Hairy Cell Leukaemia (HCL) (BSH 2011)

BRAF V600E Mutation

Immunohist: CD72+, TRAP+

Flow: CD19+, CD20+, CD22+, CD11c+, CD25+, CD103+, CD123+, FMC7+, surface Ig+

CD5-, CD23-

 

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 50 years old

 

Clinical Presentation

Incidental – FBC performed for other reasons

Symptoms of cytopenias – usually recurrent infection

Typically 1-2 cytopenias present, monocytopenia is a common finding

Splenomegaly is common

hairy cell.jpeg

 

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.

 

BMAT

  • 90% dry tap, but trephine often fibrotic & hypercellular with many ‘fried egg’ cells

  • Immunohistochemistry showing DBA.44 (CD72)+, TRAP+ has 100% sensitivity for HCL

  • Cyclin D1+ in 50%, CD10 in 20%

 

Flow

  • CD11c, CD25, CD103, CD123 – 3 out of 4 positive distinguishes HCL from other B-LPD.-

  • 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.

 

Whole exome sequencing – BRAF V600E mutation detected in all of 47 cases tested.

 

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 same as for 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

 

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 Relapse

  • Same agent if CR >2 years

  • Alternative agent if <2 years

  • Add Rituximab to either

 

Other treatments

  • Interferon alpha – might use if rapid count recovery required.

  • GCSF – no strong evidence for or against

  • Splenectomy – indicated if >10cm below costal margin and low-level BM infiltration

  • New Drugs

    • Moxetumomab Pasudotox (Anti-CD22 + pseudomonas exotoxin)

    • Vemurafenib (BRAF inhibitor).

    • Dabrafenib (BRAF inhib) + Trumetinib (Mek inhib) in combination

 

Refractory Disease

  • Rituximab weekly for 8 weeks

 

Management in Pregnancy

  • Prevalence extremely low given demographics of HCL

  • Avoid treatment if asymptomatic

  • Interferon alpha if treatment is unavoidable

 

 

Hairy Cell Leukaemia-variant (HCL-v)

Rare and likely unrelated to HCL

Does not respond to interferon alph

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-

No adequate treatment. Cladribine +/- splenectomy +/- rituximab used.