Revolutionizing Treatment for Hairy Cell Leukemia Patients

Hairy cell leukemia is a rare malignancy characterized by spleen enlargement and progressive anemia and thrombocytopenia (low platelets). Bone marrow aspirations characteristically reveal a “packed marrow.” In the past, patients were often managed with splenectomy and oral chlorambucil. Response rates were low and complications, including infection and bleeding, often ensued.

The introduction of alpha interferon into the management of this disease by Gutterman and associates at M.D. Anderson, provided a meaningful advance during the 1980s. It was at this time that I was conducting a fellowship at the Scripps Clinic in La Jolla, Calif. I had the good fortune to work with Dennis Carson, MD, and his associate Bruce Wasson. They reasoned that the accumulation of deoxyadenosine, which occurred in children with Severe Combined Immunodeficiency (SCID) and was associated with the virtual annihilation of functional lymphocytes in affected patients, could be mimicked pharmacologically. By synthesizing a 2-chloro derivative of deoxyadenosine, they created 2-CDA.

Reasoning that the drug would be T-cell specific, they began early clinical trials in T-cell lymphoma patients. Dr. Carson kindly provided me with a small aliquot of 2-CDA for study in my laboratory. The activity observed in CLL, ALL and even AML, has since been confirmed. However, what was most interesting was the activity observed in the cells removed from the spleen of a hairy cell leukemia patient. The favorable dose response curve suggested to me that 2-CDA would be an active drug in this otherwise refractory malignancy. After my departure from Scripps Clinic, a junior fellow tested this response clinically, providing curative therapy in more than 90 percent of hairy cell leukemia patients. Today, a single cycle of 2-CDA is the treatment of choice for this disease, providing durable benefit in the majority of patients with minimal toxicity.

At Rational Therapeutics we continues to study novel drugs and combinations to examine their effectiveness in treating disease. Our unique ability to test malignant cells in their native state has enabled us to garner some of the most comprehensive results of any group. We will continue to identify new treatments as we move closer to finding cures for patients.

About Dr. Robert A. Nagourney
Dr. Nagourney received his undergraduate degree in chemistry from Boston University and his doctor of medicine at McGill University in Montreal, where he was a University Scholar. After a residency in internal medicine at the University of California, Irvine, he went on to complete fellowship training in medical oncology at Georgetown University, as well as in hematology at the Scripps Institute in La Jolla. During his fellowship at Georgetown University, Dr. Nagourney confronted aggressive malignancies for which the standard therapies remained mostly ineffective. No matter what he did, all of his patients died. While he found this “standard of care” to be unacceptable, it inspired him to return to the laboratory where he eventually developed “personalized cancer therapy.” In 1986, Dr. Nagourney, along with colleague Larry Weisenthal, MD, PhD, received a Phase I grant from a federally funded program and launched Oncotech, Inc. They began conducting experiments to prove that human tumors resistant to chemotherapeutics could be re-sensitized by pre-incubation with calcium channel blockers, glutathione depletors and protein kinase C inhibitors. The original research was a success. Oncotech grew with financial backing from investors who ultimately changed the direction of the company’s research. The changes proved untenable to Dr. Nagourney and in 1991, he left the company he co-founded. He then returned to the laboratory, and developed the Ex-vivo Analysis - Programmed Cell Death ® (EVA-PCD) test to identify the treatments that would induce programmed cell death, or “apoptosis.” He soon took a position as Director of Experimental Therapeutics at the Cancer Institute of Long Beach Memorial Medical Center. His primary research project during this time was chronic lymphocytic leukemia. He remained in this position until the basic research program funding was cut, at which time he founded Rational Therapeutics in 1995. It is here where the EVA-PCD test is used to identity the drug, combinations of drugs or targeted therapies that will kill a patient's tumor - thus providing patients with truly personalized cancer treatment plans. With the desire to change how cancer care is delivered, he became Medical Director of the Todd Cancer Institute at Long Beach Memorial in 2003. In 2008, he returned to Rational Therapeutics full time to rededicate his time and expertise to expand the research opportunities available through the laboratory. He is a frequently invited lecturer for numerous professional organizations and universities, and has served as a reviewer and on the editorial boards of several journals including Clinical Cancer Research, British Journal of Cancer, Gynecologic Oncology, Cancer Research and the Journal of Medicinal Food.

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