, or cord blood due to the cost, but these medical costs are covered by Be the Match. Sometimes medical insurance will also help cover the cost of donating and personal expenses such as travel. Regardless, some people may incur lost wages when they are off work to donate. If a pregnant person wants to donate their baby’s cord blood to a public cord blood bank, this is done free of charge. If the parent wishes to store the cord blood at a commercial cord blood bank for future use by themselves or potential family members, there is a charge for this. Cord blood is harvested at birth from the umbilical cord, which contains many stem cells. After delivery, blood is drawn from the placenta before it detaches from the uterine wall. This collection of stem cells is processed and stored in a cord blood registry for future use (Ignatavicius et al., 2018; NMDP, n.d.-a).
Becoming a donor is a personal and individual choice. Nurses should direct those interested to the Be the Match website for information, resources, and contact information. Donors must be willing to donate to any patient in need. Specific health guidelines need to be met, as outlined on the Be the Match website. These health requirements are in place to protect future recipients and potential donors. Anyone meeting the donation criteria can join Be the Match on their website or by other contact methods (NMDP, n.d.-c).
There are various health requirements for HCT donation (Connelly-Smith, 2020; NMDP, n.d.-c):
- Most donors should be between the ages of 18 and 35, as this age group produces more high-quality cells than older donors. Studies have shown that receiving donor cells from younger individuals increases the chances of long-term survival. A non-relative donor must be at least 18, so they can sign their consent form. Approximately 30% of children receiving HCT obtain a donation from a minor sibling. The American Academy of Pediatrics Committee on Bioethics (AAPCOB) has established criteria that must be met for minor children to be considered donors.
- Individuals who have tested positive for HIV or other sexually transmitted infections (STIs) cannot donate.
- Individuals with life-threatening allergies to latex and other medications must consult with staff before registering as potential donors.
- Suffering from mild to moderate osteoarthritis or degenerative arthritis does not prevent someone from becoming a donor; however, having a more severe form of arthritis, such as rheumatoid or psoriatic arthritis, does prevent an individual from becoming a donor.
- An individual with asthma requiring regular corticosteroid use for symptom management is disqualified as a potential donor.
- An individual diagnosed with an autoimmune disease that affects the entire body—such as systemic lupus erythematosus, fibromyalgia, multiple sclerosis, severe psoriasis, Sjogren's syndrome, ankylosing spondylitis, or Addison's disease—cannot serve as a potential donor. Autoimmune conditions limited to one organ system, such as celiac disease in the gastrointestinal tract, are not disqualifying.
- Individuals with a severe bleeding disorder such as hemophilia or Factor V Leiden, a history of blood clots requiring the use of anticoagulants, aplastic anemia, or von Willebrand's disease are ineligible to become donors.
- Pregnant patients can register as donors; however, these individuals cannot actively donate until they are fully recovered from delivery, either vaginal or cesarean.
- Patients who have had any significant brain injury or brain surgery cannot donate even after the recovery period. Donors cannot have experienced more than six concussions in a lifetime, had a concussion resulting in unconsciousness for over an hour, or had symptoms that lasted more than 1 month. This is due to the increased risk of a brain bleed in these individuals due to stimulating stem cell production before donation.
- Patients with a precancerous condition, very localized and well-contained cancer such as healed cervical carcinoma in situ, or cancer diagnosed and treated more than 5 years ago can register as donors. Treatment cannot include radiation or chemotherapy except for localized seed radiation used for prostate cancer or radioactive iodine treatment for thyroid cancer. Patients with a history of cancer of the hematologic system cannot register to be a donor.
- Individuals with a history of chemical dependency can donate if they have completed treatment and maintained sobriety for at least 12 months.
- Persons with a mental health condition such as attention deficit hyperactivity disorder, bipolar disorder, or depression that is well treated and considered stable can become donors; however, individuals with severe mental health disorders such as schizophrenia or delusional disorder cannot donate.
- Individuals diagnosed with diabetes require an evaluation to determine their current health status. Based on the evaluation results, a decision will be made on their ability to donate. Individuals with diabetes can donate if their disease is well controlled with diet, oral medications, or insulin and if there are no secondary conditions such as heart, nerve, or eye damage.
