Abstract
CLL patients (pts) who are not eligible for initiation of treatment by the NCI Working Group criteria (1996) are traditionally monitored on a “watch and wait” approach. There is increasing interest in initiating therapy earlier in pts who are considered high risk. The most important advice pts require in the “watch and wait” category is whether they will need treatment and when. There are a number of traditional prognostic factors that potentially identify those “watch and wait” (W&W) pts most likely to need treatment. These have recently been amplified by the discovery of new prognostic factors such as the immunoglobulin (IgVH) mutation status, FISH cytogenetics, ZAP-70, and CD38 expression on CLL cells. Most reports have emphasized the new prognostic factors without consideration of traditional characteristics such as tumor burden, stage, etc. Since January 2004 FISH, IgVH mutation status, ZAP-70, and CD38 were characterized for most pts presenting to M. D. Anderson Cancer Center. We identified an early stage low tumor burden group of 826 pts (W&W) defined with as having lymph nodes < 3 cm in the longest dimension, splenomegaly < 5 cm, and Rai stage 0 – II. Twenty-four percent of these pts have received treatment in the first two years of follow-up. From the traditional prognostic factors, number of lymph node sites (cervical, axillary, and inguinal), absolute lymphocyte count (ALC), serum beta-2-microglobulin (B2M) levels were highly correlated with time-to-initial treatment (P<.001). The predictive power of these characteristics was also confirmed in an earlier historic patient population. When these three characteristics are evaluated in multivariate analysis, IgVH mutation status, ZAP-70, and FISH cytogenetics all add independent prognostic power. When these three novel characteristics were evaluated in multivariate model with the traditional characteristics, the most important were the number of node sites, ALC, B2M, FISH, IgVH mutation status, and then ZAP-70.
| . | Clinical only . | +Mutation Status . | +ZAP 70 . | +FISH . | + All 3 . |
|---|---|---|---|---|---|
| No. Lymph Node Sites | 1 | 1 | 1 | 1 | 1 |
| ALC | 2 | 2 | 2 | 2 | 2 |
| Beta-2-microglobulin | 3 | 4 | 4 | 4 | 4 |
| Mutation Status | -- | 3 | -- | -- | 5 |
| ZAP-70 | -- | -- | 3 | -- | 6 |
| FISH | -- | -- | -- | 3 | 3 |
| . | Clinical only . | +Mutation Status . | +ZAP 70 . | +FISH . | + All 3 . |
|---|---|---|---|---|---|
| No. Lymph Node Sites | 1 | 1 | 1 | 1 | 1 |
| ALC | 2 | 2 | 2 | 2 | 2 |
| Beta-2-microglobulin | 3 | 4 | 4 | 4 | 4 |
| Mutation Status | -- | 3 | -- | -- | 5 |
| ZAP-70 | -- | -- | 3 | -- | 6 |
| FISH | -- | -- | -- | 3 | 3 |
Integration of novel prognostic factors into readily clinically available characteristics will enable us to develop a nomogram for predicting probability of each patient requiring therapy at one year, two years, and eventually five years. This nomogram will be presented when completed and then will be available for validation in independent patient populations studied by other groups.
Disclosures: No relevant conflicts of interest to declare.
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