The Effect of Subsequent Therapies in the Patients with Chronic Lymphocytic Leukemia Previously Treated with Cladribine and Prednisone or Chlorambucil and Prednisone in Randomized Studies.

Previously, we reported a study on efficacy and toxicity of cladribine (2-CdA) + prednisone (P) compared with chlorambucil (Chl) + P in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia (CLL) in a randomized multicenter trial (

In 50 patients, non-responsive or with early relapse, treated originally with Chl+P who received 2-CdA+P as second line, complete response (CR) was achieved in 12 (24%) and overall response (OR) in 32 (64%). Twenty eight patients originally treated with 2-CdA+P received Chl+P and CR and OR was obtained in 1 (3,6%) and in 6 (21.4%), respectively (p=0.002 for both arms).

Thirty three patients with late relapse were retreated with 2-CdA+P and 19 patients were retreated with Chl+P. OR (CR) was 54.6% (6.1%) and 47.4% (15.8%), respectively (p=0.34).

The third line treatment was CHOP in both arms. Twenty seven patients from 2-CdA+P group and 37 patients from Chl+P group were treated with CHOP and only one patient responded.

Median survival was 3.3 and 3.75 years, respectively (p=0.63). Secondary neoplasms were observed in 8 (6.4%) patients treated with 2-CdA+P and in 4 (3.9%) treated with Chl+P as first line treatment (p=0.6). Death rates have been similar in patients treated originally with 2-CdA+P 82 (64.6%) and Chl+P 69 (66.4%) (p=0.8).

In conclusion, cladribine is significantly more effective as a second line treatment than chlorambucil. Both agents are similarly effective in retreatment of late relapsed patients. CHOP is of no value in patients previously treated with 2-CdA + P and with Chl + P. There is no significant difference in median survival of patients treated initially with Chl + P and 2-CdA + P.