Leukemia

Rituximab (Rituxan), a chimeric anti-CD20 antibody, is effective as a single agent in chronic lymphocytic leukemia (CLL), down-regulates antiapoptotic proteins in CLL cells in vivo, and is minimally immunosuppressive.

Front-line treatment of chronic lymphocytic leukemia (CLL) with single-agent fludarabine (Fludara) achieves complete remission in 35% of patients.

Wild-type bcl-2 protein is normally found within the bilaminar membrane of the mitochondrion, where it is believed to negatively regulate the release of cytochrome C into the cytoplasm after an apoptotic signal has triggered dimerization of bax protein.

Failure of treatment in chronic lymphocytic leukemia (CLL) is often characterized by increased expression of the antiapoptosis protein bcl-2. High levels of bcl-2 protein block the apoptotic death machinery at the mitochondrial level by maintaining the permeability transition pore (PTP) in the closed position.

Rituximab (Rituxan), a chimeric human-mouse anti-CD20 antibody, and alemtuzumab (Campath), a humanized rat anti-CD52 antibody, have each shown activity in chronic lymphocytic leukemia (CLL).

Although patients with small lymphocytic lymphoma and chronic lymphocytic leukemia (SLL/CLL) have CD20 expression on malignant lymphocytes, response rates with standard rituximab (Rituxan) courses in refractory patients have been low.

There have been significant advances in our understanding of the biology of acute myelogenous leukemia (AML), and to a lesser extent, in its treatment. Dr. Estey has provided an excellent overview of the current state of the clinical management of the disease. He has described both the standard therapeutic approaches, including allogeneic hematopoietic stem cell transplantation, as well as the role of investigational therapy. The present state of clinical research in AML is reviewed in some detail in the context of the broad clinical investigation of the disease at the M. D. Anderson Cancer Center. Dr. Estey makes a strong argument for the early consideration of investigational therapy, focusing on patients for whom "standard" therapy is demonstrably inadequate.

Therapeutic strategies are evolving for the treatment of patients with newly diagnosed acute myelogenous leukemia (AML), as well as for those with relapsed or refractory disease. Clinical and laboratory studies have demonstrated that AML is not a single disease, but a heterogeneous group of diseases with different clinical features and natural histories. There are variable responses to therapy depending on both the biologic characteristics of the disease and the clinical characteristics of the patient. Nevertheless, studies evaluating the outcomes of relatively large numbers of patients with newly diagnosed AML show that the majority still die of their disease.[1-3]

These reports are written by oncologists from Pacific Shores Medical Group (a large group practice in Long Beach, California). The reports are primarily based on notes taken at the American Society of Clinical Oncology yearly meeting (San Francisco, May 2001). The reports include our impressions (shown in italic type) of the clinical significance of the studies. The information is intended to help you get updated on new developments in oncology. The coverage of the meeting is not meant to be comprehensive, but rather focused on highlights that we consider most interesting or relevant.

The treatment of patients with acute myelogenous leukemia (AML) ranges from palliative care only, to standard therapy, to investigational approaches. Acute myelogenous leukemia is, in fact, several different diseases, and the percentage of clinical responses varies with disease and prognostic subsets.

HOUSTON-The farnesyl transferase inhibitor R115777 (tipifarnib, also known as Zarnestra) produced an overall response rate of 33% in patients with chronic myelogenous leukemia (CML) and decreased splenomegaly in most patients with myelofibrosis, but was not effective in multiple myeloma, reported Deborah Thomas, MD, at the 43rd Annual Meeting of the American Society of Hematology. Dr. Thomas is assistant professor in the Department of Leukemia at The University of Texas M. D. Anderson Cancer Center in Houston.

ORLANDO-Patients with chronic myelogenous leukemia (CML) who have a complete cytogenetic response (CCgR) to interferon-alfa have a long survival, and low-risk patients have a projected 10-year survival of more than 80%, Francesca

ORLANDO, Florida-Updated data from two phase II trials show that imatinib mesylate (Gleevec, STI571) continues to improve response rates for patients with chronic myelogenous leukemia (CML) who did not respond to interferon therapy or are in blast crisis. With follow-up of 12 months or more, overall and complete response rates are proving to be durable and toxicities tolerable

ORLANDO-Imatinib mesylate (STI-571, Gleevec) is showing excellent results in newly diagnosed patients with chronic myelogenous leukemia (CML) in the early chronic phase, scientists reported at the 43rd Annual Meeting of the American

ORLANDO, Florida-Two phase I/II studies indicate that combination treatment with imatinib mesylate (Gleevec, also known as STI571) produces a high rate of hematologic response in patients in the chronic phase of chronic myelogenous leukemia (CML). Dose-limiting toxicities were mainly hematologic, and researchers advocate further studies were recommended to establish efficacy and recommended dosing.

