According to recent results reported at the 43rd Annual Meeting of the American Society of Hematology, allogeneic stem cell transplants appear to improve long-term survival over moderate-dose therapies for patients with recurrent chronic lymphocytic leukemia.
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. This cancer 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, 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. Chronic lymphocytic leukemia is considered to be a slow-growing, or low-grade cancer.
There is no standard therapy for patients with CLL that continues to progress following initial treatment regimens. Additional moderate-dose chemotherapy with or without biologic therapy and high-dose therapy followed by a stem cell transplant are two treatment options for patients with this stage of disease. However, there is little information regarding long-term survival comparing these therapies for this group of patients.
High-dose chemotherapy and/or radiation tend to be more effective at killing cancer cells than lower doses of therapy. However, the high doses also kill blood-forming cells (stem cells) that are produced in the bone marrow, leaving patients susceptible to infection, anemia and uncontrolled bleeding. In order to rescue low levels of blood cells caused by the high dose therapy, stem cells are collected from either blood or bone marrow, stored and then infused into the patient following high-dose therapy. In an allogeneic transplant, stem cells are collected from a related or unrelated donor. Although high-dose therapy and stem cell transplantation may be very effective at producing a cure in some cancers, it is also associated with a high incidence of severe side effects, leaving some physicians and patients hesitant to utilize this treatment option.
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Researchers recently reported long-term results from a multi-institutional clinical trial comparing moderate-dose therapy to high-dose therapy with an allogeneic stem cell transplant in patients with relapsed CLL. All patients undergoing a stem cell transplant had a related donor. Moderate-dose therapy consisted of fludarabine-based chemotherapy, other combination chemotherapy or chemotherapy plus a monoclonal antibody (biological therapy that stimulates the immune system to fight cancer). High-dose therapy consisted of chemotherapy and/or radiation. During the first 12 months following therapy, the patients treated with high-dose therapy and an allogeneic stem cell transplant experienced a higher death rate than patients treated with moderate-dose therapy. However, after the first 12 months following treatment, patients treated with high-dose therapy had a higher survival rate than those treated with moderate-dose therapy. Five years following therapy, 45% of the patients who were treated with high-dose therapy and a stem cell transplant were alive compared to only 27% of the patients treated with moderate-dose therapy. This represents approximately a 50% increase in the survival rate 5 years following therapy for those patients treated with high-dose therapy and a stem cell transplant.
These results indicate a significant long-term survival rate for patients with relapsed CLL treated with high-dose therapy and an allogeneic stem cell transplant compared to moderate-dose therapy. Patients with relapsed CLL may wish to speak with their physician about the risks and benefits of high-dose therapy and a stem cell transplant or the participation in a clinical trial evaluating novel therapeutic approaches. Sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (cancer.gov).
(Proceedings from the 43rdAmerican Society of Hematology, abstract #2011, Orlando, Florida, December, 2001)