Hairy cell leukemia variant Pentostatin is also less active in HCL-V than in
classic HCL. Similarly, in a group of 15 patients with HCL-V reported byMatutes et al., pentostatin (DCF) induced only a PRin eight of 15 (54%) patients and no CR was achieved [3]. Of 12 patients treated with this agent in other reports, there were seven PRs and no CR [8]. There is limited information on the therapy of HCL-V with fludarabine. Only one of three patients in the series reported by Matutes et al. treated with this agent achieved a PR [3].
Monoclonal antibodies and immunotoxins
Recently, some reports indicate that the anti-CD20 monoclonal antibody, rituximab, and alemtuzumab are active in HCL-V [9–11]. Compared with PNAs, these drugs do not induce long-term bone marrow hypoplasia. It is possible that immunochemotherapy with a rituximab and PNA combination will be the most effective treatment of HCL-V, similar to the current treatment of chronic lymphocytic leukemia and other B-cell malignances. However, further clinical studies are required before rituximab can be considered as a front-line therapy for HCL-V. Promising results have been also obtained with
immunotoxin BL22, targeting CD22 [12,13]. CD22 is highly expressed in HCL, even in chemoresistant disease, and is therefore a potential target for antibody- directed therapy in refractory/resistant HCL. BL22 seems also to be very effective treatment of HCL-V. In one study, three patients refractory to 2-CdA were treated with BL22 and all of them achieved a CR lasting 8, 12, and 413 months, respectively. In these patients, circulating hairy cells began to decrease within 24 h after the first dose of immunotoxin [10]. In addition, two patients had a second CR after retreatment when relapsed. All the patients had never had a CR with chemotherapy with 2-CdA. These encouraging results suggest that BL22 may be a very effective agent in the treatment of refractory HCL-V [14]. In addition, the newer anti-CD22 immunotoxin, moxetumomab pasudotox (CAT-8015,HA22), highly active in refractory/relapsed HCL-C, needs clinical investigation in HCL-V. Moxetumomab pasudotox is a new-generation CD22-specific targeted immunotox- in composed of anti-CD22 antibody fused to the modified form of Pseudomonas exotoxin [13]. This agent has a novel mechanism of action as compared to other anti-CD22 monoclonal antibodies. Moxetumo- mab pasudotox is internalized upon binding to CD22, inhibiting protein translation and promoting apoptosis.
Conclusions
HCL-V is a distinct clinicopathological entity resis- tant to several available methods of treatment,
55
Figure 1. Proposed treatment algorithm for hairy cell leukemia variant (HCL-V). 2-CdA, cladribine; DCF, pentostatin; SCT, stem cell transplant (modified from [8]).
including PNAs and IFN-a. However, splenectomy or splenic irradiation are valuable methods of treatment for some patients with this disease, especially those with hypersplemism and a significant bulk of disease. In addition, recent data suggest that treatment with rituximab or anti-CD22 immunotox- ins is effective in HCL-V, and these agents need further investigation. Moreover, rituximab can be combined with PNAs, 2-CdA, or pentostatin, and these combinations should be further investigated in the first-line treatment of HCL-V (Figure 1).
Acknowledgements
This work was supported in part by a grant from the Medical University of Lodz, Poland (No. 503- 1093-1).
Potential conflict of interest: A disclosure form provided by the author is available with the full text of this article at
www.informahealthcare.com/lal.
References
1. Matutes E, Wotherspoon A, Catovsky D. The variant form of hairy-cell leukaemia. Best Pract Res Clin Haematol 2003; 16:41–56.
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