- Persons with a history of myocardial infarction (MI), bypass surgery, valve replacement, cerebrovascular disease, or a pacemaker cannot become donors. An individual with controlled hypertension can become a donor.
- Persons diagnosed with hepatitis B or C, or severe liver disease (cirrhosis or Wilson's disease) are not able to donate. Patients with a history of hepatitis A that is fully recovered may be eligible.
- Individuals with severe or chronic kidney disease, such as polycystic kidney disease or glomerulonephritis, are unable to donate. Donation is also not allowed for individuals after kidney removal due to disease. Patients who are missing a kidney due to donation and are fully recovered can donate.
- Patients who have received a transplant with a human organ, bone marrow or blood-forming cells, or live tissue from an animal (i.e., a xenotransplant) cannot donate. Patients who have received a transplant with human tissue, ligaments, tendons, corneas, or skin may be eligible to donate, depending on the reason for the transplant.
After meeting the health criteria and joining the registry, the donor’s tissue type is recorded with a cheek (buccal) swab. A donation does not occur until the donor is matched with a potential recipient. Once matched, additional testing is completed by the donor (NMDP, n.d.-c).
Human Leukocyte Antigens
HLAs are proteins located on the surface of most body cells (except on erythrocytes) that are unique to each person. HLA proteins distinguish what the immune system recognizes as self (i.e., an inherent part of the patient). After human conception occurs, the new fetus inherits HLA genes, which determine the HLAs present in the individual. HLA genes are in a region of chromosome 6 known as the major histocompatibility complex (MHC). This system helps determine which cells belong to the patient and which cells may be foreign invaders. When the immune system encounters cells that do not display a specific HLA, it responds by destroying the perceived antigen. The immune system cells neutralize, damage, or eliminate these invaders. A patient who needs a transplant is given HLA-matched cells from a donor to decrease the risk of rejection by the recipient’s immune system (American Association for Clinical Chemistry [AACC], 2021; Ignatavicius et al., 2018).
HLA typing—also referred to as tissue typing, histocompatibility testing, or HLA crossmatching—is done to confirm compatibility and determine the best donor for a particular patient. Theoretically, the best match would be a matched related donor followed by a matched unrelated donor, cord blood, and a haploidentical or half-matched donor. Haploidentical donors are most likely the patient's parent or child. Histocompatibility describes the similarity between the HLAs of the transplant recipient and the potential donor. The donor and recipient HLAs must match closely, increasing the probability of a successful transplant, decreasing the risk of rejection, and improving outcomes. The process of HLA typing varies depending on the source from which the stem cells were obtained, such as bone marrow, peripheral blood, or cord blood. The process also differs depending on if the transplant is autologous, allogeneic, or syngeneic (AACC, 2021; NMDP, n.d.-b).
A patient undergoing an HCT requires an almost perfect match with their donor. Blood or a buccal swab is collected from the potential donor and recipient, and testing is completed on the HLA proteins taken from the surface of leukocytes. This testing identifies HLAs that are present in the blood, as well as potential antibodies to HLAs. If there are antibodies present that could target the donated tissue, blood, or organ, this could create an immune response resulting in a failed or compromised transplant (rejection). HLA typing is analyzed at either intermediate-resolution level or high-resolution level. Intermediate-resolution testing detects the number of matched alleles between the donor and the recipient. High-resolution testing indicates the number of polymorphic alleles. The results are reported as a score that correlates with finding a match of 2 alleles for a specific HLA type. Recipients must also undergo antibody testing to determine whether they have antibodies that would target the donated cells. The desired outcome of testing is to have no mismatches and no HLA antibodies in relation to the potential donor (AACC, 2021; Khaddour et al., 2022; NMDP, n.d.-b).
Each medical facility that does transplants has protocols for HLA typing regarding the minimum number of acceptable matches. Most labs report in either an 8- or 10-point HLA match, but each provider frequently determines the level of matched HLAs they want. The NMDP and Center for International Blood and Marrow Transplant Research guidelines state that at least a 6 out of 8 HLA match should be present to increase overall survival. In haploidentical transplants 5 out of 10 HLAs match. When HLA typing cord blood, most providers and facilities require 4 out of 6 (traditional method) or 6 out of 8 (high resolution) HLAs to match (AACC, 2021; Dehn et al., 2019; NMDP, n.d.-b).
