Monoclonal B-cell lymphocytosis (MBL) is a clonal lymphoproliferation with the immunophenotype of chronic lymphocytic leukemia (CLL) but a B-lymphocyte count of less than 5 x 10(9)/l and no lymphadenopathy, organomegaly, cytopenias or symptoms. We performed a retrospective analysis of patients with MBL (n = 46), Rai stage 0 CLL (n = 112) and Rai stage > or =1 CLL (n = 54). Median follow-up and range was 30 (0.1-120) months for MBL, 60 (0.1-309) months for stage 0 CLL and 54 (0.1-309) months for stage > or =1 CLL. None of the MBL patients required treatment compared with 24 of 112 (21%) stage 0 CLL and 28 of 54 (52%) stage > or =1 CLL patients (p < 0.0003). No MBL underwent aggressive transformation compared with 1 of 112 (0.8%) stage 0 CLL and 6 of 54 (11%) stage > or =1 CLL patients (p < 0.0003). Progression-free survival (PFS) appeared improved in MBL compared to stage 0 CLL, although this did not reach statistical significant (p = 0.07) due to the relatively short follow-up in the MBL group; two year PFS was 97.2% for MBL, 93.1% for stage 0 CLL, and 68% for stage > or =1 CLL patients (p < 0.0001 for stage > or =1 CLL compared with MBL and stage 0 CLL). This is the first study of outcome in MBL which demonstrates that patients have an improved disease course compared to stage 0 CLL patients. Over a median 2.5 years of follow-up, no MBL patients required treatment or died of CLL-related causes.

Monoclonal Lymphocytosis of Undetermined Significance (MLUS) is a clonal lymphoproliferation, usually of B-cells. MLUS has the immunophenotype of Chronic Lymphocytic Leukemia (CLL) but an absolute lymphocyte count of 10 X 109/L or less and no lymphadenopathy, organomegaly, cytopenias, or symptoms attributable to the lymphoproliferation. There is little published information as to whether the clinical course of MLUS differs significantly from that of CLL. We performed a retrospective analysis of 335 consecutive patients with clonal lymphocytosis seen at St. Paul’s Hospital diagnosed between January 1969 and July 2005. Patients were identified by a search of the practice database and clinical and pathological data were abstracted by chart review. MLUS was present in 106 patients and CLL in 229. All MLUS were of B-cell phenotype and 227 patients had B-CLL. Median age at diagnosis was 64.5 (range 33–86) y for MLUS and 65 (30–94) y for CLL (p&lt;0.83). 45% of MLUS pts were male vs. 58% of CLL pts (p&lt;0.036). ECOG Performance Status was 0 in 307 pts and was not analyzed further. Lymphocyte count at diagnosis was 7 (range 3–10) x 109/L for MLUS and 14 (range 3–394) x 109/L for CLL (p&lt;0.0001). Lymphocyte doubling time (LDT) ≤12 mo (to an absolute value &gt;50 X 109/L) occurred in 14% of MLUS and 11% of CLL (p&lt;0.84) pts. Rai CLL stage 0, 1, 2, 3 and 4 were 111 pts, 48, 47, 3 and 6 respectively. Immunophenotyping was available in 202 pts; 173 were CD5+ CD19+, 2 were CD5− and 29 were CD19−. Analysis for CD38 was available in 50 pts. At a median follow-up of 49 (0–229) mo for MLUS and 64 (0–369) mo for CLL, 15 (15%) of MLUS pts required treatment, as did 96 (42%) of pts with CLL (p&lt;0.0001). The median time to treatment (TTT) for the whole group was 35 (0–243) mo. Median TTT was 65 (0–202) mo for MLUS and 26 (0–243) mo for CLL; there was no significant difference in progression to active disease as measured by TTT between MLUS and CLL either for the whole groups (p&lt;0.29) or according to age (p&lt;0.54), gender (p&lt;0.91), LDT (p&lt;0.29) or CD38 status (p&lt;0.26). Median OS for all patients was 191 (0–369) mo, for MLUS 218 (0–225) mo, and for CLL 165 (0–369) mo (p&lt;0.04). There was a significant difference in OS favoring female MLUS pts over CLL, but not for males; median OS for females not reached at 225 mo for MLUS and median 153 (0–259) mo for CLL (p&lt;0.02, see Table). There was no significant difference in OS between MLUS and CLL according to age, gender, LDT or CD38 status. One pt with MLUS underwent transformation to aggressive disease (Richter’s transformation) as compared to 15 pts with CLL (8 Richter’s and 7 prolymphocytic, p&lt;0.025). Characteristic OS at 10 years (%) P (log-rank) MLUS CLL Age ≤65 68 81 0.07 &gt;65 59 45 0.59 Gender M 38 68 0.47 F 100 76 0.02 LDT ≤12 mo 47 74 0.10 &gt;12 mo 80 47 0.93 CD38 negative 90 73 0.60 (positive ≥ 30% of cells) 3 of 3 0 of 2 0.32 Transformation events n=1 n=15 0.025 In conclusion, in this series of 335 patients with clonal lymphoproliferation, MLUS pts had significantly better OS than did pts with CLL, a difference which was seen in female MLUS pts in particular. Significantly fewer MLUS pts required treatment over their course than did pts with CLL. In CLL pts, there appeared to be an increased rate of transformation to aggressive non-Hodgkin's lymphoma or PLL.

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). Characteristic OS @ 120 mo (%) Lymphocyte count at Dx (X109/L) Group A (stable ≥ 72 mo, n=66) Group B (all others, n=269) Group C (not stable, ≥72 f/u mo, n=62) All pts 93 64 64 ≤10 100 100 100 >10 91 64 64 ≤20 93 38 38 >20 0 of 2 0 of 5 0 of 5 p (log rank) A vs. B p<0.023 A vs. C p<0.025 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.