Allogeneic Stem Cell Transplantation | Leukemia and …

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Feb 12 2019

Allogeneic stem cell transplantation involves transferring the stem cells from a healthy person (the donor) to your body after high-intensity chemotherapy or radiation.

Allogeneic stem cell transplantation is used to cure some patients who:

Allogeneic stem cell transplantation can be a high-risk procedure. The high-conditioning regimens are meant to severely or completely impair your ability to make stem cells and you will likely experience side effects during the days you receive high-dose conditioning radiation or chemotherapy. The goals of high-conditioning therapy are to:

The immune system and the blood system are closely linked and can't be separated from each other. Because of this, allogeneic transplantation means that not only the donor's blood system but also his or her immune system is transferred. As a result, these adverse effects are possible:

The immune reaction, or GVHD, is treated by administering drugs to the patient after the transplant that reduce the ability of the donated immune cells to attack and injure the patient's tissues.SeeGraft Versus Host Disease.

Allogeneic stem cell transplants for patients who are older or have overall poor health are relatively uncommon. This is because the pre-transplant conditioning therapy is generally not well tolerated by such patients, especially those with poorly functioning internal organs. However,reduced intensity allogeneic stem cell transplantsmay be an appropriate treatment for some older or sicker patients.

One goal of allogeneic stem cell transplant is to cause the T lymphocytes in the donor's blood or marrow to take hold (engraft) and grow in the patient's marrow. Sometimes the T lymphocytes attack the cancer cells. When this happens, it's called graft versus tumor (GVT) effect (also called graft versus cancer effect). The attack makes it less likely that the disease will return. This effect is more common in myeloid leukemias than it is in other blood cancers.

Unfortunately, T lymphocytes are the same cells that causegraft versus host disease(GVHD). Because of this serious and sometimes life-threatening side effect, doctors in certain cases want to decrease the number of T lymphocytes to be infused with the stem cells. This procedure, called T-lymphocyte depletion, is currently being studied by researchers. The technique involves treating the stem cells collected for transplant with agents that reduce the number of T lymphocytes.

The aim of T-lymphocyte depletion is to lessen GVHD's incidence and severity. However, it can also cause increased rates of graft rejection, a decreased GVT effect and a slower immune recovery. Doctors must be careful about the number of T lymphocytes removed when using this technique.

Stem cell selection is another technique being studied in clinical trials that can reduce the number of T lymphocytes that a patient receives. Because of specific features on the outer coat of stem cells, doctors can selectively remove stem cells from a cell mixture. This technique produces a large number of stem cells and fewer other cells, including T lymphocytes.

If you're considering allogeneic stem cell transplantation, you'll need a bone marrow donor. First, you and your siblings, if any, will have your blood or a scraping from your inside cheek tested to determine tissue type. A sibling has the potential to match you most closely because you both received your genes from the same parents.

A lab technician examines the surface of the sample tissue cells to identify the proteins that give everyone his or her own unique tissue type, called human leukocyte antigens (HLAs). If the HLA on the donor cells are identical (from identical twins, for example) or similar (such as those from siblings), the transplant is more likely to be successful. On average, you have a one in four chance of having the same HLA type as a sibling. Many patients, therefore, don't have a sibling with the same tissue type.

If a brother or sister doesn't provide a match, your doctor will search registries of volunteer donors such as theNational Marrow Donor Programfor an unrelated donor that matches your tissue type. A donor who's not related to you but who has a similar tissue type is called a matched unrelated donor (MUD).

Stem cells for transplantation are collected from three sources:

Before stem cells are collected from blood or bone marrow, the donor must undergo a thorough physical exam and blood testing for hepatitis viruses, human immunodeficiency disease (HIV) and other infectious agents or viruses.

The most common source of stem cells for transplant is peripheral blood, the blood that flows throughout our veins and arteries.

Bone marrow normally releases a small number of peripheral blood stem cells (PBSCs) into the bloodstream. To obtain enough PBSCs for a transplant, the donor takes a white cell growth factor, such as granulocyte-colony stimulating factor (G-CSF) drug, which increases the number of stem cells by drawing them out of the marrow and into the bloodstream. When a patient's own stem cells are used, both G-CSF and the chemotherapy used to treat the disease usually increase PBSCs. In patients who have myeloma and non-Hodgkin lymphoma, the drug plerixafor (Mozobil) can be used to mobilize their own stem cells.

The blood is removed from the donor and the cells collected using a process called apheresis, which involves placing a needle in the donor's vein, usually in the arm, similar to administering a blood test. The donor's blood is pumped through an apheresis machine, which separates the blood into four components: red cells, plasma, white cells and platelets. The white cells and platelets, which contain the stem cells, are collected, while the red cells and plasma are returned to the donor. It can take one to two sessions of apheresis to collect enough blood from a MUD. If you are your own donor, it may take more than two sessions.

If enough stem cells can't be retrieved from apheresis, they can be removed directly from the bone marrow. This requires the donor to undergo a minor outpatient surgical procedure.

While the donor is under anesthesia, the surgeon inserts a hollow needle into the donor's pelvic bones just below the waist and removes liquid marrow. This is done a number of times until several pints of marrow are collected. The donor can expect to stay in the hospital for six to eight hours after the procedure to recover from the anesthesia and the acute pain at the needle insertion sites. He or she may feel some lower back soreness for a few days afterward. The donor's body naturally replaces the marrow soon after the procedure. Red cells are also removed, and the donor may experience anemia, which is often treated with iron supplements.

The marrow that's removed (harvested) passes through a series of filters to remove bone or tissue fragments and is then placed in a plastic bag from which it can be infused into the recipient's vein. The marrow is usually given to the patient within a few hours and almost always within 24 hours. If necessary, however, marrow can be frozen and stored and will remain suitable for use for years. If the transplant is autologous, the marrow is usually frozen while the patient undergoes intensive chemotherapy.

A rich source of stem cells for blood cancer patients are the stored stem cells collected from the umbilical cord and placenta after a baby is born, called the cord blood unit. Parents may choose to have the cord blood unit collected after delivery. Healthy parents with healthy children and no transplant candidate in the family can choose to donate their newborn's cord blood to cord blood banks or research programs at participating hospitals. Parents with a child or a family member who could be a candidate for transplantation should discuss with their doctor the potential benefits of saving their newborn's cord blood for possible family use.

Advantages of Using Cord Blood

The advantages of using cord blood stem cells instead of donor peripheral blood or donor marrow stem cells include:

Disadvantages of Using Cord Blood

There can be disadvantages of using cord blood stem cells as well:

The decrease in marrow function often begins to take effect by the second or third day after an allogeneic stem cell infusion. You'll be kept in a protected environment to reduce contact with infectious agents. Generally within two to four weeks after the transplant, the engraftment of donated cells will be apparent from the appearance of normal white cells in your blood. You'll receive periodic transfusions of red cells and platelets until your marrow function has been restored by the transplanted stem cells.

Your doctor will carefully monitor you with physical exams, blood chemistry tests, imaging studies and other tests to ensure that your heart, lungs, kidneys, liver and other major organs are functioning normally. You'll need drugs to prevent GVHD, in addition to blood transfusions. If you're suffering from a poor appetite or diarrhea, you may need to be fed intravenously or through a duodenal tube (called hyperalimentation) to ensure you get adequate nutrition.

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