Twelvepatients without therapy‐related leukemia were studied after completing TOP2 poison chemotherapy in a high‐risk neuroblastoma regimen. One patient harbored an inv(11) that was a KMT2A rearrangement. The KMT2A‐MAML2 transcript was expressed at low level. The patient was prospectively followed. The inv(11) was undetectable in ensuing samples. Leukemia never developed after a 12.8‐year follow‐up period. Enriched etoposide‐induced TOP2A cleavage in the relevant MAML2 genomic region supports a TOP2A DNA damage mechanism. After completing TOP2 poison chemotherapies, covert KMT2A‐R clones may occur in a small minority of patients; however, not all KMT2A rearrangements herald a therapy‐related leukemia diagnosis.