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15.4.12: Bone Marrow Transplants

Transplants of Hematopoietic Stem Cells

Hematopoietic stem cells (HSCs) are the cells from which all the types of blood cells are made. They reside in the bone marrow and can be harvested from it. However, a few infusions of granulocyte colony-stimulating factor (G-CSF) — available thanks to recombinant DNA technology — causes them to be released into the blood where they can more easily be collected. They are used to treat a variety of ailments including sickle-cell disease, multiple myeloma, a cancer of plasma cells, various leukemias and some other types of cancer. In 2006, some 50,000 of these transplants were performed worldwide. High doses of chemotherapy and radiation can be used to kill off the cancerous cells in a patient, but they also destroy the patient's bone marrow, and the patient will die without a transplant of hematopoietic stem cells.

Fig. 15.4.12.1 Bone marrow transplant

These can be:

  • autologous — from hematopoietic stem cells that were
    • removed from the patient before cancer therapy began,
    • stored alive,
    • and, if there were cancer cells in the bone marrow (the case with multiple myeloma and leukemias), treated to "purge" them. Most failures of autologous stem cell transplants occur because of failure to get all the cancer cells out of the harvested cells rather than failure to eliminate them from the patient.
  • allogeneic — hematopoietic stem cells removed from someone else, often a close relative. Another source of hematopoietic stem cells is cord blood — blood drained (through the umbilical cord) from the placenta of newborn infants.

    Allogeneic stem cells

    • avoid the problem of lurking residual cancer cells but
    • should be closely matched to the major histocompatibility loci (MHC) of the patient. If not, the donor cells will attack the recipient causing often-fatal graft-versus-host disease (GVHD). Even with an exact match at the MHC, some GVHD is likely.

In one remarkable case, an AIDS patient with leukemia was given a bone marrow transplant from a donor whose cells did not express a functional version of CCR5 — a coreceptor needed by HIV to infect T cells. Two years later, the patient was not only cured of his leukemia but of AIDS as well. Autologous hematopoietic stem cell transplants also show promise of being an effective treatment for the autoimmune disorder systemic lupus erythematosus (SLE). If the patient's own marrow was not completely destroyed, the donor lymphocytes and the patient's lymphocytes can exist together. Then a later infusion of the donor's T cells may be able to kill off all the patient's remaining malignant cells leaving the patient with a bone marrow that produces donor-type cells exclusively. So hematopoietic stem cell transplants (HSCT) can be life-saving but create their own problems. (Another example: an "immediate"-type allergy like hay fever or asthma of the donor can create the same allergy in the recipient.)

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