The type of bone marrow donation determines the type of transplantation.

• Allogeneic Transplantation
  The person giving the bone marrow or stem cells is a genetically-matched family member, usually a brother or sister.
  
  

• Unrelated Allogeneic Transplantation  (MUD)
  The person donating marrow is unrelated to the patient. Chances of finding an unrelated compatible donor from the general population depends on the uniqueness of tissue type.
  
  

• Syngeneic Transplantation
  The person donating the bone marrow or stem cells is an identical twin.
  
  

• Autologous Transplantation
  The patient donates her/his own bone marrow or stem cells prior to treatment for re-infusion later.

When the patient is diagnosed to have leukemia, aplastic anemia, and some lymphomas, it becomes crucial to replace the unhealthy marrow with a healthy one. Allogeneic, unrelated, and syngeneic bone marrow transplantations (BMT's) are most commonly used in persons with those diseases. While in lymphomas and multiple myeloma, an autologous BMT is usually done.

This is a pictorial guide to the steps involved in undergoing autologous BMT. It is designed to give patients, their families, and their friends a better understanding of the steps involved in a BMT.


There are generally three steps in undergoing autologous BMT

1. Receiving chemotherapy to reduce any cancer cells in the body to a minimum

2. Collection and storage of bone marrow cells

3. Transplantation involving high doses of chemotherapy with or without radiation, re-infusing the stem cells and then, waiting for the bone marrow function to return

The specific stages are described below

1. Family members and friends
2. Chemotherapy
3. Graft collection/apheresis
4. Autologus bone marrow purification
5. Central line insertion
6. Preparative regimen
7. Transplantation
8. Recovery
9. Going home
10. Getting back to normal
11. Followup
12. Complications
13. Other complications

Family Members and Friends
It is recommended to bring a family member and/or friend to the initial consultation at the physician's clinic. Before the BMT procedure and during the inpatient hospitalization, it is not required to have a family member with the patient at all times. After the patient is discharged from the Medical Center, s/he will need to have someone stay with her/him 24 hours a day to assist with her/his care. If the patient receives an autologous BMT, a family member is required for approximately two to four weeks. If the patient undergoes an allogeneic BMT, a family member or care-giver is required for approximately 10 to 14 weeks. BMT requires a serious commitment from both the patient and the care-giver(s).
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Chemotherapy
The oncologist determines the dosage of chemotherapy needed by her/his patient. The type of chemotherapy varies from one disease to another and from one patient to another. In the autologus BMT setting, the more chemotherapy given before collecting bone marrow cells, the less disease burden there is likely to be. However, chemotherapy often damages the bone marrow normal cells, as well, and limits the collection of enough cells for transplantation. Therefore, the amount of chemotherapy given before transplantation should be maximum to achieve the least disease burden, and the minimum as not to cause damage to the bone marrow and to the collection; hence, the dose that can get cancer under control.
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Graft Collection/Apheresis
Blood cells of all types (red cells, white cells, and platelets) are generated in the bone marrow. In childhood, all the bones in the body contain active bone marrow. While getting older, the active bone marrow is confined to the central bones in the body: the spine, pelvis, ribs, skull, upper femurs, and upper humeri.

Bone Marrow Cells
The bone marrow harvest is done in the operating room, where the patient is given general anesthesia, and about one liter of bone marrow is collected. While harvesting the bone marrow, blood is removed with it. Blood loss causes some people to become anemic or low in hemoglobin. Blood transfusion is given to restore lost blood.

Or

Peripheral Stem Cells
An alternative procedure is the peripheral blood stem cell collection known, as well, as: stem cell collection, blood cell collection, blood stem cell collection, and peripheral blood progenitor cell collection. This procedure has two main advantages

1. Cells grow back faster after the transplantation.

2. It does not need general anesthesia like the bone marrow harvest.

Stem cells grow in the bone marrow and differentiate into red cells, white cells, and platelets. Stem cells also circulate in blood in small numbers. The number of stem cells circulating in blood can be increased by giving a growth factor like G-CSF (neupogen) or GM-CSF. Chemotherapy, as well, increases the number of stem cells circulating in blood. When a combination of chemotherapy and growth factor is given, a higher number of stem cells can be collected.

Stem cells circulating in blood are collected by a procedure known as "apheresis". The apheresis machine separates blood into different layers:  red cells,  white cells, stem cells,  platelets, and  plasma. The desired stem cells are collected in the middle layer. During collection, some patients might experience tingling in their fingers. This tingling is caused by the anti-coagulant used, and can be corrected by giving calcium. Other patients may feel tired the day following the collection.

The Donor

• The Patient
  When the patient's own bone marrow is collected (harvested) prior to chemotherapy and/or radiation and then re-infused during transplantation, this is called autologus BMT.
  
