CML patient with cardiovascular / metabolic / pulmonary comorbidity profile that constrai...

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

ID	`RF-CML-COMORBIDITY-COMPLEX`
Type	Red flag
Status	reviewed 2026-04-26 \| pending_clinical_signoff
Diseases	`DIS-CML`
Sources	`SRC-ELN-CML-2020` `SRC-ESMO-CML-2017` `SRC-NCCN-MPN-2025`

Red Flag Origin

Definition	CML patient with cardiovascular / metabolic / pulmonary comorbidity profile that constrains 2nd-generation TKI choice. Specifically: uncontrolled hypertension, prior arterial thrombotic event, QTc-prolongation risk (baseline QTc > 460 ms or QT-prolonging medications), pancreatitis history, pulmonary hypertension, or pleural-effusion-prone state. Drives selection toward asciminib (STAMP inhibitor, cleanest CV/QTc profile) over nilotinib (CV / QTc / metabolic risk), dasatinib (pleural effusion / pulmonary hypertension), or bosutinib (GI / hepatic) when 2nd-gen TKI is otherwise indicated by RF-CML-HIGH-RISK-ELTS.
Clinical direction	de-escalate
Category	high-risk-biology
Shifts algorithm	ALGO-CML-1L, ALGO-CML-2L

Trigger Logic

{
  "any_of": [
    {
      "finding": "uncontrolled_hypertension",
      "value": true
    },
    {
      "finding": "prior_arterial_thrombotic_event",
      "value": true
    },
    {
      "comparator": ">",
      "finding": "baseline_qtc_ms",
      "threshold": 460
    },
    {
      "finding": "qt_prolonging_medications",
      "value": true
    },
    {
      "finding": "pancreatitis_history",
      "value": true
    },
    {
      "finding": "pulmonary_hypertension",
      "value": true
    },
    {
      "finding": "pleural_effusion_history",
      "value": true
    }
  ],
  "type": "composite_score"
}

Notes

Co-determines TKI selection with RF-CML-HIGH-RISK-ELTS. The combination matters: high-risk CML *plus* CV-comorbidity → asciminib preferred (per ASCEMBL trial 3L+ data extrapolating to comorbid 1L use under expanded ELN guidance); high-risk CML without CV-comorbidity → nilotinib or dasatinib remain reasonable. Imatinib remains acceptable in low-risk comorbid patients where treatment-free remission is not the primary goal. STUB — author content above reflects published evidence but has not been clinically reviewed. Two-reviewer per CHARTER §6.1 required before this RedFlag is wired into ALGO-CML-1L / ALGO-CML-2L decision_tree branches. reviewer_signoffs: 0

Used By

Algorithms

ALGO-CML-1L - ALGO-CML-1L
ALGO-CML-2L - ALGO-CML-2L

Red flag

RF-CML-HIGH-RISK-ELTS - CML high-risk by ELTS (EUTOS Long-Term Survival score) — favors 2nd-generation TKI (nilot...
RF-SOKAL-HIGH - CML chronic phase with Sokal high risk — supports 2nd-generation TKI 1L (dasatinib / nilo...