Baseline organ dysfunction precluding standard CLL regimens: CrCl <30 (venetoclax / acala...

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ID	`RF-CLL-ORGAN-DYSFUNCTION`
Tipo	Sinal de alerta
Estado	reviewed 2026-04-27 \| pending_clinical_signoff
Doenças	`DIS-CLL`
Fontes	`SRC-ESMO-CLL-2024` `SRC-NCCN-BCELL-2025`

Origem da bandeira vermelha

Definição	Baseline organ dysfunction precluding standard CLL regimens: CrCl <30 (venetoclax / acalabrutinib dose-modify; obinutuzumab caution; FCR/BR contraindicated by renal/marrow), severe cardiac dysfunction (LVEF <40% or NYHA III-IV — ibrutinib relative contraindication; acalabrutinib / zanubrutinib preferred), bilirubin >3× ULN (Child-Pugh B/C), or active bleeding diathesis (BTKi bleeding risk).
Direcção clínica	de escalonamento
Categoria	disfunção de órgãos

Lógica de Desencadeamento

{
  "any_of": [
    {
      "comparator": "<",
      "finding": "creatinine_clearance_ml_min",
      "threshold": 30
    },
    {
      "comparator": "<",
      "finding": "lvef_percent",
      "threshold": 40
    },
    {
      "finding": "nyha_class_3_or_4",
      "value": true
    },
    {
      "comparator": ">=",
      "finding": "bilirubin_ratio_to_uln",
      "threshold": 3
    },
    {
      "finding": "active_bleeding",
      "value": true
    },
    {
      "finding": "afib_anticoagulation_required",
      "value": true
    }
  ],
  "type": "lab_value"
}

Notas

Ibrutinib cardiac toxicity (atrial fibrillation, hypertension, sudden death — 5-10% AF cumulatively) — second-generation BTKi (acalabrutinib, zanubrutinib) have substantially lower cardiac AE per ELEVATE-RR / ALPINE head-to-head data; preferred in cardiac-comorbid patients. CrCl <30: venetoclax dose-ramp unchanged but TLS prophylaxis intensified (rasburicase, IV hydration, hospitalization for first ramp). Avoid chemoimmuno (FCR/BR) entirely if any organ dysfunction. AFib requiring anticoagulation + BTKi: bleeding risk additive — consider zanubrutinib (lowest bleeding) or BCL2-based regimen (V+O).

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