毛細胞白血病

Buzzwords → Dx

Diagnostic Criteria

• Smear + flow cytometry → CD20+ CD25+ CD11c+ CD103+ CD123+ Annexin A1+, often CD200+++.
• BRAF V600E by sequencing or VE1 IHC — defines classic HCL (HCL-v is BRAF wild-type).
• Marrow biopsy — reticulin fibrosis, "fried-egg" infiltrate; aspirate often dry.

Workup

• CBC + diff + smear (look for monocytopenia + hairy cells).
• Flow cytometry on PB or marrow with HCL panel.
• Marrow aspirate + biopsy with BRAF V600E testing (PCR or VE1 IHC).
• CT abdomen for splenomegaly extent.
• HBV serology before rituximab.
• β2-microglobulin, LDH.

Treatment indications (NCCN)

• Symptomatic disease, cytopenia (Hb <11, plt <100, ANC <1.0), symptomatic splenomegaly, recurrent infections, constitutional symptoms.
• Asymptomatic HCL → observation (rare among heme malignancies).

Treatment Algorithm

flowchart TD
  A[Symptomatic HCL] --> B{First-line}
  B -- frontline --> C[Cladribine 0.1 mg/kg/d × 7d<br>or 5 d weekly × 5 wk]
  B -- pentostatin alternative --> D[Pentostatin q2wk × 4-6 mo]
  C --> E[Add rituximab if MRD+<br>or as concurrent]
  D --> E
  E --> F{Response?}
  F -- CR/PR --> G[Observation]
  F -- relapse <2 yr --> H[Repeat cladribine + rituximab<br>OR moxetumomab pasudotox]
  F -- refractory or HCL-v or BRAF-driven relapse --> I[Vemurafenib ± rituximab<br>or BRAF + MEK combo<br>or moxetumomab]

Pearls / Pitfalls

• Monocytopenia on differential — pathognomonic gestalt (HCL is the only common cause among lymphoproliferative diseases).
• Cladribine is given as a single 7-day infusion (or 5-day weekly × 5–6 wk) — most patients don't need a second cycle for years. Picking "weekly cycles indefinitely" is the wrong answer.
• Rituximab + cladribine concurrent (or sequential MRD-driven) → deeper, more durable remissions vs cladribine alone.
• HCL-v (variant) is BRAF-negative, CD25-negative, more aggressive; treat with rituximab + cladribine + later vemurafenib + rituximab is ineffective (no BRAF target).
• Moxetumomab pasudotox (anti-CD22 immunotoxin) — capillary leak syndrome, hemolytic uremic syndrome (HUS) toxicities; fluid overload risk.
• Vemurafenib + rituximab (BRAF + anti-CD20) shows high CR in R/R BRAF-mutant HCL — alternative to repeat purine analogue.
• PJP and HSV/VZV prophylaxis during cladribine (lymphopenia lasts months).
• Splenectomy is rarely needed in the cladribine era; reserved for symptomatic massive spleen with cytopenia despite therapy or pregnancy.

Cross-references

• Drug Regimens — cladribine, pentostatin, vemurafenib
• Cytogenetics Atlas — BRAF V600E
• Splenic MZL — DDx

相關題目

• Q-017 — HCL — diagnostic gestalt with monocytopenia
• Q-018 — HCL — frontline therapy
• Q-019 — HCL-variant — distinguishing from classic HCL

Sources