Background: Treatment failure in patients who have chronic myeloid leukemia (CML) using tyrosine kinase inhibitors is common due to development of secondary mutations. Amanita phalloides (Amanita) contains low dose of alpha-amanitin (amanitin),which inhibitis RNA polymerase II (RNAP) leading to slowing down of the growth of tumor cells without affecting normal cells.
Aim: To determine if Amanita inhibits the growth of Philadelphia chromosome (Ph1) carrying leukocytes in CML.
Methods: A patient with leukocytes carrying a Ph1 and loss of Y chromosome was treated with Amanita as the only tumor specific therapy. Pre-treatments with the tyrosine kinase inhibitors Imatinib and Nilotinib had to be terminated because of severe side effects. Monitoring was performed with blood cell count and quantitation of bcr-abl fusion transcripts.
Results: The disease state could be stabilized for nearly two years until now with Amanita alone. Whereas leucocyte´s tumor growth was inhibited, and cell count remained low, the percentage of bcr-abl fusion transcripts rose. Although the relative amount of lymphocytes decreased transiently, it remained stable in the range of 1.5/nl [0.6-4.7/nl] blood. Compared to the initial phase of CML diagnosis in 2008, leukocyte count is 5 fold reduced due to the Amanita therapy.
Conclusions: Amanita can inhibit tumor growth of cells carrying Ph1. However, the cells with Ph1 and loss of Y chromosome have growth advantage over the cells without these mutations. The percentage of potential tumor cells increased, but without complications.