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34 R. J. Kreitman et al.
results, and a pivotal trial is being planned in this but may offer palliation [55]. Splenectomy should be
disease. avoided in patients being considered for recombinant
immunotoxin experimental treatment [36], but
should always be considered in patients with even
Approach to patients with relapsed hairy cell
mild or moderate splenomegaly who have exhausted
leukemia
other options and risk fatal complications of the
Many different treatment approaches to the relapsed disease [55,56]. Finally, purine analogs alone or
patient exist, and lack of randomized data prevents with other agents may be employed in the palliative
discounting most of them as inappropriate. A setting, but their declining potential benefit with
suggested algorithm for the treatment of early and repeated use must be considered along with their
relapsed HCL is shown in Table I. Because of the cumulative and often non-reversible toxicities.
long-term immunosuppression of purine analogs and
their decreased efficacy with retreatment, a general
Prevention of relapse by combining rituximab
strategy has been to avoid multiple courses of these
with cladribine
agents with short time intervals in between. After first
relapse with first purine analog response duration less Early treatment with rituximab and cladribine. One
than 1–2 year, or after multiple relapses from purine hypothesis is that relapse in HCL may be prevented
analog, salvage treatment with rituximab or experi- or delayed by eliminating the minimal residual
mental treatment with LMB-2, BL22 or HA22 disease (MRD) left over after CR to cladribine. A
(CAT-8015) has shown positive outcomes [28,29, preliminary report shows excellent activity of ritux-
35,36,40,41,59,60]. Combined treatment with both imab in eliminating MRD when used 4 weeks after
purine analog and rituximab has been successfully cladribine in 13 patients [61]. This trial was not
employed in both the 1st line and relapsed setting designed to determine whether rituximab should be
[5,61–64], although this approach is not standard used during 1st or 2nd line cladribine because
and long-term suppression of both normal B- and comparison with cladribine alone was not done. To
T-cells is expected. Physicians with patients who are determine the benefit of adding rituximab to first or
eligible for recombinant immunotoxin clinical trials 2nd line cladribine, a randomized study is underway
may choose to consider HA22 (CAT-8012) after at the National Cancer Institute which also allows
failure of at least 2 courses of purine analog. Patients patients to be treated by their local physicians.
with512 month response to initial purine analog are Patients with 0 or 1 prior course of cladribine are
considered primarily refractory and not appropriate randomized separately. Within each of these stratifi-
for repeat courses of purine analog, thus their cations, half of the patients receive rituximab begin-
physicians may consider rituximab as 2nd line ning with the 1st dose of cladribine, half receive
treatment and HA22 (CAT-8015) thereafter. Inter- cladribine without rituximab, and all patients receive
feron is clearly inferior to purine analog for achieve- delayed rituximab at least 6 months later if MRD can
ment of response [45], and has significant toxicities, be demonstrated in the blood. Thus the 1st goal is to
Figure 1. Flow-chart for the suggested treatment of early and relapsed HCL.
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