ABOUT HAIRY CELL LEUKAEMIA (HCL)

Hairy cell leukaemia (HCL) is a relatively rare disease affecting B-lymphocytes[1], as in chronic lymphocytic leukaemia (CLL).  It is ten times less frequent than chronic lymphocytic leukaemia and affects mainly men, with a median age of 50 years.  The male: female ratio is 5:1 (in chronic lymphocytic leukaemia it is 2:1).  Almost all patients with a diagnosis of hairy cell leukaemia need treatment at presentation (in contrast to chronic lymphocytic leukaemia, where 15-20% may never require active therapy).  Hairy cell leukaemia has no enlarged nodes but an enlarged spleen in 50-60%.  The main clinical problems result from cytopenias[2]: neutropenia[3], anaemia[4] and/or thrombocytopenia[5].  In addition, patients lack circulating monocytes[6], a unique feature of this disease.  This feature predisposes patients to opportunistic infections which rely on monocytes for immune surveillance.  Most patients have a low white blood count (leucocyte count) but a minority has circulating “hairy cells”.  These can be identified under the microscope on peripheral blood or bone marrow films.  The name derives from the long villi or projections that characterise these cells, which do not exist in normal individuals.

DIAGNOSIS

Hairy cell leukaemia is one of several B-lymphoid leukaemias or lymphomas which can be confused with chronic lymphocytic leukaemia and needs to be considered in any differential diagnosis.  The main diagnostic test is a bone marrow trephine biopsy, as bone marrow aspirates are difficult to obtain and peripheral blood flow cytometry analysis is not sufficient for diagnosis.  This also contrasts with chronic lymphocytic leukaemia which, according to current guidelines, can be accurately diagnosed by flow cytometry of blood samples, and where a bone marrow test is only required before and after treatment, if this is indicated.

 TREATMENT

A remarkable feature of hairy cell leukaemia is its great sensitivity to chemotherapeutic agents.  For many years, since the disease was first described in 1958, there was no adequate treatment.  Patients with an enlarged spleen would undergo a splenectomy[7].  This results in improvement in the cytopenias but it only leads to long-term benefit in a minority (c.5% of cases) who may not require further treatment for ten or twenty years.   A first breakthrough was reported in 1984 with alpha-interferon.  In fact, in 90% of patients the abnormal blood counts, including the monocytopenia[8], are corrected within 3 to 6 months with subcutaneous injections three times a week.  A drawback with this treatment is that complete remissions (CRs) are rare (10-15%) despite improvements in the bone marrow, and patients usually relapse within one year when treatment is discontinued.  Long-term maintenance was often used to keep the partial remission (PR) status and some patients have endured this treatment, which is not well tolerated, for 2-10 years.

A second breakthrough occurred in the mid-1980s with the advent of a potent nucleoside[9] analogue[10], Pentostatin.  Again, the majority (>80%) of patients responded. But this time, and in contrast to alpha-interferon, the remissions were complete (CR) and were long-lasting after treatment (which is given intravenously at intervals over a 3-4 month period) was discontinued.

A further breakthrough was reported in the mid-1990s, with a similar high complete remission rate achieved after a single week of continuous intravenous treatment with another nucleoside analogue, Cladribine. 

An important development with Cladribine is the possibility of using this agent by the subcutaneous[11] route over 5 days, with a similar success rate as when given intravenously.  This has resulted in patient convenience and cost savings as it avoids hospital admissions or clinic visits.

There are no major differences in effectiveness between Pentostatin and Cladribine apart from the fact that therapy with Pentostatin is lengthy (three to four months) and requires intravenous administration.

WHAT TO DO AFTER FIRST LINE TREATMENT

With Cladribine and Pentostatin treatments, an important end point is to achieve complete remission.  If only partial remission is obtained, then retreatment is necessary until the bone marrow is cleared of any detectable hairy cells. This is assessed by bone marrow trephines and careful immunohistochemical stainings.  Such complete remissions often last over ten years and, in fact, the overall survival of hairy cell leukaemia patients has improved dramatically in the last 20-30 years.

Despite the above improvements, further progress has been made with the addition of the monoclonal antibody Rituximab to either nucleoside analogue to improve the quality of the response.  At present, these combinations are reserved for relapses, or for patients failing to achieve a complete remission with the first line of treatment.  Both agents cause a degree of immunosuppression and lymphopenia and therefore special care is needed to prevent viral and bacterial infections, usually for the first six months of treatment.

Thanks to LIPOMED AG who initiated and funded this article for the CLLSA

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