A suggested algorithm for the selection of patients for CNS-directed staging investigations and criteria for use of CNS prophylaxis. ^aCNS diagnostic tests: magnetic resonance imaging (preferred) of the head or computed tomography scan of the head; CSF for cytology and flow cytometry. A CNS evaluation should also be performed with response assessment. ^bKidney/adrenal or uterine involvement and only low-risk CNS-IPI is exceedingly rare. If present, CNS diagnostics are recommended. Note: for patients with MYC+BCL2+ DHIT or THIT DLBCL, all patients should undergo CNS diagnostic tests and receive prophylaxis.