Bone Marrow Transplants and HLA Typing Nursing CE Course

der will order multiple diagnostic tests to characterize the individual candidate's health and confirm the medical diagnosis. The provider must ensure the potential candidate is physically capable of undergoing the transplant. If the patient is determined to be a candidate for transplant, the patient will have a central line inserted to prepare for the infusion of the cells as well as medications and blood products (NCI, 2013).

Becoming a donor

There is a significant need for community members to become donors as many transplants come from unrelated individuals whose generous donation has saved lives. The National Marrow Donor Program (NMDP) is a nonprofit organization that operates the most extensive registry, managing over eleven million donors and cord blood units. They are responsible for the Be the Match campaign, which assists patients with finding matching donors. Many people worry about the cost of donating bone marrow, stem cells, or cord blood, but the 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 for the time they are off work to donate. If a pregnant woman wants to donate her baby’s cord blood to a public cord blood bank, this is done free of charge. If the mother wishes to store the cord blood at a commercial blood bank for future use by herself or potential family members, there is a charge for this (NCI, 2013). Cord blood is harvested at birth from the umbilical cord, which contains large numbers of 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 to be used in the future (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b; NCI, 2013).

Becoming a donor is a personal and individual choice, but the nurse should direct those persons who are interested in the Be the Match website for information, resources, and contact information if they have questions. Donors must be between the ages of 18 and 44 and willing to donate for any patient that is in need. There are health guidelines that need to be met, which are available to review on the site. Potential donors need to recognize the health requirements are in place to protect future recipients as well as potential donors. Anyone meeting the criteria can join Be the Match on their website or by other contact methods. The following information is an outline of the health requirements for BMT donation, but the complete list can be found on the website (Be the Match, 2019b).

• Age-most donors should be between the ages of 18 and 44 as this age group produces more high-quality cells than older donors. Be the Match does take persons between the ages of 18 and 60. Studies have shown that receiving donor cells from younger donors increases the chances of long-term survival. The donor must be at least 18, so they can sign their consent form.
• AIDS/HIV-if individuals have tested positive for HIV or have been diagnosed with AIDS; they will not be able to donate.
• Allergies-individuals with severe allergies to latex and other medications will need to consult with staff.
• Arthritis-mild to moderate osteoarthritis would not prevent you from becoming a donor; however, having a more severe form of arthritis such as rheumatoid arthritis would prevent the person from becoming a donor.
• Asthma-the regular use of corticosteroids will disqualify a potential donor.
• Autoimmune disorders- autoimmune diseases that affect the entire body, such as systemic lupus erythematosus, will disqualify a potential donor. Autoimmune conditions that are limited to one organ system, such as celiac disease in the gastrointestinal tract, are not disqualifying.
• Bleeding disorders-having a severe bleeding disorder such as hemophilia or a clotting disorder that requires the use of anticoagulants would make a person ineligible to become a donor.
• Head/brain injury or surgery-these disorders, if significant, would be a deterrent to becoming a donor as well as if the person has had six or more concussions in their life.
• Cancer-patients who have had a precancerous condition, very localized and well-contained cancer such as cervical carcinoma in situ, or cancer that was diagnosed and treated more than five years ago can register to become a donor. Patients who have had cancer of the hematology system cannot register to be a donor, nor can someone who has had chemotherapy or radiation in the past.
• Chemical dependency and mental health concerns- persons who have had chemical dependency but have been sober for at least one year and have no other health issues may register for donation. Persons who have a mental health condition that is well treated and controlled can become donors, but persons with severe mental health diseases such as schizophrenia may not become donors.
• Diabetes mellitus-this disorder will require an evaluation and a decision made based on the individual health of the person and the control of the disease.
• Heart disease/cerebrovascular disease and hypertension-a donor with controlled hypertension can become a donor provided that they do not have a history of heart or cerebrovascular disease in addition to their hypertension. Persons with cardiac or cerebrovascular disease will not be eligible to donate except for some cardiac conditions that could be evaluated for a potential donor.
• Hepatitis and liver disease- patients with a history of hepatitis B or C or severe liver disease are not able to donate. Patients with hepatitis A that meet specific parameters may be eligible.
• Kidney disease-persons with kidney disease are not able to become donors.
• Organ, tissue, marrow, or stem cell transplant recipient- patients that have received a human organ, bone marrow, or blood-forming cells or live tissue from animals known as a xenotransplant are not able to donate.
• Weight- patients that are significantly under or overweight would be denied (Be the Match, 2019b).

