急性淋巴球性白血病

Buzzwords → Dx

Diagnostic Criteria

• WHO 5e/ICC 2022: B-ALL or T-ALL with recurrent genetic abnormalities (Ph, Ph-like, KMT2A, ETV6::RUNX1, hyperdiploidy, hypodiploidy, iAMP21, TCF3::PBX1, BCL2/MYC, T-ALL-NOS, ETP-ALL).
• Marrow ≥20 % lymphoblasts (or extramedullary mass with bone involvement). Some texts use ≥25 %.
• Distinguish from lymphoblastic lymphoma: if marrow <20–25 %, classify as LBL.
• Early T-cell precursor (ETP)-ALL: distinct adverse subtype with myeloid markers (CD117, CD13, CD33).

Workup

• Marrow aspirate + biopsy with flow cytometry, karyotype + FISH (BCR::ABL1, KMT2A, ETV6::RUNX1, hypodiploidy, iAMP21), NGS panel (IKZF1, CRLF2, JAK2, NOTCH1).
• CSF studies + diagnostic LP (cytology + flow). All ALL pts get CNS-directed therapy regardless of CSF status.
• TLS labs + uric acid; rasburicase if high-risk (high WBC, T-ALL, mediastinal bulk).
• Echo / MUGA before anthracycline; HBV/HCV/HIV; TPMT/NUDT15 before 6-MP.
• HLA typing if HCT possible; counsel on fertility preservation.

Treatment Algorithm

flowchart TD
  A[Newly diagnosed ALL] --> B{Phenotype + cytogenetics}
  B -- B-ALL Ph+ --> C[Dasatinib or ponatinib<br>+ chemo OR + blinatumomab<br>D-ALBA backbone]
  B -- B-ALL Ph- --> D{Age?}
  D -- AYA / fit adult --> E[Pediatric-inspired<br>CALGB 10403 / BFM]
  D -- older / unfit --> F[Hyper-CVAD<br>or low-intensity + blinatumomab<br>+ inotuzumab]
  B -- T-ALL --> G[Pediatric-style<br>+ asparaginase<br>+ nelarabine if T-ALL]
  C --> H{MRD post-induction}
  E --> H
  F --> H
  G --> H
  H -- MRD+ --> I[Blinatumomab × ≥1 cycle<br>then HCT consideration]
  H -- MRD- standard --> J[Continue chemo<br>± maintenance × 2-3 yr]
  H -- high-risk MRD-<br>Ph-like, KMT2A, ETP --> K[Allo-HCT in CR1]
  I --> L{Relapse / refractory?}
  J --> L
  K --> L
  L -- B-ALL R/R --> M[Tisa-cel CAR-T age ≤25<br>brexu-cel adults<br>blinatumomab / inotuzumab bridge]
  L -- T-ALL R/R --> N[Nelarabine<br>or experimental]

Pearls / Pitfalls

• MRD is the single best prognostic factor in ALL — outweighs cytogenetics. MRD+ post-induction → switch to blinatumomab (BLAST trial showed OS benefit) before consolidation/HCT. Picking "continue same chemo" for MRD+ is the wrong answer.³
• All ALL patients get CNS-directed therapy regardless of CSF cytology at diagnosis — IT MTX/Ara-C ± CNS-penetrating systemic chemo (HD-MTX, HD-Ara-C). The exam trap: "CSF clear, no CNS prophylaxis needed" — wrong.
• Ph+ ALL = TKI + chemo (or + blinatumomab); HCT may be omittable in deep MRD response. D-ALBA (dasatinib + blinatumomab) showed durable MRD-negativity without upfront chemo. Older Ph+ pts may avoid intensive chemo entirely.⁴
• AYA (15–39 y) with Ph- ALL → pediatric-inspired regimen (CALGB 10403), NOT adult Hyper-CVAD. AYAs treated on pediatric protocols have markedly better OS (improvement driven by asparaginase intensity).
• Asparaginase toxicities to know: pancreatitis, hepatotoxicity, thrombosis (depletes antithrombin, protein C/S), hypersensitivity (PEG-asparaginase tolerated if Erwinia-naïve allergy). DVT during induction is classic.
• Blinatumomab: CRS + neurotoxicity (similar but milder than CAR-T); CD19-loss is escape mechanism. Inotuzumab ozogamicin (CD22 ADC): VOD/SOS — avoid back-to-back HCT or use shorter spacing.
• CD19 CAR-T (tisa-cel, brexu-cel): post-CD19 antigen-loss escape → consider CD22 CAR-T (investigational) or AlloHCT. CRS + ICANS standard toxicities.
• TPMT/NUDT15 polymorphism testing before 6-mercaptopurine — homozygous deficient = severe myelosuppression; heterozygous → reduced dose. NUDT15 variants common in East Asians (incl. Taiwan).

Cross-references

• Cytogenetics Atlas — Ph, Ph-like, KMT2A, hyperdiploidy
• Drug Regimens — Hyper-CVAD, CALGB 10403, blinatumomab, inotuzumab
• AML — contrast lineage and MRD
• CD19 CAR-T (tisa-cel, brexu-cel)
• TLS — high-risk in T-ALL, mediastinal mass

相關題目

• Q-008 — ALL — MRD-positive post-induction strategy
• Q-009 — ALL — Ph+ ALL frontline therapy (D-ALBA-era)
• Q-010 — ALL — asparaginase toxicity profile
• Q-154 — Allo-HCT — VOD/SOS recognition

Sources