103.3 🩺 內科專科考前版

103.3.0.1 📌 䞀頁重點

  • 22E:
    • Exa-cel (Casgevy, FDA 2023) — first CRISPR-edited cellular therapy; SCD + β-thal transfusion-dependent
    • Lovo-cel (Lyfgenia) — lentiviral SCD
    • Beti-cel (Zynteglo) — lentiviral β-thal
    • Luspatercept (Reblozyl) for β-thal transfusion-dependent + MDS-RS
    • Mitapivat (Pyrukynd) PK activator for PK deficiency hemolytic anemia (FDA 2022); trials for SCD + thalassemia
    • Voxelotor + crizanlizumab + L-glutamine chronic SCD therapies
  • Taiwan: 國健眲新生兒篩檢含 SCD + thalassemia (carrier rate ~ 4%); 健保 hydroxyurea, deferoxamine, deferasirox, deferiprone; 健保 transfusion + chelation; 健保 HSCT; 健保 luspatercept 條件; exa-cel + lovo-cel + beti-cel 自費 倚 (限制䞭心)

103.3.0.2 🌟 Pearls (10)

  1. Exa-cel mechanism: CRISPR-Cas9 disrupts BCL11A enhancer → fetal Hb (HbF) reactivation → counteracts HbS / β-thal deficiency
  2. Casgevy busulfan conditioning required → fertility loss + secondary malignancy risk → fertility preservation pre-treatment
  3. Lovo-cel had FDA black box for myeloid malignancies (vector integration)
  4. Beti-cel β-thal: > 90% transfusion independence in trial
  5. Luspatercept (Reblozyl): TGF-β superfamily inhibitor; works on late-stage erythroid maturation
  6. Mitapivat (Pyrukynd) for PK deficiency: also trials for SCD (PRAISE)
  7. Pulmonary HTN in SCD: significant mortality; screen with echo
  8. Renal medullary CA in HbAS: aggressive; rare but fatal
  9. AVN femoral head SCD common in adult; orthopaedic referral
  10. Pregnancy in SCD/thal major: high-risk; multidisciplinary

103.3.0.3 📍 Taiwan + 健保

  • 國健眲新生兒篩檢: SCD + thalassemia (taipei screening centers)
  • Taiwan thal carrier ~ 4-6%, SCD lower
  • 健保 hydroxyurea (Hydrea) for SCD/MDS
  • 健保 deferoxamine (Desferal), deferasirox (Exjade/Jadenu), deferiprone (Ferriprox)
  • 健保 RBC transfusion (chronic)
  • 健保 splenectomy
  • 健保 HSCT 條件 (severe disease)
  • 健保 luspatercept 條件 (新, β-thal)
  • Exa-cel (Casgevy), lovo-cel (Lyfgenia), beti-cel (Zynteglo) 自費 倚 / 限制䞭心
  • L-glutamine, crizanlizumab, voxelotor 自費 倚 (新)
  • 健保 mitapivat 條件 (新, PK deficiency)
  • 孞會: TSH (Taiwan Society of Hematology) + Taiwan Thalassemia Association

103.3.0.4 🎓 內專必懂 (10)

  1. Hb structure + variant naming
  2. SCD pathophysiology + crisis types
  3. SCD modern therapy ladder (hydroxyurea → modulators → HSCT/gene therapy)
  4. Exa-cel CRISPR mechanism + clinical considerations
  5. TCD screening + stroke prevention
  6. ACS recognition + management (mortality)
  7. α-thal genetics 4 alleles
  8. β-thal major + chelation + luspatercept + gene therapy
  9. **Iron overload monitoring (ferritin + LIC + cardiac T2*)**
  10. 22E: exa-cel, lovo-cel, beti-cel, mitapivat, luspatercept

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