According to results recently presented at the 43
rd annual meeting of the American Society of Hematology, allogeneic mini-transplants appear to produce significant anti-cancer responses and are safer than high-dose regimens in patients with advanced CLL.
Chronic lymphocytic leukemia (CLL) is a cancer involving the lymph (immune) system, which includes lymph nodes, blood, and blood vessels found throughout the body, as well as the spleen, thymus, and tonsils. CLL is found in large amounts in circulating blood and bone marrow (spongy material inside large bones that produces blood forming cells). Chronic lymphocytic leukemia is characterized by the production of atypical lymphocytes. Lymphocytes are specialized immune cells, of which there are two types: B and T-cells. These cells are produced in the bone marrow and each has a very specific function in aiding the body to fight infection. The large majority of CLL cases involve mature B-lymphocytes that tend to live much longer than normal, accumulating in the blood, bone marrow, lymph nodes and spleen. This results in overcrowding of these areas, thereby suppressing the formation and function of blood and immune cells that are normally present. Additionally, the cancerous lymphocytes themselves do not function normally, leading to a further decrease in the ability of the body to fight infection.
Standard treatment for CLL is chemotherapy, with the only known curative option for advanced disease being intensive or high-dose chemotherapy followed by a stem cell transplant. High-dose chemotherapy kills more cancer cells than standard chemotherapy; however, it also causes more damage to the blood cells, particularly those in the bone marrow. The bone marrow (and circulating blood) contains early blood-forming cells called stem cells, which grow and mature into 3 blood cell types: white blood cells, which protect the body from infection; red blood cells, which carry oxygen to the tissues; and platelets, which help the blood to clot. When bone marrow is destroyed, stem cells are depleted, leading to low levels of circulating blood cells. When these cells reach critically low levels, complications such as anemia, bleeding and infection can occur, which may result in death. Thus, it is imperative to restore stem cell levels as quickly as possible.
A stem cell transplant is a procedure that replaces the stem cells that are destroyed by high-dose chemotherapy with healthy stem cells, thereby allowing more rapid recovery and production of the red blood cells, white blood cells, and platelets that the body needs. During an autologous stem cell transplant, stem cells that were collected directly from the patient prior to the delivery of the high-dose chemotherapy are re-infused following treatment. In contrast, an allogeneic stem cell transplant involves stem cells collected from a donor. In addition to the anti-cancer effect of the high-dose therapy, an allogeneic stem cell transplant induces a second anti-cancer effect. Graft-versus-leukemia effect is a term used to describe the process that occurs after an allogeneic transplant, whereby the presence of the foreign donor stem cells (i.e., the graft) and immune system attacks the remaining cancer cells.
Unfortunately, standard allogeneic stem cell transplant regimens have been associated with a high treatment related mortality rate in patients with CLL. In addition, many patients suffer from chronic treatment-related causes, including graft-versus host disease. Graft-versus-host disease (GVHD) is an attack on the patient’s healthy tissues by the donor lymphocytes.
Recently, researchers have developed treatment strategies that take advantage of the graft-versus-leukemia effect, while attempting to reduce complications caused by the transplant procedure. One strategy being evaluated involves the use of lower doses of chemotherapy and/or radiation therapy followed by an allogeneic stem cell transplant, called a mini-transplant.
Researchers from the European Blood and Marrow Transplant Group (EBMT) recently conducted a clinical trial further evaluating allogeneic mini-transplants in 63 patients with recurrent CLL. Patients were treated with either total-body radiation, chemotherapy or a combination of both prior to stem cell infusion. One year following treatment, 80% of all patients were alive and the chance of a cancer recurrence was 16%. The overall treatment-related death was 19% at one year after treatment. The use of radiation as treatment prior to stem cell infusion and the use of unrelated donor stem cells were variables that were shown to decrease chances of survival. Acute GVHD occurred in 32% of patients and chronic GVHD occurred in 75% of patients.
These results indicate that allogeneic mini-transplants appear to produce significant anti-cancer activity and are safer than stem cell transplants utilizing high-dose therapy in patients with recurrent, advanced CLL. Patients with advanced CLL that continues to progress with standard treatment and/or are not candidates for high-dose regimens may wish to speak with their physicians about the risks and benefits of a mini-transplant or the participation in a clinical trial further evaluating this or other promising therapies. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (
Proceedings from the 43
rd annual meeting of the American Society of Hematology
, abstract # 3095, Orlando, Florida, December 11-14, 2001)