Lymphoma

The optimal choice of treatment for early-stage Hodgkin’s disease depends on (1) knowledge of the prognostic factors that may influence treatment outcome and (2) the risk of acute and long-term complications incurred by treatment. For prognostic and therapeutic considerations, patients are divided into those with early-stage, favorable-prognosis disease (clinical stage I/II without risk factors) and those with early-stage, unfavorable-prognosis or intermediate-stage disease (clinical stage I/II with risk factors).

WASHINGTON-After further review, a committee of the Institute of Medicine (IOM) has rescinded its earlier finding of a suggestive link between the exposure of veterans to herbicides used during the Vietnam War and an increased risk of their offspring developing acute myelogenous leukemia (AML). The committee’s reanalysis followed the finding that one study that it had relied on was in error.

The Genitope Corporation is sponsoring a phase III double-blind, randomized trial of recombinant idiotype immunotherapy in previously untreated patients with follicular lymphoma.

Currently, patients with early-stage chronic lymphocytic leukemia (CLL) without active disease are observed. However, those patients with elevated beta-2-microglobulin levels appear to have a shorter median survival (6 years vs 10+ years).

ORLANDO-European researchers have found involved-field and extended-field radiotherapy following chemotherapy to be equally effective in treating patients with intermediate-stage Hodgkin’s disease. Andreas Engert, MD, University of Cologne, Germany, reported the results of the multicenter, international study at the 43rd Annual Meeting of the American Society of Hematology (abstract 3199).

Pure red cell aplasia is a rare occurrence in patients with chronic lymphocytic leukemia (CLL). This report is based on two cases-CLL patients with documented pure red cell aplasia who responded remarkably to anti-CD20 or rituximab (Rituxan

The humanized monoclonal antibody apolizumab (Remitogen, Hu1D10), directed against a polymorphic determinant of HLA-DR expressed on normal and malignant B cells, is capable of inducing antibody-dependent cellular cytotoxicity, complement-mediated lysis, and direct apoptosis of lymphoma cell lines (Int J Cancer 93:556-565, 2001).

The FM (fludarabine [Fludara], mitoxantrone [Novantrone]) combination is an effective strategy in follicular lymphoma. From October 1999, patients from 12 Italian centers were randomized for a comparative study of FM vs CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy with the addition of rituximab (Rituxan) in selected cases.

Alemtuzumab (Campath), a CDR-grafted monoclonal antibody, recognizes the CD52 antigen which is expressed on normal B and T cells as well as on leukemic B-cell chronic lymphocytic leukemia (B-CLL) cells.

The antiapoptotic protein bcl-2 is associated with chemotherapy failure in untreated large B-cell lymphomas, and with the recently described poor-prognosis large B-cell lymphoma subtype displaying an activated B-cell genotype (Nature 403:503, 2000).

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.

Advanced follicular lymphomas are incurable with conventional chemotherapy regimens. The Southwest Oncology Group (SWOG) investigated the safety and efficacy of a novel treatment approach by administering six cycles of standard CHOP chemotherapy (cyclophosphamide [Cytoxan, Neosar] at 750 mg/m², doxorubicin HCl at 50 mg/m², vincristine [Oncovin] at 1.4 mg/m², and oral prednisone at 100 mg for 5 days), given at 3-week intervals, followed by radioimmunotherapy. Four weeks after completion of the last cycle of CHOP, patients with a partial (PR) or complete remission (CR) to chemotherapy underwent dosimetry with 450 mg of unlabeled tositumomab (anti-CD20) antibody and 35 mg of trace-labeled iodine-131 tositumomab (Bexxar).

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.

ORLANDO-Treatments credited with improving 5-year survival rates for patients with childhood Hodgkin’s disease may lead to an increased risk of leukemia, breast cancer, and other neoplasms years later, according to a study by the Late Effects Study Group (LESG) presented at the American Society of Hematology annual meeting (abstract 3198).

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]

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.

This phase II study aimed to evaluate the tolerability and activity of the monoclonal anti-CD20 antibody rituximab (Rituxan) in patients with either untreated or relapsed biopsy-proven extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type, with measurable or evaluable disease.

At the 2000 Annual Meeting of the American Society of Hematology, we presented the benefits of rituximab (Rituxan) combined with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone), known as R-CHOP, in comparison with CHOP alone for the treatment of elderly patients with diffuse large B-cell lymphoma (DLCL).

Rituximab (Rituxan), when combined with CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) chemotherapy (R-CHOP) in the treatment of patients with CD20-positive diffuse large B-cell lymphoma (DLCL), significantly prolongs event-free and overall survival (GELA [Groupe d’Etude des Lymphomes de l’Adulte] LNH 98-5 study). Our objective was to estimate the cost-effectiveness of R-CHOP based on the evidence currently available.

ORLANDO-High-dose therapy with stem cell support improves event-free survival in patients with mantle cell lymphoma when performed in first remission, according to results of a European Intergroup study presented at the 41st Annual Meeting of the American Society of Hematology (abstract 3572).

Previously untreated mantle cell lymphoma (MCL) is an uncommon disorder with a poor prognosis when treated with CHOP-like (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) regimens. Typically the complete remission (CR) rate is 20% to 30%, median failure-free survival (FFS) is 10 to 16 months, and median overall survival (OS) is 3 years.

Front-line treatment for previously untreated follicular B-cell lymphoma with the iodine-131-labeled anti-CD20 antibody tositumomab (Bexxar) has been reported to result in a 97% response rate and a 74% complete response rate. Although the median duration of response has not yet been reached with a median follow-up of 2.7 years, concerns have been raised over the tolerability of salvage treatments upon relapse of disease. We have reviewed the clinical course of the 28 patients that have relapsed among the original group of 76 patients treated with tositumomab/iodine-131 tositumomab as front-line therapy.

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