Implications of minimal residual disease in hairy cell leukemia after cladribine using immunohistochemistry and immunophenotyping

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 constitute MRD are 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.