The British Journal of Haematology recently published data suggesting that acute leukemia relapsing after stem cell transplant (SCT) may be effectively treated with reduced intensity chemotherapy and a second allogeneic SCT.
Acute leukemias, which include acute myeloid leukemia and acute lymphoid leukemia, are cancers of white blood (immune) cells. The bone marrow produces early blood-forming cells, called stem cells, which grow and mature into 3 different types of blood cells: red blood cells to supply oxygen to tissues, platelets to aid the blood in clotting and white blood cells which fight infection. Acute leukemias are characterized by uncontrolled growth of immature types of white blood cells in the bone marrow, resulting in excess accumulation of these cells. These leukemia cells crowd the bone marrow, suppressing formation and function of other blood cells, and ultimately invade other parts of the body including the blood, lymph system and vital organs. Acute leukemias are rapid growing cancers and treatment must be aggressive for optimal chance of cure.
High-dose chemotherapy and/or high-dose radiation therapy are aggressive treatments that are highly effective at killing cancer cells. Unfortunately, these treatments do not distinguish between cancer cells and healthy cells, often destroying bone marrow stem cells; this can lead to life threatening complications such as anemia, bleeding and infection. The treatment strategy utilizing SCT is an attempt to restore the blood-forming stem cells after high-dose treatment has reduced them to dangerously low levels. In allogeneic SCT, healthy stem cells are collected from a donor and infused into the patient following therapy. In addition to restoring low levels of blood-forming cells, the donor cells mount an attack on the leukemia cells, known as the graft-versus-leukemia effect.
Unfortunately, cancer can recur even after allogeneic SCT. Currently, one conventional treatment option for such relapse requires infusion of more donor leukocyctes (a specific type of white blood cell) into the patient to take advantage of the graft-versus-leukemia effect. While this therapy is effective for other forms of leukemia, most acute leukemias fail to respond to this treatment. Researchers looking for alternatives are investigating the use of Fludaraâ-containing chemotherapy regimens followed by a second allogeneic SCT. Previous studies suggest that one-third of patients with leukemia treated with Fludaraâ respond to treatment, even though their cancer is resistant to standard chemotherapy regimens, and Fludaraâ appears to be less destructive to the immune system.
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Researchers recently conducted a clinical trial involving 14 patients with relapsed acute leukemia following an allogeneic SCT. All patients were treated with combination chemotherapy containing Fludaraâ, high-dose cytosine arabinoside and granulocyte colony-stimulating factor with or without idarubicin (FLAG±Ida). This treatment was followed by a second allogeneic SCT from the original donor. At 58 months post treatment, 60% of the patients were still alive and 26% were still cancer-free. Normal blood cell production and function returned rapidly after the second SCT. Remissions after the second allogeneic SCT lasted significantly longer than remissions after the first allogeneic SCT. The chemotherapy and SCT were well tolerated, with no treatment-related deaths. The only major complication was graft-versus-host-disease, but it did not cause any patient deaths.
Results from this clinical trial indicate that FLAG±Ida chemotherapy followed by a second allogeneic SCT suggest may effectively treat acute leukemias relapsed after a first allogeneic SCT. Individuals with relapsed acute leukemia may wish to speak with their physician regarding the risks and benefits of this novel therapeutic approach or about participating in a clinical trial. Two sources of information regarding ongoing clinical trials include comprehensive, easy-to-use listing services provided by the National Cancer Institute (cancer.gov) and www.eCancerTrials.com. eCancerTrials.com also provides personalized clinical trial searches on behalf of patients. (British Journal of Haematology, Vol 115, No 3, pp 622-629, 2001)
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