40th annual meeting of the American Society of Hematology.

A highly sensitive and specific assay is now available for measuring plasma and intracellular levels of oblimersen sodium (Genasense®, Genta) and target down-regulation of Bcl-2 messenger RNA (mRNA) expression in older patients with acute myeloid leukemia (AML). Investigators found that this new antisense agent, directed against Bcl-2 protein, produced robust intracellular levels of drug in target tissue in vivo, which resulted in clinically relevant target down-regulation and correlated with disease response. Twenty-nine patients older than 60 years of age who had not undergone earlier chemotherapy for AML received intravenous (IV) induction therapy with oblimersen, cytarabine (ara-C, DepoCyt®, Chiron/SkyePharma), and daunorubicin (e.g., Cerubidine®, Ben Venue). Upon achieving complete remission, the patients underwent two cycles of consolidation therapy of IV cytarabine (on days four to eight) and oblimersen (on days one to eight). The enzyme-linked immunosorbent assay (ELISA)-based test, developed at the university’s cancer center, was used to measure plasma and intracellular levels of oblimersen. Bcl-2 mRNA and protein levels were quantified with real-time polymerase chain reaction (RT–PCR) testing and ELISA, respectively. The overall response rate in the total patient population was 58.6% (17 patients); 61.4% (eight of 13 patients) had primary AML, and 56.2% (nine of 16 patients) had secondary AML. In the overall patient population, there were 14 complete responses (CRs): seven in the primary AML patients and seven in those with secondary AML. There were three incomplete responses: one in patients with primary AML and two in patients with secondary AML. The first evidence that measurable in vivo uptake of antisense occurred in bone marrow cells in AML patients was obtained following 72 hours of oblimersen infusion. Intracellular levels of oblimersen appeared higher in the patients who achieved CRs (5.62 pmol/mg protein) than in the nonresponders (1.84 pmol/mg protein). In 22 patients who were evaluable for both clinical response and Bcl-2 levels, the intracellular Bcl-2 protein content at the baseline assessment was significantly higher in the patients with CRs than in the nine nonresponders. After 72 hours of oblimersen IV infusions, the evaluable CR patients showed a marked reduction of Bcl-2 content, compared with a statistically significant increase in Bcl-2 content in the nonresponders. A trend toward higher intracellular oblimersen concentrations was also observed in the evaluable CR patients compared with the nonresponders. More than 20,000 physicians, research scientists, radiologists, nurses, and other health care professionals attended the 46th annual meeting of the American Society of Hematology (ASH) in San Diego, California, from December 4 to 7, 2004, to hear the latest developments on malignant and nonmalignant hematological diseases. Some unique approaches included a new antisense agent/chemotherapy combination for elderly patients with acute myeloid leukemia; a novel arsenic compound for adults or children with acute promyelocytic leukemia; a protein-tyrosine kinase inhibitor for newly diagnosed chronic myeloid leukemia; a monoclonal antibody and chemotherapeutic agent combination for relapsed chronic lymphocytic leukemia; two immunotherapeutic approaches for both previously untreated patients with non-Hodgkin’s lymphoma and patients with relapsed or refractory disease; a proteasome inhibitor for first-l ine multiple myeloma therapy; an immunomodulatory agent for maintenance therapy in myeloma; an investigational iron chelation agent for beta-thalassemia and transfusion-related iron overload; and a low-molecular-weight heparin as a bridging anticoagulant for patients with a mechanical prosthetic heart valve who need to discontinue warfarin therapy temporarily. Meeting Highlights