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  • Title: Zeta-chain associated protein 70 and CD38 combined predict the time to first treatment in patients with chronic lymphocytic leukemia.
    Author: Del Giudice I, Morilla A, Osuji N, Matutes E, Morilla R, Burford A, Maravelaki S, Owusu-Ankomah K, Swansbury J, A'Hern R, Brito-Babapulle V, Catovsky D.
    Journal: Cancer; 2005 Nov 15; 104(10):2124-32. PubMed ID: 16211545.
    Abstract:
    BACKGROUND: Zeta-chain associated protein (ZAP)-70 has been proposed as a surrogate marker for immunoglobulin heavy-chain variable region (IgVH) mutation in chronic lymphocytic leukemia (CLL), but it is still not clear whether it is an independent prognostic factor. METHODS: The authors evaluated ZAP-70 expression by flow cytometry in 201 untreated patients and correlated ZAP-70 levels with CD38 expression, genetic abnormalities detected by fluorescence in situ hybridization (FISH), and the time from diagnosis to first treatment. RESULTS: Fifty-seven patients (28%) were positive for ZAP-70 (> or = 20%). Positive ZAP-70 status was associated with advanced disease stage, atypical morphology, CD38-positive status, trisomy 12, del(6q), or no detectable abnormalities; negative ZAP-70 status was correlated with del(13q) as a sole abnormality. The treatment-free interval (TFI) was 17.7 months for ZAP-70-positive patients and 44.6 months for ZAP-70-negative patients (P < 0.001). Multivariate analysis in 117 patients identified advanced stage, CD38 > or = 7%, and the absence of del(13q) as a sole abnormality as independent factors for short TFI. Excluding FISH, ZAP-70 status acquired independent prognostic value along with CD38 status. The authors proposed a risk model that combines ZAP-70 and CD38 to identify patients who are likely to progress. When both markers were positive, the TFI was 12 months; when both were negative, the median TFI was 54 months; a median TFI of 26 months was observed in patients who had discordant results (P < 0.00001). CONCLUSIONS: The current findings suggested that both ZAP-70 and CD38 should be tested prospectively in all patients with early-stage CLL.
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