Leukemia & Lymphoma, June 2011; 52(S2): 53–56
Management of hairy cell leukemia variant
TADEUSZ ROBAK Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland
Abstract Hairy cell leukemia variant (HCL-V) is now included in the World Health Organization (WHO) classification as a provisional entity and is no longer considered to be biologically related to classic HCL (HCL-C). The clinical course of HCL-V is variable but usually more aggressive, and the median survival of patients with HCL-V is significantly shorter than that of HCL-C. The therapeutic approach to HCL-V is still debated. Various treatment approaches active in HCL- C achieve partial response (PR) or no response in HCL-V, and remission is usually shorter than in HCL-C. In addition, HCL-V seems to be resistant to therapeutic modalities usually highly effective in the treatment of HCL-C. Cladribine (2- CdA) is significantly less active in HCL-V than in HCL-C. In addition, the majority of patients with HCL-V require more than one cycle of 2-CdA to maintain PR. Patients with HCL-V treated with pentostatin also have a poorer clinical outcome and a lower response rate than those of patients with HCL-C. Recently, some reports indicate that monoclonal antibodies, rituximab and alemtuzumab, are active in HCL-V. Promising results have also been obtained with anti-CD22 immunotoxin, BL22. A new generation of CD22-specific immunotoxins, moxetumomab pasudotox (CAT-8015, HA22), highly active in refractory/relapsed HCL-C, also need clinical investigation in HCL-V. Currently, immunochemotherapy with rituximab and purine nucleoside analogs (PNAs) should be considered as the treatment of choice in previously untreated patients.
Keywords: Hairy cell leukemia variant, purine nucleoside analogs, cladribine, pentostatin, rituximab, immunotoxins
Introduction Hairy cell leukemia variant (HCL-V) is an uncom- mon B-cell neoplasm accounting for 10–20% of patients with classical HCL (HCL-C) and 0.4% of chronic lymphoid malignancies, representing about 60–75 new patients with HCL-V each year in the USA [1]. HCL-V is a distinct clinicopathological entity [2]. Distinguishing HCL-V from HCL-C and splenic marginal zone lymphoma (SMZL) remains a problem. Both HCL-V and HCL-C are associated with pronounced splenomegaly and circulating neo- plastic cells with ‘hairy’ projections. However, patients with HCL-V are usually older, splenomegaly is less common, and leukopenia with granulocytope- nia and monocytopenia are usually not seen. Bone marrow is typically easily aspirable, and hypercellular with mild myelofibrosis. The clinical course of HCL- V is chronic and usually benign, but survival time of patients with HCL-V is usually shorter than for those with HCL-C [1,3]. Its features are intermediate between those of HCL-C and prolymphocytic leukemia. Leukemic cells contain abundant villi, an
intensely basophilic cytoplasm, and central, round, occasionally bilobed, indented hyperchromatic nu- clei with prominent nucleoli [1,2]. In comparison to HCL-C, HCL-V cells are smaller, have higher nuclear cytoplasmic ratios, and have no ribosome– lamella complexes. Several markers including CD11c, CD25, CD27, CD103, CD123, ANXA1 and tartrate resistant acid phosphatase (TRAP) are claimed to distinguish HCL-V from HCL-C and SMZL. HCL-V cases lack CD25, CD27, and ANXA1 and might lack CD103 but express other HCL-associated antigens. The analysis of immuno- globulin heavy variable gene (IGHV) mutational status of HCL-V cells has shown that most patients are unmutated, in contrast to HCL-C. In addition, VH4-34 gene expression is associated with symptoms characteristic of HCL-V. HCL-V is now included in the World Health Organization (WHO) classification as a provisional entity, and is no longer considered to be biologically related to HCL-C [2]. The clinical course of HCL-V is variable, but usually more aggressive than HCL-C. In one study, median survival was approximately 9 years, with only 15%
Correspondence: Professor Tadeusz Robak, Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, 93-510 Lodz, Ul. Ciolkowskiego 2, Poland. Tel: þ48-42-689-51-91. Fax: þ48-42-689-51-92. E-mail:
robaktad@csk.umed.lodz.pl
ISSN 1042-8194 print/ISSN 1029-2403 online 2011 Informa UK, Ltd. DOI: 10.3109/10428194.2011.566392
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