Leukemia & Lymphoma, October 2009; 50(S1): 27–31
Importance of minimal residual disease in hairy cell leukemia:
monoclonal antibodies as a therapeutic strategy
DEBORAH A. THOMAS, FARHAD RAVANDI, MICHAEL KEATING, &
HAGOP M. KANTARJIAN
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX, USA
Abstract
With the use of nucleoside analogs as frontline therapy, the prognosis of hairy cell leukemia (HCL) has improved
dramatically. Unfortunately, disease recurrence remains problematic. Eradication of minimal residual disease (MRD)
persisting after therapy may further improve outcome. The evolution of available techniques used to assess MRD, and the
potential incorporation of novel agents such as monoclonal antibodies (MoAbs) into the treatment armamentarium for HCL
mandate that MRD analyses be performed concurrently with routine assessments of disease status. Herein, the available data
regarding the prevalence and clinical relevance of MRD after therapy for HCL is reviewed.
Keywords: Minimal residual disease, rituximab, prognosis
[FR] 1-3 regions of IgH, [cpPCR] with sensitivity
Introduction
ranging 1610
4
–1610
5
) or more sensitive PCR
Hairy cell leukemia (HCL) is a chronic B-lineage techniques with clone specificity (sensitivity
lymphoproliferative disorder which has a character- 1610
6
). Herein the prevalence and clinical rele-
istic immunophenotype (expression of CD19, CD20, vance of detection of MRD after therapy for HCL is
CD22, CD25, CD79a, CD11c, CD103, surface reviewed.
immunoglobulin [sIg]). The presence of these
unique markers allows the use of flow cytometric
Comparison of techniques for the assessment of
(FC, sensitivity usually in range of 1 cell in 10 000)
minimal residual disease in hairy cell leukemia
and immunohistochemical (IHC) techniques for
detection of minimal residual disease (MRD) not Ellison et al. [2] reported the use of IHC (L26
readily discernable by routine microscopy. IHC [CD20], DBA.44) on BMs to determine status of the
staining of bone marrow biopsies (BMs) with anti- disease at 3, 6, 12 and 24 months after therapy with
CD20 (lineage specific pan-B cell), DBA.44 (marks cladribine (2-CdA) for HCL. A characteristic pattern
subsets of B-cells, hairy cells, and some B-cell of staining with L26 and/or DBA.44 was insufficient;
lymphomas), PAX-5 [1] (B-cell follicles, B-lymphoid presence of nuclear and cytoplasmic morphologic
neoplasms) or CD79a antibodies facilitates identifi- features of hairy cells was also required. A semi-
cation of residual hairy cells in cases where complete quantitative assessment was used to classify BMs into
remission (CR) as defined by conventional criteria categories: negative, indeterminate (IHC stains
has been achieved after treatment. The presence or positive without morphological features), rare (45
absence of molecular disease after therapy can also be HCs meeting criteria), and positive (further categor-
evaluated by assaying for immunoglobulin heavy ized51%, 1–3%, 3–5% or45% of total cell
chain (IgH) gene rearrangements via polymerase population). Serial BMs were deemed positive for
chain reaction (PCR) amplification, either using MRD by IHC an average of 50% of the cases
consensus V primers (usually for the framework assessed at the various time points, with the majority
Correspondence: Deborah A. Thomas, MD, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, TX 77030, USA.
Tel: þ1-713-745-4616. Fax: þ1-713-563-5974. E-mail: debthomas@mdanderson.org
ISSN 1042-8194 print/ISSN 1029-2403 online C211 2009 Informa Healthcare USA, Inc.
DOI: 10.3109/10428190903142224
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