Allogeneic Bone Marrow & Stem Cell Transplantation

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What is a stem cell?

Stem cells are immature, blood-forming cells that are found mostly in your bone marrow. Bone marrow is the soft, spongy tissue inside your bones where blood cells are produced. Stem cells rapidly divide and multiply in the bone marrow and eventually produce into mature red blood cells, white blood cells, and platelets. When these mature cells enter your bloodstream, some stem cells may get into the bloodstream as well. These stem cells in the bloodstream are called peripheral blood stem cells.

Stem Cells developing into Red blood cell, white blood cell, and platelets

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  • Red blood cells carry oxygen from the lungs to all parts of your body and remove carbon dioxide. When your body does not make enough red blood cells, it is known as anemia. Symptoms of anemia include weakness, fatigue, shortness of breath and headache, which occur because your organs are not getting enough oxygen.
  • White blood cells fight infections and dangerous substances that invade the body. A low white blood cell count could weaken your body's immune system and its ability to fight disease and infection.
  • Platelets help stop bleeding and form a clot on a wound. If your platelet count is low, you may experience easy bruising or bleeding, which can sometimes be severe or life-threatening.

What is a stem-cell transplantation? Why is it performed?

Normal blood cells versus abnormal, immature blood cells

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Certain types of cancer and cancer treatments can destroy your bone marrow and deplete your blood cells. Leukemia, lymphoma, and multiple myeloma can cause your bone marrow to be taken over by a large number of defective and immature blood cells that can interfere with or even shut down normal blood cell production. Doctors perform stem-cell transplantations in these cases to restore your blood cell counts to optimal levels. In treating other types of cancer, doctors often need to give high doses of chemotherapy (and sometimes radiation) to destroy the malignant cells. These treatments can destroy healthy cells and bone marrow as well as malignant cancer cells, because they target all rapidly dividing cells in the blood. Stem-cell transplantation replenishes stem-cells that are destroyed by these treatments, allowing patients to receive high doses of chemotherapy and radiation to treat their cancer.

What are the different types of stem-cell transplantation?

There are two main types of stem-cell transplantation, depending on where the stem cells come from:

Patients who undergo autologous transplants have a lower risk of infection because their immune system tends to recover more rapidly when receiving their own stem cells. Autologous transplants may carry some (usually quite low) risk of graft rejection (i.e. the patient’s own stem cells fail to “take”). They carry no risk of GVHD. However, for certain types of cancer, autologous transplants may lead to a higher risk of recurrence if there are any contaminating cancer cells in the stem-cell harvest. An advantage of allogeneic transplants is that stem-cells and immune cells from another donor's immune system may actually be able to fight off the cancer cells better than your own. This document focuses mainly on allogeneic transplants.

What is HLA Typing?

H.L.A. typing

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HLA typing is the method doctors use to identify a good donor match for allogeneic transplants. HLA, or human leukocyte antigens, is a complex of proteins located on the surface of cells in your body that recognizes foreign cells and tells your immune system to attack them. It is very important to find a donor whose HLA antigens match yours as closely as possible. If you find a good match, your transplant will be more likely to settle in your bone marrow (engraftment) and begin forming new blood cells. If your HLA antigens do not match your donor's well enough, you are also more likely to develop graft-versus-host disease (GVHD), in which the transplanted cells see your body as foreign and attack it. For every full sibling (i.e. same father and mother), there is about a 25% chance of having a sibling whose HLA proteins perfectly match yours because you inherit half of your HLA antigens from each parent. If you don't have a sibling with an HLA match, your doctor will look for a suitable match from a national or international registry of volunteer donors. If a good (i.e. “complete”) match is not found among family members (usually siblings) or a registry, transplant doctors may sometimes suggest the use of cord blood units (i.e. blood obtained from the placenta after the delivery of a baby) or family donors who are not complete matches (i.e. “mismatched” or “haploidentical” donors, usually parents or son/daughter). In these latter cases (often referred to as "alternative donor transplants"), however, the allogeneic transplantation tends to be riskier and can lead to more serious and possibly life-threatening complications. The risk of graft rejection (i.e. the donor's own stem cells failing to "take") is usually higher. You should carefully discuss these options with your transplant doctor.

What is GVHD?

Graft-versus-host-disease (GVHD) is a condition in which the transplanted stem cells and immune cells see your body as foreign and attack it. There are two types of GVHD: acute and chronic. Acute GVHD may occur within weeks (usually during the first 100 days) after your transplant once the new stem and immune cells (called lymphocytes) have engrafted in your bone marrow. Chronic GVHD may occur many months or even years after your transplant. The symptoms of GVHD depend on the specific organ affected. Acute GVHD may cause a skin rash (i.e. like sunburn), jaundice, liver impairment, nausea, vomiting, diarrhea, abdominal pain. Chronic GVHD can cause skin tightening, shortness of breath, wheezing, joint and muscle pain and contractures, dryness of skin, mouth and eyes, recurrent infections. Both acute and chronic GVHD can vary from very mild to severe or even life-threatening.

What is GVC?

Graft-versus-cancer effect

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The graft-versus-cancer effect is a condition in which the transplanted cells actually fight off cancer cells, often better than the patient's own immune system. Graft-versus-cancer is one advantage of allogeneic transplants. Not only does the stem cell transplant allow the patient to tolerate high-doses of chemotherapy and radiation, but the cells in the transplant itself can attack and destroy cancer cells.

What is a non-myeloblative transplant?