After reviewing all the test results, many components are considered, especially the HLA matching. Minimizing potential side effects for the patient and finding as close of a match as possible is the desired outcome. A closely matched HLA is crucial for preventing GVHD, which is a serious complication. Having a transplant from a sibling usually produces a good match, but only about 25% to 35% of patients will have a sibling who is a desirable match. Through increasing numbers of donors and better screening options, the chance of finding an acceptable unrelated donor is about 50%. Each potential donor and recipient should be of the same ethnic and racial background, if possible, as this will increase the probability of matching. An area that still needs improvement is increasing the diversity of available donors, as some ethnic and racial groups lack an adequate donor pool. The odds of a non-Hispanic black individual finding a match is 29% compared to 79% for a non-Hispanic white individual. The best possible match would be from an identical twin, which is rare, but the risk of GVHD and other types of rejection is minimal with a perfect genetic match (NMDP, n.d.-b).
Harvesting and Transplanting
Once a suitable donor has been established, the harvesting or collection of the transplant source will be initiated. The procedure varies with each type of donation. When patients undergo a PBSCT, they complete three steps: mobilization, apheresis (the collection phase), and reinfusion. Transplant facilities will admit the recipient for the conditioning process 4 to 7 days before the transplant, but this varies for each patient. During conditioning, chemotherapy or radiation is administered to prepare the bone marrow to receive the transplant. These days are considered minus days until the patient reaches the transplant, which is regarded as day 0. Each subsequent day is termed day 1, day 2, etc. until the patient is discharged. From day 0 to day 14, the patient will require close medical and nursing care to monitor for fever, hypertension, nausea and vomiting, hypovolemia, and electrolyte imbalances (Ignatavicius et al., 2018; Negrin, 2022).
Once a patient receives the transplant via a central line, the cells will travel throughout the body and eventually go to the bone marrow. Over time, the cells begin to make new blood cells—including leukocytes, erythrocytes, and thrombocytes—in a process known as engraftment. On average, after 14 to 21 days, engraftment should begin, requiring the patient to have close medical and nursing care monitoring for signs of engraftment syndrome, including fever and weight gain. The engraftment process can take several weeks or longer and varies from patient to patient. The process is monitored daily by checking neutrophil and platelet counts. Once the absolute neutrophil count (ANC) is above 500 cells/mm3 for three days in a row and the platelet count is between 20,000/mm3 and 50,000/mm3, without platelet transfusions, engraftment is considered complete. Patients are often discharged from the acute care setting after 35 days; however, they are advised to live within reasonable driving distance of the facility for at least 100 days post-transplant. If the patient had an autologous transplant, full recovery takes several months; for syngeneic and allogeneic patients, it can take 1-2 years. HCPs will evaluate each recipient for any side effects or complications and manage those accordingly. Throughout recovery, complete blood counts and bone marrow biopsies will be monitored to assess the effectiveness of the transplant (Ignatavicius et al., 2018; Majhail, 2021; Negrin, 2022).
If the transplant is autologous, the patient will need growth factor injections or chemotherapeutic agent(s) to increase their stem cell production. Not only do the growth factor injections help produce more stem cells, but they also move the stem cells into circulation quicker. The phase of harvesting that utilizes doses of growth factor or chemotherapy is known as mobilization. Patients with hematologic cancer may be given the medication plerixafor (Mozobil) to help with the cancer cells and growth factors. This medication limits the number of apheresis collections the patient will need to undergo. The patient will prepare for apheresis when adequate cells are available in circulation. Autologous transplants do not carry incompatibility risks like other types of transplants do; however, the body must have the ability to produce enough cells to harvest (Ignatavicius et al., 2018; Majhail, 2021; Negrin, 2022).
The procedure for collection is known as apheresis. For any transplant involving the harvest of stem cells, approximately 1 to 5 rounds of apheresis (1 per day) are needed to obtain enough cells unless plerixafor (Mozobil) is used. Due to its effects as a bone marrow stimulant, enough stem cells can be obtained in 1 day of apheresis. Each apheresis attempt takes 2 to 4 hours to complete. The blood circulates through a machine that separates the blood into its various components. The stem cells are removed, frozen, and used in the future during the reinfusion phase. The remainder of the blood is reinfused into circulation. For an autologous HCT, the bone marrow is treated for any remaining cancer and is frozen for later use (Ignatavicius et al., 2018; Majhail, 2021; Negrin, 2022).
