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Recent breakthroughs in common adult leukemia highlighted in New England Journal of Medicine

When the most common adult leukemia in the United States was last reviewed by the New England Journal of Medicine (NEJM) in 1995, it was seen through the eyes of theories that dated back to the 1960s. As such, the journal recently invited three of the world's foremost experts on chronic lymphocytic leukemia (CLL) to write an authoritative update covering the transformation in the scientific community's knowledge of CLL that has occurred over the past decade. The review appears in the February 24 issue.

Two of the expert authors are with the North Shore-Long Island Jewish (LIJ) Health System (www.northshorelij.com): Nicholas Chiorazzi, MD, director and CEO of the Institute for Medical Research at North Shore-LIJ in Manhasset, NY, who also serves as Professor of Medicine at New York University School of Medicine, and Kanti R. Rai, MB, BS, investigator at the Institute for Medical Research, chief of hematology-oncology at LIJ Medical Center in New Hyde Park, NY, and the Joel Finkelstein Cancer Foundation Professor of Medicine at Albert Einstein College of Medicine. The third author, Manlio Ferrarini, MD, is with the National Institute for Cancer Research in Genoa, Italy (Istituto Nazionale per la Ricerca sul Cancro, Genova, Italia).

"Previous theories about the development and progression of chronic lymphocytic leukemia require revision. With new molecular and protein markers now identified, patients with features that portend poor outcomes may soon be treated earlier and more effectively," said Dr. Chiorazzi.

"Once these new prognostic markers are clinically available to doctors, and after large-scale trials testing early intervention are completed, the 'watchful waiting' practice may be abandoned in many cases," said Dr. Rai, who treats many CLL patients. "New and upcoming discoveries made collectively by us and many other scientists around the world may alter the natural history of this currently incurable leukemia," he added.

A decade ago, CLL was considered a uniform disease of immature white blood cells that didn't die, with the slow rise in leukemia cell count seen in patients due to an accumulation of these immature and incompetent white blood cells. Scientists have since discovered that CLL cells do indeed turn over, with the accumulation over time a result of the difference in the birth and death rates of the leukemia cells.

Scientists have also since discovered that CLL is not a uniform disease but rather a disease that follows two distinct clinical courses in patients. Some patients require no treatment and have a lifespan of more than 20 years after diagnosis. Since the disease most often strikes older adults, the patients whose disease follows this course usually die with the disease, not because of it. CLL may also follow a more aggressive course. In these cases, patients do require chemotherapy and have a lifespan of only about six to eight years after diagnosis despite treatment.

Scientists, including Drs. Chiorazzi, Rai and others at North Shore-LIJ, as well as other research groups in Bethesda, MD, San Diego, CA, and Barcelona, Spain, have identified genetic and protein markers that can predict whether a CLL patient will follow the benign or aggressive course. Some markers are not yet available for clinical use, however according to the review, measurement of one protein marker called ZAP-70 is becoming more widely available. The authors note that ZAP-70 may actually be the most reliable indicator of prognosis known to date.

After discussing B lymphocytes -- the type of white blood cell that gives rise to CLL, the biology of leukemic lymphocytes and the clinical course of CLL as it relates to the biology, the authors then offer a unifying hypothesis for the development, growth and evolution of the disease, and complete the review with a discussion of the clinical implications for practicing physicians.


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Source:North Shore Long Island Jewish Health System


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