Correspondence
Treatment of Hairy-Cell Leukemia
N Engl J Med 2001; 345:1500-1501November 15, 2001
- Article
To the Editor:
Kreitman et al. (July 26 issue)1 report that an anti-CD22 recombinant immunotoxin (BL22) induced complete remissions in 11 of 16 patients with hairy-cell leukemia that was resistant to cladribine. Although BL22 represents an exciting new approach to the treatment of this disease, the results need to be interpreted cautiously, given the potential life-threatening toxicity of this agent (the hemolytic–uremic syndrome developed in two patients).
When a single course of cladribine was administered by continuous intravenous infusion for seven days to 349 patients with hairy-cell leukemia at Scripps Clinic, 319 patients (91 percent) had an initial complete response, and 22 (6 percent) had a partial response.2 Ninety patients (26 percent) relapsed after a median of 29 months. Of 53 patients treated with second courses of cladribine at the time of the first relapse, 33 (62 percent) had complete responses, and 14 (26 percent) had partial responses. Thus, cladribine resistance in patients with hairy-cell leukemia is indeed a rare occurrence. Kreitman et al. should therefore clarify their definition of cladribine resistance as “an inadequate response.” Also, despite the structural and mechanistic homology between cladribine and pentostatin (2'-deoxycoformycin), cladribine induced durable complete responses in patients with hairy-cell leukemia that was truly resistant to pentostatin, suggesting the absence of cross-resistance between these two agents.3
The 16 patients of Kreitman et al. had hairy-cell leukemia with an unusual resistance to systemic chemotherapy. The features predicting this resistance were the marked lymphocytosis in five patients, the abdominal masses in two patients, and the aberrant display of CD antigens in three patients.4
4 ReferencesAlan Saven, M.D.
Scripps Clinic, La Jolla, CA 92037
saven.alan@scrippshealth. org 1
Kreitman RJ ,Wilson WH ,Bergeron K , et al. Efficacy of the anti-CD22 recombinant immunotoxin BL22 in chemotherapy-resistant hairy-cell leukemia. N Engl J Med 2001;345:241-247
Full Text | Web of Science | Medline2
Saven A ,Burian C ,Koziol JA ,Piro LD . Long-term follow-up of patients with hairy cell leukemia after cladribine treatment. Blood 1998;92:1918-1926
Web of Science | Medline3
Saven A ,Piro LD . Complete remissions in hairy cell leukemia with 2-chlorodeoxyadenosine after failure with 2'-deoxycoformycin. Ann Intern Med 1993;119:278-283
Web of Science | Medline4
Tetreault SA ,Robbins BA ,Saven A . Treatment of hairy cell leukemia-variant with cladribine. Leuk Lymphoma 1999;35:347-354
CrossRef | Web of Science | Medline
Author/Editor Response
The authors reply:
To the Editor: All 16 patients with hairy-cell leukemia in our study had an inadequate response to their last treatment with cladribine. Two had brief complete remissions that lasted 4 and 15 months. The other 14 patients had a partial response or no response to the last course of cladribine, and in only 1 of them was the cytopenia corrected. Five patients had no response to the first course of cladribine, an unusual finding in patients with hairy-cell leukemia, whereas 11 patients had resistance to cladribine after one to five relapses, a more typical finding. We agree with Saven that cladribine is associated with a high rate of complete remission in patients who have not previously been treated and in those with a first relapse, but almost 5 percent of patients have no response or have persistent cytopenia after their first course of cladribine.1 Furthermore, the rate of complete remission and the time to treatment failure decrease with subsequent courses of the drug, and there is no plateau in disease-free or overall survival.2-4
Long-term follow-up data after three or more courses of cladribine have not been published. The median follow-up in the study cited by Saven was 58 months, and the study ended in mid-1987.1 No other trial has reported longer follow-up data. In contrast, our patients were enrolled a median of eight years after diagnosis, and most had received other treatments in addition to cladribine. The 11 patients in our study who had received more than one course of cladribine began BL22 treatment 2 to 10 years (median, 7) after the first course of cladribine.
We believe that BL22 is a potentially important investigational therapy for cladribine-resistant hairy-cell leukemia, since it produces complete remission without irreversible toxicity.
4 ReferencesRobert J. Kreitman, M.D.
Wyndham H. Wilson, M.D., Ph.D.
Ira Pastan, M.D.
National Cancer Institute, Bethesda, MD 20892
kreitmar@mail.nih. gov 1
Saven A ,Burian C ,Koziol JA ,Piro LD . Long-term follow-up of patients with hairy cell leukemia after cladribine treatment. Blood 1998;92:1918-1926
Web of Science | Medline2
Hoffman MA ,Janson D ,Rose E ,Rai KR . Treatment of hairy-cell leukemia with cladribine: response, toxicity, and long-term follow-up. J Clin Oncol 1997;15:1138-1142
Web of Science | Medline3
Cheson BD ,Sorensen JM ,Vena DA , et al. Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine via the Group C protocol mechanism of the National Cancer Institute: a report of 979 patients. J Clin Oncol 1998;16:3007-3015
Web of Science | Medline4
Tallman MS ,Peterson LC ,Hakimian D ,Gillis S ,Polliack A . Treatment of hairy-cell leukemia: current views. Semin Hematol 1999;36:155-163
Web of Science | Medline
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