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Thread: A brief description of stem cell transplants

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    Super Moderator Top User po18guy's Avatar
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    A brief description of stem cell transplants

    Note: If you happen to find any inaccuracy in the content, please send a PM and I will make correction. Thank you.

    Organ transplants have been done for decades now, and the concept is easily understood. If a person's kidney(s) has failed, a kidney from another person (donor) may be transplanted into the patient's (recipient) body. However, some organs are not as well-defined as the kidney. The immune system is a very complex internal organ involving various structures, as well as the blood and lymph. Occasionally, as with other organs, our immune systems are weakened or simply fail. Until about 40 years ago, there was virtually nothing that could be done to correct this. However, researchers discovered that the bone marrow, where our blood and immune cells are created, could be successfully transplanted from one human being into another. This effectively replaced their failed immune system with that of a healthy person. Further research found that this could also be done with blood "stem cells" and umbilical cord blood from newborn babies.

    Regarding stem cell transplants (SCT), the term "stem cell" refers to what are known as "pluripotent" cells - newly created cells in the marrow which have the ability to diversify into several different types of blood and immune cells. This is the same action by which we developed in our mother's womb. In the body, the bone marrow may be likened to a womb where the immune system is born. There are two main types of stem cell transplants: autologous (one's own cells) and allogeneic (donor cells).

    Autologous Stem Cell Transplants

    In certain diseases (or the unavailability of a suitable donor), one's own stem cells may be "harvested" from the blood and used immediately or stored. Attempts are made to have the disease in full remission for this harvesting. In preparation, the patient receives injections of a drug which stimulates the marrow to produce excess stem cells. These cells overflow into the blood, where they may be separated out by a process known as apheresis. Being in a state of remission is important for best results, but not absolutely necessary. In preparation for the transplant, some form of standard chemotherapy and/or radiation is given, causing the patient's marrow to be either heavily suppressed or eliminated. Then the patient's own stem cells are prepared for re-infusion. Note: If the cells were frozen, they retain their viability for years - one figure states 95% viability after 5 years' storage.

    The stem cells are infused exactly like a blood transfusion. Once re-introduced into the bloodstream, they enter the marrow and begin producing new blood stem cells. A huge difference between autologous (one's own cells) and allogeneic (donor) transplants is that there are no rejection issues involved when one is receiving their own cells back. Those cells originated in the patient's body, fully know the patient's body and therefore do not reject any part of it. For various reasons, receiving one's own cells back may or may not be the best option, which is also true regarding donor cells. Autologous transplants can be done with curative intent, or to produce a remission of unknown duration, or in combination with a subsequent donor (allogeneic) transplant. It is heavily dependent upon the nature of the disease as well as other treatment options available.

    An autologous stem cell transplant is akin to re-booting a computer. This re-booting of the immune system may restore perfect immune function, but any inherent problems may appear once again. Any cancer eliminated by the transplant may relapse at some point in the future.

    Allogeneic Stem Cell Transplants

    While organ and even autologous stem cell transplants are easily understood, the situation is completely reversed in the case of allogeneic (donor bone marrow/stem cell) transplantation. The recipient's body and organs remain exactly the same. What is being transplanted is someone else's immune system into the recipient's body. That immune system knows and recognizes only the cells in the body it came from, and not those of the body into which it has been transplanted. So, as it gains strength after transplantation, it may reject portions of the host's body. Therefore, a donor must be a close HLA match to the recipient for the best outcome. If rejection occurs, the transplanted immune system must be controlled so that any attack that it launches on the body does not place the recipient at risk. Fortunately, experience with solid organ transplants has produced extensive knowledge in the area of immune system suppression.

    When rejection occurs, it indicates that the transplanted immune system has sensed an "enemy" and, just as it does when it finds bacteria, viruses or fungi, it triggers an immune attack on that enemy - which is not an enemy, but the recipient's own body. This can have disastrous results unless the new immune system is suppressed so that its ability to attack the recipient's body is under control. This raises another issue: we now have a very delicate balancing act in which the new immune system must be allowed to grow strong enough to defend the body against common infection, but not so strong as to attack the body's tissues or organs. Once again, this is accomplished with drugs that suppress the immune system. Fortunately, there are adaptive elements in the immune system that normally allow it to tolerate the recipient's body.

    Regarding our "old" immune system, once cancer (or another marrow disease) occurs, it is desirable that the marrow be replaced completely. Before, or early in the transplant process, our old immune system must be greatly weakened or eliminated. This is part of what is called "conditioning". To accomplish this, chemotherapy and/or radiation are used. Those of us who have undergone chemotherapy know that it often lowers blood counts. That is a negative side effect which causes damage (suppression) to the bone marrow, and which greatly reduces the number of blood cells produced by the marrow. In a complete turnabout, what is undesirable during chemotherapy is absolutely necessary for a transplant. Depending upon the type of transplant, doctor can decide to either weaken or eliminate the old marrow. Both approaches have benefits as well as risks.

    Marrow or stem cells?

    Even though it provides hope for a cure, transplanting bone marrow is an invasive and somewhat risky open surgical procedure for both donor and recipient. The recipient ends up with an incision that is subject to infection at a time when they have almost no immune system to fight infection. Thanks to continuing research, it was found that freshly created "stem cells" within the marrow could be collected from the blood and transplanted to accomplish the same thing. This required no invasive surgery, reducing infection and increasing success rates. One advantage is that marrow transplantation tends to reduce rejection issues.

    Donor stem cells or umbilical cord blood stem cells?

    Even though there are something like 9.5 million registered donors in the world registry of marrow/stem cell donors, there may still be difficulty locating a suitable match for a given recipient. The vast majority of registered donors are caucasian, so those of other or mixed racial backgrounds may have even greater difficulty locating a donor. For this reason, close family should be tested for compatibility. Normally, full-blood brothers or sisters are most likely be a suitable match. If they are not, one's children can be tested. If a child is suitable, it is considered a half-match, or haploidentical transplant.

    Umbilical cord blood stem cells are another possibility, but their availability is limited. The umbilical cord contains only a tiny amount of blood, although a way has been found to multiply those cells, thus making them a much more viable source for transplant. One other downside is that there is an increased risk of rejection issues when using umbilical cord blood stem cells. Current research suggests also that there is increased risk to umbilical cord blood transplant patients under 30 or over 60 years of age. This is a statistical observation and no reason for it is known.

    Rejection issues, also known as Graft versus Host Disease (GvHD)

    As to rejection issues in donor (allogeneic) transplants, it is known as "Graft versus Host Disease" (GvHD) and can be serious, or occasionally fatal. The "graft" refers to the stem cells which have been grafted in, with the "host" being the recipient. When it occurs, it indicates that the new immune system has engrafted in the marrow and is functioning, but is now reacting to and attacking, certain parts of the recipient's body. It is very likely to be to be controlled with certain drugs, but not in 100% of cases. It may appear and then recede, or may be present for life. It is controlled by immune suppressing drugs. Thus, a donor transplant must be entered into being fully aware of potential lifetime side effects.

    Graft versus Tumor Effect (aka Graft versus Leukemia or Lymphoma)

    This is the main benefit of allogeneic transplants. The grafted-in immune system has never encountered the cancer cells before and is thus much more likely to recognize them as foreign and kill them. Once it does so, it can "remember" those cancer cells and attack them also in the future. In this regard, it may do what chemotherapy cannot.

    There is much more, but this is a start.
    Last edited by po18guy; 11-19-2015 at 08:57 AM. Reason: Additions


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