After apheresis is complete, some patients must undergo additional conditioning with high-dose chemotherapy or radiation to destroy as many cancer cells as possible. This process also suppresses the patient's immune system to lessen the chance of rejection and prepares the body to receive new cells or marrow. During this process, the patient may experience nausea, vomiting, diarrhea, loss of all or some of their hair, mucositis, infection, anemia, and other potential adverse effects. Depending on the patient and their condition, they may need reduced-intensity conditioning, lessening the doses of chemotherapy and radiation. Once the conditioning process is complete, the patient will receive an infusion of stem cells directly into their circulatory system through a process known as reinfusion. Once introduced to the recipient, the stem cells migrate to the bone marrow and start to produce new stem cells. Recipients require close monitoring for signs of chemotherapy or total body irradiation toxicity, infection, or graft failure following the transplant (Ignatavicius et al., 2018; Majhail, 2021; Negrin, 2022).
Patients undergoing an allogeneic transplant will receive cells or marrow from a donor. Based on multiple factors, the provider and transplant team will decide to use stem cells or actual bone marrow from the donor. If PBSCs are to be used, the process is similar to autologous donation, except the stem cells come from a donor. During allogeneic HCT using bone marrow, the donor is taken to an operating room. The surgeon aspirates 500 to 1000 mL of bone marrow through a large-bore needle from multiple aspiration sites, such as the iliac crest or other long bones. This type of donation is done less frequently due to the advances made in PBSCT and cord blood transplants. The donated marrow is then filtered, prepared, and transplanted into the recipient. The donor will regenerate their marrow within a few weeks after donation. The patient could also receive an allogeneic transplant using cord blood (Ignatavicius et al., 2018; Majhail, 2021; Negrin, 2022).
Some patients receiving an allogeneic transplant must undergo the same conditioning process described earlier. When conditioning is complete, the patient will receive an infusion of stem cells directly into their circulatory system. The stem cells will migrate to the bone marrow and start to produce new stem cells. Patients will require close monitoring following either form of HCT (Ignatavicius et al., 2018; Majhail, 2021; Negrin, 2022).
For patients receiving a syngeneic transplant from an identical twin, the processes for harvesting and transplanting are essentially the same as in allogeneic transplantation. Adverse effects from the conditioning process can still occur, and these recipients are at risk of developing infections, GVHD, organ toxicity, pulmonary edema, fluid overload, and heart failure (Ignatavicius et al., 2018; Majhail, 2021; Negrin, 2022).
Patients may experience multiple side effects because of the chemotherapy and radiation used before HCT. Since chemotherapy targets rapidly multiplying cells, patients can experience mucositis and diarrhea caused by damage to the rapidly dividing epithelial cells in the mouth and gastrointestinal tract and alopecia due to damage to the hair follicles. Hair begins to return 2 to 3 months after the cessation of chemotherapy and radiation. Patients may also experience abdominal pain, nausea, and vomiting (Negrin, 2022).
Recipients undergoing HCT face multiple risks, depending on the disease that prompted the transplant, age, overall health, and the transplant process. Many complications can occur, including GVHD, graft failure, potential damage to other internal organs, post-transplant infection, reproductive concerns, the development of new cancers, and death. Permanent infertility may affect patients who undergo chemotherapy or radiation; however, the risk highly depends on the type of treatment used and the dosage given. There is a risk of secondary cancer developing following HCT. Secondary cancer usually develops 3 to 5 years after HCT and is often attributed to radiation therapy the patient may have undergone before the HCT. The patient will remain in the hospital for days to months post-transplant, depending on their individual needs. They may need continued transfusions to support the bone marrow until it is stable and produces enough cell types. If the patient shows signs of anemia, a transfusion of whole blood or packed red blood cells (RBCs) may be required. Platelet transfusions are indicated if the patient shows any signs of bleeding or to prevent bleeding (Ignatavicius et al., 2018; NMDP, n.d.-e).
