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A New York physician who has played a leading role in testing the Novartis drug Gleevec against leukemia is also finding it effective against a second disease involving blood-cell overproduction.

Dr. Richard T. Silver—Professor of Medicine at Weill Cornell Medical College, Attending Physician at NewYork-Presbyterian Hospital Weill Cornell Medical Center, and Medical Director of the Cancer Research & Treatment Fund—will report the encouraging, if preliminary, findings Monday morning, December 9, at the annual meeting of the American Society of Hematology (ASH) in Philadelphia.

Later in the day, he will report other encouraging results—on the high two-year survival rates of patients treated with Gleevec in the accelerated stage of chronic myeloid leukemia (C.M.L.).

The second disease in question, polycythemia vera (P.V.), is one of a group of conditions called myeloproliferative disorders because they entail overproduction of bone-marrow cells that are precursors of blood cells.

Chronic myeloid leukemia, the most lethal of the myeloproliferative disorders, is characterized by rampant proliferation of immature white blood cells. In polycythemia vera, which afflicts about 7,000 people a year in the U.S., the major problem is overproduction of mature red blood cells. This leads to increased blood volume and viscosity that, if not controlled, can cause fatal clots or hemorrhages.

Even for the many patients who enjoy a normal life span, P.V. can be a difficult disease to live with. Symptoms include headaches, vertigo, lightheadedness, blurred vision, and pruritis (itching without visible eruption on the skin, particularly after a hot bath or shower). Spontaneous bruising, peptic ulcers, and gastrointestinal hemorrhage are seen as the disease progresses.

The principal treatment for P.V. is phlebotomy, which entails removing one pint of blood weekly until the patient's hematocrit (the percentage of blood volume occupied by red cells) falls to a normal level. Thereafter, phlebotomy is performed as needed—that is, when overproduction of new red cells pushes the hematocrit above normal.

Chemotherapeutic agents, such as hydroxyurea, have been used to suppress blood-cell formation but can cause leukemia; interferon alpha has been administered to good effect (Dr. Silver pioneered its use), but can cause severe side effects.

In the study to be reported Monday, Dr. Silver treated seven P.V. patients with Gleevec—four women and three men ranging in age from 29 to 76. All were initially phlebotomized to a normal hematocrit, then were given 400 to 800 milligrams of Gleevec per day.

In six to nine months on Gleevec, the six patients remaining in the trial (one had to drop out early because of dermatitis) have enjoyed a considerable reduction in the need for phlebotomies. Before treatment with Gleevec, the six patients collectively required about 16 phlebotomies per quarter—in other words, almost three per patient. While on Gleevec, they have collectively had about seven phlebotomies a quarter, a drop of more than 50 percent. One patient was phlebotomy-free for over eight months, and one for nearly seven months.

In the case of two patients who had palpably enlarged spleens, one spleen returned to normal a month after treatment with Gleevec was initiated, while the other has been reduced by about 75 percent. Four patients with abnormally high platelet counts saw the levels return to normal.

Gleevec's effectiveness against chronic myeloid leukemia derives from its ability to block a protein within the cell that plays a key role in growth, differentiation, and regulation. The drug's effectiveness against p. vera probably derives from its ability to block a cell-surface receptor called c-kit, which, Dr. Silver suspects, plays a critical role in driving the overproduction of red blood cells.

Following up on the encouraging findings to date, Dr. Silver, with support from Novartis and the Cancer Research & Treatment Fund, has embarked on a larger trial involving doctors from three other medical centers: Duke, Johns Hopkins, and Mt. Sinai of New York.

Dr. Silver will be presenting his findings on polycythemia vera in Session 153, Monday at 8:30 a.m., in Room 201. His report on "Gleevec Against Chronic Myeloid Leukemia, Accelerated Phase," will be at 3:15 p.m., in Ballroom A.