Presenting Features Predictive of Long-Term Stability in Chronic Lymphocytic Leukemia.

Prognostic factors to predict an aggressive clinical course in chronic lymphocytic leukemia (CLL) such as CD38, ZAP-70 and IgH mutation status have been well described, however, readily available presenting features predictive of long-term stability are less well defined. We performed a retrospective analysis of 335 consecutive patients with CLL seen at St. Paul’s Hospital from January 1969 to July 2005. Patients were identified from the practice data-base and clinical and pathological data abstracted by chart review. Long-term stability was defined as no requirement for treatment for at least 6 years (n=66, group A). Characteristics of group A were compared to all other pts (group B, n=269), and, to avoid follow-up bias, to pts followed for ≥6 y who required treatment (group C, n=62). 65 pts in group A were B-cell in phenotype and 1 was T-cell; group B 268 pts B-cell, 1 T-cell; group C all 62 B-cell. Median age at diagnosis for groups A, B and C were 59.5 (range 33–80) y; 68 (30–94) y; and 60 (30–82) y, respectively (p<0.0001 for A vs. B and p<0.42 for A vs. C). Male pts comprised 52%, 54.3% and 53% of groups A, B and C respectively (p<0.85). Rai stages were: stage 0, 1, 2, 3, and 4; 111, 48, 47, 3 and 6 respectively. ECOG Performance Status was 0 in 307 pts and was not analyzed further. Lymphocyte count at diagnosis (LCD) for groups A, B and C were 9 (4–50 X 10⁹/L), 10 (3–394) and 12 (3–155; p<0.0001 for A vs. B and p< 0.01 for A vs. C); in group A, 25 (38%) of pts had a LCD ≤10, as did 81 (30%) in group B and 10 (16%) in group C. In groups A, B and C, 9 (13.6%), 21 (11.5%), and 7 (11.3%) pts, respectively, had a lymphocyte doubling time (LDT) ≤12mo (to an absolute value ≥50X10⁹/L; p<0.65). Immunophenotyping was available in 202 pts; 173 were CD5+ CD19+, 2 were CD5- and 29 CD19-. Analysis for CD38 was available in 50 pts; in groups A, B and C, 5 of 36 (14.3%), 2 of 14 (16.7%) and 0 of 7, respectively, were CD38+ (defined as ≥30% of cells; p<0.84). Median follow-up for groups A, B and C was 110.5 (76–369) mo, 43 (0–309) mo, and 134.5 (72–309 mo; p<0.0001 for A vs. B and p<0.67 for A vs. C). Pts in group A did not require treatment by definition; time to treatment (TTT) for group B was median 35 (0–243) mo and group C 66 (0–243) mo (p<0.0001). Median OS for all pts was 191 (0–369) mo. Two deaths occurred in group A; 1 of Richter’s transformation at 77 mo and 1 of unknown causes at 78 mo; median OS for groups B and C was 189 (0–311) mo and 127 (69–311) mo respectively (p<0.025). In group A, 1 pt (1.5%) transformed, as did 15 (5.6%) in group B (8 Richter’s and 7 PLL) and 4 (6%) in group C (1 Richter’s, 3 PLL, p<0.46). At a cutoff in LCD of 10 and 20 the difference in OS between groups was maintained (see Table).

In conclusion, in this series of 335 patients with CLL, lower lymphocyte count at diagnosis predicted for long-term stability, decreased requirement for treatment and improved OS.