Bone marrow transplantation is a treatment approach that is applicable to only a subset of CLL patients. Until recently, CLL patients were generally not considered candidates for bone marrow transplantation because of their age at presentation and the indolent nature of CLL. However, increasing consideration is being given to CLL patients with high-risk disease and poor prognostic factors such as, lymphocyte doubling time of less than 12 months, diffuse bone marrow infiltration, and adverse cytogenetics.

There are two main types of transplants. Autologous transplantation uses the patient's own bone marrow or stem cells. After the cells are removed from the patient, they may be treated in an attempt to remove leukemic cells--a process called purging--and are then given back to the patient. Allogeneic transplantation uses bone marrow or stem cells collected from a matched donor who may be related or unrelated to the patient.

The advantage of autologous transplantation is the opportunity to achieve remission without the risk of graft-versus-host disease (GVHD). Approximately eighty percent of autologous transplant patients achieve complete remissions. The disadvantage centers on the possibility that leukemic cells will be given back to the patient. The relapse rate with autologous transplantation is approximately 50 percent four years after transplant, and overall survival at the four year mark is between 50 and 80 percent. Unfortunately, there is no plateau in disease-free survival curves which, coupled with the high relapse rate, suggests that autologous transplantation does not cure CLL. Patients with disease that is sensitive to treatment and who are transplanted while in compete remission usually achieve the best outcomes.

Allogeneic transplantation offers the possibility of long-term control and perhaps even cure. Two types of allogeneic transplants are used in CLL: standard and non-myeloablative. The latter is the so-called mini transplant procedure. In both procedures, the donor cells given to the patient are totally free of leukemia. The disadvantage of allogeneic transplantation is that the donated cells may attack the patient's body, which is called graft-versus-host disease (GVHD). Ideally, the donor cells will come from a matched related donor--usually a sibling. If this is not possible, cells from a matched unrelated donor (MUD) can be used. Standard MUD transplants carry the greatest risk of all the transplant procedures with a three in ten chance the patient will die from the procedure itself. Treatment related mortality (TRM) in non-myeloablative transplants is somewhat lower. With allogeneic transplants the relapse rate ranges from 10 to 25 percent, and there is a plateau in disease-free survival curves, which suggests that a fraction of patients is cured with this procedure.

Transplant is usually considered only for patients with progressive disease who are running out of other treatment options and therefore have a poor prognosis. When the risk of CLL becomes greater than that of transplantation, the transplant option comes into consideration.

Age is also a factor when considering transplant. Younger patients tend to want, and are often able to better withstand, aggressive treatment. In some cases, aggressive treatment also seems to be more effective in younger patients. Older patients frequently don't want aggressive therapy, because they don't want to go through all of the potential side effects. The ability to rebound from high dosage chemotherapy also diminishes with age, and the risk of graft-versus-host disease is well established to increase with advancing years. As a rule of thumb, allogeneic transplantation becomes less of an option after a patient reaches 60 years of age, and autologous transplantation is usually ruled out after 65 years of age. However, it is important to note that there are some 65 year olds who are otherwise very fit and healthy and could be candidates for transplant, while there are some 45 year olds who would not survive the procedure. The overall fitness of the patient is therefore somewhat of an overriding factor in determining the age-limit for transplant.

Transplant should not be considered or undertaken too early in the disease when the patient may have many more quality years of life with or without treatment. Similarly, it is important not to wait until the patient has already failed all other forms of treatment. In the latter situation, it is very difficult to perform a bone marrow transplant and achieve a good result. In summary, there is a window of time during the course of CLL when transplant makes the most sense to consider.

Patients who are considering transplant are encouraged to seek institutions and physicians that are performing this procedure in conjunction with CLL research. If this is not possible, patients are urged to find facilities that are experienced in transplants and have the skilled staff and state-of-the-art support services required to undertake this procedure.