REPLY
Cross-Resistance to Purine Analogs in Hairy Cell Leukemia
Alan Saven, MD, and
Lawrence D. Piro, MD
1 February 1994 | Volume 120 Issue 3 | Pages 247-248
IN RESPONSE:
The two patients refractory to 2-CdA after not responding to both dCF and fludarabine phosphate appear to show resistance to all three of the newer purine analogs. They represent important sources of insight into the mechanisms of purine nucleoside drug action and resistance. It would be important to know whether the study patients showed sensitivity to interferon-
because of its differing mechanism of action and if they had atypical morphologies or aberrant immunophenotype profiles.
The sensitivity of lymphocytes to the action of 2-CdA is determined in part by the ratio of deoxycytidine kinase levels to 5'-nucleotidase. Patients with hairy cell leukemia who do respond tend to have lower ratios of deoxycytidine kinase levels to 5'-nucleotidase than do patients who do not respond [1]. Similar considerations apply to fludarabine phosphate; for dCF, however, the intracellular level of adenosine deaminase is more relevant for predicting response [2]. Because the enzymes of importance for 2-CdA and dCF differ, one might expect to see some lack of cross-resistance between them; however, because both 2-CdA and fludarabine phosphate depend on deoxycytidine levels for activation, cross-resistance is more likely.
Four patients whose chronic lymphocytic leukemia did not respond to fludarabine phosphate have been reported to respond to 2-CdA therapy [3]; however, the experience at our institution with more patients has been much less favorable [4]. Despite the small number of patients, our data show that cross-resistance between 2-CdA and dCF may not occur in some patients with hairy cell leukemia. Whether this will be borne out in studies with larger numbers of patients and whether this can be applied to cross-resistance between purine nucleoside agents in other lymphoid malignancies remains to be determined.
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Author and Article Information
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Scripps Clinic and Research Foundation; La Jolla, CA 92037
1. Kawasaki H, Carrera CJ, Piro LD, Saven A, Kipps TJ, Carson DA. Relationship of deoxycytidine kinase and cytoplasmic 5'-nucleotidase to the chemotherapeutic efficacy of 2-chlorodeoxyadenosine. Blood. 1993; 81:597-601.
2. O'Dwyer PJ, Cheson BD, Leyland-Jones B, King SA, Hoth DF. Deoxycoformycin: an active new drug for indolent lymphomas and hairy cell leukemia. Oncology. 1988; 2:17-22.
3. Juliusson G, Elmhorn-Rosenborg A, Liliemark J. Response to 2-chlorodeoxyadenosine in patients with B-cell chronic lymphocytic leukemia resistant to fludarabine. N Engl J Med. 1992; 327:1056-61.
4. Saven A, Lemon RH, Piro LD. 2-chlorodeoxyadenosine for patients with B-cell chronic lymphocytic leukemia (Letter). N Engl J Med. 1993; 328:812-3.
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