The last fifty years have seen major advances in the field of medical research, many of which were translated into clinical applications. In general these applications have brought immense benefits to patients. As many of these new clinical applications are quite radical and often controversial, they inevitably challenge conventional ethical principles. Solid organ transplantation is one such advance which has generated and continues to generate issues involving ethics, law and morality. Organ transplantation has become an effective form of treatment particularly for end stage heart, liver and kidney failure. Except for kidney failure, organ transplantation is the only form of possible treatment for the other organ failure states, like the heart or the liver.The success rate in solid organ transplantation generally has improved since the first heart transplant 40 years ago, and this is as a result of our ability to control the transplant patient’s immune response. This has reduced the incidence of acute graft loss and the side effects of immunosuppressive regimens and given greater confidence among transplant surgeons who now believe that organ transplantation should no more be reserved for life-threatening organ failure but should also be available for structural non-life threatening defects. Thus we have increasingly seen hand transplants, laryngeal transplants along with knees, nerves, and flexor tendon apparatus of the hand. But these are reconstructive transplants and need to be differentiated from the more complex organ transplantation.
From the beginning, issues involving ethics have dominated the field of organ transplantation. This is not surprising as transplantation involves the use of human donors who may be alive or dead. Further the persistent shortage of organs in relation to the number of patients needing transplantation has led to problems of allocation. The success of transplantation, as measured by survival of the transplanted organs, has improved considerably in recent years. But the continued shortage of organs for transplantation has led to an unsavory aspect of transplantation, that of trafficking in organs, with all the attendant social, moral and ethical issues. Ethical issues in organ transplantation can be broadly categorized into issues relating to organ donation and those that relate to organ allocation.Hematopoietic stem cell transplantation (HSCT) is the transplantation of blood stem cells derived from the bone marrow (that is, bone marrow transplantation) or blood. Stem cell transplantation is a medical procedure in the fields of hematology and oncology, most often performed for people with diseases of the blood, bone marrow, or certain types of cancer.Stem cell transplantation was pioneered using bone-marrow-derived stem cells by a team at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology and Medicine. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells. His work also reduced the likelihood of developing a life-threatening complication called Graft-versus-host disease.Hematopoeitic stem cell transplantation remains a risky procedure with many possible complications; it has always been reserved for patients with life-threatening diseases.Most recipients of HSCTs are leukemia patients who would benefit from treatment with high doses of chemotherapy or total body irradiation. Other conditions treated with stem cell transplants include sickle-cell disease, myelodysplastic syndrome, neuroblastoma, lymphoma, Ewing's Sarcoma, Desmoplastic small round cell tumor, Hodgkin's disease, and multiple myeloma. More recently non-myeloablative, or so-called "mini transplant," procedures have been developed that require smaller doses of preparative chemo and radiation.
Hematopoietic Stem Cell Transplant- Graft Types/Donors/HSC Sources & Storage:
Graft types: Autolgous Graft Allogeneic Graft
Autologous HSCT involves isolation of HSC from the patient, storage of the harvested cells hematopoeitic stem cells in a freezer, high-dose chemotherapy to eradicate the patient's malignant cell population at the cost of also eliminating the patient's bone marrow stem cells, then return of the patient's own stored stem cells to their body. Autologous transplants have the advantage of a lower risk of graft rejection and infection, since the recovery of immune function is rapid. The incidence of a patient experiencig graft-versus-host diseaseis close to none , the donor and recipient are the same individual.
Allogeneic HSCT involves two people, one is the (normal) donor and one is the (patient) recipient. Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient. Matching is performed on the basis of variability at three or more loci of the (HLA) gene, and a perfect match at these loci is preferred. Even if there is a good match at these critical alleles, the recipient will require immunosuppressive medications to mitigate graft-versus-host disease. Allogeneic transplant donors may be related (usually a closely matched HLA sibling) or unrelated(donor who is not related and found to have very close degree of HLA matching ) . Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells.
Sources of HSC Peripheral blood stem cells are now the most common source of stem cells for HSCT. They are collected from the blood through a process known as apheresis. The donor's blood is withdrawn through a sterile needle in one arm and passed through a machine that removes white blood cells. The red blood cells are returned to the donor. The peripheral stem cell yield is boosted with daily subcutaneous injections of Granulocyte-colony stimulating factor, which mobilizes stem cells from the donor's bone marrow into the peripheral circulation
Umbilical cord blood is obtained when parents elect to harvest and store the blood from a newborn's umbilical cord and placenta after birth. Cord blood has a higher concentration of HSC than is normally found in adult blood.
Storage of HSC Unlike other organs, bone marrow cells can be frozen for prolonged time periods (cryopreserved) without damaging too many cells. This is necessary for
autologous HSC because the cells must be harvested months in advance of the transplant treatment. In the case of allogeneic transplants fresh HSC are preferred in order to avoid cell loss that might occur during the freezing and thawing process. Allogeneic cord blood is stored frozen at a cord blood bank because it is only obtainable at the time of childbirth. To cryopreserve HSC a preservative, DMSO, must be added and the cells must be cooled very slowly in a control rate freezer to prevent osmotic cellular injury during ice crystal formation. HSC may be stored for years in a cryofreezer which typically utilizes liquid nitrogen because it is non-toxic and it is very cold (boiling point -196°C.)
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