After meeting the health criteria listed and joining the registry, the donor’s tissue type is recorded with a cheek (buccal) swab. They do not donate until they appear to be a match for a potential recipient, and then they would need to have additional testing completed if contacted to donate (Be the Match, 2019b).

Medical testing for transplants

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 is recognized by the immune system as being self or an inherent part of the patient. As human conception occurs, the new fetus will inherit HLA genes, and these genes will determine the HLAs that are present. The HLA genes are in a portion of chromosome 6, known as the major histocompatibility complex (MHC). This system helps determine what cells belong to the patient and what cells might be foreign invaders.  When the immune system encounters cells that do not display a specific HLA, the immune system will respond by destroying what would be an antigen. The immune system cells would 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], 2019; Ignatavicius et al., 2018).

HLA typing also referred to as tissue typing, histocompatibility testing, and HLA crossmatching is done to confirm compatibility. Histocompatibility describes the similarity between the HLAs from the transplant recipient and the potential donor. It is essential that the donor and recipient HLAs match closely, as this would indicate a higher probability of a successful transplant. Each type of transplant, whether it is bone marrow or solid organ, has particular requirements for HLA matching. A patient who is having a BMT requires an almost perfect match with the donor.  Blood is collected from the potential donor and recipient; medical 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). The results will list how many antigens match and how many mismatches are present. The desired outcome would be to have zero mismatches and zero HLA antibodies in relation to the potential donor. (AACC, 2019; Be the Match, 2019a).

These tests are performed on a blood sample and sometimes a buccal swab. It is often difficult to find a match for the patient. HLA genes have many possible forms or alleles, which are known as polymorphic. Within the HLA gene family on chromosome 6, there can be as many as 200 different genes. These factors contribute to numerous possibilities, making it difficult to find a match for each patient. When a child is conceived, it will inherit one haplotype from each parent (HLA genes in a group). This process can translate to family members having the same group of HLA alleles, which would make familial transplant donation a better option (AACC, 2019; Be the Match, 2019a).

Each medical facility that does transplants will have their own protocol for HLA typing regarding the minimum number of acceptable matches. Most labs report in either an eight- or ten-point HLA match, but frequently it is the provider who determines the level of matched HLAs they want. Be the Match requires that at least a six out of eight HLAs match for their specific donors and patients. There is also something known as a haploidentical transplant, which indicates that five out of ten HLAs match. These donors are most likely the patient's parent or child. When HLA typing cord blood, most providers/facilities require four out of six HLAs to match (AACC, 2019; Be the Match, 2019a).

Many components are considered after reviewing all the test results, especially the HLA matching. Minimizing potential side effects for the patient is critical, and finding as close of a match as possible is the desired outcome. Closely matched HLA is crucial in the prevention of the serious complication of GVHD. Having a transplant from a sibling usually produces a good match, but only about 25-35% of patients will have a sibling that is a desirable match. Because there is an increasing number of donors and better screening options currently, the chance of finding an acceptable unrelated donor is about 50%. The potential donor and recipient need to be of the same ethnic and racial background if possible, as this will also increase the probability of matching.  An area that still needs improvement is the number of available donors, as some ethnic and racial groups still lack adequate donors. The best possible match would be from an identical twin, which is inherently rare, but the risk of GVHD and other types of rejection are minimal with a perfect genetic match (NCI, 2013; Be the Match, 2019a).