Recipients have an increased risk of infection for months to years following a stem cell transplant. Each patient should receive discharge recommendations on decreasing their risk of infection. Nurses should ensure hand hygiene and other infection control methods are fully explained to patients and their families before discharge. A patient may be treated with medications such as prophylactic antibiotics to prevent infection and immunosuppressive drugs, which increase the risk of infection in the hospital and upon discharge. These patients will require frequent follow-up visits even after discharge (Ignatavicius et al., 2018; NMDP, n.d.-e).
A serious complication following an HCT is the risk of developing GVHD. Patients may be started on immunosuppressive medications such as cyclosporine (Neoral), tacrolimus (Prograf), methotrexate (Reditrex), corticosteroids, mycophenolate mofetil (Cellcept), or anti-thymocyte globulin (Atgam) to prevent this complication from occurring; however, these medications increase the risk of infection by suppressing the immune response. Patients are at the greatest risk for GVHD if they have had an allogeneic transplant, but GVHD is also possible in autologous transplantation if a strong immune response is initiated. In GVHD, the donor's T-cells recognize the recipient's cells or tissues as foreign antigens. Mild GVHD in an allogeneic recipient could be a positive sign if the transplant were for cancer treatment. This indicates that the transplant is working to destroy the malignant cells; statistically, cancer patients with mild GVHD have a decreased reoccurrence rate. Approximately 25% to 50% of all allogeneic transplant patients have some degree of GVHD, and about 15% will die from the complications. A mild presentation of GVHD indicates engraftment (Ignatavicius et al., 2018).
GVHD can be acute or chronic based on timing and clinical presentation. Acute GVHD usually appears within the first 3 months following the transplant; however, delayed-onset acute GVHD can occur after 3 months. The first symptoms of acute GVHD are mild dermatitis, liver dysfunction, and gastrointestinal disturbances. Chronic GVHD can happen months or years after transplantation, affecting multiple organs and causing severe damage. It occurs in 30% to 70% of recipients of an allogeneic transplant. Signs and symptoms of chronic GVHD include musculoskeletal pain; respiratory symptoms such as shortness of breath, dyspnea, and a cough; dry eyes; integument changes such as a rash and jaundice; or gastrointestinal symptoms such as xerostomia, mucositis, nausea, vomiting, and diarrhea (Khaddour et al., 2022; NMDP, n.d.-e; National Organization for Rare Disorders [NORD], 2021).
GVHD can be a severe and life-threatening complication and must be recognized and treated promptly to reduce morbidity and mortality. Treatment includes the use of steroids and additional immunosuppressive medications. If a patient is already taking immunosuppressive drugs, the dose may need to be increased, or classifications may need to be changed. HCPs will need to carefully monitor the extent of immunosuppression to avoid inducing infection or suppression to the point that the new cells cannot engraft. In 2017 the FDA approved ibrutinib (Imbruvica) to treat chronic GVHD in adults after the failure of one or more other therapies. In 2021 the FDA approved abatacept (Orencia) for the prevention of acute GVHD—the first drug approved for this indication (NMDP, n.d.-e; NORD, 2021).
Graft failure occurs when there is a loss of bone marrow or no improvement in function after an HCT. This often happens when cord blood is used or the donor is haploidentical due to the higher HLA disparity between the donor and recipient versus an autologous or matched donor sibling. The most common cause of graft failure is a recipient's immune system rejecting and attacking the donor cells. Other causes include a small number of cells received by the recipient, damage to the cells during the collection process or cryopreservation, inadequate preparation of the recipient, or an infection. To ensure proper engraftment and a successful transplant, the recipient should be checked for chimerism (cells in the blood from a different person). This is done by checking the expression of CD33 and CD3, which indicate the presence of granulocytes and T cells from the donor. If graft failure occurs, the patient will need to repeat the process and undergo another transplant with either the same donor or a different donor; if cord blood was used for the first HCT, the donation used would need to be changed to a different cord blood unit or an adult donor (Ignatavicius et al., 2018; Khaddour et al., 2022; NMDP, n.d.-e).
Organ Injury and Toxicity
Treatments used in conjunction with HCT may cause organ injury or toxicity. The lungs, liver, and bones are at the highest risk of damage. Organ injury and toxicity following HCT can include hepatic sinusoidal obstruction syndrome (SOS, also called veno-occlusive disease [VOD]), renal failure, and pulmonary toxicity. Pulmonary complications can occur in response to immunocompromise, raising an individual's risk of bacterial, fungal, and viral lung infections. Chronic kidney disease (CKD) can result from treatment with total body irradiation before transplant but may not present until 3 to 6 months after treatment. SOS/VOD occurs due to biliary obstruction from damage to the hepatic sinusoids caused by chemotherapy; symptoms usually appear within 6 weeks of HCT (Khaddour et al., 2022; Negrin, 2022; NMDP, n.d.-e).
