Hairy Cell Leukaemia (HCL) (2011)

BRAF V600E Mutation

Immunohist: CD72+, TRAP+

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

CD5-, CD23-



-       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.



–      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%



– 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)



-       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


-       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




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 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-

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