Hydroxyurea (HU) resistance or intolerance in essential thrombocythemia (ET), triggering...

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

ID	`RF-ET-HU-RESISTANT-INTOLERANT`
Type	Red flag
Status	reviewed 2026-05-08
Diseases	`DIS-ET`
Sources	`SRC-ESMO-MPN-2015` `SRC-NCCN-MPN-2025`

Red Flag Origin

Definition	Hydroxyurea (HU) resistance or intolerance in essential thrombocythemia (ET), triggering switch to 2L cytoreduction. ELN/BCSH resistance criteria: platelets ≥600 ×10⁹/L despite HU ≥2 g/day for ≥3 months; failure to achieve platelet <400 ×10⁹/L AND WBC <10 ×10⁹/L on adequate HU dose; thrombotic event occurring on HU therapy. ELN intolerance criteria: ANC <1 ×10⁹/L or Hgb <10 g/dL on any dose of HU; HU-related mucocutaneous toxicity (oral ulcers, leg ulcers, skin atrophy) grade ≥2 at any dose; fever ≥38°C attributable to HU. Anagrelide is the ELN/NCCN 2L standard after HU failure — platelet- selective, non-leukemogenic, preferred in younger patients (ANAHYDRET trial: anagrelide non-inferior to HU in event-free survival, better arterial thrombosis rate). Pegylated IFN (ropeginterferon) is the preferred alternative in pregnancy/planning or JAK2-V617F dominant disease but is not yet a separa...
Clinical direction	de-escalate
Category	prior-therapy-class
Shifts algorithm	ALGO-ET-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "hu_resistance",
      "value": true
    },
    {
      "finding": "hydroxyurea_resistance",
      "value": true
    },
    {
      "finding": "hu_intolerance",
      "value": true
    },
    {
      "finding": "hydroxyurea_intolerance",
      "value": true
    },
    {
      "finding": "cytoreduction_failure_class",
      "value": "HU"
    },
    {
      "finding": "cytoreduction_failure_class",
      "value": "hydroxyurea"
    },
    {
      "finding": "hu_status",
      "value": "resistant"
    },
    {
      "finding": "hu_status",
      "value": "intolerant"
    },
    {
      "finding": "thrombosis_on_hu",
      "value": true
    },
    {
      "comparator": ">=",
      "condition_context": "on_max_tolerated_hu_3mo",
      "finding": "platelet_on_hu",
      "threshold": 600
    }
  ],
  "type": "prior_therapy_failure"
}

Notes

Note: ALGO-ET-2L step 2 already includes RF-PV-ET-HIGH-THROMBOSIS-RISK in its any_of — this RF augments (not replaces) that gate, adding the explicit HU-failure criterion. Since anagrelide is the only 2L IND in the KB, both true and false branches at step 2 route to anagrelide; the RF primarily provides trace evidence for why the switch was made. Age <60 preferring non-cytotoxic option is a clinical preference condition not mapped to a finding — retained as free-text in the algo. Step 3 is degenerate (both → anagrelide) and intentionally not wired. Missing IND-ET-2L-PEG-IFN: peg-IFN α-2a / ropeginterferon is the preferred 2L in pregnancy or JAK2-driven disease (ELN 2018, BSH 2024) but is not modeled — flagged as OOS gap in the algo notes. Draft pending two-reviewer clinical co-lead signoff (CHARTER §6.1).

Used By

Algorithms

ALGO-ET-2L - ALGO-ET-2L