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Dr. Silver and members of CR&T medical board present findings at national hematology meeting

Recent presentations at a major national meeting by Dr. Richard T. Silver, medical director of CR&T, have provided new evidence of the therapeutic powers of Gleevec, the new anti-leukemia pill from Novartis Pharmaceuticals.

Dr. Silver was one of four physician-scientists associated with CR&T to present at the annual meeting of the American Society of Hematology in Philadelphia. Drs. Morton Coleman, Eric J. Feldman, and Shahin Rafii, members of CR&Tís medical advisory board, were also represented by studies at the December meeting.

Gleevec, the major focus of Dr. Silverís presentations, has excited great interest among physicians and scientists by demonstrating unprecedented effectiveness against chronic myeloid leukemia and other cancers. In a featured session of the December meeting, Dr. Silver reported that Gleevec achieves a marked improvement in survival with minimal side effects even for patients in the accelerated phase of chronic myeloid leukemia.

CML can remain in a chronic phase for many years, but, when the disease enters the accelerated phase, it commonly leads to a fatal blast crisis within a matter of months. But, when patients at the accelerated stage are treated with Gleevec, Dr. Silver reported, about two thirds survived for at least two years with few if any side effects, and about 60 percent survived for at least three years. At the latter point, about two thirds of the survivors had not moved beyond the accelerated phase to a blast crisis.

The report, which had 21 co-authors, involved 181 patients with confirmed accelerated disease at 18 centers in Europe and the United States.

Unsurprisingly, survival reflected the body's response to therapy. Among patients who had a complete hematological remission of four weeks or more -- meaning an apparent complete absence of blast cells in their marrow or blood -- the three-year survival rate was about 85 percent, whereas patients who had only a transitory hematological remission or none at all had a three-year survival rate of only about 20 percent. Overall, 72 percent of the patients had a sustained hematologic response -- that is, for four weeks or more -- of which the majority were complete remissions.

Commented Dr. Silver: "While Gleevec is not the final answer to chronic myeloid leukemia, it brings us much closer than we've ever been." In a separate presentation, Dr. Silver reported encouraging, if preliminary, findings in using Gleevec against a second disease involving blood-cell overproduction. The disease in question, polycythemia vera (P.V.) is one of a group of conditions called myeloproferative 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. In the study presented in December, Dr. Silver treated seven P.V. patients with Gleevec -- four women and three men ranging in age from 29 to 76. In six to nine months on Gleevec, the six patients remaining in the trial (one had to drop out early because of dermatitis) 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 collectively had about seven phlebotomies per quarter, a drop of more than half. One patient was phlebotomy-free for over eight months, and one for nearly seven months.

Following up on these encouraging findings, 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. Other reports at the meeting involving physician-scientists associated with CR&T included the following:
•Dr. Coleman and associates reported encouraging results in the use of personalized vaccines against mantle cell lymphoma. By accelerating and extending the vaccination schedule, they were able to improve significantly on previous treatments that employed such vaccines.
•Dr. Feldman and associates reported on a preliminary test of two anti-cancer drugs, bryostatin and fludarabine, in combination against chronic lymphocytic leukemia and non-Hodgkins lymphoma. The results were sufficiently encouraging, they concluded, to justify a larger trial of this combination chemotherapy.
•Dr. Rafii and colleagues reported that radiation of mice resulted in an upsurge in body chemicals that increased the blood supply to tumors and thereby enhanced their growth. The investigators therefore proposed that drugs that counter this effect be administered in conjunction with radiotherapy for cancer patients.

For additional information, please contact:
Keith Muhleman, CR&T.
Phone: 212-288-6604
Fax: 212-288-7704 or 212-746-8246
e-mail: kmuhleman@crt.org