Study points to new role for donor natural killer cells

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 disease fighting 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.

Did you know?
Peter C. Doherty, PhD, of the St. Jude Immunology department, won the Nobel Prize for Physiology or Medicine in 1996. He shares the award with Rolf M. Zinkernagel, MD, of the University of Zurich. Their findings have led to breakthroughs in the understanding and treatment of viral infections and cancers, and in the development of organ transplant procedures and vaccines.

Ryan's story
DIAGNOSIS:
Ryan was found to suffer from acute lymphoblastic leukemia (ALL), the most common form of childhood cancer, in February 2009.

RYAN'S STORY:

In November 2008, Valencia was bathing her youngest son, Ryan, when she noticed a pea-sized bump near his groin area. Worry flashed through her mind, but she dismissed thoughts that Ryan could be sick because he was always so full of energy.

But just a few months later, that energy began to wane. Ryan would come home from school extremely tired. He needed a nap before homework and dinner. Along with the new lethargy, Valencia noticed two little knots on the right side of Ryan's neck. The worry from months before returned.

Days later, Ryan had a nosebleed that would not stop.

Valencia took her son to the doctor immediately. The pediatrician referred Ryan to an ear, nose and throat specialist, who ran blood tests. The results were devastating.

Ryan suffered from acute lymphoblastic leukemia, the most common form of childhood cancer. "I'm an optimistic person," Valencia said. "At that moment, I thought Ryan was going to die. I didn't know there were types of cancer that are curable." Doctors at the local hospital referred the family to St. Jude Children's Research Hospital.

AT ST. JUDE

After arriving at St. Jude, Ryan began a two-and-a-half year chemotherapy treatment plan. He has responded well to treatment.

"I didn't know anything about childhood cancer before this happened," Valencia said. "Now I know St. Jude is a place of hope. They're saving lives at St. Jude, they're curing kids."

Ryan is an affectionate child who loves his older brother and sister. He participated in home bound school and likes to play the Wii® and video games

St. Jude Children's Research Hospital®, located in Memphis, Tenn., is one of the world's premier pediatric cancer research centers. Its mission is to find cures for children with cancer and other catastrophic diseases through research and treatment. St. Jude is internationally recognized for its pioneering work in finding cures and saving children with cancer and other catastrophic diseases. St. Jude is the first and only pediatric cancer center to be designated as a Comprehensive Cancer Center by the National Cancer Institute. Founded by late entertainer Danny Thomas, St. Jude freely shares its discoveries with scientific and medical communities around the world. St. Jude is the only pediatric cancer research center where families never pay for treatment not covered by insurance. No child is ever denied treatment because of the family's inability to pay. St. Jude is financially supported by ALSAC, its fundraising organization. For more information, please visit www.stjude.org.

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