Leukemia & Lymphoma, June 2011; 52(S2): 72–74
Chemo-immunotherapy for hairy cell leukemia
FARHAD RAVANDI Department of Leukemia, University of Texas – M. D. Anderson Cancer Center, Houston, TX, USA
Abstract With the introduction of the nucleoside analogs cladribine and pentostatin the treatment of patients with hairy cell leukemia (HCL) has been revolutionized, and the majority of patients achieve a long-lasting complete remission with rare patients ever needing the traditional treatment strategies such as splenectomy. However, in the studies employing either of these nucleoside analogs, a proportion of patients do not respond to the initial therapy and the event-free survival curve does not reach a plateau, with up to 40% of patients relapsing within a few years. New therapeutic modalities including monoclonal antibodies such as rituximab and immunotoxins such as BL22 are now available. Furthermore, progress in the identification of minimal residual disease (MRD) using consensus primer or patient specific polymerase chain reaction for the immunoglobulin heavy chain variable region gene (IGHV), as well as multiparameter flow cytometry, allows for the detection and eradication of MRD. Whether this will translate to a reduction in the rate of relapse will require large prospective randomized trials. Alternatively, it may be possible to identify patients who are more likely to relapse using pretreatment characteristics such as the mutational status of IGHV and apply these strategies solely to them.
Keywords: cladribine, rituximab, minimal residual disease, hairy cell leukemia Introduction
The treatment of patients with hairy cell leukemia (HCL) has changed dramatically over the last few decades. Splenectomy, historically the prime mod- ality of treatment, is now relegated to rare instances in multiply refractory patients, and initial therapy with the nucleoside analogs cladribine and pentosta- tin results in complete response (CR) rates of 80– 90% [1,2]. However, up to 40% of patients relapse after a follow up of 3–4 years, with little difference between the two drugs in achieving and maintaining a response [3]. Clearly, the quality of the initial response can predict its duration, being longer in those achieving a CR rather than lesser responses [4]. Therefore, we and others have undertaken efforts to identify and eradicate minimal residual disease (MRD) after the initial therapy [5]. Wheaton and colleagues noted that detection of
MRD by immunohistochemistry in paraffin-em- bedded bone marrow sections of patients with HCL
in CR after receiving cladribine was predictive of relapse [6]. More sensitive methods of MRD detection such as immunophenotyping by flow cytometry and polymerase chain reaction (PCR) of consensus primer or clone specific immunoglobulin heavy chain genes have been evaluated recently, and can be used to monitor the disease course [5,7]. However, the importance of MRD detection and eradication continues to be a subject of discussion, with reports of long-term remission in patients with persistent MRD and even morphological evidence of HCL [8].
Cladribine followed by rituximab for treating hairy cell leukemia
We have conducted a clinical trial in which patients with newly diagnosed HCL or those relapsing after one prior course were treated with clardribine 5.6 mg/m2 intravenously over 2 h daily for 5 days followed by, approximately 28 days later, eight
Correspondence: Farhad Ravandi, Department of Leukemia, The University of Texas - M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 428, Houston, Texas 77030, USA. Tel: 713-745-0394. Fax: 713-563-5774. E-mail:
fravandi@mdanderson.org
ISSN 1042-8194 print/ISSN 1029-2403 online 2011 Informa UK, Ltd. DOI: 10.3109/10428194.2011.565096
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