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History of prior topoisomerase-II inhibitor exposure — etoposide, teniposide, anthracycli...

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

IDRF-IATROGENIC-TOPO2-TAML-PREVENTION
TypeRed flag
Statusreviewed 2026-05-18 | pending_clinical_signoff
DiseasesDIS-AML
SourcesSRC-NCCN-AML-2025 SRC-NCCN-BREAST-2025

Red Flag Origin

DefinitionHistory of prior topoisomerase-II inhibitor exposure — etoposide, teniposide, anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin, mitoxantrone) — ≥1 year prior. Therapy-related AML following topoisomerase-II-inhibitor exposure has distinctive features that differ from alkylator-related t-AML: SHORTER median latency (2-3 years post-exposure vs 5-7y for alkylators), characteristic cytogenetics with balanced translocations involving 11q23 (KMT2A/MLL), 21q22 (RUNX1), or t(15;17) (PML-RARA, APL-like), absence of preceding MDS phase, lower TP53 mutation frequency. Higher per-dose risk than alkylators in some series. Highest risk: breast cancer survivors (anthracycline + cyclophosphamide), pediatric ALL/AML survivors (etoposide), testicular cancer survivors (etoposide in BEP). Prevention-persona RedFlag (§20 v0.3 iatrogenic pilot).
Clinical directioninvestigate
Categoryother

Trigger Logic

{
  "any_of": [
    {
      "finding": "prior_etoposide_exposure",
      "value": true
    },
    {
      "finding": "prior_anthracycline_exposure_ge_1y_ago",
      "value": true
    },
    {
      "finding": "prior_topoisomerase_ii_inhibitor_chemo",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notes

Prevention-persona RedFlag for prior topoisomerase-II inhibitor exposure. Distinct from alkylator t-AML: shorter latency (2-3y vs 5-7y), characteristic 11q23/21q22 cytogenetics, often APL-like t(15;17). Engine routes to PreventionPlan recommending CBC q3mo for first 5y post-chemo + low threshold for marrow evaluation. STUB pending two-Clinical-Co-Lead signoff per CHARTER §6.1 dev-mode. Note: anthracycline exposure also fires RF-IATROGENIC-ANTHRACYCLINE-CARDIO-PREVENTION (separate cardio + t-AML surveillance overlap).

Used By

Indications

Red flag