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Once a suitable donor has been identified, stem cells are harvested (collected) from either the bone marrow or from the bloodstream and the cells are frozen for later use. The patient (transplant recipient) then begins and completes a cycle of high-dose chemotherapy to destroy the remaining cancer cells. Patients are also given antirejection drugs such as tacrolimus or cyclosporine (sometimes in combination with prednisone or methotrexate) in order to reduce the likelihood that the patient will reject the donor's transplanted stem cells. The donor's frozen stem cells are then thawed and infused back into the recipient via an intravenous line.

Currently, allogeneic stem cell transplantation is the only potentially curative treatment for CLL. Unfortunately, the standard type of allogeneic stem cell transplant, known as a myeloablative transplant , requires the use of very high doses of chemotherapy to destroy (ablate) the recipient's residual leukemic cells which makes the standard myeloablative transplant too risky for most CLL patients. A study published in 2002 in the journal Cytotherapy (Volume 4; pp. 217-221) reported that, although myeloablative allogeneic stem cell transplantation was found to be very effective in terms of controlling CLL in 28 test subjects, it was associated with a very high (11%) early mortality rate.

Allogeneic stem cell transplantation may offer a potential cure in younger patients with relapsed CLL or younger patients in the high-risk stages (Rai Stages III and IV; Binet Stage C), however, the potential benefits must be carefully weighed against the high risk of treatment-related morbidity and mortality.

Nonmyeloablative Allogeneic Transplants

More recently, a newer type of allogeneic stem cell transplantation procedure, known as a nonmyeloablative transplant (also called a reduced-intensity transplant or "mini-transplant"), that uses much lower doses of chemotherapy to destroy the recipient's residual leukemic cells, has become available to doctors. This type of transplant is much less toxic to the recipient than the standard myeloablative transplant. To date, encouraging results have been reported with nonmyeloablative transplants in terms of controlling CLL, including reports of complete remission in some patients.

In contrast to a standard myeloablative allogeneic stem cell transplant, a nonmyeloablative transplant uses significantly lower doses of chemotherapy (or radiation) and is, therefore, less toxic to the patient. This lower-dose chemotherapy strategy approach, however, destroys only some of the remaining cancer cells but does not completely destroy the patient's diseased bone marrow blood-forming cells. The patient then receives an allogeneic transplant of the donor's bone marrow or stem cells. The donor's transplanted immune cells serve as a "booster" to the recipient's own immune system by recognizing and destroying the remaining cancer cells that have not been killed by the low-dose chemotherapy or radiation therapy. This phenomenon is known as the "graft-versus-tumor" or "graft-versus-leukemia" effect because the donor's transplanted immune cells (the graft) are used as a means of targeting and destroying the patient's residual cancer cells.

Although nonmyeloablative transplants are becoming more common and have been used for patients with a wide range of cancers, they appear to be most effective for patients with chronic myelogenous leukemia (CML). The outcomes for patients with other types of hematological malignancies have varied depending upon the specific type of nonmyeloablative regimen used. In general, nonmyeloablative transplants are usually reserved for older patients (over age 60) or patients with serious underlying conditions who cannot tolerate a standard myeloablative allogeneic stem cell transplant.

Autologous Stem Cell Transplantation