Canterbury DHB

Context

Hairy Cell Leukaemia (HCL)

Hairy Cell Leukaemia is a rare condition, but one that responds well to relatively simple cytotoxic treatment. Prolonged remission usually follows.

In This Section

Clinical and Laboratory Assessment

Prognosis

Management

Clinical and Laboratory Assessment

The median age of onset 50-55 with a 3.5:1 male predominance.

The commonest presentation is with splenomegaly, pancytopenia, and a dry tap on bone marrow aspirate. Usually a few hairy cells may be seen on the blood film or bone marrow aspirate smears. Monocytopenia is characteristic. The trephine appearances may be strongly suggestive, but the diagnosis is made by immunophenotypic analysis.

Immunophenotype shows surface immunoglobulin, CD 19, 20, 22, 11c, 25 and 103 positive. CD 5, 10 and 23 are typically negative.

Recently, a mutation in the B-raf proto-oncogene (BRAF gene) was identified in up to 80–90% of HCL cases. The mutation occurs in exon 15 at position 1799, leading to valine (V) being substituted by glutamate (E) at codon 600 (V600E) of the BRAF protein. The mutation is now considered a molecular hallmark of the disease.

HCL needs to be differentiated from hairy cell leukaemia variant (HCL-v), a lymphoid disorder that resembles HCL, but has some variant cytological and haematological features. HCL-v cells usually display prominent nucleoli that is not seen in HCL and is not associated with monocytopenia in the peripheral blood. The malignant cells express B cell markers CD19, 20, 22, CD11c and CD103. However, it is usually negative for CD25 and CD123 dim/negative. BRAF V600E mutation is not detected. HCL-v is associated with a worse prognosis due to its resistance to conventional HCL therapy.

For more information see:

Prognosis

Before the introduction of interferon alpha and the nucleoside analogues, median survival for non-splenectomised and splenectomised patients was 4.6 years and 6.9 years respectively. With the introduction of pentostatin and then cladribine, the 5 and 10 year survival rates are similar to the general population.

See Else, M., C. E. Dearden, et al. (2009). "Long-term follow-up of 233 patients with hairy cell leukaemia, treated initially with pentostatin or cladribine, at a median of 16 years from diagnosis." Br J Haematol.

Management

The nucleoside analogue cladribine is the current treatment of choice and should be initiated in patients with symptomatic disease or if their hematological parameters are declining (Hb <110 g/L, platelet <100 x 109/L, or neutrophil < 1 x 109/L).

For a review of management see:

Dosage Schedule

If cytopenias are severe - consider admission, and give cladribine 0.15 mg/kg SC once a week for a total of six weeks.

If cytopenias are moderate or mild - outpatient treatment may be appropriate. Cladribine 3.4 mg/m2 SC daily for seven days should be given. A second course may be required if assessment at 6-8 weeks indicates continuing evidence of HCL.

Note: A copy of the prescription sheet for cladribine is available. You must print this out and use it for the prescription to be sent to Pharmacy.

Myelo and immuno suppression are the main complications of cladribine treatment. The patient needs to be aware of this and, if an outpatient, to contact the department if unwell or febrile. They should take and record their temperature four times daily and maintain a fluid intake of >2-3L/day.

For further details of myelosuppression, dose adjustment in renal impairment and post treatment assessment and follow up, see the Cladribine Data Sheets on Medsafe.

Some other Aspects of Cladribine Treatment

Irradiated Blood Products must be given for a minimum of 6 months from the end of treatment. If there is ongoing immunosuppression with CD4 count <0.4 x 10 9/L, continue with irradiated blood products until the CD4 count rises above 0.4 x 10 9/L.

Myelosuppression can be severe and prolonged, but usually starts to improve within one to three weeks of beginning therapy. If an outpatient, monitor blood counts at least three times a week.

Fever needs to be managed in the same way as for any neutropenic patient. It may, however, be due to cladribine itself.

Mild nausea, local irritation at injection sites, and very rarely tumour lysis syndrome may be seen. Allopurinol 300 mg PO, for the initial 10-14 days should be considered. Discuss with Consultant.

If renal impairment, do not give cladribine if creatinine clearance <30 mL/min. And reduce by 50% if Crcl is 30-60 mL/min.

Give pneumocystis prophylaxis, start co-trimoxazole, 480 mg once daily, as soon as blood counts start to rise, i.e., within 2-3 weeks of starting treatment. Discuss with Consultant if cytopenias persist.

Relapsed/resistant disease

In the past, splenectomy, interferon alpha, and pentostatin have all been effective in some patients with HCL. For the patient refractory to cladribine, these treatments could be considered, but good responses have also been seen in HCL to the anti-CD 20 monoclonal antibody, Rituximab. Monoclonal antibodies are not currently funded for this purpose in New Zealand.

See Treatment of relapsed Hairy cell leukaemia.

About this Canterbury DHB document (5516):

Document Owner:

Andrew Butler (see Who's Who)

Issue Date:

September 2018

Next Review:

September 2021

Keywords:

Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer

Topic Code: 5516