Hairy Cell Leukaemia (HCL) (BSH 2020)

BRAF V600E Mutation

Immunohist: CD72+, TRAP+

Flow: CD19+, CD20+, CD22+, CD11c+, CD25+, CD103+, CD123+, Annexin A1+, Cyclin D1+

CD5-, CD23-, CD27-, CD38-

 

Intro

Uncommon – 6-8x rarer than CLL

2% of all leukaemias, 8% of all mature B/T cell LPDs

Male > Female 4.5:1

Median Age at diagnosis: 58 years

 

Clinical Presentation

Incidental – FBC performed for other reasons

Symptoms of cytopenias – usually recurrent infection

Typically 1-2 cytopenias present, monocytopenia is almost always present

Splenomegaly is common

hairy cell.jpeg

 

differential diagnosis

Hairy Cell Leukaemia Variant, Splenic Marginal Zone Lymphoma, B-PLL, Splenic diffuse red pulp small B cell lymphoma (SDRPL)

Diagnostic Tests

Film

  • Hairy cells. Twice the size of normal lymphocytes with round, oval or kidney bean shaped nucleus. Loose chromatin. Cytoplasmic projections (hairy). Monocytopenia.

 

BM Biopsy

  • 90% dry tap, but trephine often fibrotic & hypercellular with many ‘fried egg’ cells. ‘Blood lake’ appearance describes pseudo-sinus formation with extravasation of red cells into the affected areas.

  • Immunohistochemistry: CD20, DBA44, Annexin A1, CD25, Cyclin D1, SOX11, TRAP, BRAFV600E protein.

  • Cyclin D1+ in 50%, CD10 in 20%

 

Flow

  • ‘Hairy Cell Panel’ = CD11c, CD25, CD103, CD123 —> 3 out of 4 distinguishes HCL from other B-LPD.-

  • Also: CD20+, CD22+, TBX21+, Annexin A1+, FMC7+, CD200+, Cyclin D1+, CD27-, CD38-

  • Annexin A1 is specific, not expressed in other B cell lymphomas

  • Post treatment FSc/SSc plot will look unchanged because with the hairy cells gone, normal monocytes will re-populate and fill the same space on the graph.

 

Molecular

  • BRAF V600E mutation is a disese-defining event, present in virtually all cases.

  • Usually IGHV mutated

 

MRD Monitoring – best done by flow, but test only as good as the sample provided (dry taps)

 

Staging

No agreed system of staging

CT staging not essential. Though the 10% pts with abdominal LN have poorer response

PR rather than CR after purine analogue treatment is a very poor prognostic sign

Prognosis

Median PFS 16 years

OS is close to that of age-matched controls (compared to median OS of 4 years in 1974)

Death from HCL itself very rare

 

Treatment

 

W&W reasonable if asymptomatic with minimal cytopenias

Consider asymptomatic patients for treatment if significant neutropenia + monocytopenia

Direct patients to support services (e.g. Cancer Research UK)

 

1st Line: Purine Analogues

  • Irradiated blood products

  • Pentostatin and Cladribine both have >80% CR rate with >10 year disease free survival

  • Pentostatin – every fortnight until maximum response. Need normal renal function

  • Cladribine – many routes/regimens. SC daily for 5 days is the simplest. Rash common

  • Aciclovir + Septrin prophylaxis

 

Assess disease response

  • Rpt BMAT 4-6 months after cladribine

  • CR = absence of hairy cells from blood and bone marrow + normal FBC + no organomeg.

  • PR = normal FBC + 50% improvement in organomegaly or bone marrow infiltration

  • If PR, re-treat with cladribine +/- Rituximab

 

Treatment of Relapsed/Refractory Disease (Approx 50% of patients)

  • Offer clinical trial

  • CR lasting >2 years:

    • Re-treat with same agent & can add Rituximab to either

  • CR lasting <2 years:

    • Whichever purine analogue wasn’t use first line

    • Moxetumumab pasudotox (Anti-CD22 + pseudomonas exotoxin)

      • NICE decision expected late in 2020

      • SE: HUS, Capillary leak syndrome

    • BRAF inhibitors (Vemurafenib, Dabrafenib)

      • High efficacy, access via trial/compassionate access

    • R-Bendamustine

    • Ibrutinib

 

Other treatments

  • Interferon alpha – might use if rapid count recovery required, e.g. presenting with severe infection.

  • Splenectomy – Rarely required. May be indicated if >10cm below costal margin + low-level BM infiltration

  

Management in Pregnancy (from previous 2011 guideline)

  • Prevalence extremely low given demographics of HCL

  • Avoid treatment if asymptomatic

  • Interferon alpha if treatment is unavoidable

 

 

Hairy Cell Leukaemia-variant (HCL-v)

Unrelated to HCL

Rare

Does not respond to interferon alpha

Poorer responses to cladribine and pentostatin

Different to HCL in that:

  • Leukocytosis, WBC usually 40-60

  • No monocytopenia

  • Cells are villous and large with nucleolus resembling B-PLL

  • CD11c+, CD25-, CD103-, HC2-

  • MAP2K1 mutation is the most common molecular finding (BRAFV600E mutation not present)

No adequate treatment.

Cladribine + Rituximab recommended first line.

Moxetumumab pasudotox & Ibrutinib both shown to have activity. Not currently routinely available.

Splenectomy may have a palliative role.