INCLUSION OF TOTAL BODY CT SCAN IN THE INITIAL WORK-UP OF CLL PATIENTS WITH EARLY-STAGE ON CLINICAL GROUNDS: PRELIMINARY RESULTS OF A PROSPECTIVE, MULTICENTER O-CLL1-GISL STUDY

Background. The clinical staging systems proposed by Rai and Binet represent the backbone for assessing prognosis in patients with Chronic Lymphocytic Leukemia (CLL). However, staging systems are not devoid of some limitations, among the most significant of which is the lack of recognition of early-stage patients who will progress. Unlike the guidelines for assessing the response to therapy for most other types of non-Hodgkin’s lymphomas, the widely-used NCI-WG guidelines for patients with CLL do not incorporate use of computed tomography (CT) scans in the algorithm. However, two recent retrospective study challenged this notion. highlighting the importance of prospective validation of CT scans before routine inclusion in CLL work up. Aims. In the present study, we investigated whether total body CT scan allowed to individuate among Binet stage A CLL patients, included in the prospective multicenter O-CLL01 GISL study, cases in more advanced stage and whether this subgroup showed a different expression of clinical and biological prognostic markers. Patients. Up to date, 275 patients have been enrolled in the trial started in April 2007 and total body CT scan were available in 87 patients. Fifty-two patients (60%) were male and the median age was 61 years (range, 33 to 71 years). All patients are in Binet stage A, while 83 patients were at low risk (0-I stages) and 4 at intermediate risk (II stage) by Rai classification. LDH was elevated in 11.5% of cases and B2-microglobulin in 24%. Twenty-eight patients (33%) were IgVH unmutated, 31 patients (36%) had a high ZAP-70 expression, 17 patients (20%) were CD38 positive (>30%). Fluorescence in situ hybridization (FISH) data are available in 61/87 cases; the most frequent abnormality was del(13)(q14) (29 pts 33%), followed by trisomy 12 (5 pts, 6%), del(17p13) (4 pts 5%) and del(11q22.3) (2 pts 2%), 21 cases (24%) were normal. Cytogenetic abnormalities were clustered in 3 risk groups [i.e. low (del(13q14) and normal), intermediate (trisomy 12) and high risk (del(11q22) and del(17p13)] as suggested by others. Results. Considering total body CT scan, 22 out of 83 analyzed (25%) patients were converted into Binet stage B. Notably, 64% were male, LDH was elevated in 18% of cases and B2-microglobulin in 18%, 41% were IgVH unmutated, 27% had a high ZAP-70 expression, 27% were CD38 positive, 4,5% showed a high-risk FISH. Both main clinical characteristics and biological prognostic markers failed to correlate with a more advanced stage. In fact, no statistically different distribution of gender, age, LDH and b2-microglobulin, such as IgVH mutational status, CD38 and ZAP-70 expression and cytogenetic abnormalities were observed between Binet A cases and Binet B. According the Rai classification 14/83 (17%) low risk patients became at intermediate risk with the integration of total body CT scan. Also this subset of patients did not show a statistically different expression of all prognostic markers, but a higher rate of cases with elevated B2-microglobulin (p=0.003), than patients at low risk. Finally, total body CT scan allowed to early individuate a second neoplasia in 2 cases (lung cancer 1 pt, renal cell carcinoma 1 pt). Conclusions. In line with literature information, our preliminary data indicate that the integration of total body CT scans in the clinical staging allowed to individuate among Binet A CLL cases on clinical grounds 25% of cases with a more advanced stage. Although a more advanced stage did not correlate with both clinical and biological variables reflecting bad prognosis. A longer follow-up will allow to demonstrate whether the inclusion of total body CT scan in the initial work-up of patients with early-stage on clinical grounds provide relevant prognostic information.