Targeted treatment shows promise for older patients with advanced leukemia
(21 November 2009: VIDYYA MEDICAL NEWS SERVICE) -- Older people are at higher risk of complications during treatment for some types of leukemia. For this reason, patients over the age of 55 are often treated with lower-intensity regimens, but consequently, the risk of disease relapse remains high. Now researchers at Fred Hutchinson Cancer Research Center have shown that combining radioactive iodine (I131) with an antibody can focus radiation at disease sites while sparing healthy tissues in older patients. This increased treatment efficacy while maintaining levels of side effects similar to what is seen in younger patients with better prognoses. Their report appeared in the November 5 issue of Blood.
The phase I study was designed to determine the maximum tolerated dose of the radioactive antibody when used with a reduced-intensity regimen of chemotherapy, total body irradiation, and hematopoietic stem cell transplant in older patients with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) for whom all previous treatments had failed. Fifty-eight patients ages 50 to 74 participated.
The patients were first injected with trace amounts of the radioactive antibody, which targets the CD45 protein found on leukemia cells. Researchers then used a special camera to determine the location and concentration of the antibody throughout the patientís body over the next 3 days. These studies showed that the antibody delivered multiple times more radiation to the bone marrow, lymph nodes, and spleen than to the liver, lungs, or kidneys.
Eight to 14 days later, patients received a therapeutic dose of the radioactive antibody, followed by 3 days of chemotherapy with the drug fludarabine, total body irradiation, and a transplant with blood-forming stem cells. The maximum tolerated dose of antibody radiation, received by 21 patients, was found to be 24 Gy to the liver.
All patients went into remission immediately after treatment, and all of them showed engraftment of the donated stem cells by 28 days after their transplant. The 1-year survival estimate for all patients in the trial was 41 percent (46 percent for those treated at the maximum tolerated dose). The rate of relapse was 40 percent, one that the authors indicated is still high, but similar to that seen in younger cohorts.
While acknowledging that their study was not designed to test efficacy, the authors were optimistic that the approach could be used to improve cure rates for older patients with AML or MDS who need to be treated with reduced intensity regimens. They noted that other radioactive compounds, as well as antibodies against other targets in the disease, should also be explored.
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