Blood and Marrow Stem Cell Transplantation

Each year 9,000 people in North America undergo stem cell transplantation for leukemia, lymphoma or myeloma. In Singapore the number of transplants is about 100..The procedure continues to be improved in anticipation of making it available to even more patients each year. There are two major types of stem cell transplants: autologous and allogenic.

Autologous transplantation uses the patient’s own marrow. The marrow is collected while the patient is in remission, and it may be treated with chemotherapy agents or monoclonal antibodies before being given back. Such procedures cleanse the marrow of the small proportion of leukemia and lymphoma cells that might still be present.

An allogenic transplant uses marrow from a normal donor, usually a brother or sister with the same tissue type. If a sibling is not available, a search of the National Marrow Donor Program registry of tissue-typed volunteers could be made for a matched unrelated donor.

The rationale for stem cell transplantation is based on the fact that all blood cells (e.g., red cells, phagocytes and platelets) and immune cells (lymphocytes) arise from the stem cells, which are present in the marrow.

Stem cells circulate in the blood in very small numbers. Drugs are available that increase the numbers of stem cells in the blood by drawing them out of the marrow. Sufficient quantities of these stem cells for transplantation are recovered by circulating large volumes of blood through a hemapheresis apparatus and skimming off a population of cells that contain stem cells.

Blood is an increasingly frequent source of stem cells for transplantation. Thus, bone marrow transplantation (BMT) as a generic term for the procedure had to be modified to mean blood or marrow transplantation, permitting the continued use of the familiar acronym, BMT. In many cases, the more specific term stem cell transplantation (SCT) is now used.

Disorders that may be treated with stem cell transplantation include:

  • Immune deficiency. Children born with severe immune cell deficiencies and are unable to make the cells that help the body combat infection are candidates for stem cell transplants.
  • Inherited Severe Blood Cell Diseases. Marrow transplantation is now being used to treat diseases such as thalassemia or sickle cell disease in which a mutant gene is inherited.
  • Other Inherited Disorders. There is a group of inherited diseases that have a defect in the monocytes.
  • Marrow Failure. Human stem cell transplantation has been used successfully to restore the function of marrow that has been injured. This type of marrow failure, referred to as aplastic anemia, can be drug induced, autoimmune or, more rarely, inherited. As a result of exposure to certain drugs or to an external noxious agent, such as a chemical or unintended radiation exposure, marrow failure can occur.

When severe, aplastic anemia can be treated by stem cell transplantation if a compatible donor can be found. In this situation, pre-treatment of the patient with chemotherapy and or irradiation is required to suppress the immune system of the patient and enhance the likelihood of success of the transplant. Chemotherapy or radiation prior to the transplant decreases the risk that the recipient’s immune cells will reject the transplanted stem cells. In addition, since the disease is often the result of the attack by the patient’s own lymphocytes on developing blood cells (autoimmune disease), the conditioning treatment helps to rid the recipient of these disordered lymphocytes. After the transplant, the donor’s lymphocytes and blood cells will replace those of the patient, curing the disease.

Acute leukemia, lymphoma and myeloma have a remission and cure rate that increases in relationship to the amount of chemotherapy given to the patient. Chemotherapy doses that were developed for the treatment of acute leukemia and considered tolerable by most individuals are insufficient to induce remissions or lead to cures in many patients. Very high dose chemotherapy and radiotherapy are often required to treat refractory or relapsed acute leukemia. The capability of the marrow to make normal blood cells is so severely impaired after these treatments that few patients would survive long enough to derive the benefits. They would succumb as a result of infection because of the absence of white cells or of hemorrhage because of the absence of blood platelets.

A method to restore normal blood cell production had to be developed if larger doses were to be administered. With the infusion of sufficient stem cells from a closely matched donor, such as a sibling, marrow function and blood cell production might be restored rapidly enough to allow recovery from the intensive treatment. After several decades of research, discovery and clinical trials, allogeneic stem cell transplantation is used successfully to cure patients who are at high risk of relapse, who do not respond fully to treatment or who relapse after prior successful treatment.

The age, medical condition, likelihood of response of the malignancy to the conditioning regimen and the availability of an HLA-matched donor are all considerations in the decision to use allogeneic transplantation. In some circumstances autologous stem cells (which are obtained from the blood and marrow of the patient) can be used.

Thus, leukemia, myeloma and lymphoma, if poorly responsive to standard therapy or if biological features are present that are known to predict a poor response to chemotherapy, may be treated with very intensive chemotherapy and/or radiotherapy, which requires complementary stem cell transplantation.