Interferon-a (IFN-a) and, more recently, nucleoside analogs (NA) such as 2-CDA and pentostatin have been used with significant success to treat HCL. A single course of 2-CDA produces response rates over 75%, with responses maintained for 4 years in 75% of pts. Similar results have been observed with pentostatin. (

Dearden et al,
Br J Haematol
1999
;
106
:
515
). To learn more about long-term outcome, we reviewed 234 pts with untreated HCL seen at the MDACC over a 30-year period; their median follow-up was 122 months from diagnosis (up to 387 months). Their median age at diagnosis was 50 years (range 23–83 years). Survival was superior among the 173 pts given either 2-CDA (n = 161) or pentostatin (n = 12) compared to those never given either NA (p = 0.042).

Relapse occurred in 32 of 176 pts who received 2-CDA as their first chemotherapy either at MDACC or before presenting to MDACC. Therapy for relapse after 2-CDA included rituximab (N=9), a second course of 2-CDA (n=9), a second course of 2-CDA followed by rituximab (n=8), and other (n=6). No statistically significant differences in survival were seen possibly due to small pt numbers. The estimated 10-year and 20-year survival (from diagnosis) for the 176 pts who received 2-CDA as first chemotherapy was 84%, and 65%, respectively.

The majority of pts who died were not in remission at time of death and thus presumably died of HCL. Hence alternatives to NA are needed in at least some pts, and we are evaluating whether covariates exist that might distinguish pts who do and do not relapse and, among the former, pts whose remissions are short. Pending identification of the latter and keeping in mind the length of the average remission, alternatives to NA should have very little toxicity. We have begun to add rituximab to 2-CDA to lengthen remission duration and thus extend survival in pts with untreated HCL.