Hairy Cell Leukaemia (HCL) (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

 

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

 

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:

o   Leukocytosis, WBC usually 40-60

o   No monocytopenia

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

o   CD11c+, CD25-, CD103-, HC2-

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