造血與幹細胞生物學

Buzzwords → Dx

Diagnostic / Functional Concepts

• Stem cell hierarchy:
  • HSC (CD34+ CD38- CD90+ Lin-) — long-term self-renewing
  • Multipotent progenitor (MPP)
  • Common myeloid (CMP) → granulocyte-macrophage (GMP) and megakaryocyte-erythroid (MEP) progenitors
  • Common lymphoid progenitor (CLP)
• Stem cell sources for transplant:
  • Bone marrow (BM): classical; collected by aspirate; lower chronic GVHD vs PB.
  • Peripheral blood (PB): mobilized by G-CSF ± plerixafor; higher CD34+ yield; faster engraftment but more chronic GVHD.
  • Cord blood (CB): naive T cells; smaller cell dose; tolerant of HLA mismatch; slower engraftment.

Mobilization & Collection

• Autologous mobilization: G-CSF 10 µg/kg/d × 4–5 d → apheresis when CD34 count rises.
• Plerixafor (CXCR4 antagonist) for poor mobilizers (lymphoma, MM, prior chemo).
• Allogeneic donor mobilization: G-CSF 10 µg/kg/d × 4–5 d; collect on day 5.
• CD34+ target dose: ≥2 × 10⁶/kg minimum; ≥5 × 10⁶/kg preferred for autologous; allogeneic typically higher for engraftment.

Treatment Algorithm (mobilization)

flowchart TD
  A[Need stem cell collection] --> B{Source?}
  B -- autologous --> C[G-CSF 5-10 d]
  B -- allogeneic donor --> D[G-CSF 5 d]
  C --> E{Mobilization adequate?<br>peripheral CD34 >10/µL}
  E -- yes --> F[Apheresis collection]
  E -- inadequate --> G[Add plerixafor]
  G --> F
  D --> F
  F --> H{CD34+ dose ≥2 × 10⁶/kg?}
  H -- yes --> I[Cryopreserve or proceed to transplant]
  H -- no --> J[Re-collect next day or remobilize]

Pearls / Pitfalls

• CHIP (clonal hematopoiesis of indeterminate potential) — age-associated somatic mutations (DNMT3A, TET2, ASXL1) without overt MDS/AML; increased CV mortality (atherosclerosis); ~0.5–1 %/yr progression to hematologic malignancy.
• CCUS (clonal cytopenia of undetermined significance) — CHIP + cytopenia; closer surveillance; some progress to MDS.
• Clonal hematopoiesis post-chemotherapy — can drive therapy-related MDS/AML; preserve t-MN risk via TP53-mutated clone selection.
• Plerixafor for poor mobilizers — esp. MM, lymphoma, prior bendamustine/lenalidomide.
• G-CSF and AML/MDS risk — controversial; routine G-CSF use after chemotherapy not associated with definite increase.
• TPO mimetics (eltrombopag, romiplostim) — used in ITP, AA, and now CMML/MDS investigationally.
• Iron in marrow — stainable iron stores (Prussian blue) on marrow biopsy; "early aspirate" iron / late iron / ringed sideroblasts.
• Embryonic hematopoiesis — yolk sac → AGM → fetal liver → marrow; tested as developmental anatomy concept.
• Marrow cellularity by age: 100 % at birth, decreases by ~10 % per decade ("100 minus age" rule); MDS hypocellularity = below age-adjusted normal.
• Aplastic anemia — empty marrow; HSC immune destruction.
• Fanconi anemia / dyskeratosis congenita — congenital HSC failure syndromes.

Cross-references

• Allo-HCT
• Auto-HCT — mobilization
• MDS — clonal hematopoiesis precursor
• Aplastic anemia — HSC failure
• G-CSF clinical use

相關題目

• Q-142 — Stem cell mobilization — plerixafor for poor mobilizers
• Q-143 — CHIP — clonal hematopoiesis of indeterminate potential
• Q-144 — HSC markers and stem cell biology

Sources