Student of the Month

Post date: Jun 17, 2010 2:44:14 PM

Hematopoietic stem cell transplantation (HSCT)

Swati Saxena, B.Tech.(Biotechnology) Student, Amity University, Lucknow Campus, India

The last fifty years have seen major advances in the field of medical research, many of which were translated into clinical applications and have brought immense benefits to patients. 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 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.

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 with 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, as that of organ trafficking and other ethical issues.

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 since 1950s through the 1970s led by E. Donnall Thomas, whose work was later recognized with a Nobel Prize in Physiology and Medicine. Thomas discovered 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.

With the availability of the stem cell growth factors GM-CSF and G-CSF, most hematopoietic stem cell transplantation procedures are now performed using stem cells collected from the peripheral blood, rather than the bone marrow. Collecting stem cells provides a bigger graft, and does not require that the donor be subjected to general anesthesia to collect the graft.

Hematopoietic 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.

Figure 1. Distinguishing Features of Progenitor/Precursor Cells and Stem Cells. A stem cell is an unspecialized cell that is capable of replicating or self renewing itself and developing into specialized cells of a variety of cell types. The product of a stem cell undergoing division is at least one additional stem cell that has the same capabilities of the originating cell. Shown here is an example of a hematopoietic stem cell producing a second generation stem cell and a neuron. A progenitor cell (also known as a precursor cell) is unspecialized or has partial characteristics of a specialized cell that is capable of undergoing cell division and yielding two specialized cells. Shown here is an example of a myeloid progenitor/precursor undergoing cell division to yield two specialized cells (a neutrophil and a red blood cell).

Hematopoietic Stem Cell Transplant- Graft Types/Donors/HSC Sources & Storage:

Graft types: Autolgous Graft Allogeneic Graft

Autologous HSCT involves

the 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 eliminating the patient's bone marrow stem cells,
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 diseases 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 matching with that of 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.)

References

· David Z Levine : Ethical Issues in Living Organ Donation, American journal of Kidney Diseases, Vol. 32, No. 4 (October), 1998; pp676- 691.

· J Radcliffe – Richards, A S Dear, R. D Guttman et al : The case for allowing kidney sales. The Lancet Vol 351, June 27, 1998

· Human Organ Transplantation – A report on developments under the auspices of WHO (1987-1991). World Health Organisation. Geneva 1991