Leukemia & Lymphoma, October 2009; 50(S1): 12–17
Cladribine in the treatment of hairy cell leukemia: initial and
subsequent results
EDWARD HUYNH, DARREN SIGAL, & ALAN SAVEN
Division of Hematology/Oncology, Scripps Clinic, La Jolla, CA, USA
Abstract
Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder associated with pancytopenia, splenomegaly, and
recurrent infections. Although interferon a and pentostatin were initially found to be effective in this disease, cladribine has
emerged as the preferred initial therapy. Cladribine given as a single continuous intravenous seven-day infusion is the dosing
schedule with the most durable complete remissions and evaluated in the greatest number of patients with HCL. Patients
who relapse after purine analogue therapy, whether it be cladribine or pentostatin, can be successfully retreated with
cladribine. Patients with HCL may develop complications of recurrent infection and second malignancies. Although both
complications are postulated to be related to therapy, they may also be due to the duration and burden of the disease.
Minimal residual disease detected on bone marrow biopsy is thought to predict for future relapse. We will review the initial
and subsequent results of cladribine in the management of HCL.
Keywords: Cladribine, 2-CDA, hairy cell leukemia
growth in vitro by inhibiting DNA synthesis [4].
Introduction
Since that discovery, cladribine has been extensively
The year 2008 marked both the fiftieth anniversary of studied in HCL.
the American Society of Hematology and also the Figure 1 illustrates the mechanism of action of
description of hairy cell leukemia (HCL) as a distinct cladribine in resting and dividing cells.
clinicopathologic entity. HCL was first described as
leukemic reticuloendotheliosis by Bouroncle et al.in
Initial treatment results with cladribine
1958 [1]. In 1966, Schrek and Donnelly coined the
term ‘‘hairy’’ cells based on the characteristic cyto- The most common indication for treatment of HCL
plasmic projections seen under light microscopy [2]. is cytopenias (absolute neutrophil count (ANC)
50.5610
9
/L–1.0610
9
/L, hemoglobin 58–10 g/
Mechanism of action
dL, or platelet count 550610
9
/L–100610
9
/L).
The discovery of cladribine, or 2-chlorodeoxyadeno- Less commonly, patients require treatment for
sine, as a cytotoxic agent was made possible by the symptomatic splenomegaly, bulky lymphadenopathy,
observation that children with adenosine deaminase or constitutional symptoms such as fever and night
(ADA) deficiency develop lymphopenia and immu- sweats. Historically, interferon a and splenectomy
nodeficiency disease [3]. ADA deficiency causes the were used as initial therapy. 2
0
-Deoxycoformycin
accumulation of toxic deoxyadenosine nucleotides (pentostatin) was found to have a significantly higher
resulting in the death of lymphocytes, which have response rate and relapse-free survival rate than
high deoxycytidine kinase and low 5
0
-nucleotidase interferon a in a prospective, randomized trial [5].
levels. Carson et al. discovered that 2-chlorodeoxy- Piro et al. first published the results of 12 patients
adenosine (cladribine) was resistant to ADA deami- with HCL given cladribine at a dose of 0.1 mg/kg per
nation and prevented malignant lymphoblast cell day by continuous intravenous infusion over seven
Correspondence: Alan Saven, MD, Division of Hematology/Oncology, Scripps Clinic, 10666 N. Torrey Pines Road, MS 217, La Jolla, CA 92037, USA.
Tel: (858) 554-8388. Fax: (858) 554-6941. E-mail: saven.alan@scrippshealth.org
Presented at the American Society of Hematology meeting in San Francisco, California on December 5, 2008 (Friday Satellite Symposium).
ISSN 1042-8194 print/ISSN 1029-2403 online C211 2009 Informa Healthcare USA, Inc.
DOI: 10.3109/10428190903142083
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