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the latter case with the durable CR achieved with combination therapy. The two cases with continued splenomegaly after treatment underline the impor- tance of waiting for a bone marrow biopsy to assess response. Patients with HCL who may benefit from combin-
ing rituximab with a purine analog are, first, patients relapsing after any therapy, as demonstrated here. Second, those failing to achieve CR after 8–10 doses of pentostatin or a single course of cladribine may benefit from further treatment with the same agent plus the addition of rituximab. We have given rituximab to two patients (not included in this series) starting 9–12 months after they achieved only a PR following first-line treatment, in one case after a second course of cladribine and in the other case after 12 doses of pentostatin. Both achieved a CR and both remained in remission at 33 months and 52 months, respectively. Third, considering the rela- tively poor outlook for patients with a low hemoglo- bin (510 g/dL) and/or platelet (51006109/L) count at presentation [1,3–4 ,7], it could be argued that treating such patients with rituximab concur- rently with a purine analog, at first line, may be beneficial. However, we do not have data to support this last suggestion, nor do we have evidence relating to the use of this combination treatment in the rare patients whose disease is non-responsive to purine analogs from the outset. The number of patients who have received the
combination treatment is currently small and the median follow-up is only 3 years. However, the results presented here suggest that the addition of rituximab, in combination with a purine analog, is a safe and effective treatment for patients with recur- rent HCL, resulting in a greater likelihood of obtaining a CR and a durable remission compared with a purine analog alone.
Acknowledgements
Monica Else was funded by the Arbib Foundation. We would like to thank A. Morilla and R. Morilla for conducting flow cytometry and A. Wotherspoon for his critical review of bone marrow histology. C.E.D. has acted as a consultant for Roche, BSPharma, and Genzyme, Inc.; D.C. has acted as
a consultant for Hospira, Roche, GlaxoSmithKline, and Celgene.
Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at
www.informahealthcare.com/lal.
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