Co-Expression of CD38 and ZAP-70 Predictive of Early Treatment

[Guest guest]

[4945] Co-Expression of CD38 with Zap-70 Is Predictive of Treatment

Intervention in Patients (pts) with Early Stage Chronic Lymphocytic

Leukemia (CLL). Session Type: Publication Only

Jean- Coignet, Swaminathan Padmanabhan, Rami Manochakian, Kena

C. , Wallace, AnneMarie Block, Asher Alban Chanan-Khan

Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA; Pathology

and Lab Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA;

Clinical Cytogenetics, Roswell Park Cancer Institute, Buffalo, NY, USA

Introduction: CLL is a heterogeneous disease where advanced stage pts

have compromised survival despite treatment, while early stage pts

may not require any intervention. Based on current NCI-WG guidelines,

most early stage (Rai stage 0 and 1) CLL pts do not require treatment

until the development of progressive or symptomatic disease, though

eventually over 70% of CLL pts will receive therapy. Currently, there

are no markers to predict this subset of pts. Several markers of

adverse prognosis, including ZAP-70+, CD38+, un-mutated IgVH gene and

cytogenetic aberrations (17p-, 11q-, +12) have been identified. These

markers are primarily studied in context of aggressive clinical

course and survival outcome. The value of these markers to predict

the necessity of treatment intervention in early stage CLL pts has

not yet been completely evaluated. We investigated the expression

pattern of Zap-70 and CD38 to examine their predictive value in

identifying early stage CLL pts who will require therapeutic

intervention.

Results: 93 CLL pts were evaluated since 2002 at our institution.

Flow cytometry was used to determine Zap-70 and CD38 expression on

CD19+ CLL cells obtained from peripheral blood. Pts were considered

to be positive for Zap-70 and CD38 expression if > 20% and > 30% of

the cell stained for these proteins, respectively. For the Zap-70

analysis we used similar methodology as described by Crespo et al.1

Thirty-six (19M, 17F) pts had limited stage CLL, based on Rai staging

criterion. Median age was 65 years (range 43-86) with stage 0 or 1

observed in 14 and 22 pts, respectively. Median time from diagnosis

is 2 years (range <1-17). Increased expression of either Zap-70 or

CD38 was seen in 22 and 7 pts, respectively. Five (14%) pts were

positive for both. All (100%) pts with concurrent increased

expression of Zap-70 and CD38 required treatment (p=0.003), as

compared to 30% of patients requiring treatment that were negative

for both proteins or positive for only protein. Among the pts that

required treatment 4 had 13q- and one had trisomy 12 on cytogenetic

analysis.

Conclusion: Our study, demonstrates for the first time, the clinical

utility of CD38 and Zap-70 co-expression in determining the

probability of treatment intervention in early stage CLL pts.

Although the number of pts studied is small, our findings highlight a

potentially important use of these markers in the management of early-

stage CLL pts. These observations warrant validation in a larger

cohort of pts early stage CLL pts as well as correlation with other

prognostic markers such as cytogenetic and IgVH gene mutational

status.

1. Crespo M, Bosch F, Villamor N, et al: ZAP-70 expression as a

surrogate for immunoglobulin-variable-region mutations in chronic

lymphocytic leukemia. N Engl J Med 348:1764-75, 2003.