造血幹細胞移植併發症

Buzzwords → Dx

Diagnostic Criteria

• VOD/SOS (EBMT criteria, adult): within 21 d (classical) or beyond (late-onset):
  • Bilirubin ≥2 mg/dL
  • • 2 of: painful hepatomegaly, ascites, weight gain >5 %.
  • Severity grading by ALT, Cr, encephalopathy, MOF.
• TA-TMA (Jodele 2014):
  • Schistocytes >1/HPF
  • Thrombocytopenia (or doubling of baseline)
  • LDH > ULN
  • Decreased haptoglobin
  • • Hypertension, proteinuria (>30 mg/dL random), neuro / GI / renal involvement
  • • sC5b-9 elevated (complement activation)

Workup

• Daily weights, abdominal exam, LFTs, plt, Cr post-HCT.
• Ultrasound liver Doppler (reversed portal flow in VOD/SOS).
• Smear (schistocytes for TA-TMA).
• Complement panel + sC5b-9 for TA-TMA suspicion.
• CXR / HRCT for pulmonary complications.
• Bronchoscopy + BAL for IPS / DAH / infection differentiation.
• Viral PCRs (CMV, EBV, BK, adenovirus, HHV-6).

Treatment Algorithm

flowchart TD
  A[New post-HCT symptom] --> B{Pattern}
  B -- weight gain + ↑bili + thrombocytopenia + RUQ --> C[VOD/SOS: defibrotide<br>+ supportive ascites mgmt]
  B -- schistocytes + AKI + HTN + proteinuria --> D[TA-TMA: stop CNI if possible<br>eculizumab / ravulizumab<br>+ supportive]
  B -- fever + rash + capillary leak around engraftment --> E[Engraftment syndrome:<br>supportive ± methylprednisolone]
  B -- bilateral pulmonary infiltrates + non-infectious --> F[Bronchoscopy + BAL<br>r/o infection<br>etanercept investigational for IPS]
  B -- chronic ↓FEV1 + air trapping --> G[BOS: high-dose steroids + ruxolitinib<br>ICS-LABA + azithromycin + treat as chronic GVHD]
  B -- CMV viremia --> H[Letermovir (ppx)<br>ganciclovir / valganciclovir for active]
  B -- new lytic / mass --> I[EBV PTLD: rituximab ± reduce immunosuppression]

Pearls / Pitfalls

• VOD/SOS treatment = DEFIBROTIDE (Defitelio) — reduces mortality. Risk factors: prior gemtuzumab ozogamicin or inotuzumab ozogamicin (within 6 mo), Bu-based conditioning, prior HCT, advanced disease, age extremes. Inotuzumab → high VOD risk in subsequent allo-HCT — use prophylactic defibrotide consideration.
• TA-TMA — eculizumab / ravulizumab (anti-C5) effective in complement-dysregulation TMA. Always check complement panel + sC5b-9.
• CNI-associated TMA: stopping calcineurin inhibitor often improves; if not, eculizumab.
• Engraftment syndrome ≠ infection ≠ GVHD — fever + rash + capillary leak around engraftment, biopsy if unclear; usually self-limited with steroids.
• CMV in HCT: letermovir prophylaxis (Marty NEJM 2017) is now standard for CMV-seropositive recipients; preemptive ganciclovir if active. Don't miss CMV pneumonitis (BAL + CMV PCR).
• Post-transplant lymphoproliferative disease (PTLD) — usually EBV-driven; rituximab + reduce immunosuppression for early; full chemo for monomorphic.
• BOS (chronic GVHD lung) — early FEV1 decline + air trapping → treat aggressively with steroids + ruxolitinib + ICS-LABA + azithromycin (FAM/FAMR protocols).
• DAH (diffuse alveolar hemorrhage) — bloody return on serial BAL; high mortality; steroids + supportive.
• Late effects of HCT: secondary malignancies (skin, oral, breast, lung, MDS/AML), endocrine (gonadal, thyroid, adrenal), bone disease, cataracts, infertility, chronic GVHD, late infections.
• Survivorship clinic essential post-HCT lifelong.

Cross-references

• Allo-HCT — primary context
• GVHD — distinguish from complications
• Infection prophylaxis post-HCT
• TMA differential
• Inotuzumab → VOD risk
• Drug Regimens — defibrotide, eculizumab, letermovir

相關題目

• Q-154 — Allo-HCT — VOD/SOS recognition
• Q-155 — TA-TMA — recognition and management
• Q-156 — Post-transplant lymphoproliferative disorder (PTLD)

Sources