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Teaching pack: Hairy cell leukaemia

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9 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.

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  1. Teaching pack · Cancer · haematologic

    Hairy cell leukaemia

    Hairy cell leukaemia is a rare, slow B-cell leukaemia with a single defining mutation (BRAF V600E) that is unusually curable: one week of a purine analogue puts most people into remission for years, and BRAF drugs rescue those who relapse.

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  2. What it is

    In two paragraphs

    Classic hairy cell leukaemia (HCL) is a mature B-cell neoplasm with a distinctive morphology and immunophenotype (CD11c, CD25, CD103, CD123, annexin A1) and BRAF V600E in essentially all cases (Tiacci 2011); the variant HCL-v lacks BRAF V600E, is CD25-negative, and behaves worse (often MAP2K1-mutant). Patients present with pancytopenia, splenomegaly and infections.

    Purine analogues (cladribine or pentostatin) give complete remission in 80-90% with a single course, and adding rituximab (concurrent or delayed) deepens responses and achieves MRD negativity in most (Chihara et al.). Relapse is treated with a second purine analogue course plus rituximab; BRAF inhibition (vemurafenib ± rituximab) gives durable remissions in multiply relapsed disease (Tiacci 2021, NEJM), and BRAF+MEK combinations are an option. Moxetumomab pasudotox (anti-CD22 immunotoxin) was approved in 2018 and withdrawn commercially in 2023. Ibrutinib has modest activity. Overall survival is now close to age-matched controls.

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  3. Standard of care

    What is given today, by setting

    SettingApproachGuideline
    First line, symptomaticCladribine (5-7 days) or pentostatin, with rituximab concurrent or delayed (improves MRD-negative CR).NCCN Category 1 (cladribine ± rituximab)
    Relapse after >2 yearsRepeat purine analogue + rituximab.NCCN Category 2A
    Early relapse or refractoryVemurafenib + rituximab (or dabrafenib-trametinib); ibrutinib; moxetumomab pasudotox where still available; clinical trial.NCCN Category 2A
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  4. State of the art

    Where the field stands

    • One week of cladribine remains one of the most effective single treatments in oncology.
    • BRAF V600E is universal in classic HCL; vemurafenib-rituximab produces MRD-negative remissions in most relapsed patients without chemotherapy.
    • Life expectancy is near normal; the residual problems are infection during induction and the aggressive variant.
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  5. History

    How we got here

    1. 1958Bouroncle describes 'leukemic reticuloendotheliosis'
    2. 1984Interferon alfa: first effective therapy
    3. 1990Cladribine: durable remissions after one course (Piro, NEJM)
    4. 2011BRAF V600E found in all classic HCL (Tiacci, NEJM)
    5. 2015Vemurafenib active in relapsed HCL
    6. 2018Moxetumomab pasudotox approved
    7. 2021Vemurafenib + rituximab: chemo-free durable remissions (NEJM)
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  6. Pipeline

    What is coming

    • Vemurafenib (product)
    • Dabrafenib + trametinib (product)
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  7. Open problems

    What nobody has solved

    • Variant HCL and IGHV4-34 disease respond poorly to purine analogues.
    • Infection risk during induction neutropenia.
    • Whether MRD eradication should be a treatment goal.
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  8. Quiz

    Check understanding

    1. Why does blocking BRAF alone cause problems that adding a MEK inhibitor fixes?
      Answer
      BRAF inhibitor monotherapy causes paradoxical MEK/ERK reactivation through CRAF dimers (and secondary skin cancers); blocking MEK downstream closes the escape and improves PFS and OS in melanoma.
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  9. Sources

    Read the primary sources

    • NCCN Guidelines: Hairy Cell Leukemia: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1481
    • Hairy Cell Leukemia Foundation: https://www.hairycellleukemia.org/
    • Tiacci 2011 NEJM: https://doi.org/10.1056/NEJMoa1014209
    • Wikipedia: https://en.wikipedia.org/wiki/Hairy_cell_leukemia
    • Guideline: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1481
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