Harvesting and Transplanting of Marrow or Cells

Once a suitable donor has been established, the harvesting or collection of the transplant source will be initiated. The procedure is varied with each type of donation. When patients are preparing for a PBSCT, it is a three-step process: mobilization, apheresis (the collection phase), and reinfusion. Transplant facilities will admit the recipient for the conditioning process four to seven days before the transplant, but this varies for each patient. During conditioning, chemotherapy or radiation is used to prepare the bone marrow to receive the transplant. These days are considered minus days until the patient reaches the transplant, which is considered day 0. Each subsequent day is termed day 1, day 2, etc. until the patient is discharged. From day 0 to about day 14, the patient will require close medical and nursing care. On day 14, the engraftment should occur, which still requires the patient to have close medical and nursing care. The discharge date will vary from patient to patient (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b; NCI, 2013).

• If the transplant is autologous, the donor will need injections of growth factor or chemotherapeutic agent(s) to increase their stem cell production. Not only do the growth factor injections help the patient produce more stem cells, but they also hasten to move them into circulation quicker. This phase of harvesting that utilizes doses of growth factor or chemotherapy is known as mobilization. Patients that have hematologic cancer may be given a medication plerixafor (Mozobil) to help with the cancer cells in addition to growth factors. This medication limits the number of apheresis collections the patient will need to undergo. When there are adequate cells available in circulation, the patient will prepare for apheresis. Autologous transplants do not carry incompatibility risks as other types of transplants do; however, the body has to have the ability to produce enough cells to harvest.
• (Ignatavicius et al., 2018; Mayo Clinic, 2019b, 2019c; NCI, 2013).
• The procedure for collection is known as apheresis. For any transplant involving the harvest of stem cells, it will take approximately one to five procedures to obtain enough cells. Each of the apheresis attempts takes two to four hours to complete unless plerixafor (Mozobil) is used. The blood will be circulated through a machine that will separate various components of the blood. The stem cells are removed, frozen, and used in the future during the reinfusion phase. The remainder of the blood is reinfused to circulation. If the patient is doing an autologous BMT, the bone marrow is treated for any remaining cancer and is frozen for later (Ignatavicius et al., 2018; Mayo Clinic, 2019b, 2019c; NCI, 2013).
• After apheresis is complete, some patients will need to undergo additional conditioning with high doses of 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 it 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 many other potential adverse effects. Depending on the patient and their condition, they may need to have what is known as reduced-intensity conditioning, which lessens the doses administered. Even though the immune system is not entirely suppressed, the new cells will fight cancer. Once the conditioning process is complete, the patient will receive an infusion of stem cells directly into the circulatory system, or reinfusion. The stem cells migrate to the bone marrow and start to produce new stem cells. Patients will require close medical care following the transplant (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b, 2019c; NCI, 2013).
• Patients who will be having an allogeneic transplant will be receiving cells or marrow from a donor. The provider and transplant team will decide based on multiple factors to use stem cells or actual bone marrow from the donor. If the stem cells are to be used, the process would be similar to autologous donation, except the stem cells are coming from a donor. During allogeneic BMT, the donor is taken to an operating room; the surgeon will aspirate 500 to 1000 ml of bone marrow through a large-bore needle from multiple aspirations sites such as the iliac crest or other long bones. This type of donation is done less often now due to the advances in PBSCT and cord blood transplants. The donated marrow is then filtered, prepared, and transplanted into the recipient. The donor will regenerate their own marrow within a few weeks after donation. The patient could also receive an allogeneic transplant using cord blood (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019c; NCI, 2013).
• Some patients receiving an allogeneic transplant will need to undergo the same conditioning process described above. When conditioning is complete, the patient will receive an infusion of stem cells directly into the circulatory system. The stem cells will migrate to the bone marrow and start to produce new stem cells. Patients will require close medical care following the transfusion or BMT (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019c; NCI, 2013).
• 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 can still produce harmful side effects. These recipients are still at risk for infection and other complications (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019c; NCI, 2013).

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, which is known as engraftment. The process of engraftment can take several weeks or longer and varies from patient to patient. Even though engraftment takes place, immune system recovery will take longer. If the patient had an autologous transplant, recovery takes several months; for syngeneic and allogeneic patients, it takes anywhere from one to two years. The patient may experience a variety of symptoms during this period and needs to have close medical attention to monitor vital signs and diagnostic studies. The nurse and provider will evaluate the recipient for any side effects and manage those accordingly. Throughout recovery, complete blood counts and bone marrow biopsies will be monitored to evaluate the effectiveness of the transplant (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b, 2019c; NCI, 2013).

