Abstract
Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, but it is relatively rare in infants. However, infant ALL exhibits distinct biological characteristics and an aggressive course, with a high proportion of cases involving MLL gene rearrangements (particularly the MLL-AF4 fusion gene). Leukemia driven by MLL-AF4 is extremely rare across all populations but represents a critical and poor-prognosis subtype within infant ALL.ALL driven by the MLL-AF4 fusion is exceptionally rare and particularly fulminant. We report monochorionic monozygotic twins who presented simultaneously with MLL-AF4 positive ALL. Both neonates exhibited fever, pallor, hepatosplenomegaly and extreme leucocytosis. After achieving complete remission with the St.Jude Total Therapy XV (TOTXV) protocol, the twins experienced molecular relapse and were successfully rescued with sequential CD19- and CD22-directed CAR-T-cell therapy. Owing to parental preference and financial constraints, neither patient proceeded to allogeneic haematopoietic stem-cell transplantation; instead, they received consolidative chemotherapy. At 8 years of age, both children remain in sustained molecular remission and enjoy age-appropriate development. This concordant twin pair illustrates the natural history of MLL-AF4-positive infant ALL, supports the curative potential of CAR-T-cell therapy in this ultra-high-risk population, and emphasises the importance of prolonged molecular surveillance.