Bone Marrow Transplantation: Autologous and Allogeneic …

Posted: March 14, 2019 at 1:46 am

Hematopoietic stem cell transplantation (HSCT) is the new name for bone marrow transplantation.

The bone marrow is home to hematopoietic stem cells (HSCs), also called pluripotent stem cells because they can give rise to any cell your body requires at any given moment. These specialized cells play an essential role in replenishing our blood supply on a daily basis to maintain blood counts in a healthy host. These cells can be collected either by performing repeated bone marrow aspirations or by mobilizing HSCs into the circulation using special medications called cytokines (like GCSF, also called neupogen), and filtering them out of your blood using a highly specialized process called apheresis. After they are collected from your body, these stem cells can be preserved by storing them in a chemical called DMSO, and placing them in a freezer. Stem cell transplantation refers to a process whereby the patients HSCs are replaced by new cells (either from yourself [autologous] or someone else [allogeneic] that grow into a healthy hematopoietic system.

There are many types of HSCTs depending on the source of stem cells as described below:

Autologous Stem Cell Transplantation:

Autologous stem cell transplants are predicated on a simple concept: if a little chemotherapy has the potential to cure, than a lot could be even better. For lymphoma that has come back after conventional chemotherapy, this disease is not usually sensitive to lower doses of chemotherapy, so there is a need to consider higher doses. The challenge of course, is that higher doses of chemotherapy, while effective at treating the lymphoma, can also destroy all your bodys normal blood cells. Hence, after receiving high dose chemotherapy, there is a need to re-infuse your own normal stem cells, collected before you get the high dose therapy.

The use of your own stem cells, collected and frozen prior to the high dose therapy, is referred to as an autologous stem cell transplant. The most common indications for this kind of stem cell transplant are recurrent non-Hodgkin lymphoma and Hodgkin lymphoma. Typically, the patient undergoes chemotherapy to put their cancer into remission. At some point during their treatment they are assessed for HSCT that includes evaluation of the marrow to ensure healthy stem cells as well as adequate heart, lung and liver function. If they qualify then the stem cells are collected usually by apheresis.

In this process, stem cells that have been stimulated to divide and mobilized by medications (ex: GCSF or Neupogen) are filtered out of the circulation through an IV and stored for future use. Once the stem cells are collected, the patient undergoes further conditioning chemotherapy to destroy all cancer cells in their body. This kind of treatment can be toxic to stem cells and may result in long term inability to produce blood. The previously collected stem cells are infused back into the patient and after 7 to 10 days the blood counts recover and the patient can go home. Since these are the patients own cells there is no danger of graft rejection or graft versus host disease. The immune system may take up to a year to fully recover.

Allogeneic Stem Cell Transplantation:

Unlike autologous stem cell transplants, allogeneic stem cell transplants are predicated on the idea that if your immune system could not detect and destroy your lymphoma before it became obvious, then maybe an immune system from someone else (a sibling or an unrelated but matched person), can identify your lymphoma as foreign, and mount an immune response against it. The problem of course is that while the donor immune system, now transplanted and growing in a new host (that is the patient), can recognize the lymphoma as foreign (graft versus lymphoma effect, or GVL), it can also recognize the normal organs of the host as foreign, and mount a graft versus host (GVHD) response against your skin, lung, liver, and gastrointestinal tract. Drugs to suppress the immune system, called immunosuppressants, are often used to help control GVHD, but can obviously compromise some of the GVL effect as well. It is a double edge sword you want GVL without the GVHD, but unfortunately the two go and-in-hand. Indications for allogeneic stem cell transplant typically include acute myeloid leukemia, aggressive lymphomas, and stem cell disorders. A donor for a patient is defined by HLA typing of blood and tissues.

HLA stands for Human Leukocyte Antigen, and describes a series of proteins that exist on the surface of all cells in your body, and which is defined genetically. The degree of relatedness between individuals can be described by the similarities or differences in these genes that code for the HLA proteins, and are used to determine who might be a suitable donor for any given patient. The more closely related the individuals (say identical twins), the lower the risk of GVHD, but the lower the risk of GVL. The greater the difference in the HLA, the greater the risk of GVHD, but consequently, the greater the GVL benefit. Of course, if the toxicity of the GVHD is so great, producing increased mortality, then the GVL benefit becomes inconsequential. Thus, allogeneic transplanters walk a very fine line in assessing each patients individual risk and benefit with this type of transplant.

An HLA matched donor is needed for the host to allow the donor blood cells to engraft in the marrow, otherwise they will be rejected by the bodys immune system. The best donor, usually meaning the least degree of graft versus host disease (GVHD), is usually a sibling. Each person has about a 25% chance of having an HLA matched sibling donor. HLA matching is different from blood typing and can be done by a simple blood test or obtaining a swab from the inside of a persons mouth. Should no siblings be identified as a match, than a search is initiated to find an unrelated HLA match through the National Marrow Donor Program (NMDP). Once a match is identified, the patient is admitted to the hospital to receive conditioning chemotherapy and / or radiation therapy. At the end of this treatment, stem cells from the donor are infused into the patient and allowed to engraft. Even with an HLA matched donor there is a considerable risk of GVHD where the new grafted donor cells will attack the patients organs.

After the transplant, the patient is given immunosuppressive medications to prevent this condition, and is required to be on these for a considerable period of time.

Cord blood transplants:

Umbilical cord blood is an excellent source of stem cells and can be used as a source of stem cells in cases where an unrelated donor cannot be found. This has saved the lives of many patients. HSCT is a complicated process that requires a commitment from the patient and their families for the best outcome .You will be referred to a specialized center for HSCT where you will receive further details and education about the process.

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Bone Marrow Transplantation: Autologous and Allogeneic ...

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