Study points to new role for donor natural killer cells

    Wing Leung, MD, PhD and Jeffrey Rubnitz, MD, PhD

    Powerful but rare immune cells taken from a parent might provide a safe, effective and affordable approach to preventing cancer’s return in young patients with acute myeloid leukemia (AML), according to new St. Jude research.

    The finding is important because relapse is a key reason AML cure rates remain about 70 percent. AML, a cancer of certain white blood cells, is diagnosed in about 500 children and teenagers annually in the U.S.

    This work builds on earlier St. Jude research into natural killer or NK cells, including how to match NK cell donors and recipients to ensure patients receive the most potent cancer-killing donor cells.

    NK cells are the body’s first line of defense against cancer and infections, but they account for less than 10 percent of the diseasefighting immune cells.

    Ten young AML patients who had completed standard therapy and who were in remission participated in the pilot study, which was designed to test the therapy’s safety.

    The work appeared in the January 19 online edition of the Journal of Clinical Oncology.

    The patients received several days of low-dose chemotherapy before receiving an infusion of a parent’s NK cells. Treatment with cyclophosphamide and fludarabine was designed to dampen the patients’ immune systems long enough to give the donor NK cells a chance to kill any of the remaining cancer cells.

    Patients were also treated with interleukin 2, a protein messenger the immune system makes to spur the growth and activity of NK and certain other immune cells. The patients’ immune systems eventually recovered and killed the donor NK cells.

    The investigators reported the donor cells survived in patients for an average of 10 days. Nearly two years after the last patient completed the experimental therapy, all 10 are alive and cancer free.

    The study’s lead author, Jeffrey Rubnitz, MD, PhD, Oncology, said it was too early to know what role the NK cells might have played in the continued remission.

    The donor NK cell therapy was well tolerated, sending patients to the hospital for an average of two days. A second, larger study of effectiveness and other questions is now underway at St. Jude.

    “NK cell therapy appears to be a safe and relatively inexpensive treatment that will likely have few late effects,” the researchers noted.

    None of the patients in this study was considered at high enough risk for cancer relapse to undergo a hematopoietic stem cell transplant. The treatment, which involves replacing the patient’s own blood producing stem cells with stem cells from a genetically identical donor, is expensive, risky and an option for only the roughly one-third of patients with genetically matched donors.

    Senior author of this study is Wing Leung, MD, PhD, director of Bone Marrow Transplantation and Cellular Therapy. Other St. Jude authors are Stanley Pounds, PhD, Biostatistics; Hiroto Inaba, MD, PhD, and Barbara Rooney, both of Oncology; Raul Ribeiro, MD, director of Leukemia/Lymphoma Division and International Outreach; and Ching-Hon Pui, MD, Oncology chair.

    February 2010