異體造血幹細胞移植

Buzzwords → Dx

Diagnostic / Decision Concepts

• Indications:
  • Hematologic malignancies: high-risk AML CR1, AML/ALL CR2+, CML accelerated/blast phase, MDS higher-risk, MM (rare), Hodgkin/NHL after auto failure, MPN with adverse risk.
  • Non-malignant: severe AA, severe SCD, β-thal major, congenital BMF (Fanconi, dyskeratosis), inherited immunodeficiency.
• Disease risk index + HCT-CI (comorbidity index) + age + donor availability drive decision.

Workup Pre-HCT

• Disease assessment + HLA typing of patient + family + registry search.
• HCT-CI score + cardiac (EF), pulmonary (DLCO), renal, hepatic.
• Infection screening — HBV / HCV / HIV / CMV / EBV / VZV / HSV / toxoplasmosis / TB / syphilis (donor + recipient).
• Vaccination history (re-vaccinate 6–12 mo post-HCT).
• Donor selection + conditioning regimen + GVHD prophylaxis decision.
• Fertility preservation discussion.
• Psychosocial assessment.

Treatment Algorithm

flowchart TD
  A[Indication for allo-HCT] --> B[HLA typing + donor search]
  B --> C{Donor available?}
  C -- matched sibling --> D[MSD allo-HCT preferred]
  C -- matched unrelated 10/10 or 8/8 --> E[MUD allo-HCT]
  C -- only haploidentical --> F[Haplo + post-transplant cyclophosphamide]
  C -- only cord --> G[Cord blood transplant]
  D --> H{Conditioning}
  E --> H
  F --> H
  G --> H
  H -- young, fit, aggressive disease --> I[Myeloablative MAC<br>Bu/Cy or TBI/Cy]
  H -- older, comorbid, indolent --> J[Reduced-intensity RIC<br>Flu/Bu or Flu/Mel]
  I --> K[GVHD prophylaxis<br>tacrolimus + MTX standard<br>PTCy + tacro + MMF for haplo]
  J --> K
  K --> L[Engraftment day +14-30<br>support transfusions, antimicrobials]
  L --> M{Complications}
  M -- acute GVHD day +100 --> N[See GVHD topic]
  M -- VOD/SOS day +30-100 --> O[Defibrotide, supportive]
  M -- TA-TMA --> P[See HCT_Complications]
  M -- infection (CMV, fungal, PJP, BKV) --> Q[See Infection_Prophylaxis]
  M -- relapse --> R[DLI, second HCT, immunosuppressant taper]

Pearls / Pitfalls

• HLA matching at high-resolution 10/10 (HLA-A, B, C, DRB1, DQB1) for adult unrelated donors; 8/8 (A, B, C, DRB1) often acceptable. Sibling matched at HLA-identical is preferred.
• Haplo + PTCy has revolutionized donor availability — day +3 + +4 cyclophosphamide selectively kills alloreactive T cells; outcomes approach MUD in many settings.
• MAC vs RIC choice: age + comorbidity index (HCT-CI) + disease burden. RIC enables HCT in older / sicker pts; relies on GVL.
• CMV reactivation is the most common viral complication post-HCT — preemptive letermovir prophylaxis if seropositive (CMV+ recipient and/or donor); ganciclovir/valganciclovir for active infection.
• PJP prophylaxis (TMP/SMX) for ≥6–12 mo post-HCT; antifungal prophylaxis with posaconazole or voriconazole during prolonged neutropenia and steroid use.
• Vaccination resumption at 6–12 mo (inactivated) and 24 mo (live vaccines after no immunosuppression × 3 mo).
• Iron overload management: ferritin > 1000 → consider chelation post-HCT (deferasirox).
• Survivorship issues post-HCT: secondary malignancies, infertility, endocrine dysfunction (gonadal, thyroid), bone density loss, cataracts, chronic GVHD, late infections.
• Relapse post-HCT: options include withdraw immunosuppression early, DLI (donor lymphocyte infusion), second HCT, novel agents per disease.
• DLI is highly effective in CML chronic phase relapse, less in AML; significant GVHD risk.
• TBI vs chemo conditioning — TBI causes more late effects (cataracts, secondary cancers, infertility); chemo (Bu/Cy) used in many centers.
• Donor-specific antibodies (DSA) in recipient → graft rejection risk; PEX + IVIG + rituximab desensitization.

Cross-references

• GVHD — acute and chronic
• HCT Complications — VOD/SOS, TA-TMA
• Autologous HCT — different indications
• Hematopoiesis & Stem Cell Biology
• AML — HCT in CR1 for adverse risk
• Letermovir, antifungal, PJP ppx
• Iron chelation post-HCT

相關題目

• Q-148 — Allo-HCT — donor selection hierarchy
• Q-149 — Allo-HCT — myeloablative vs reduced-intensity
• Q-150 — Post-allo-HCT — CMV prophylaxis

Sources