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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Leukaemia diagnosed in the first year of life is a different disease from leukaemia in older children: most cases carry a broken KMT2A gene and respond poorly to chemotherapy, and fewer than half of infants were cured for twenty years. One course of the immune drug blinatumomab after induction raised two-year disease-free survival from about half to over 80 percent in a pilot study.
Infant ALL presents with very high white counts, organomegaly, central nervous system involvement and often skin infiltrates. About 75 to 80 percent of cases carry a rearrangement of KMT2A (MLL) with one of many partner genes, commonly AFF1 (AF4), MLLT1 (ENL) or MLLT3 (AF9); the blasts are CD10-negative, express myeloid markers, and can switch lineage to a myeloid phenotype under CD19-directed therapy. KMT2A-rearranged infant leukaemia has one of the quietest genomes in cancer, with almost no other mutations, and depends on the fusion protein's partnership with menin and DOT1L to keep the HOXA gene programme switched on. Age under six months, a white count above 300 x 10^9/L and a poor response to a week of prednisone define the high-risk group.
The Interfant consortium has run the world's infant ALL trials since 1999. Interfant-99 reported four-year event-free survival of 47 percent with a hybrid ALL and AML regimen. Interfant-06, which randomised early intensification with AML-type courses against ALL-type courses, found no difference: six-year event-free survival was 46.1 percent and overall survival 58.2 percent overall, and allogeneic transplant helped only the high-risk group. In 2023 the consortium reported a pilot of 30 KMT2A-rearranged infants given one 28-day course of blinatumomab after Interfant-06 induction: two-year disease-free survival 81.6 percent against 49.4 percent in matched Interfant-06 controls, and overall survival 93.3 percent against 65.8 percent, with no infant relapsing during blinatumomab and no lineage switch in the first two years. Interfant-21 now gives blinatumomab to every KMT2A-rearranged infant.
| Setting | Approach | Guideline |
|---|---|---|
| Induction | Interfant backbone: a week of prednisone, then dexamethasone, vincristine, cytarabine, daunorubicin and asparaginase with intrathecal therapy. | not mapped |
| Post-induction, KMT2A-rearranged | One 28-day course of blinatumomab after induction (Interfant-21), then Interfant-06 consolidation and maintenance. | not mapped |
| High risk | Allogeneic transplant in first remission after blinatumomab and consolidation. | not mapped |
| Relapsed or refractory | Revumenib (approved from the age of one) or trials of menin inhibitors; blinatumomab or CD19 CAR T-cells; transplant. | not mapped |