A non-myeloblative or reduced-intensity transplant, sometimes also referred to as a "mini-transplant," is a less aggressive form of stem-cell/bone marrow transplantation in which your doctor uses lower doses of chemotherapy and/or radiation in the conditioning phase. These low doses suppress the immune system enough to allow the new stem cells to engraft, but don't actually kill many cancer cells. In non-myeloblative transplants, doctors rely mainly on the graft-versus-cancer effect as the primary cancer-fighting treatment. These type of transplant are particularly suited for older patients and patients with medical conditions. There are many different types of non-myeloblative or “mini” transplants nowadays, and you should discuss with your transplant doctor what the best option for your case is.

Allogeneic Transplant Procedure

Allogeneic transplant procedure

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  1. Collection: Your doctor (or, in the case of a volunteer donor from a registry, a doctor at a different hospital), will remove stem cells from a donor’s blood or bone marrow.
  2. Processing: Your doctor may send the stem cells to a lab to be checked. The lab may perform special maneuvers to change the cell composition.
  3. Preservation: The stem cells will be frozen (or, in the case of a volunteer donor from the registry, stored at a cool temperature then shipped through a courier) and preserved for after your chemotherapy and/or radiation treatments.
  4. Chemotherapy/Radiation: Your doctor will administer high doses of chemotherapy and/or radiation. Radiation is much less commonly used nowadays.
  5. Reinfusion: The donor’s stem cells will be thawed (if previously frozen) and reinfused into your bloodstream intravenously. These cells will settle in your bone marrow and help you produce healthy blood cells.

Collection from Bone Marrow

Collection from Bone Marrow

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  • A doctor will use a large needle to aspirate ("harvest") bone marrow from the donor's hip bones.
  • A doctor will perform this procedure in a hospital and under general or spinal anesthesia. The donor may be able to leave within a few hours after surgery, or may need to stay overnight.
  • The donor may experience soreness or bruising in the lower back or hip for a few days after the procedure. He or she may also feel tired or weak due to a loss of blood cells.

Collection from Blood

Collection from Blood

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  • A doctor will give your donor subcutaneous shots of a growth-factor drug that causes their bone marrow to make excess stem cells and release them into the bloodstream.
  • The donor's blood will go through an apheresis machine from a catheter placed into a vein (usually in the arm). Sometimes a catheter (i.e. a sterile flexible plastic tube placed into a vein) may be necessary. The apheresis machine will separate the stem cells from other blood cells, which are then reinfused intravenously back into the donor.
  • Apheresis is usually an outpatient (i.e. not requiring hospitalization) procedure that takes about three to four hours. The donor's doctor may need to perform this procedure for a few days in a row in order to collect enough stem cells.

Processing Stem Cells

Processing stem cells
  • After collecting your donor's stem cells, your doctor may send them to a lab to be checked. The lab may perform special maneuvers to change the cell composition.
  • If the stem cells were taken from the donor’s bone marrow, they will be filtered through very fine screens in order to make sure there are no tiny bone or fat particles in the product.

Preservation of Stem Cells

Cryopreservation of stem cells

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  • Your donor's bone marrow or peripheral blood stem cells will be frozen and saved for when you complete chemotherapy and/or radiation. Once frozen, they will last for many months or even several years. They may also be infused fresh (particularly bone marrow).
  • When the donor’s stem cells are infused, patients may occasionally experience side effects due to the preservatives used when freezing and storing the cells. These may include high or low blood pressure, hives or fever. Dimethyl sulfoxide (DMSO) is the main preservative used and may cause you to have strange tastes in your mouth or strange body odors.

Chemotherapy and/or Radiation Treatment

Reinfusion and Recovery
Chemotherapy or Radiation treatment

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  • Your doctor will give you high doses of chemotherapy and/or radiation to kill the cancer cells in your body.
  • Your doctor will also administer these treatments as part of a process known as "conditioning." Conditioning uses chemotherapy and/or radiation to kill the defective cells in your bone marrow and make room for the new ones. Conditioning also suppresses your immune system so that the donor's stem cells can engraft and prevent GVHD. Radiation is much less commonly used nowadays, and if used, the radiation dose is usually lower than in the past, so it is usually better tolerated.
  • While chemotherapy can be given through a peripheral (i.e. arm) vein, your transplant doctor will usually recommend the placement of a catheter (i.e. a sterile flexible tube and needle placed into a large vein under local anesthesia, usually in the neck or upper chest area). Some of these catheters can be implanted under the skin (i.e. “ports”).

Infusion and Recovery

Reinfusion and Recovery
Reinfusion and Recovery
  • After chemotherapy and/or radiation, your doctor will infuse the donor's stem cells into your bloodstream intravenously.
  • Reinfusion can be an outpatient procedure with no anesthesia. More commonly, it will take place in a hospital room.
  • After reinfusion, your stem cells will start to settle in your bone marrow and produce healthy blood cells again (engraftment). You can expect your blood cells to return to normal in about two to four weeks after reinfusion, and you can expect to remain in the hospital during this time period. Your doctor may give you shots of growth factors for blood forming cells to try to expedite the engraftment process. Your new marrow will produce white cells first, followed by red cells and platelets. In some cases, however, the recovery of blood counts may be delayed, and blood and platelet transfusions may be needed for a longer period of time. These can be given out of the hospital.
  • Isolation (i.e. “bubble”) rooms are rarely used nowadays, although hospital room for transplant patients are usually equipped with special air filters to keep microbes, molds and dust away. Visitors are also frequently allowed, although you should ask your doctor about specific policies to be followed in the hospital rooms. It is often possible to visit one of the hospital floors or rooms ahead of time.
  • Your doctor may give you antibiotics after reinfusion to prevent you from developing an infection while your white blood cells are still low from conditioning.
  • Your doctor may give you blood transfusions to return your red blood cells and platelets to normal levels while you wait for your stem cells to engraft and produce new cells.
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