14 E. Huynh et al.
a durable complete remission after one or two daily versus 2% for the weekly protocol, p¼0.64)
courses with a median follow-up duration of 20 [16]. The conclusion of the trial was that the weekly
months. Neutropenic fever that required intravenous dosing is equally effective but not safer than the 5-day
antibiotics occurred in 28 patients (38%) [14]. dosing schedule.
Lauria et al. published on 25 patients treated with
cladribine 0.15 mg/kg per week by intravenous
Retreatment with cladribine after primary purine
infusion weekly for 6 consecutive weeks. Nineteen
analogue therapy
patients (76%) achieved a complete remission with a
median disease-free survival of 14.7 months. Four Cladribine has also been shown to be effective in
patients (16%) developed severe neutropenia and patients who relapse after pentostatin. Cheson et al.
only two patients (8%) suffered an infectious reported on 979 patients, who received cladribine via
episode [15]. the Group C Protocol mechanism of the National
Robak et al. published the results of a prospective, Cancer Institute. Of 68 patients who had received
randomized clinical trial comparing cladribine in a pentostatin prior to cladribine, 54 patients (79%)
weekly versus daily schedule. One hundred and achieved a response [17]. There appeared to be a lack
thirty-two patients were randomized to receive either of cross-resistance between pentostatin and cladri-
cladribine at 0.12 mg/kg in a 2-h intravenous bine despite mechanistic similarities.
infusion daily for five days or 0.12 mg/kg in a 2-h Of the 341 responding patients treated at Scripps
intravenous infusion once a week for 6 weeks. Clinic with cladribine, the relapse rate at 48 months
Complete remission rates, progression-free survival was 19% overall, 16% for complete responders, and
and overall survival were not significantly different 54% for partial responders. Of 53 patients treated
between the two schedules. There was not a with a second course of cladribine after first relapse,
statistically significant difference in the rate of grade 33 patients (62%) achieved a CR and 14 patients
3/4 infections (18% for daily versus 26% for weekly (26%) a partial response (PR) [7].
schedule, p¼0.28) and septic deaths (3% for the Table II details the course of patients with relapsed
disease after cladribine therapy. These data were
updated among 209 patients who had at least 7 years
of follow-up. Seventy-six patients (37%) relapsed
after initial therapy with cladribine. The median time
to first relapse was 42 months for all responders.
Sixty-seven patients (88%) had a prior CR and nine
patients (12%) had a prior PR. Of 60 patients (79%)
who received a second course of cladribine after
relapse, 44 patients (75%) achieved a CR and 10
patients (17%) achieved a PR [13]. Thus, patients
who relapse can be successfully retreated with
cladribine. Comparative data between cladribine
and pentostatin in this subset of patients are lacking.
Figure 3 illustrates a suggested treatment algo-
rithm for patients with relapsed or refractory HCL.
Complications from cladribine
Figure 2. Time to treatment failure of 207 patients after the first
course of cladribine, stratified by response. CR, complete
Acute. After the administration of cladribine, 71% of
response; PR, partial response. p50.0005. patients experienced grade 4 neutropenia (ANC
Table II. Responses of relapsed patients with HCL after prior cladribine.
Responses
Investigator Relapse No. of patients CR (%) PR (%) NR/NA (%) Median response
Goodman et al. [13] 207 196 (95) 11 (5) 0 98 mo. (8–172 mo.)
1 59 44 (75) 10 (17) 5 (8) 35 mo. (4 days–92 mo.)
2 9 6 (67) 2 (22) 1 (11) 20 mo. (10–49 mo.)
3 2 1 (50) 0 1 (50) 42þmonths
Dearden et al. [12] 1 5 4 (80) 1 (20) 0
HCL, hairy cell leukemia; CR, complete response; PR, partial response; NR/NA, no response/not assessable.
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46