How to Transform an Exceptional Case Report Into a Therapy: Following the Frog Out of the Box

摘要

Once upon a time in Europe, a 56-year-old man was diagnosed with an acute myeloid leukemia (AML) presenting molecular abnormalities associated with poor outcome (trisomy 8, mutation of ASXL1, SRSF2, IDH2, and RUNX1; Figure ​Figure1A).1A). According to the knowledge bank approach,1 his 3-year survival probability was estimated at 11% under intensive chemotherapy regimen (Figure ​(Figure1B).1B). He refused the proposed therapy (induction chemotherapy with allogeneic hematopoietic stem cell transplantation in case of complete remission). Instead, he decided to test Kambô, a traditional ritual used by some communities of the southwest Amazon for diverse purposes such as increasing hunting abilities.2 The ritual consists in the application on the skin of secretions from the arboreal frog Phyllomedusa bicolor after having superficially burned the skin of the recipient with a sharp instrument. The secretions contain a venom, whose effects are rapid and induce various manifestations such as nausea, vomiting, diarrhea, and anaphylactic reactions; some of them are potentially serious, and some fatal cases have been reported.3,4 To date, despite the absence of any formal demonstration of the therapeutic effects of Kambô, this ritual is proposed by New Age therapists all over the world for people suffering from depression, addiction, or various other conditions.5 The leukemic patient went through the Kambô ritual 7 times: after the second time, he became transfusion independent and his blood count was normalized (Figure ​(Figure1C).1C). A year later, a cytological and cytogenetic complete remission were observed after bone marrow evaluation. He went back to work and was free of disease for four and a half years, when he was diagnosed with AML again. Of note, this AML had a sharply different cytological, immunophenotypical, and cytogenetical profile compared with the first AML diagnosed (Figure ​(Figure1A),1A), suggesting that it was not a relapse but a new and unrelated AML. At the molecular level, some gene mutations were shared with the first AML (ASXL1, SRSF2, IDH2), whereas additional private mutations were observed, such as an internal tandem duplication of FLT3 and another mutation in RUNX1, suggesting a phenomenon of evolutionary convergence (Figure ​(Figure1A).1A). The patient received an induction chemotherapy composed of daunorubicin, aracytine, and midaustorin, but his disease was refractory to treatment, and he died from invasive aspergillosis 2 months later.