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. 2013 Dec 15;19(24):6873-81.
doi: 10.1158/1078-0432.CCR-13-1752. Epub 2013 Nov 25.

Cladribine with immediate rituximab for the treatment of patients with variant hairy cell leukemia

Robert J Kreitman  1 , Wyndham Wilson, Katherine R Calvo, Evgeny Arons, Laura Roth, Jeffrey Sapolsky, Hong Zhou, Mark Raffeld, Maryalice Stetler-Stevenson
Affiliations

Cladribine with immediate rituximab for the treatment of patients with variant hairy cell leukemia

Robert J Kreitman et al. Clin Cancer Res. .

Abstract

Purpose: In contrast with the classic form, variant hairy cell leukemia (HCLv) responds poorly to single-agent purine analogs, expresses unmutated BRAF, has shorter overall survival, and lacks effective standard therapy. No treatment has achieved a high complete remission (CR) rate even in small series, and of 39 reported cases from six studies, overall response rate after cladribine was 44% with 8% CRs. Rituximab has been found to increase the sensitivity of malignant cells to cladribine, suggesting that combination with cladribine might improve response in HCLv. To test this hypothesis, patients with HCLv were treated with simultaneous cladribine and rituximab.

Experimental design: Patients with HCLv with 0 to 1 prior courses of cladribine received cladribine 0.15 mg/kg for days 1 to 5, with eight weekly doses of rituximab 375 mg/m(2) beginning day 1. Restaging was performed, and minimal residual disease (MRD) in blood and marrow was quantified using PCR, immunohistochemistry, and flow cytometry.

Results: By 6 months, 9 (90%) of 10 patients achieved CR, compared with 3 (8%) of 39 reported cases treated with cladribine alone (P < 0.0001). Of the 9 CRs, 8 remain free of MRD at 12 to 48 (median 27) months of follow-up. No dose-limiting toxicities were observed when beginning cladribine and rituximab on the same day, although most patients required short-term steroids to prevent and treat rituximab infusion reactions. Cytopenias in CRs resolved in 7 to 211 (median 34) days without major infections.

Conclusion: Although cladribine alone lacks effectiveness for early or relapsed HCLv, cladribine with immediate rituximab achieves CRs without MRD and is feasible to administer.

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Figures

Figure 1
Figure 1. Time course of response after cladribine plus rituximab
For each of the indicated patients, tumor burden is quantified either by flow cytometry (A) or by soluble CD22 level (B).
Figure 2
Figure 2. Minimal residual disease before and after cladribine plus rituximab
HCLv patients, identified as in Fig. 1, were tested for flow cytometry of blood (A), immunohistochemistry of bone marrow biopsy (B) and flow cytometry of bone marrow aspirate (C), with positive results indicated by solid and negative results by open markers.
Figure 3
Figure 3. Thrombocytopenia after cladribine plus rituximab
Patients identified as in Fig 1. The beginning of treatment is considered day 1.
See this image and copyright information in PMC

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