B-ALL risk groups (NCI criteria, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, IKZF1, CNS status)

What is measured: the risk group that sets the intensity of therapy in B-cell acute lymphoblastic leukaemia. How: age and white cell count at diagnosis (NCI standard risk is age 1 to under 10 with a count under 50 x 10^9/L), CNS status on the diagnostic lumbar puncture (CNS1 no blasts, CNS2 blasts with fewer than 5 white cells per microlitre, CNS3 5 or more with blasts or a cranial nerve palsy), karyotype and FISH (ETV6::RUNX1, BCR::ABL1, KMT2A, TCF3::PBX1, the RUNX1 probe for iAMP21, hypodiploidy), DNA index, SNP array or MLPA for IKZF1 deletion (IKZF1-plus when combined with CDKN2A/B, PAX5 or PAR1 deletions without ERG deletion), RNA-based classifiers for Ph-like, DUX4, ZNF384, MEF2D and PAX5-altered subtypes, the day 8 blast response to prednisone in BFM protocols, and flow or PCR measurable residual disease at the end of induction (day 29) and of consolidation at the 0.01 percent threshold, which outweighs everything else. Frequencies: ETV6::RUNX1 and high hyperdiploidy each about a quarter with event-free survival near 95 percent; hypodiploidy under 44 chromosomes 1 to 2 percent, with germline TP53 testing in low hypodiploidy; iAMP21 about 2 percent, needing high-risk therapy; IKZF1 deletion about 15 percent. What a result changes: standard versus high-risk arms (anthracycline, intensified consolidation, extra delayed intensification), the amount of intrathecal therapy, imatinib or dasatinib for Ph-positive disease, blinatumomab in consolidation for standard-risk children (AALL1731, 2024), transplant for hypodiploidy with residual disease, and TPMT and NUDT15 genotyping before mercaptopurine. Where it matters: the paediatric ALL pages (standard risk, high risk, Ph-positive, Ph-like, infant, relapsed) and adult ALL.