The Risk to the Donor

If the patient undergoes the apheresis process, the nurse or other personnel should monitor the donor during the procedure. The catheter that is inserted into the vein to harvest the cells can become clotted despite the use of anticoagulants. Because anticoagulants are used during apheresis, the donor is at risk for hypocalcemia and should be monitored for signs and symptoms of hypocalcemia such as numbness and tingling in the feet or fingers, muscle spasms or cramps, muscle weakness, twitching or symptoms as severe as having a seizure. The provider may order calcium supplements if the donor does experience any symptoms or positive lab findings. The apheresis process requires a change in fluid volume that has the potential to cause hypotension, so the donor's vital signs should be monitored at least every hour during the procedure (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b; NCI, 2013).

When a donor has had bone marrow extracted, the nurse will want to monitor for potential fluid loss. The donor has likely had some anesthesia and will need to be monitored appropriately based on the type of anesthesia that was used. Because the donor may have multiple aspiration sites from the procedure, pain at the sites will need to be managed with both pharmaceutical and nonpharmaceutical methods. Nursing will assess the donor with standard postoperative monitoring: vital signs, airway/breathing, neurological function, dressings for signs of bleeding, and fluid volume status. The donor should receive intravenous fluids before the harvest and in the postoperative period. Donors will likely be admitted and discharged on the day of the procedure; thus, nursing should educate the patient/family regarding signs of excess bleeding or infection at the harvest sites (Ignatavicius et al., 2018; Mayo Clinic, 2019b, 2019c; NCI, 2013).

Donors may also experience fatigue related to the decreased number of cells available for their use until their bone marrow recovers and is fully functioning. Recovery will vary donor to donor, but most are recovered in two to three days. It can take up to four weeks for a full return of strength (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b; NCI, 2013).

Potential Transplant Complications and Nursing Roles

There are multiple risks for the patient having a BMT, which are dependent on the disease that prompted the transplant, age, overall health, and the transplant process. Many disorders or complications can occur, including but not limited to GVHD, failure of the graft, potential damage to other internal organs, post-transplant infection, reproductive concerns, potential development of new cancers, and death. 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 producing enough cell types. If the patient is showing signs of anemia, the patient may require a transfusion of whole blood or packed red blood cells. Transfusion of platelets is indicated if the patient is showing any signs of bleeding or for prevention of bleeding (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b, 2019c; NCI, 2013).

There is an increased risk of infection for months or years following a stem cell transplant. The patient should receive discharge recommendations regarding decreasing the risk of infection. The patient may be treated in the hospital as well as upon discharge with medications such as antibiotics attempting to prevent infection or immunosuppressive medications, which increase the risk of infection even further. The patient will require frequent follow-up visits even after discharge. The nurse should ensure that hand hygiene and other infection control education is fully explained to the patient and family prior to discharge (Ignatavicius et al., 2018; Mayo Clinic, 2019c; NCI, 2013).

A serious concern for patients who have had a BMT is the risk of developing GVHD. Patients may be started on immunosuppressive medications to try and prevent this disorder. However, as previously mentioned, being on these medications increases the risk of infection by suppressing the immune response. The patient is at greatest risk for GVHD if they have had an allogeneic transplant, but it is also possible in autologous transplantation if a strong immune response is initiated. In GVHD, the donor's lymphocytes start to attack the recipient's cells or tissues that appear to be foreign. Mild GVHD in an allogeneic recipient could be a positive sign if the transplant was for cancer treatment. This indicates the transplant is working to destroy the malignant cells, and statistically, cancer patients with mild GVHD have a decreased rate of re-occurrence. Approximately 25-50% of all allogeneic transplant patients have some degree of GVHD, while about 15% will die from the complications. It is important to note that a mild presentation of GVHD indicates engraftment (Ignatavicius et al., 2018; Mayo Clinic, 2019c; NCI, 2013).