Risks to Donors
Donors must be monitored closely during apheresis. The intravenous catheter used to harvest the cells can become clotted despite anticoagulant use. Since anticoagulants are used during apheresis, donors are at risk for hypocalcemia. They should be monitored for numbness and tingling in the feet or fingers, muscle spasms or cramps, muscle weakness, twitching, or seizures. HCPs may order calcium supplements if a donor develops symptoms of hypocalcemia. The apheresis process drops the donor’s intracellular fluid volume, which can cause hypotension. The donor's vital signs should be monitored at least every hour during the procedure, and they should be directed to change positions slowly to prevent lightheadedness or loss of consciousness (Ignatavicius et al., 2018).
When a donor has bone marrow extracted, they must also be monitored closely for complications. For this procedure, the donor is given anesthesia and must be monitored appropriately based on the type of anesthesia used. Nurses should follow standard postoperative monitoring and assess the donor's vital signs, airway and breathing, neurological function, dressings for signs of bleeding, and fluid volume status. Because the donor may have multiple aspiration sites from the procedure, pain at the sites must be managed with pharmaceutical and nonpharmaceutical methods. This includes administering analgesics and repositioning to offload pressure from the puncture sites. The donor should receive intravenous fluids before the harvest and during the postoperative period. Donors will likely be admitted and discharged on the day of the procedure; thus, nurses should educate the donor and their family on infection control, signs of complications, and post-donation restrictions. After the procedure, the donor may experience fatigue until their bone marrow recovers. Recovery will vary from donor to donor, but most are recovered in 2 to 3 days, with a return to full strength in 4 weeks (Ignatavicius et al., 2018).
As the recipient is recovering from their transplant, they must monitor and maintain their weight. Some patients may struggle with weight loss due to nausea related to chemotherapy and radiation treatments, while others may gain weight due to medication side effects or attempting to control nausea. There are concerns of potential foodborne illnesses from consuming raw fruit and vegetables, unshelled nuts, soft cheeses, deli meats, and raw honey. Patients should be encouraged to drink fluids and limit the sodium content of all foods and beverages. Patients should avoid alcohol until approved by their provider. They may be taking immunosuppressive medications, and the calcineurin inhibitors will interact with grapefruit and grapefruit juice, which should be avoided. HCPs will recommend a level of physical activity appropriate for the patient; exercise will help with weight control, keep the musculoskeletal system strong, encourage the healing process by increasing stamina and endurance, and promote cardiac health. Patients should be educated about reducing the risk of reoccurrence or developing secondary cancer. Nurses should explain the need for follow-up visits for continued transplant care and routine screenings for health maintenance and monitoring (Giaccone et al., 2020; Ignatavicius et al., 2018; Negrin, 2022).
Having a transplant can be emotionally challenging for patients and their families. The patient likely underwent extensive chemotherapy and radiation, with associated adverse effects, followed by the transplant and the risk of multiple complications, which can be emotional and energy-draining. Nurses should help patients maintain a positive attitude and hope through their medical journey, encouraging them to play an active role in their recovery. Patients who participate in their care plan may have fewer complications and an earlier discharge out of the hospital. Nurses should encourage patients to share their feelings, concerns, fears, and all questions as needed (Giaccone et al., 2020; Ignatavicius et al., 2018; Negrin, 2022).
Nurses must continue to help patients recognize their abilities and limitations and educate them on the importance of energy conservation. While a patient may feel better some days, expending too much energy can result in a setback. A nurse and their patient should discuss the patient's schedule, prioritize what is necessary to accomplish each day, and add only a few daily tasks as tolerated. The goal is to help the patient increase their endurance and reach the goal of discharging from the healthcare facility and returning to their pre-transplant routine. The nurse may need to complete referrals for home health care and home medical equipment as directed by the provider (Giaccone et al., 2020; Ignatavicius et al., 2018; Negrin, 2022).
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