  
• Relative
  Unless the patient is having an autologous transplant, a bone marrow/stem cell donor must be identified to give the former new stem cells. Often, it is a brother, sister, or another family member. A sibling offers as much as a 25 percent chance of being a good match. Having an identical twin sets the patient up for a perfectly matched syngeneic transplant.
  
  
• Unrelated Donor
  When a related donor cannot be found, a search begins to locate a "Matched Unrelated Donor" (MUD). Two factors are important in locating a match. The first is a test known as HLA (Human Leukocyte Antigen) typing. A simple blood test is all it takes to begin the process of HLA typing. Most HLA typing, today, is performed using a DNA-based method which provides highly specific information used to match patients and donors. DNA testing allows patients and donors to be more closely matched. The goal is to find a match for six key antigens.

• lines that are totally embedded under the skin, for example "Portacath"

• lines that come out through the skin, for example the "Hickman Line"

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Preparative Regimen
Most patients are  admitted to the Medical Center for the entire transplantation procedure that is from three to four weeks. Recently, treatment is being given on an outside basis, and patients are admitted only when complications arise. 

Large doses of chemotherapy and/or radiation are required to eliminate the cancerous stem cells. These therapies not only destroy cancerous cells but can destroy normal cells found in the bone marrow. BMT allows physicians to treat lymphomas and other cancers with aggressive chemotherapy and/or radiation by allowing the replacement of the diseased or damaged bone marrow after chemotherapy/radiation treatment.

The preparative regimen is dependent on the type of cancer. It is a combination of medication and/or radiation.  Patients with cancers that respond well to radiation are given total body radiation (similar to X-Rays but in much greater amounts). Most patients tolerate the radiation. Some patients may develop nausea and mouth ulcers days after the completion of treatment. Generally, BMT regimens consist of six doses/fractions of radiation over three days. The lungs are shielded for one dose because they are more sensitive to radiation than the rest of the body. Radiation is mostly given with at least one chemotherapy drug. If not,  different drugs are then combined. The high-dose chemotherapy, which is given through a central line, may cause some nausea that is usually controlled with anti-nausea drugs.
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Transplantation
It is mandatory to wait for one or two days after the chemotherapy or radiation therapy has been given to allow  for the elimination of the medication from the body prior to transplantation. In the autologous BMT setting, the stem cells are rapidly thawed in a warm water bath. Then, they are immediately injected into the patient's body through the central line. If there is more than one bag to thaw, the second bag is thawed after the cells from the first bag have been given.

Re-infusion of stem cells is generally well tolerated by most patients. Some patients, however, develop DMSO preservative symptoms, such as  altered taste,  flushing, and  distinctive smell of  the breath. Rarely does the heart rate slow down or speed up. DMSO side effects are related to the amount and type of stem cells preserved. Side effects are more prominent with bone marrow cells than peripheral stem cells.

The stem cells are injected quickly within five to ten minutes. The infused stem cells go to the patient's bone marrow where they attach to the supporting cells there and start to grow.
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Recovery
Red cells, white cells, and platelets start to appear in the patient's blood after eight to twelve days post transplantation. Neutrophils, which are one type of white cells, are needed for fighting bacterial infections. As such, the return of neutrophils to their normal level is very crucial. Neutrophils have a normal count of 2 to 8 x 10⁹ /l . If the count, however, is above 0.5, the patient is unlikely to get infections. This is even less likely if it is above one. Neutrophils are usually the first cells to return, especially if a growth factor, like G-CSF, is given. Neutrophils are followed by  platelets. Platelets are fragments of cells living in the bone marrow and are important in stopping wound bleeding. Sometimes, the platelets may take a longer time to recover even though the neutrophils may have returned on time. Red cells usually start growing at this stage too, but because the formation of red cells takes up to 120 days, it is not uncommon for patients to need a blood transfusion after going home. When the white cell count is normal again, the body self-healing process begins. At this stage, the patient recovers from fever and antibiotic administration can be stopped. Patients who have had poor appetites start to improve, and they start eating and drinking by themselves.
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Going Home
Most people are more than both ready and scared to go home at this stage, as they got used to having the medical and nursing staff ready and available at all times. However, this resolves soon after the patient returns home. Patients are given a list of phone numbers to call in case they have a question or are feeling unwell.
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Getting Back To Normal
After  transplantation, most people feel tired, especially if they do any activity or try to concentrate, but they improve quite quickly over the first couple of weeks. It may take, however, three to six months and occasionally longer to feel as fit as before. The immune system quickly returns to normal after the transplantation. Patients are not at much risk of getting unusual infections but tend to get common coughs and colds more easily and take longer time to recover, especially in the first year after the transplantation.

