Leukemia & Lymphoma, October 2009; 50(S1): 18–22
Combination therapies to improve the long-term outcome in hairy cell
leukemia
FRANCESCO LAURIA & FRANCESCO FORCONI
Department of Hematology and Transplant, University of Siena, AOUS, Siena, Italy
Abstract
Since its first description in 1958, hairy cell leukemia (HCL) had a long period of different unsatisfactory treatments till the
early 1980s, when interferon-alfa and subsequently purine analogs (PAs) pentostatin or cladribine, or pentostatin were
described to determine durable responses. However, second lines of treatments are very often needed in the life span of
patients with HCL and a small minority of patients are refractory and with poor prognosis. These disadvantages have led to
test the efficacy of additional compounds, mainly monoclonal antibodies, combined with PAs. The objective of this
presentation is to review the current knowledge of combination treatments in HCL. Combination treatments have been used
or proposed for different purposes in HCL: to reduce acute toxicity, to improve complete remission (CR) rate, to overcome
resistance/refractoriness, to prolong disease-free survival, or to prolong overall survival. The type of patients to be selected for
the combinations and the perspectives of combinations of PAs with monoclonal antibodies will also be discussed.
Keywords: Hairy cell leukemia, purine analogs, rituximab, combination therapy, outcome
the most specific CD103 expressed at high intensity
Introduction
[2]. Recent analyses have also identified a new
Hairy cell leukemia (HCL) was described for the first marker, ANXA-1, that is specifically expressed by
time in 1958 by Bouroncle et al., who identified a tumor B-cells of HCL only and is now included in
novel clinic–hematologic entity initially defined as the new World Health Organization 2008 Classifica-
leukemic reticuloendoteliosis and subsequently re- tion of Tumors of Hematopoietic and Lymphoid
named as HCL because of the presence of cells with Tissues [2,3]. The memory B-cell marker CD27 is
typical long cytoplasmic projections [1]. HCL is a another antigen that may easily help to differentiate
rare disease with an incidence of 51 out of 100,000 HCL from other B-cell neoplasms. After an initial
cases/year. It represents52% of lymphoid leukemias analysis of a few cases, we have confirmed that CD27
and affects mainly the male gender (male:female was selectively not expressed in over 70 classical
ratio, 4:1) in working age (median age at diagnosis HCLs, while it was conserved on the surface of
55 years). leukemic cells of all other peripheral B-cell neo-
The clinical features of HCL are splenomegaly in plasms, including variant HCL and splenic marginal
480% patients, while lymph nodes are rarely zone B-cell lymphomas [4].
enlarged, pancytopenia with monocytopenia, with First generation gene expression profiling of HCL
the typical ‘hairy’ cells (HCs) documented in the as compared with the other B-cell non-Hodgkin
peripheral blood and in the bone marrow. Bone lymphomas and purified normal germinal center
marrow aspirate is often difficult (‘dry tap’) and (GC), naive, and memory B-cells suggested that
histology often reveals the ‘fried-egg’ pattern of HCs HCLs were more related to memory cells [5].
separated from one another in the form of the However, HCL is peculiar in many features that are
cytoplasmic projections and increased reticulin unique among any other mature normal and tumor
fibrosis [2]. HCL typically expresses an ‘activated’ B-cells. Different from other mature B-cell tumors,
phenotype with CD25, CD11c, CD20, FMC7 and HCL has a highly stable genomic profile, with no
Correspondence: Francesco Lauria, Sezione di Ematologia e Trapianti, Dipartimento di Medicina Clinica e Scienze Immunologiche, Universita` di Siena,
AOUS, Viale Bracci – 53100 Siena, Italy. Tel: þ39-0577-586798. Fax: þ39-0577-586185. E-mail: lauria@unisi.it
ISSN 1042-8194 print/ISSN 1029-2403 online C211 2009 Informa Healthcare USA, Inc.
DOI: 10.3109/10428190903142273
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