- "The Candlelighters Guide to Bone Marrow Transplants in Children", The Candlelighters Childhood Cancer Foundation et al., 1994"

What is a Bone Marrow Transplant?
Indications for Bone Marrow Transplantation
Types of Transplants
Pre-Bone Marrow Transplant Evalutations

What is a Bone Marrow Transplant?

A bone marrow transplant is a procedure in which normal bone marrow cells are infused into a person. The infusion is a simple process similar to a blood transfusion. What the bone marrow cells do and why we transplant them is not as simple.

Bone marrow is located inside the core of most bones and has a specific job to do, just as other body organs and tissues do. The bone marrow is responsible for manufacturing our blood cells. There are specialized cells in the marrow called stem cells which are actually transplanted. The stem cells produce the blood cells in the bone marrow, the cells mature in the bone marrow environment, and then are released out into the bloodstream when they are ready to perform their functions.

Red blood cells are responsible for carrying oxygen to all parts of the body. Oxygen is used as fuel for the body’s cells to perform their function. This oxygen-carrying capacity of the red blood cells is measured by the amount of hemoglobin in the blood. When the hemoglobin is low, the red blood cells will carry less oxygen to the tissues, resulting in a person feeling tired and looking pale.

White blood cells are responsible for fighting infections. There are several types of white blood cells, each with its own specified job to do. The two most important types are: (1) neutrophils (also called polymorphs or polys) which attach bacteria, and (2) lymphocytes which produce antibodies to fight viruses, fungi and some bacteria. The white blood cells and the antibodies they produce make up part of the immune system, which protects the body from becoming sick as it is constantly exposed to infectious organisms in the environment. White blood cells are counted under the microscope to determine the body’s infection-fighting ability at any given time.

Platelets are responsible for clotting the blood to stop bleeding. Platelets are also counted under the microscope. When platelets are low, bruising appears on the skin and bleeding can be severe when the body is injured or even can occur spontaneously.

Indications for Bone Marrow Transplantation

Bone Marrow is most commonly transplanted to:

  1. Cure diseases in which there are life-threatening abnormalities in the red cells, white cells or platelets;
  2. Provide supportive care for patients with various types of cancer requiring very intensive chemotherapy or radiation treatments;
  3. Provide enzymes missing in patients suffering from rare disorders called metabolic storage diseases.

Most often bone marrow transplants are done to treat patients suffering from leukemias. In leukemia, the bone marrow produces cancer cells instead of healthy blood cells. Pre-transplant preparative treatments are aimed at killing the defective bone marrow, thereby killing the cancer, and replacing it with healthy bone marrow. This can also be done for other cancers that invade the bone marrow, such as neuroblastoma.

Non-cancerous blood diseases treated with transplant include aplastic anemia, in which the bone marrow has shut down and stopped making any cells, and thalassemia and sickle cell anemia where the bone marrow is making defective red blood cells. Healthy bone marrow cells are then transplanted to make normal blood cells.

Some immune deficiencies are corrected with bone marrow transplants. It my not be necessary to kill the defective bone marrow in this case, but just to add marrow cells to produce the white blood cells that are deficient or abnormal. Severe combined immune deficiency syndrome (SCIDS) is one such disease.

Many malignant solid tumors, such as brain tumors, Hodgkin’s and non-Hodgkin’s lymphomas, and neuroblastoma are treated with very high doses of chemotherapy and/or radiation therapy which would normally destroy the patient’s normal marrow. In this situation, the patient donates his/her own marrow, which is transfused after the anti-cancer therapy to protect against irreversible marrow damage.

Certain congenital or inherited metabolic storage disorders may also be treated with bone marrow transplantation. In these diseases, there is a missing enzyme which can be replaced by providing the cells that produce the enzyme. Mucopolysaccaridoses such as Hurler’s or Hunter’s disease are examples of such metabolic enzyme leukodystrophies. Osteopetrosis, although it is not a metabolic enzyme deficiency, is similar in that a particular cell called a osteoclast is present but does not function, causing a potentially fatal build-up of calcium in the body. This can be cured by transplanting marrow containing normal osteoclasts.

Types of Transplants

There are three types of marrow transplants: augologous, allogeneic, and syngeneic.

Autologous bone marrow transplant is the process is the process of collecting and storing the patient’s own bone marrow cells, treating the patient with high doses of chemotherapy, and then re-infusing the bone marrow. The goal of this type of transplant is to enable use of the highest doses of chemotherapy to kill the cancer cells, knowing that as a side effect, the bone marrow is also killed or severely damaged. The stored marrow cells are re-infused to regrow, replacing the damaged marrow. It is really more accurate to call this treatment "high dose chemotherapy with autologous bone marrow rescue or support) than to call it a transplant.