The following vaccinations are recommended one year post transplantation to boost immunity towards normal:

1. Tetanus and diphtheria toxoid: two doses four months apart

2. Inactivated polio vaccine (im): once

3. Hepatitis B: three times at zero, two, and twelve months

4. Influenza: yearly

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Followup
Patients are required to come for followup visits where blood tests are performed to assess the patients' response to the graft. Patients are required to come for check up visits twice a week for one to two weeks post discharge from the Medical Center, then once a week for a couple of weeks, then every two weeks, then monthly during the first three months after transplantation. Patients are required to come for a general check up visit after the 100^th day of transplantation, where the patient's condition is evaluated to see if the disease is under control. It is recommended that patients see their oncologist for further followup to check for late complications, such as low thyroid function.
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Complications
Patients may experience a number of both temporary and relatively minor, as well as life threatening, complications after transplantation.

The common temporary minor complications include: hair loss or alopecia, nausea and vomiting, fatigue, loss of appetite, mouth sores (mucositis), and skin reactions. Gastrointestinal problems, high blood pressure, and in some cases, seizures and problems with vision are the side effects caused by the drugs given to prevent or treat the more severe complications of transplantation. The growth factors that were used for mobilization may also cause side effects, such as bone pain, muscle aches, and flu-like symptoms.

However, the most feared and greatest risk for post-transplantation patients is infection. In fact, for allogeneic BMT, during the first few weeks post transplantation, the patient is immuno-suppressed and is at high risk for viral, fungal, and bacterial infections. Cytomegalovirus (CMV) and Aspergillus fungal infections are among the most frequent causes of life-threatening infections.

CMV is a type of virus which may cause infections in healthy individuals but is dangerous to immune-suppressed patients. CMV is a member of the herpes family. This virus may manifest itself as pneumonia, colitis, or hepatitis. CMV infects half of the general population during their lifetime; most are unaware of having the virus. A simple test is performed before the BMT to determine whether or not CMV is present in the patient's body. If not, the patient is "CMV negative", and care is taken to prevent exposure to CMV. If  the patient was exposed in the past, then, s/he is "CMV positive", and CMV can reoccur when the patient is immuno-suppressed. The symptoms of CMV can be mild or may become life-threatening if the virus invades the blood, lungs, liver, or other organs. Anti-viral medications are given to help prevent and treat this viral infection.

Aspergillus is a fungus that is found in soil. It is rarely identified in the general population and is most commonly diagnosed in immune-compromised patients. Aspergillosis occurs when the organisms (spores) become airborne and invade the lungs and sinus. Aspergillus grows and destroys tissue. The fungus can also invade the bloodstream and move into the brain and kidneys. Symptoms include fever, chills, coughing, chest pain, difficulty in breathing, fever, night sweats, and sinus pain. Symptoms provide the strongest clues for diagnosis. The incubation period is unknown, but it can take days for the fungus to grow and symptoms to appear. Despite the use of antifungal drugs, like amphotericin B, fungal infections  caused a high rate of illness and deaths.

Mucositis is an inflammation of the gastrointestinal tract. Epithelial cells have a high turnover rate and are damaged by the high-dose therapy and reduction of white cells. It manifests as burn-like or ulcerative lesions. Mucositis usually appears within five to seven days after a patient undergoes high-dose chemotherapy or radiation therapy. The best treatment is meticulous oral hygiene to reduce potential for infection and pain medication as needed. Mucositis usually disappears in two to four weeks.

Herpes zoster is a viral infection that produces painful skin eruptions of fluid-filled blisters. This is caused by the varicella-zoster virus that causes chickenpox. The virus enters the cell bodies of the spinal and cranial nerves. Reactivation may occur in patients with suppressed immune systems.
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Other Complications
In the first few weeks of transplantation when the platelet count is low, nosebleeds, bleeding gums, and more serious bleeding, are frequent. The bleeding is treated by platelet transfusions until the patient's own cells can support their needs.

Graft-Versus-Host Disease (GVHD) is exclusive to allogeneic transplantation recipients and is the reaction of the donor marrow against the tissue of the patient. When the donor’s lymphocytes recognize the patient’s body as foreign material, even though the white blood cell types are the same, they attack and destroy the patient’s tissues. GVHD primarily affects the skin, liver, and gastrointestinal tract. Symptoms range from mild to severe where GVHD can be fatal. The most common symptoms are skin rashes, jaundice, liver disease, and diarrhea. To reduce the chances that GVHD  occurs, patients routinely receive a prophylaxis by cyclosporin and methotrexate.

Liver disease  occurs in the few months following a BMT. Possible causes include: toxic effects of drugs and radiation, obstructed veins in the liver (veno-occlusive disease), viral hepatitis, fungal infections, and GVHD.
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