Abstract

The aim of the study was to determine the efficacy and toxicity of cladribine alone (2-CdA) and in combination with cyclophosphamide - CY (CC) or CY and mitoxantrone - MIT (CMC) in previously untreated patients with progressive or symptomatic chronic lymphocytic leukemia in a randomized, multicenter study. 2-CdA was given at a dose of 0.12 mg/kg/d in 2 h I.V. infusion for 5 consecutive days in monotherapy and for 3 days in combination. In CC and CMC programmes cyclophosphamide was administered at a dose of 650 mg/m2 I.V. on day 1 and additionally mitoxantrone 10 mg/m2 I.V. on day 1 in CMC. Courses were repeated at 28 day intervals or longer if myelosuppression and/or infection developed, for a maximum of 6 courses. The response criteria were those recommended by NCI sponsored Working Group. Minimal residual disease (MRD) were evaluated by flow cytometry if CR was achieved.

In conclusion, the results of our study indicate that 2-CdA combined with CY or CY+MIT as first line therapy give higher CR rate than 2-CdA alone. However, CMC is more toxic than 2-CdA or CC. We recommend CC combination for further studies.

Treatment 2-CdA CC CMC p value 
Entered pts 167 169 163  
Evaluated pts 143 152 139  
CR 37 (25.9%) 43 (28.3%) 55 (39.6%) 0.03 
OR 106 (74.1%) 125 (82.2%) 110 (79.1%) 0.2 
MRD 15 (46.9%) 22 (82.2%) 25 (56.8%) 0.7 
Median OR duration (years) 1.67 1.81 1.43 0.1 
Relapse 48 (45.3%) 45 (29.6%) 43 (30.9%) 0.2 
AIHA 10 (7.0%) 10 (6.6%) 5 (3.6%) 0.4 
Thrombocytopenia grIII/IV 25 (17.5%) 25 (16.4%) 32 (23.0%) 0.3 
Neutropenia grIII/IV 27 (18.9%) 43 (28.3%) 52 (37.4%) <0.001 
Infections 39 (27.3%) 47 (30.9%) 53 (38.1%) 0.07 
Died 39 (27.3%) 30 (19.7%) 37 (26.6%) 0.4 
Treatment 2-CdA CC CMC p value 
Entered pts 167 169 163  
Evaluated pts 143 152 139  
CR 37 (25.9%) 43 (28.3%) 55 (39.6%) 0.03 
OR 106 (74.1%) 125 (82.2%) 110 (79.1%) 0.2 
MRD 15 (46.9%) 22 (82.2%) 25 (56.8%) 0.7 
Median OR duration (years) 1.67 1.81 1.43 0.1 
Relapse 48 (45.3%) 45 (29.6%) 43 (30.9%) 0.2 
AIHA 10 (7.0%) 10 (6.6%) 5 (3.6%) 0.4 
Thrombocytopenia grIII/IV 25 (17.5%) 25 (16.4%) 32 (23.0%) 0.3 
Neutropenia grIII/IV 27 (18.9%) 43 (28.3%) 52 (37.4%) <0.001 
Infections 39 (27.3%) 47 (30.9%) 53 (38.1%) 0.07 
Died 39 (27.3%) 30 (19.7%) 37 (26.6%) 0.4 

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