30 D. A. Thomas et al.
explored. Cervetti et al. [30] treated 10 HCL patients and alemtuzumab) or bulky fludarabine refractory
with standard dose rituximab for 4 weeks in an CLL and warrants further study in HCL [40].
attempt to eradicate MRD detectable by cpPCR after
one course of therapy with 2-CdA. Two patients
Future directions
were in CR, six had achieved PR, and two had failed
to respond to therapy with 2-CdA. All patients with Therapeutic interventions toward a curative strategy
active disease achieved CR after rituximab, assessed will require a cooperative effort to develop prospec-
within 2 months after therapy. Sequential assess- tive rationally designed clinical trials assessing MRD
ments of cpPCR showed either a reduction in the in a systematic fashion. The prognostic relevance of
levels or molecular negativity in several patients; in MRD in HCL can only be determined in the context
some cases this latter response was achieved as late as of uniform definitions, methodology, and therapy.
12 months after completion of rituximab. A subse- Clinical trials further exploring the potential for
quent report included extended follow-up (median MoAbs to eradicate MRD and thereby improve
36 months) of this cohort and inclusion of an disease outcomes in the setting of nucleoside analog
additional 17 patients; durable complete molecular therapy are underway.
response rate was 70% after rituximab therapy
(median of 4 months after 2-CdA, range 1.5–113 Declaration of interest: The authors report no
months) [31]. Two-year progression-free survival conflicts of interest. The authors alone are respon-
correlated with quality of response to rituximab sible for the content and writing of the paper.
therapy (94% for CR versus 50% for PR, p50.001)
and MRD status (100% if negative versus 30% if
positive, p50.001).
References
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