Immunomodulatory effects of the Agaricus blazei Murrill-based mushroom extract AndoSan in patients with multiple myeloma undergoing high dose chemotherapy and autologous stem cell transplantation: a randomized, double blinded clinical study.

Jon-Magnus Tangen, Anne Tierens, Jo Caers, Marilene Binsfeld, Ole Kristoffer Olstad, Anne-Marie Siebke Trøseid, Junbai Wang, Geir Erland Tjønnfjord, Geir Hetland

Journal: BioMed research international 2015;2015():718539

PMID: 25664323

Free Full Text on ORBi (University of Liege) View on PubMed

Plain Language Summary

Multiple myeloma is a cancer caused by malignant transformation of plasma cells causing bone marrow failure, bone lesions, and renal insufficiency. Beta-glucans from Agaricus blazei Murrill (AbM), the main ingredient of AndoSan, have been shown to have an antitumor effect both in vitro and in animal models. This randomised, double-blind study investigated the effects of AndoSan in multiple myeloma patients who received standard treatment. Patients received either 60ml AndoSan or placebo, orally, for approximately 70 days. 16 patients in the AndoSan group and 17 in the placebo group completed the trial. The study investigated (1) changes in serum levels of blood parameters relevant in multiple myeloma (cytokines, chemokines, and growth factors), (2) differences in expression levels of genes involved in immune activation, and (3) differences in the stem cells of a number of cells associated with the immune system. A significant increase in serum levels of some but not all blood parameters was observed in the AbM group, compared to the placebo group. Gene expression studies suggested that AndoSan may be effective in modulating the immune system. There was no significant difference in treatment response, health related quality of life or survival between the two groups. The authors conclude that AndoSan shows a number of potentially beneficial effects on the immune system when used as adjuvant therapy in patients with multiple myeloma. A limitation of the study was the small sample size which may account for the lack of statistically significant differences in clinical outcomes. It was found after completion of the study that beta-glucan content of AndoSan was only 0.09% rather than the assumed 28%, which raises the question which other constituents may have led to the observed effects.

Abstract

Forty patients with multiple myeloma scheduled to undergo high dose chemotherapy with autologous stem cell support were randomized in a double blinded fashion to receive adjuvant treatment with the mushroom extract AndoSan, containing 82% of Agaricus blazei Murrill (19 patients) or placebo (21 patients). Intake of the study product started on the day of stem cell mobilizing chemotherapy and continued until the end of aplasia after high dose chemotherapy, a period of about seven weeks. Thirty-three patients were evaluable for all study endpoints, while all 40 included patients were evaluable for survival endpoints. In the leukapheresis product harvested after stem cell mobilisation, increased percentages of Treg cells and plasmacytoid dendritic cells were found in patients receiving AndoSan. Also, in this group, a significant increase of serum levels of IL-1ra, IL-5, and IL-7 at the end of treatment was found. Whole genome microarray showed increased expression of immunoglobulin genes, Killer Immunoglobulin Receptor (KIR) genes, and HLA genes in the Agaricus group. Furthermore, AndoSan displayed a concentration dependent antiproliferative effect on mouse myeloma cells in vitro. There were no statistically significant differences in treatment response, overall survival, and time to new treatment. The study was registered with Clinicaltrials.gov NCT00970021.

Address: Deparment of Haematology, Oslo University Hospital, 0424 Oslo, Norway ; Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway.; Department of Pathology, Oslo University Hospital, 0424 Oslo, Norway ; Laboratory Medicine Program, Toronto General Hospital, University Health Network, Toronto, ON, Canada M5G 2C4.; Laboratory of Hematology, GIGA-Research, University of Liege, 4000 Sart Tilman, Belgium.; Department Medical Biochemistry, Oslo University Hospital, 0424 Oslo, Norway.; Department of Pathology, Oslo University Hospital, 0424 Oslo, Norway.; Institute of Clinical Medicine, University of Oslo, 0372 Oslo, Norway ; Department of Immunology and Transfusion Medicine, Oslo University Hospital, 0424 Oslo, Norway.

DOI: 10.1155/2015/718539