Zeta-chain associated protein 70 and CD38 combined predict the time to first treatment in patients with chronic lymphocytic leukemia.
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.
Del Giudice
Ilaria
I
Section of Hemato-Oncology, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Morilla
Alison
A
Osuji
Nnenna
N
Matutes
Estella
E
Morilla
Ricardo
R
Burford
Anna
A
Maravelaki
Sonia
S
Owusu-Ankomah
Kwasi
K
Swansbury
John
J
A'Hern
Roger
R
Brito-Babapulle
Vasantha
V
Catovsky
Daniel
D
D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012307:Risk Factors; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D051746:ZAP-70 Protein-Tyrosine Kinase; D051997:ADP-ribosyl Cyclase 1