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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.
High-risk childhood leukaemia means a child aged ten or over, a very high white cell count, T-cell disease, spread to the brain or testes, or adverse genetics, and it is treated with longer and more intensive chemotherapy. Most children are still cured; the T-cell form gained the drug nelarabine after the AALL0434 trial, and cranial radiotherapy has been dropped for almost everyone.
High risk is set at diagnosis by age ten or over or a white count of 50 x 10^9/L or more, by T-cell immunophenotype, by central nervous system or testicular disease, and by adverse genetics: hypodiploidy, KMT2A rearrangement, iAMP21, TCF3::HLF and BCR::ABL1-like signatures. It is revised after induction by measurable residual disease, so a standard-risk child with residual disease above 0.01 percent joins this group and a high-risk child who clears it may be spared the most intensive blocks. T-ALL makes up around 15 percent of childhood ALL, presents with high counts and mediastinal masses in adolescent boys, and the early T-cell precursor subtype is treated by residual disease response rather than by immunophenotype.
The augmented Berlin-Frankfurt-Münster regimen, tested by the Children's Cancer Group in the 1990s for slow early responders, is the backbone: four-drug induction adding an anthracycline, consolidation with cyclophosphamide, cytarabine, mercaptopurine and asparaginase, and two interim maintenance and delayed intensification blocks. AALL0232 found high-dose methotrexate with leucovorin rescue superior to escalating Capizzi methotrexate for high-risk B-ALL, and dexamethasone superior to prednisone in children under ten. AALL0434, the largest T-ALL trial ever run, showed the opposite for T-ALL, Capizzi methotrexate beating high-dose methotrexate, and added nelarabine for intermediate- and high-risk T-ALL: five-year disease-free survival 88.2 percent against 82.1 percent, now standard. AALL1231 then removed prophylactic cranial irradiation for all but the highest-risk T-ALL and showed that bortezomib helped T-lymphoblastic lymphoma but not T-ALL. Allogeneic transplant in first remission is reserved for induction failure, hypodiploidy and persistent residual disease at the end of consolidation.
| Setting | Approach | Guideline |
|---|---|---|
| Induction (four weeks) | Four-drug induction: vincristine, dexamethasone or prednisone, daunorubicin and pegylated asparaginase with intrathecal methotrexate; MRD at day 29. | not mapped |
| Consolidation and interim maintenance, high-risk B-ALL | Augmented BFM consolidation with cyclophosphamide, cytarabine, mercaptopurine and asparaginase; high-dose methotrexate with leucovorin rescue (AALL0232); blinatumomab or inotuzumab ozogamicin added in current trials. | not mapped |
| T-cell ALL | Augmented BFM with Capizzi escalating methotrexate and nelarabine courses for intermediate- and high-risk disease (AALL0434); cranial irradiation only for CNS3 or the highest risk (AALL1231). | not mapped |
| Delayed intensification and maintenance | Two delayed intensification blocks with vincristine, dexamethasone, doxorubicin, cyclophosphamide, cytarabine and thioguanine; maintenance with mercaptopurine, methotrexate and vincristine-steroid pulses. | not mapped |
| Very high risk: induction failure, hypodiploidy, persistent residual disease | Blinatumomab to clear residual disease, then allogeneic transplant in first remission; CD19 CAR T-cells as consolidation in trials. | not mapped |