Hematologic and Cytogenetic Responses to Imatinib Mesylate in Chronic Myelogenous Leukemia

The t(9;22) translocation that forms the Philadelphia chromosome of chronic myelogenous leukemia (CML) also forms a fusion gene, BCR-ABL. The new gene encodes an abnormal tyrosine kinase, which causes the leukemia. Imatinib mesylate inhibits the function of the BCR-ABL protein and can induce remission of CML. This large trial found that imatinib induced cytogenetic and hematologic responses in most patients in whom standard therapy with interferon alfa had failed.

This study provides further encouraging evidence that imatinib, a well-tolerated oral agent, is effective against CML. However, since the cytogenetic response was not evaluated by the highly sensitive polymerase chain reaction, it is likely that most patients who responded have residual disease and will require continuous therapy with the drug.

Intravenous Zoledronic Acid in Postmenopausal Women with Low Bone Mineral Density

Bisphosphonates ameliorate osteoporosis, yet gastrointestinal side effects have limited patients' adherence to oral regimens. Intermittent intravenous therapy is effective, but the optimal interval between doses is unknown. This study examined five intravenous regimens of the potent bisphosphonate zoledronic acid (a total of 1 to 4 mg in one to four doses over the course of one year) and compared them with placebo in postmenopausal women with low bone mineral density.

Lumbar-spine bone mineral density increased similarly in all five zoledronic acid groups. Zoledronic acid infusions at intervals of up to one year produce effects on bone turnover and bone density similar to those achieved with daily oral bisphosphonates. An annual infusion of zoledronic acid might be effective as therapy for postmenopausal osteoporosis.

Proteolytic Antibodies against Factor VIII in Patients with Hemophilia A

Patients with severe hemophilia A in whom inhibitors of factor VIII developed during replacement treatment were found to have IgG antibodies with the ability to hydrolyze factor VIII. Such antibodies were found in more than half the patients with an inhibitor against factor VIII.

Inhibitors of factor VIII create major problems in the treatment of hemophilia because they nullify the therapeutic effect of replacement therapy. The cost of treating patients with inhibitors is enormous. The hydrolytic mechanism described in this article could lead to new approaches to the care of patients with hemophilia who have antibodies that neutralize factor VIII.

Related Editorial

Eosinophilic Meningitis after Travel to the Carribbean

In the weeks after a group of 23 young adults returned from a trip to Jamaica, eosinophilic meningitis developed in 12. Symptoms included headache, neck pain, visual disturbances, and hyperesthesias. Nine of the travelers required hospitalization. A case–control study showed that consumption of a Caesar salad at one dinner was strongly associated with the development of aseptic meningitis.

Although the parasitic infection was not confirmed directly, the clinical manifestations plus the serologic data offer strong evidence that the nematode (roundworm) Angiostrongylus cantonensis was the etiologic agent of this outbreak. This parasitic infection has rarely been documented in the Western Hemisphere.

Images in Clinical Medicine: Syphilitic Aortitis

Examination of a 74-year-old man with a one-year history of mild, stable angina revealed a murmur consistent with the presence of aortic regurgitation.

Clinical Practice: Aortic Stenosis

A 60-year-old man is evaluated for a heart murmur. He jogs regularly and has no cardiac symptoms. Examination reveals a delayed carotid upstroke and a grade 3/6 late-peaking systolic ejection murmur. Echocardiography shows normal systolic function and a heavily calcified aortic valve, with a peak Doppler transvalvular gradient of 64 mm Hg and a calculated valve area of 0.7 cm².

This article discusses the management of aortic stenosis, which can be a challenging problem even for experienced clinicians.

Drug Therapy: Targeted Treatment of Malignant Disorders with Imatinib Mesylate

This review discusses the development and uses of imatinib mesylate, a protein tyrosine kinase inhibitor useful in the treatment of chronic myelogenous leukemia and gastrointestinal stromal tumors that was recently approved by the Food and Drug Administration. Imatinib targets platelet-derived growth factor receptor, inhibits the fusion product of the Philadelphia chromosome, and targets c-kit, a protein tyrosine kinase. The drug may also be effective in the treatment of other tumors that express platelet-derived growth factor receptor or c-kit.

Imatinib mesylate is an anticancer drug with increased capacity to target defined pathways of neoplastic development.

Health Policy Report: Protecting Research Subjects — The Crisis at Johns Hopkins

In June 2001, Ellen Roche, a healthy young technician at the Johns Hopkins Asthma and Allergy Center, died during an asthma study. The tragedy prompted several intensive investigations of research oversight at Johns Hopkins and led to the temporary suspension of all federally funded research projects at the institution. In this Health Policy Report, Steinbrook provides a detailed discussion of the outcome of the investigations, the response from Johns Hopkins, and the wider lessons for all involved in clinical investigation.

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