Study shows haploidentical natural killer cells may provide hope for some patients with AML

December 05, 2004

A University of Minnesota Cancer Center study indicates natural killer cells obtained from a family member and artificially stimulated may provide renewed hope for some patients who have advanced acute myelogenous leukemia (AML), a highly fatal cancer of the bone marrow, that has become resistant to standard treatment with chemotherapy.

Natural killer cells are part of the body's immune system. The cells play an important role in defending the body against infection and against some cancers, particularly leukemia. In patients with AML, the killer cells have lost most of their natural ability to fight the aggressive cancer cells.

This study is the first to successfully demonstrate that half-matched donor (haploidentical) natural killer cells that are transfused into a patient with AML can survive and persist to actively attack and kill the deadly cancer cells. As a result, the disease may go into remission and make the patient eligible for bone marrow transplant, an effective long-term treatment option for AML.

Jeffrey Miller, M.D., lead researcher, will present the findings of this study - the successful remission of poor prognosis AML patients after transfer of human haploidentical natural killer cells - at the 46th annual meeting of the American Society of Hematology (ASH) on Dec. 5 in San Diego. A hematology physician-researcher, Miller is a professor of medicine at the University of Minnesota Medical School and leader of The Cancer Center's Blood and Marrow Transplant Program.

According to Miller, the goal of the study was to try to stimulate the immune system of patients with advanced AML to fight the cancer by giving the patients natural killer cells that were donated by family members and activated by a drug called interleukin-2. (Typically, interleukin-2 is a protein substance naturally produced by the body to stimulate natural killer cells and other cells to do their job of fighting infections and cancer. However, in patients with AML, the cancer may suppress the ability of interleukin-2 to optimally stimulate the patient's own natural killer cells.)

The result of Miller's study was this: the donated natural killer cells thrived in some patients for more than 28 days, and five of 19 patients achieved remission.

"Admittedly we need to do more research, but we believe that we may have found another option, opened another door to potentially broaden our treatment capabilities of AML and give more hope to some patients who have been told there was nothing more that could be done for them," Miller says.

AML is the most common acute leukemia. In people over age 65, AML has increased about 10 percent in the last 25 years. Of the nearly 12,000 people who will be diagnosed with AML this year, about 90 percent will be adults age 65 and older. Approximately 8,870 people with AML will die this year.

Miller and his research team found in previous studies that natural killer cells derived from the patient did not provide the anti-tumor effect. In this study, the team set out to determine if natural killer cells that were obtained from a family member, artificially stimulated with interleukin-2 and then infused into the patient could have an anti-tumor effect.

A total of 19 patients with AML were compared to a control group of eight patients with renal cancer. The patients with renal cancer received a low intensity outpatient immune suppressive dose of the chemotherapy drug, fludarabine. The patients with AML received a higher intensity inpatient treatment of the chemotherapy drugs, cyclophosphamide and fludarabine. Both sets of patients received interleukin-2, a protein substance that makes infection-fighting cells multiply and mature. The data showed that the infused natural killer cells expanded in the AML patients to achieve anti-tumor efficacy. There were no notable responses in the patients with renal cancer.

Additionally, the study indicated that interleukin-15, also a protein substance and similar to interleukin-2, played a role in the expansion of the natural killer cells. Patients with AML had significant increases in their interleukin-15, while renal cancer patients in the control group showed only a slight increase. This finding suggested that the chemotherapy combination of cyclophosphamide and fludarabine allowed for the expansion of infused natural killer cells.

"We are encouraged by our findings," Miller says. "Now we have data indicating that haploidentical natural killer cells have a role in the treatment of AML, whether used alone or in combination with a bone marrow transplant."
-end-
This study was funded by a research grant from the National Cancer Institute.

University of Minnesota

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