移植物抗宿主病

Buzzwords → Dx

Diagnostic Criteria

• Acute GVHD (Modified Glucksberg / IBMTR scales):
  • Stage by organ: skin (rash % BSA), GI (diarrhea volume), liver (bili level).
  • Overall grade I-IV: combines stages.
• Chronic GVHD (NIH 2014 consensus):
  • Diagnostic features: poikiloderma, lichen planus, sclerosis, esophageal web, BOS, etc.
  • Distinctive features: with histology — needs supportive features for diagnosis.
  • Severity: mild / moderate / severe based on number of organs + functional impact.

Workup

• Skin biopsy + GI biopsy (if accessible) + liver biopsy (rarely) for tissue confirmation.
• CMV / EBV / adenovirus / HHV-6 PCR to rule out viral mimics.
• C diff toxin for diarrhea.
• PFTs (FEV1) at baseline + serial for BOS surveillance.
• Eye exam + Schirmer test + slit lamp for chronic ocular GVHD.
• Lung HRCT if BOS suspected.

Treatment Algorithm

flowchart TD
  A[GVHD suspected] --> B[Confirm with biopsy<br>rule out infection / mimic]
  B --> C{Acute or chronic?}
  C -- acute grade I --> D[Topical steroids skin<br>budesonide GI<br>maintain CNI]
  C -- acute grade II-IV --> E[Methylprednisolone 2 mg/kg/d<br>+ continue tacro/sirolimus]
  E -- response --> F[Slow taper over weeks-months]
  E -- steroid-refractory after 5-7 d --> G[Ruxolitinib REACH-2 — 2L acute<br>OR ECP / MMF / sirolimus]
  C -- chronic mild --> H[Topical steroids + tacrolimus eye drops + supportive]
  C -- chronic moderate-severe --> I[Systemic steroids + CNI<br>add ruxolitinib REACH-3 if refractory]
  I -- steroid-dependent / refractory --> J[Belumosudil ROCK2<br>or ibrutinib<br>or ECP<br>or rituximab if antibody-mediated<br>or low-dose IL-2]
  G --> K[Infection prophylaxis intensified<br>antifungal / antiviral / PJP]
  J --> K

Pearls / Pitfalls

• Ruxolitinib (JAK1/JAK2) is now standard 2L for both acute and chronic steroid-refractory GVHD (REACH-2 acute, REACH-3 chronic).
• Belumosudil (ROCK2) approved 2L+ chronic GVHD (ROCKstar trial).
• Ibrutinib — first FDA-approved for steroid-refractory chronic GVHD (iNTEGRATE trial).
• Mogamulizumab + immediate allo-HCT = severe acute GVHD risk — wait ≥50 d after last dose before HCT.
• Acute GVHD GI can be confused with infection (CMV, C. diff) or conditioning toxicity — biopsy when unsure; consider duodenal vs colonic involvement.
• BOS (chronic GVHD) = irreversible if untreated — early FEV1 monitoring + treat with high-dose steroids + ruxolitinib + ICS-LABA + azithromycin.
• Photopheresis (ECP) is steroid-sparing for skin / liver / chronic GVHD; well-tolerated.
• Tacrolimus / cyclosporine drug levels matter — monitor; nephrotoxicity, hypertension, neurotoxicity (PRES), hyperkalemia are common AEs.
• PTCy (post-transplant cyclophosphamide) day +3 + +4 dramatically reduces GVHD in haplo and increasingly all donors.
• Refractory chronic GVHD can need lifelong therapy; quality of life issues paramount.
• Late-onset acute GVHD — clinical features of acute GVHD presenting >day +100; treated like acute.
• Engraftment syndrome (auto-HCT) is NOT GVHD — fever, rash, capillary leak around engraftment; supportive ± steroids.

Cross-references

• Allo-HCT — GVHD prophylaxis context
• HCT Complications
• Infection ppx during steroid + ruxolitinib
• Drug Regimens — ruxolitinib, belumosudil, ibrutinib

相關題目

• Q-151 — aGVHD — first-line therapy
• Q-152 — Steroid-refractory aGVHD — ruxolitinib
• Q-153 — cGVHD — bronchiolitis obliterans (BOS)

Sources