Abstract
The prognosis of patients with CLL has been traditionally assessed by using clinical stages. Clinical stages, however, are a mere reflection of the biological diversity of CLL. In this regard, we and others have recently shown that ZAP-70 expression separates CLL into two clinical forms with different outcome. The aim of this study was to analyze the distribution of age, gender, and different prognostic parameters according to ZAP-70 expression in 222 pts with CLL (median age, 62 yrs; female/male: 89/133). ZAP-70 was determined by flow cytometry, a high expression being defined as >20% ZAP-70 positive CLL cells. Median follow-up of the series was 7.1 years. Clinical stages at diagnosis were: Binet stage A, 187 pts; B, 21 pts; and C, 14 pts. Rai Stage 0, 123 pts; I, 53 pts; II, 28 pts; III, 7 pts; and IV, 11 pts. Overall median survival was 13 years. Parameters associated with a high ZAP-70 expression were lymphocyte doubling time >12 mos., atypical morphology, bone marrow infiltration > 60%, increased serum LDH and timidin kinase, CD38 expression >20%, del(13q14), unmutated status of IgVH, and development of Richer syndrome. Interestingly, ZAP-70 expression distribution correlated with Rai’s stage (0 vs. 1 to 4). Also, CD38 expression was able to separate two subpopulations with different survival among CLL cases with low ZAP-70 expression (median survival 18 yrs vs. 13 yrs), but not in pts. with ZAP-70>20%. About 50% of pts in Binet A progressed during the follow-up. Median time to progression for patients with high ZAP-70 expression was 3.3 years whereas it was not reached for patients with low ZAP-70 expression. Median survival of pts with low ZAP-70 expression was 16.3 years, whereas it was of 8.5 years in those with high ZAP-70 expression. In conclusion, ZAP-70 expression identifies a subgroup of patients with CLL with unfavorable prognostic factors related to the proliferation and progression of the disease.
Prognostic Parameters according to ZAP-70 expression
| Variable . | ZAP-70 >20% . | ZAP-70 < 20% . | p= . |
|---|---|---|---|
| Median age | 60 yrs | 63 yrs | |
| Gender (female) | 39% | 41% | |
| LDT < 12 mos | 42% | 23% | 0.009 |
| Atypical morphology | 54% | 12% | 0.000 |
| BM infiltration >60% | 50% | 33% | 0.03 |
| Increased LDH | 13% | 4% | 0.028 |
| Increased TK | 66% | 28% | 0.000 |
| CD38 > 20% | 67% | 32% | 0.000 |
| Del(13q14) | 38% | 55% | 0.027 |
| Unmutated IgVH | 88% | 11% | 0.000 |
| Richter Syndrome | 8% | 2% | 0.039 |
| Rai Stage > 0 | 53% | 37% | 0.039 |
| TTP (Binet A) | 3.3 yrs | NR | 0.000 |
| Median Survival | 16.3 yrs | 8.5 yrs | 0.000 |
| Variable . | ZAP-70 >20% . | ZAP-70 < 20% . | p= . |
|---|---|---|---|
| Median age | 60 yrs | 63 yrs | |
| Gender (female) | 39% | 41% | |
| LDT < 12 mos | 42% | 23% | 0.009 |
| Atypical morphology | 54% | 12% | 0.000 |
| BM infiltration >60% | 50% | 33% | 0.03 |
| Increased LDH | 13% | 4% | 0.028 |
| Increased TK | 66% | 28% | 0.000 |
| CD38 > 20% | 67% | 32% | 0.000 |
| Del(13q14) | 38% | 55% | 0.027 |
| Unmutated IgVH | 88% | 11% | 0.000 |
| Richter Syndrome | 8% | 2% | 0.039 |
| Rai Stage > 0 | 53% | 37% | 0.039 |
| TTP (Binet A) | 3.3 yrs | NR | 0.000 |
| Median Survival | 16.3 yrs | 8.5 yrs | 0.000 |
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