Collecting autologous bone marrow cells can be complicated. Traditionally, bone marrow is harvested from the hip bones, which are rich in marrow stem cells. The marrow in people who previously have been treated with chemotherapy and/or radiation near the pelvis, however, may be dilute. In this case a larger volume of marrow needs to be collected in order to achieve the desired number of stem cells.

A second option for harvesting, which is increasing in use, is to collect the stem cells which are found in lesser concentrations in the peripheral blood. This peripheral stem cell harvesting (PST) procedure requires a special catheter and two to eight sessions processing on a pheresis machine, similar to a dialysis machine.

Patient selection for augologous marrow or peripheral blood stem cell infusion is important. It is best to choose a type of disease that does not invade the bone marrow, so that cancer cells are not harvested and re-infused. Several solid tumors are amenable to this treatment. Occasionally an attempt may be made to treat, though autologous re-infusion, leukemia or neuroblastoma that has invaded the bone marrow. The harvested bone marrow is treated or purged to remove cancer cells before the marrow is frozen and stored.

Autologous marrow or blood cells do not need to be tissue typed, since they belong to the patient. Rejection of the marrow cells and rejection of the body by the new cells (graft-versus-host disease or GVHD) do not occur, lessening post-transplant complications in comparison to allogeneic transplant.

Allogeneic bone marrow transplant is the transplant procedure in which bone marrow cells from a healthy person are infused into the patient. The patient is treated with high-dose chemotherapy and/or radiation aimed at killing the defective or cancerous bone marrow. Healthy donated bone marrow cells are then infused to regrow marrow cells in the patient.

In order for body cells to be transplanted from one person into another, the two people need to be genetically similar. Most often a brother or sister has a genetically similar immune system and cell type. The chance that any brother or sister will match genetically is one in four, based on which genetic pattern was inherited from the parents. This genetic pattern is determined by a blood test called human leukocyte antigen (HLA) testing. Usually a minimum of six genetic types (called A,B, and D related) are mapped out from this test. Once it is determined that the HLA matches a second blood test is performed to see how each person’s lymphocytes (the cells responsible for rejection or GVHD) behave when exposed to the other person’s lymphocytes. This mixed lymphocyte culture (MLS) lets us know the likelihood that: (2) the patient’s cells will attack the donated cells once they are transplanted, causing rejection, or (2) the donated cells will attack the patient’s body once transplanted, causing GVHD. Both rejection and GVHD may occur, however, even when the MLC test is negative or compatible.

At times it is necessary to use marrow cells from a family-member donor who does not match on all six of the HLA genetic types. This is a mismatched related allogeneic transplant. A parent may fall into this category for a child. When the HLA is not a complete match, the MLC is not expected to be, either. It may be necessary to remove some of the lymphocytes from the marrow before transplanting it in order to lessen the chances of GVHD. This manipulation is called T-cell (or T-lymphocyte) depletion.

Matched unrelated transplants are now being done more frequently performed for patients needing a marrow transplant who do not have a suitable donor in the family. There are several registries containing lists of people willing to donate their bone marrow for someone in need. HLA types of volunteer donors are kept on computer files to be matched against the patient’s HLA typing. The MLC test and a very sophisticated genetic test called the DNA test are done to study further the extent of the match. The volunteer unrelated donor donates marrow at a hospital in his/her hometown, remaining anonymous. The marrow is hand-carried to the transplant center.

Although unrelated donors offer more people a chance for a transplant, this type of transplant is more complex than the matched related allogeneic type, and may not be indicated for many patients. Although genetic tests currently available can indicated a match between patient and donor, there are many genetic areas on people’s cells for which we cannot type. Because there is a greater chance of a mismatch on these genetic areas between unrelated individuals there is a much higher risk of GVHD and rejection in matched unrelated transplants.

A syngeneic transplant is similar to an allogeneic transplant except that the donor is the patient’s identical twin. Identical twins match completely on the HLA, so there is virtually not chance of significant GVHD.

Pre-Bone Marrow Transplant Evaluations

Once the donor has been chosen, he/she will need to have a physical examination, laboratory studies, and counseling to determine health status and understanding of what he/she is being asked to do. The patient will also undergo pre-transplant laboratory work and testing to evaluate the functions of vital organs such as the heart, lungs, kidney, and liver. Other x-rays or tests may be required depending on the patient’s disease and clinical condition and the transplant center’s procedures.