department of medicine
fox chase temple bone marrow transplant program
Transplant Information
Introduction to Stem Cells
Autologous Stem Cell Transplant
Allogenic Stem Cell Transplant
A bone marrow transplant may involve administering chemotherapy alone or in combination with total body Irradiation in attempts to rid the body of disease. The process involves destroying a person's bone marrow, including their immune system. Healthy bone marrow from the patient or a donor is then infused into the patient.
Sometimes the general term of bone marrow transplant is also used to describe peripheral blood stem cell transplant or simply stem cell transplant. The difference between the two is the origin of the replacement cells and the method of collection.
Bone marrow is collected in the hospital under general anesthesia. It is a liquid that resembles blood and is taken from the center of large bones, generally the hipbone, using a large needle and syringe. The entire process can take up to 6 hours. In a stem cell collection, stem cells, which are the most immature cells in the bone marrow, can also be found in the peripheral blood, that is the blood in your veins. This procedure is performed in the outpatient clinic. It is similar to giving blood; however, only stem cells are removed via a pheresis machine and the remaining blood components are returned to your vein. It takes approximately 3 to 4 hours. It is a painless procedure and there is no anesthesia involved; however, the collection process may occur over a period of 2 to 5 days.
Receiving the transplant is similar to receiving a blood transfusion. The healthy cells seek their place in the bone marrow and begin to make a new population of healthy blood cells.
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| Introduction to Stem Cells |
The term "stem cell" refers to a cell that can give rise to a variety of other cells like the stem of a flower can give rise to leaves, other stems and flowers, etc. There are many different kinds of stem cells. One type that is getting a lot of attention in the media these days is the "embryonic" stem cell. These cells are usually isolated from an unborn fetus and under the right circumstances have the ability to make virtually any cell in our bodies. The use of this kind of stem cell is an exciting future prospect though there are certain moral issues that cloud the research.
Another type of stem cell is the "hematopoietic" stem cell. This kind of stem cell can be isolated from fully formed individuals and has the capability to make all of the cells in our blood and immune system including infection-fighting white blood cells, oxygen-carrying red blood cells and blood-clotting platelets. The hematopoietic stem cell is what our transplant program uses when we perform a "stem cell" transplant. In adults, these cells are found chiefly in the bone marrow but, under the right circumstances, they can be induced to go out into the blood stream.
Because hematopoetic stem cells are found in the marrow, they were historically collected through a bone marrow harvesting procedure in the operating room before we learned that we could "mobilize" them into the blood. Bone marrow is harvested in a one-hour hospital procedure using anesthesia. Typically, several small cuts (not requiring stitches) are made in the skin over the large bones at the base of your back and a large needle is used to withdraw bone marrow through these cuts. Today, stem cells are more commonly obtained from the bloodstream by a process called apheresis after being "mobilized". Apheresis is a safe outpatient procedure. Both bone marrow harvesting and apheresis provide stem-cell support that allows doctors to give intensive therapy without permanently harming a cancer patient's immune system or causing irreversible marrow damage.
Hematopoietic stem cells can also be isolated from the umbilical cord blood from a newborn baby. These "cord blood" stem cells can also be used for transplant but because they are low in number and the infant's immune system is not fully formed, they are more difficult transplants for adults. Our program is not currently using cord blood stem cells but may in the near future.
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| Autologous Stem Cell Transplant |
Autologous = Self Donor. In this procedure the patient's own stem cells are collected and frozen down. Some time later, the patient is admitted to the hospital to undergo intensive treatment with chemotherapy or radiation. After this intensive therapy, the previously collected stem cells are transplanted back into the patient in a manner similar to a regular blood transfusion. This autologous transplant procedure helps patients overcome dangerous side effects resulting from the destruction of white and red blood cells and platelets from the intensive treatment. Without new stem cells, patients would have too few white cells to ward off a life-threatening infection. They would also develop anemia because of low numbers of red cells and bleeding problems caused by too few platelets, which help blood clot.
Why High Dose Therapy?
Certain cancers can respond to chemotherapy with a decrease in the number of cancerous cells with every cycle of chemotherapy. However, there is sometimes a point reached where a small number of residual cancer cells remain that do not respond as well to the standard repeated doses of chemotherapy. These cells may respond to higher doses of chemotherapy. As long as patients receive adequate stem-cell support, chemotherapy doses several times higher than the conventional maximum can show impressive results and have few side effects. High-dose chemotherapy with bone-marrow or peripheral-blood transplants has improved "cure" rates for both leukemia and lymphoma--advances that have paved the way for improvements in solid-tumor therapy.
Even when high doses of chemotherapy with stem cell support does not cure certain cancers, it can often cause the cancer cells to be severely depleted and suppressed. Clinical trials have shown that diseases like multiple myeloma and follicular lymphoma, that usually involve the bone marrow, can be controlled for longer periods using higher doses of chemotherapy. Therefore, the goal of some autologous transplant procedures is "disease control" rather than "cure".
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| Allogenic Stem Cell Transplant |
Allogeneic = Non Self Donor. In this procedure a donor's HLA matched stem cells are collected and transplanted into the patient. HLA matching is the process of determining if the donor and the patient share certain critical genes that educate the immune system. The safest allogeneic transplants occur when donors and patients share the same HLA genes. Because these genes are all on one of our chromosomes and because we each inherit a chromosome from each parent, there is a 1:4 chance that a brother or sister will have the same HLA genes. When there is not a brother or sister who is a match for the patient, we can often find a close match among the millions of volunteer donors in the international HLA registry.
Before an allogeneic transplant, the patient is admitted to the hospital to undergo intensive treatment with chemotherapy or radiation. Sometimes the goal is simply to replace the patient's bone marrow and immune system with new cells from the donor rather than kill huge numbers of cancer cells. In this case, less intensive therapy can be used in a "mini" allogeneic transplant. The appropriate use of this kind of transplant is complicated and will be discussed with you if it is an option. After the treatment, standard or "mini", the previously collected donor stem cells are transplanted back into the patient in a manner similar to a regular blood transfusion.
This allogeneic transplant procedure helps patients overcome dangerous side effects resulting from the destruction of white and red blood cells and platelets from the intensive treatment and provides a new immune system for the patient. Without new stem cells, patients would have too few white cells to ward off a life-threatening infection. They would also develop anemia because of low numbers of red cells and bleeding problems caused by too few platelets, which help blood clot. The new donor immune cells can serve as another potential treatment for the patient's cancer (see the next section).
The Engrafted Immune System and GVHD
After and allogeneic (donor) stem cell transplant, the patient's bone marrow cells will be replaced with new healthy donor cells. These cells will produce the white blood cells, red blood cells and platelets that the patient needs for a healthy blood system. Moreover, all of the cells that comprise the patient's immune system will be replaced resulting in a completely new immune system. These new donor immune cells can often recognize any residual cancer cells in the patient as "foreign invaders" and directly attack and kill them. Hence, this is a very useful therapy for patients who do not respond well to other standard therapies. Every cancer has a different sensitivity to this immune attack so this treatment does not work with all cancers. Fortunately, most cancers of the bone marrow do respond.
Unfortunately, there is a potential downside to this form of therapy in that the new immune cells can sometimes recognize some normal parts of the patient as "foreign invaders" and attack these normal cells. This complication is called "graft versus host disease" where "graft" refers to the donor cells and "host" refers to the patient. The better the HLA match between the donor and patient the lower the chances of severe graft versus host disease. This can be a life-threatening problem and is the major complication of an allogeneic transplant. If an allogeneic transplant is part of your therapy, we will discuss this issue with you extensively.
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