MANNHEIM, Germany-Despite encouraging initial responses, patients with chronic myelogenous leukemia (CML) frequently become resistant in the advanced, or blast crisis, phase of the disease after initially responding to selective inhibition of the Bcr-Abl tyrosine kinase by imatinib (Gleevec, also known as STI571).

ROME-Best outcomes from donor lymphocyte infusion in chronic myelogenous leukemia (CML) occur when the first dose does not exceed 0.2 × 108 mononuclear cells/kg, Cesare Guglielmi, MD, reported in a presentation at the 43rd Annual Meeting of the American Society of Clinical Oncology.

MIAMI BEACH-Histone deacetylase (HDAC) inhibitors have emerged as promising new candidates in T-cell lymphoma therapy. Phase I data reported by National Cancer Institute (NCI) investigators showed responses in all patients treated with

MIAMI BEACH -The Bcr-Abl tyrosine kinase inhibitor PD173955 (PD17) binds to the target ATP binding pocket even more efficiently than STI-571 (imatinib mesylate, Gleevec). It shows 15 to 20 times greater efficacy in chronic myelogenous leukemia (CML) cell lines because it can bind to either open or closed activation loops.

EAST HANOVER, NJ-Novartis has submitted a supplemental new drug application (sNDA) to the FDA seeking approval for Gleevec (imatinib mesylate) for the treatment of patients with unresectable and/or metastatic malignant gastrointestinal stromal tumors (GISTs). Last May, Gleevec received FDA approval for the treatment of patients with chronic myeloid leukemia in the blast crisis, accelerated phase, or in chronic phase after failure of interferon-alfa.

WASHINGTON-The National Cancer Institute will expand its support for trials of imatinib mesylate (Gleevec, also known as STI-571), recently approved for use in chronic myeloid leukemia (CML), to explore the drug’s potential in several other types of malignancies, director Richard D. Klausner, MD, told the National Cancer Advisory Board (NCAB).

n WHITE PLAINS, NY-The Leukemia & Lymphoma Society has joined in a collaborative partnership with Novartis to educate the public about imatinib mesylate (Gleevec, also known as STI-571), Novartis’ new oral medication approved by the FDA for patients with Philadelphia-chromosome-positive chronic myelogenous leukemia (CML) who have failed interferon therapy.

SOUTH SAN FRANCISCO-The FDA has approved a supplemental biological license application (sBLA) for Rituxan (rituximab), the monoclonal antibody developed by Genentech, Inc. and IDEC Pharmaceuticals (San Diego) for treatment of patient with relapsed or refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL). The new product labeling includes re-treatment with rituximab after a prior course, initial treatment with eight weekly infusions instead of four, and treatment of bulky disease.

WASHINGTON-A new evaluation of existing scientific studies has found "limited or suggestive" evidence to link servicemen’s wartime exposures to herbicides in Vietnam with the development of acute myelogenous leukemia (AML) in their children. However, the Institute of Medicine (IOM) committee that reported the finding emphasized that the evidence for the association is not conclusive.

WASHINGTON -The Food and Drug Administration, acting with dispatch, has approved the marketing of Gleevec (imatinib mesylate, Novartis) for the treatment of chronic myeloid leukemia (CML). The agency granted the drug priority review and orphan drug status, and approved it under the FDA’s "accelerated approval" regulations less than 3 months after the sponsor submitted its marketing request.

Novartis recently announced that the United States Food and Drug Administration (FDA) approved its signal transduction inhibitor Gleevec (imatinib mesylate) as an oral therapy for the treatment of patients with chronic myeloid leukemia (CML) in

NEW YORK-Novel treatment strategies targeting specific cytokines may provide an additional therapeutic window for the treatment of chronic lymphocytic leukemia (CLL), Janice L. Gabrilove, MD, of Mount Sinai School of Medicine, New York, said at the Chemotherapy Foundation Symposium XVIII.

The exact mechanism of development of autoimmune hemolytic anemia (AIHA) in chronic lymphocytic leukemia (CLL) is unclear, but the imbalance among lymphocyte subsets is considered to be the basis for the emergence of an autoimmune

Treatment options for patients with relapsed chronic lymphocytic leukemia (CLL) are limited. In this report, we present our preliminary results of a biochemotherapy combination using rituximab (Rituxan, a monoclonal antibody against CD20) with

Initial treatment of chronic lymphocytic leukemia (CLL) with fludarabine (Fludara) or fludarabine/cyclophosphamide (Cytoxan, Neosar) resulted in complete remission (CR) rates of 28% and 35%, respectively. Recently, rituximab (Rituxan)