Cladribine in hairy cell leukemia 15
50.5610
9
/L), and 42% developed neutropenic a, cladribine, and pentostatin. The incidence ratios
fever. Only 13% of patients had documented viral were calculated using data from the Connecticut
or bacterial infections. Filgrastim (Neupogen) was Tumor Registry. There was a nonsignificant increase
evaluated for cladribine-induced neutropenic fever in in the incidence of second malignancies observed at 6
a phase II study conducted at Scripps Clinic. Thirty- months after diagnosis with an observed-to-expected
five patients received cladribine at 0.1 mg/kg per day ratio of 1.34, p¼0.08. There was, however, no excess
by continuous intravenous infusion for over seven of solid tumor malignancies among patients in any of
days. Filgrastim was given at 5 m g/kg per day by the treatment groups. There was an excess of
subcutaneous injection on days -3, -2, and -1 as lymphoproliferative disorders, most notably myeloma
‘‘priming,’’ and after cladribine infusion until the and lymphoma [19]. Of 379 patients treated with
ANC was C212610
9
/L on two consecutive days. cladribine at Scripps Clinic, there was a slight increase
These 35 patients were compared to 105 historic in second malignancies with the observed-to-expected
controls treated with cladribine alone. The median ratio of 2.03, as compared with the National Cancer
number of days to an ANC 41.0610
9
/L was nine Institute SEER data. Logistic regression analysis
in the filgrastim-treated group versus 22 among demonstrated that the risk of second malignancy was
historic controls (p510
75
). The percentage of 2.45-fold greater for individuals in successive age
febrile patients, number of febrile days, and fre- quartiles [13]. Thus, as patients aged, their risk of
quency of admissions for antibiotics were not second malignancy increased.
statistically different in the two groups and thus the Table III demonstrates the risk of second malig-
routine adjunctive use of filgrastim cannot be nancies in patients with HCL.
recommended [18].
Minimal residual disease after cladribine
Chronic. Patients with HCL were found to have
an increased incidence of second malignancies. Approximately 95% of patients treated with cladri-
Kurzrock et al. published data from M.D. Anderson bine achieved a CR. A CR was defined as the absence
Cancer Center on 350 patients treated with interferon of hairy cells in bone marrow biopsies on routine
Figure 3. Treatment algorithm of patients with relapsed or refractory HCL.
Table III. Risk of second malignancies in HCL.
No. of patients No. 2nd Observed-to-
Investigator with HCL malignancies % Prior Rx expected ratios Comments
Au et al. [20] 117 36 (31%) All 2.60 Increase risk; not Rx related
Kurzrock et al. [19] 350 26 (7%) All 1.34 Increase myeloma/NHL only;
not RX related
Kampmeier et al. [21] 69 13 (19%) IFN 4.33 Increase risk
Cheson et al. [22] 2,014 (CLLþHCL) 111 (6%) Flud/dCF/2-CdA 1.43 No increase risk
Flinn et al. [23] 241 39 (16%) dCF 1.26 No increase risk
Goodman et al. [13] 379 47 (12%) 2-CdA 2.03 Slight increase risk
HCL, hairy cell leukemia; IFN, interferon; CLL, chronic lymphocytic leukemia.
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