Postmortem flow cytometry and genetic analysis confirmed the diagnosis of pro-B ALL positive for the <i>KMT2A::AFF1</i> fusion gene.<h4>Conclusion</h4>This case illustrates an exceptionally aggressive manifestation of adult <i>KMT2A</i>-rearranged ALL, characterized by the concurrent development of ICH and spontaneous TLS prior to the initiation of any leukemia-specific therapy. This evidence concerns the gene AFF1 and leukemia.