Conventional blood and marrow transplant (BMT) requires the use of high-dose chemotherapy or chemoradiotherapy. This high-dose therapy is designed to destroy all cancer cells, but as a side effect, it also damages the patient's own healthy bone marrow. This is one reason why stem cells must be transplanted into the patient after the high-dose therapy has been completed. The second reason that a donor's stem cells may be necessary for a successful transplant outcome is that the donor's immune system cells in the stem cells (the "graft") are also capable of killing cancer cells (often referred to as the "graft-versus-leukemia" or "graft-versus-tumour" effect).
While high dose therapy is effective in destroying cancer cells, it also poses the risk of severe damage to the liver, lungs, heart and other major organs. There is a higher risk of this especially if the patient is older or has a pre-existing health problem. For this reason, high dose therapy and consequently a conventional BMT are not recommended for all patients.
Over the past 10 years, a new BMT procedure has been specifically developed for patients that had previously not been considered suitable for a conventional BMT. The concept of the reduced intensity conditioning ("RIC") transplant is that high-dose therapy may not be necessary in order to have the patient accept a donor's stem cells. This avoidance of high-dose therapy makes the procedure safer in patients of older age or with pre-existing health problems.
Instead, patients receive relatively less toxic conditioning therapy. Depending on the degree of reduction, the conditioning therapy is sometimes given in the Outpatient Unit rather than admitting the patient to the Inpatient Unit. The reduced-intensity conditioning is designed to suppress the patient's immune system enough so that it will accept the donor stem cells. Once the donor's cells take over the patient's bone marrow ("engraftment"), it is hoped that this new immune system will then fight residual cancer cells through a graft-versus-tumour effect.
It is important to know that RIC-transplants are not considered standard therapy and many centres still look upon this treatment as experimental and in need of further study. RIC-transplants are not generally recommended in situations where there is good evidence that a conventional BMT will lead to a reasonable chance of a cure. While almost all patients having a RIC-transplant will have a high percentage of donor cells in their bone marrow one month after transplant and serious organ damage is less likely with reduced intensity conditioning, a number of problems have been identified with the procedure.
First, when the donor cells approach 100%, graft-versus-host disease (GVHD) usually develops and it is, not uncommonly, life-threatening (even in the RIC-transplant setting). The development of GVHD and associated infections is usually slower after RIC-transplants but it is not yet clear whether these specific complications are any less severe than with a conventional BMT.
Second, there is a relatively high incidence of recurrent leukemia/cancer after RIC- transplants, particularly if the patient has residual leukemia/cancer at the time of the RIC-transplant. In this situation, it is often necessary to increase the amount of conditioning therapy given in order to prevent recurrent cancer but this results in a higher risk of organ damage.
In Vancouver, RIC-transplants from related donors are being evaluated for eligible patients. Unrelated donor RIC-transplants are also offered in select circumstances although the experience is less than with related donor transplants.