epiglucan and Leukemia--Lymphocytic--Chronic--B-Cell

Relatively few cancers arise in mature, differentiated cells. The propensity of mature B cells to transform has been linked to their longevity and proliferative potential, and stimulation of the B cell receptor (BCR) by cognate antigen may promote the transformation process. A study in this issue (Hoogeboom et al.) lends support to this notion, showing that cancer cells from a subset of patients with chronic lymphocytic leukemia (CLL) express a BCR specific for a sugar expressed by commensal yeast species. Another study, in contrast, suggests that B-CLL cells uniquely acquire the ability to signal in the complete absence of ligand.

Topics: beta-Glucans; Epitopes; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Receptors, Antigen, B-Cell; Yeasts

Poly-[1-6]-β-glucopyranosyl-[1-3]-β-glucopyranose (PGG) beta glucan is a Saccharomyces cerevisiae derived 1,3/1,6 glucose polymer with innate immune system activation potential. This phase I/II clinical trial enrolled 20 eligible patients with chronic lymphocytic leukemia with high-risk biological markers for early initial treatment with alemtuzumab, rituximab and PGG beta glucan (1-2-4 mg/kg/dose) over 31 days. PGG beta glucan at 4 mg/kg was well tolerated and used for the phase II study. There were three grade 3-4 toxicities at least possibly attributed to treatment. Nineteen (95%) patients responded to treatment with 13 (65%) complete responses. All patients were alive at a median follow-up of 24.4 months (range: 9.5-37). Eleven patients had progressive disease (median 17.6 months, 95% confidence interval [CI]: 9.7, 32.1) and eight patients were retreated (median 35.3 months, 95% CI: 17.9, not reached). We conclude that PGG beta glucan, alemtuzumab and rituximab treatment is tolerable and results in a high complete response rate.

Topics: Aged; Alemtuzumab; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Biomarkers, Tumor; Chromosome Aberrations; Disease Progression; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Remission Induction; Rituximab; Treatment Outcome

Beta-(1,3)/(1,6) D-glucan, a component of the fungal cell wall, has been shown to stimulate the immune system, enhance hematopoiesis, amplify killing of opsonized tumor cells and increase neutrophil chemotaxis and adhesion. In view of these attributes, the beta-glucans should be studied for both their therapeutic efficacy in patients with cancer as well as an adjunctive therapy in patients receiving chemotherapy as a maneuver to limit suppression of hematopoiesis.In this study, twenty patients with advanced malignancies receiving chemotherapy were given a beta-(1,3)/(1,6) D-glucan preparation (MacroForce plus IP6, ImmuDyne, Inc.) and monitored for tolerability and effect on hematopoiesis. Our results lead us to conclude that beta-glucan is well-tolerated in cancer patients receiving chemotherapy, may have a beneficial effect on hematopoiesis in these patients and should be studied further, especially in patients with chronic lymphocytic leukemia and lymphoma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; beta-Glucans; Female; Hematopoiesis; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma; Male; Middle Aged; Neoplasms; Proteoglycans

B cell chronic lymphocytic leukemia (CLL), the most common leukemia in adults, is a clonal expansion of CD5(+)CD19(+) B lymphocytes. Two types of CLLs are being distinguished as carrying either unmutated or somatically mutated immunoglobulins (Igs), which are associated with unfavorable and favorable prognoses, respectively. More than 30% of CLLs can be grouped based on their expression of stereotypic B cell receptors (BCRs), strongly suggesting that distinctive antigens are involved in the development of CLL. Unmutated CLLs, carrying Ig heavy chain variable (IGHV) genes in germline configuration, express low-affinity, poly-, and self-reactive BCRs. However, the antigenic specificity of CLLs with mutated IGHV-genes (M-CLL) remained elusive. In this study, we describe a new subset of M-CLL, expressing stereotypic BCRs highly specific for β-(1,6)-glucan, a major antigenic determinant of yeasts and filamentous fungi. β-(1,6)-glucan binding depended on both the stereotypic Ig heavy and light chains, as well as on a distinct amino acid in the IGHV-CDR3. Reversion of IGHV mutations to germline configuration reduced the affinity for β-(1,6)-glucan, indicating that these BCRs are indeed affinity-selected for their cognate antigen. Moreover, CLL cells expressing these stereotypic receptors proliferate in response to β-(1,6)-glucan. This study establishes a class of common pathogens as functional ligands for a subset of somatically mutated human B cell lymphomas.

Topics: Aspergillus; B-Lymphocytes; beta-Glucans; Candida; Case-Control Studies; Cell Proliferation; Epitopes; Humans; Immunoglobulin Heavy Chains; Immunoglobulin M; Immunoglobulin Variable Region; Leukemia, Lymphocytic, Chronic, B-Cell; Mutation; Receptors, Antigen, B-Cell; Recombinant Proteins; Saccharomyces; Trichosporon; Yeasts

A 66-year-old male with ischaemic cardiomyopathy and chronic lymphocytic leukemia developed signs of severe systemic inflammatory response syndrome. Serial blood cultures were negative and a SeptiFast test detected the presence of Aspergillus fumigatus DNA. Afterwards, detection of galactomannan and 1,3-β-D-glucan showed a positive result. Autopsy revealed the presence of branched fungal structures suggestive of Aspergillus.

Topics: Aged; Aspergillosis; Aspergillus fumigatus; Autopsy; beta-Glucans; Cardiomyopathies; DNA, Fungal; Endocarditis; Fatal Outcome; Galactose; Histocytochemistry; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mannans; Microscopy; Proteoglycans