Leukemia & Lymphoma, June 2011; 52(S2): 65–68
Implications of minimal residual disease in hairy cell leukemia after cladribine using immunohistochemistry and immunophenotyping
MARTIN S. TALLMAN Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA
Abstract Hairy cell leukemia (HCL) is a highly treatable, but generally incurable B-cell lymphoproliferative disorder with a long natural history. The purine analogs cladribine and pentostatin are the treatments of choice and both induce complete remission (CR) by peripheral blood counts and morphologic examination of the marrow in the large majority of patients. However, some patients, otherwise in apparent CR, have evidence of minimal residual disease (MRD) as detected by a number of different techniques, including immunohistochemistry, immunophenotypying by flow cytometry, and polymerase chain reaction (PCR). Immunohistochemistry is readily available, but precise criteria which constituteMRDare not uniform. Immunophenotyping can identify a characteristic immunophenotype, but leukemia cells may be difficult to obtain from a fibrotic bone marrow. Patient-specific PCR, while highly specific, is not readily available. Furthermore, the introduction of newer effective therapies such as the monoclonal antibody rituximab and immunoconjugate BL22 following a purine analog or concurrently with a purine analog may eradicate MRD. However, the optimal method for detecting MRD is not known. Furthermore, whether the eradication of MRD improves overall survival has not been established.
Keywords: Hairy cell leukemia, purine analogs, stem cell toxicity, second malignancy Introduction
Remarkable advances in the treatment of hairy cell leukemia (HCL) have been realized since the intro- duction of the purine analogs in the late 1980s and early 1990s. The complete remission rates with either cladribine or pentostatin are approximately 80–90%, and although there is no plateau on disease-free survival curves, the overall survival at 10 years is 90– 100% [1,2]. However, at about 10 years of follow-up, approximately 25–50% of patients relapse [1–3]. Not all patients require treatment at relapse. The progression-free survival among 86 patients treated with a single cycle of cladribine after first relapse at 12 years was 54% [1]. Nevertheless, in a recent long- term follow-up study of 19 patients treated with a single cycle of cladribine at a median time from cladribine treatment of 16 years in continuous complete remission, 47% of patient sample bone marrows had no evidence of residual disease, 37% had minimal residual disease (MRD), and 16% had morphologic evidence of disease [4]. Therefore, some patients may be cured of their disease. However, patients who do relapse have an inferior
outcome compared with those who do not [5]. Therefore, several questions remain to be addressed regarding the detection and management of MRD in HCL. First, which is the most sensitive and specific method for detecting MRD? Second, does detecting MRD have predictive value with respect to outcome? Third, will intervention effectively eradicate MRD? Fourth, will eradication of MRD improve outcome?
Detection of minimal residual disease
Minimal residual disease after purine analog therapy for HCL can be detected by several techniques including immunohistochemistry (IHC) [6], immu- nophenotyping by flow cytometry (FC) [7], and by molecular techniques such as polymerase chain reaction (PCR) [7,8]. Immunohistochemistry has the benefit of utility in patients with hypocelluar bone marrows and in those patients with fibrotic bone marrows, circumstances when the aspirate, and therefore leukemia cells, may be difficult to obtain for immunophenotyping. In addition, IHC can be helpful when the infiltrates are interstitial rather than focal. Imunohistochemistry is generally carried out
Correspondence: Martin S. Tallman, MD, Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 380, New York, NY 10065, USA. Tel: 212-6393842. Fax: 212-6393841. E-mail:
tallmanm@mskcc.org
ISSN 1042-8194 print/ISSN 1029-2403 online 2011 Informa UK, Ltd. DOI: 10.3109/10428194.2011.566393
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