Prognostic factors are tools to address heterogeneity in clinical behavior and survival in patients with disease. They are particularly relevant for patients with malignancy, including chronic lymphocytic leukemia (CLL). There is striking heterogeneity in overall survival (OS) of patients with CLL as well as in response to treatment, time to treatment failure (TTF), and time to progression (TTP) following response. Serum β2 microglobulin (β2M) has previously been reported to correlate with OS and TTP in patients with CLL. We performed a retrospective analysis of 659 Rx-naive and 1062 previously treated patients with CLL enrolled on clinical trials from 5/74 to 7/05 at MD Anderson Cancer Center evaluating for predictors for response to treatment, amount of treatment given, incidence of myelosuppression, TTF, TTP in responders, and OS. Univariate analysis was performed, then significant factors were used to develop multivariate models for these endpoints. Groups were analyzed separately. The clinical factors evaluated included: age, Rai stage, # nodal sites, liver and spleen size, β2M, WBC, ALC, HGB, PLT, serum LDH, Cr, ALB, CD38 expression, and serum Ig levels, and refractoriness to alkylating agents and fludarabine and # prior treatments for previously treated patients. In the Rx-naive group, characteristics (median and range) were as follows: age=57 yrs(17–86); β2M=3.3 mg/L(1.1–16.4); WBC=74.7k/μL(2.1–552); ALC= 63k/μL(1–512); HGB=12.7 g/dL(5.7–18.7); PLT=156 k/μL(8–450); LDH=545 IU/L(103–3600); and IgG=754 mg/dL(45–5000). Patients with Rai stage 0=28; Rai I-II=402; and Rai III-IV=196. In the previously treated group, characteristics (median and range) were as follows: age=61 yrs(25–83); β2M= 4.4 mg/L(1.4–59.4); WBC= 43 k/μL(.6–953); ALC=36 k/μL(0–829); HGB=11.4 g/dL(3.8–17.6); PLT= 121 k/μL(2–703); LDH=597 IU/L(21–4739); and IgG=586 mg/dL(14–5000). Patients with Rai stage 0=37; Rai I-II=392; and Rai III-IV=563. Multivariate models identified the following predictors (p