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Cross-Resistance to Purine Analogs in Hairy Cell Leukemia
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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-α 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.
Alan Saven, MD
Lawrence D. Piro, MD
Scripps Clinic and Research Foundation; La Jolla, CA 92037
The Editors welcome submissions for possible publication in the Letters section. Authors of letters should:
•Include no more than 300 words of text, three authors, and five references
•Type with double-spacing
•Send three copies of the letter, an authors' form signed by all authors, and a cover letter describing any conflicts of interest related to the contents of the letter.
Letters commenting on an Annals article will be considered if they are received within 6 weeks of the time the article was published. Only some of the letters received can be published. Published letters are edited and may be shortened; tables and figures are included only selectively. Authors will be notified that the letter has been received. If the letter is selected for publication, the author will be notified about 3 weeks before the publication date. Unpublished letters cannot be returned.
Annals welcomes electronically submitted letters.
- Copyright ©2004 by the American College of Physicians