GVHD can be acute or chronic; the acute type will develop within the first two months or up to the first 100 days after transplant. Chronic GVHD can happen months or years later and affect multiple organs causing significant damage. The organs that are frequently impacted include the skin, liver, and intestinal tract.  Signs and symptoms of chronic GVHD include musculoskeletal pain, respiratory symptoms such as shortness of breath, dyspnea, and cough; dry eyes; integument changes including rash and jaundice; or gastrointestinal symptoms such as xerostomia, mucositis, nausea, vomiting, and diarrhea. GVHD can be a severe complication and must be recognized and treated promptly. Treatment includes the use of steroids and additional immunosuppressive medications. If the patient is already taking immunosuppressive drugs, the doses may need to be increased, or classifications changed. The provider will need to monitor the level of immunosuppression carefully to avoid inducing infection or suppression to the point that the new cells cannot engraft (Ignatavicius et al., 2018; Mayo Clinic, 2019c; NCI, 2013).

The failure to graft is also a concern for transplant patients as the cells that were transplanted have not started to grow or carry out normal functions. Patients should be counseled before the transplant that this is a possibility. Some of the causes of failure to engraft include possible attack or rejection by the immune system, insufficient healthy cells being transplanted, possible infection of the cells, and other factors with unknown etiologies. The patient will need another transplant as soon as possible, or they may die (Ignatavicius et al., 2018; NCI, 2013).

As the patient is recovering from the transplant, it is essential for the patient to monitor and try to maintain their weight without gaining excessive weight. Some patients may struggle with weight loss due to nausea related to chemotherapy and radiation treatments, while others may gain weight due to medications or attempting to control nausea. There are concerns with potential infection from certain foods such as fresh fruit and vegetables, at least for a while. The patient is encouraged to drink appropriate fluids but to limit the sodium content of all foods and beverages. The patient should avoid alcohol until approved by their provider. The patient may be taking immunosuppressive medications, and the calcineurin inhibitors will interact with grapefruit and grapefruit juice, which should be avoided. As the provider feels it is safe, they will recommend a level of physical activity appropriate to the patient. Not only will the exercise help with weight control, but it will also keep the musculoskeletal system strong, help the healing process by increasing stamina and endurance, and promote cardiac health. The patient should be educated about ways to reduce the risk of acquiring other forms of cancer or reoccurrence. The nurse will also want to explain the need for follow-up visits with their provider for continued transplant care as well as routine screenings they will need for health maintenance (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b).

Having a transplant can be emotionally challenging for the patient and their family. The patient likely underwent extensive chemotherapy and radiation, with associated adverse effects, followed by the transplant and the risk of multiple complications. All of this can be emotional and energy-draining. The nurse wants to help the patient maintain a positive attitude and hope through this challenging time. It is vital for nursing and all staff to encourage the patient to play an active role in their recovery. Patients who are a part of the care plan may have fewer complications and earlier discharges. The nurse should encourage the patient to share their feelings, concerns, fears, and all questions they might have (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b; NCI, 2013).

The nurse must continue to help the patient to recognize their abilities and limitations; educate the patient on the importance of conserving their energy. While the patient may feel better some days, expending too much energy can result in a setback. The nurse and patient should discuss the patient's schedule, prioritize what is necessary to accomplish each day, and add only a few things per day as the patient can tolerate. The goal is to help the patient increase their endurance, reaching for the goal of discharge and return to their routine. The nurse may need to complete referrals for home healthcare if needed by the patient and directed by the provider (Ignatavicius et al., 2018; Mayo Clinic, 2019a, 2019b; NCI, 2013).

Research

There are several types of transplants that are currently being studied in clinical trials. A mini-transplant, non-myeloablative, or reduced-intensity transplant is considered allogeneic and currently being studied for certain types of hematology cancers. Clinical trials are using lower doses of chemotherapy and or radiation before transplant, which could reduce the number of adverse complications. While using lower doses does not destroy all the bone marrow, it also does not kill all the cancer cells. This may prove to be a benefit it certain types of patients (NCI, 2013).

Another example is an autologous transplant called a tandem transplant. It is also indicated in the use of hematology cancers and involves administering two courses of high-dose chemotherapy followed by HSCT. These procedures are done twice over several weeks to several months, hoping to prevent reoccurring cancers, particularly multiple myeloma and germ cell cancer (NCI, 2013).

Tandem transplants have also been used in pediatric clients diagnosed with neuroblastoma. Past treatment involved autologous transplants after intensive treatment with chemotherapy. After the chemotherapy, the child would undergo an autologous stem cell transplant to rebuild bone marrow. This type of treatment did improve outcomes with an increase in the five-year survival rate from approximately 25% in the 1990s to a little less than 50% in the early 2000s. While that was notable progress, there was room to improve that outcome. In a more recent trial, patients were split into two groups. One group received the traditional treatment, and another group received the tandem transplant, which consisted of chemotherapy followed by the HSCT and then the second round of chemotherapy and another transplant. The second transplant is considered the tandem transplant. Follow-up that was done three years after the treatment illustrated that 48% of the participants that had the traditional treatment were still alive and cancer-free compared to 61% of the second group who had the tandem transplant. The tandem transplant procedure is now the standard of treatment for pediatric patients with high-risk neuroblastoma. Studies continue in this area because while there is an improvement in survival rates, the complications of intensive chemotherapy remain a concern. Clinical trials are ongoing to establish chemotherapy agents that are less abrasive or other treatment options. Several areas that are being researched to achieve this goal are molecular biology and immune research (NCI, 2017).

One of the most serious complications of transplants remains GVHD. A medication known as ibrutinib (Imbruvica) was approved by the Food and Drug Administration (FDA) in 2017. This medication was previously used in the treatment of lymphoma and leukemia but is now approved to treat chronic GVHD that is not responding to traditional treatment. As discussed previously, a large percentage of patients who undergo transplants will develop some degree of GVHD, but many respond to traditional treatment. In the study that led to the drug’s FDA approval, most of the patients had some type of leukemia, and 90% of the patients had at least two organs affected. The medication helped 67% of the patients in the trial: 21% achieved a full response, 45% had a partial response, and at least 48% maintained a positive response for at least 20 weeks. While the improvement was enough evidence to gain FDA approval, research continues to find other options for those patients who have chronic refractory GVHD (Voelker, 2017).

                                                                                          References

American Association for Clinical Chemistry (2019). HLA testing. Retrieved from https://labtestsonline.org/tests/hla-testing

Be the Match (2019a). How donors and patients are matched. Retrieved from https://bethematch.org/transplant-basics/matching-patients-with-donors/how-donors-and-patients-are-matched/

Be the Match (2019b). Medical guidelines-Who can Join? Retrieved from https://bethematch.org/support-the-cause/donate-bone-marrow/join-the-marrow-registry/medical-guidelines/

Grossman, S., & Porth, C. (2014). Porth’s pathophysiology concepts of altered health states (9^th ed.). Philadelphia, PA: Wolters Kluwer Lippincott Williams & Wilkins.

Ignatavicius, D., Workman, M., & Rebar, C. (2018). Medical-surgical nursing concepts for interprofessional collaborative care (9^th ed.). St. Louis, MO: Elsevier.

Mayo Clinic (2019a). Allogeneic stem cell transplant. Retrieved from https://www.mayoclinic.org/test-procedures/allogeneic-stem-cell-transplants/

Mayo Clinic (2019b). Autologous stem cell transplant. Retrieved from https://www.mayoclinic.org/test-procedures/autologous-stem-cell-transplants/

Mayo Clinic (2019c). Bone marrow transplant. Retrieved from https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/about/pac-20384854

The National Cancer Institute (2013). Blood-forming stem cell transplants. Retrieved from https://www.cancer.gov/about-cancer/treatment/types/stem-cell-transplant/stem-cell-fact-sheet

The National Cancer Institute (2017). Using tandem transplants to treat neuroblastoma. Retrieved from https://www.cancer.gov/research/areas/childhood/julie-park-tandem-transplants-treat-neuroblastoma

Voelker, R. (2017).  Relief for graft-vs-host disease. JAMA, 318(11), 996. doi: 10.1001/jama.2017.12982