Cladribine combined with cyclophosphamide and mitoxantrone as front-line therapy in chronic lymphocytic leukemia

Abstract

The objective of the study was to determine the effectiveness and the toxicity of a combined chemotherapy consisting of cladribine (2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in the treatment of previously untreated B cell chronic lymphocytic leukemia (B-CLL). From August 1998 to December 2000 2-CdA was administered at a dosage of 0.12 mg/kg for 3 (CMC3) or 5 (CMC5) consecutive days, mitoxantrone at 10 mg/m 2 on day 1 and cyclophosphamide at 650 mg/m 2 on day 1 to 62 patients with advanced or progressive B-CLL. The cycles were repeated at 4 week intervals or longer if severe myelosuppression occurred. Twenty patients received CMC5 and 42 patients CMC3. Within the analyzed group an overall response (OR) rate (CR+PR) of 64.5% (95% CI: 52.7-76.3%) was reported, including 29.0% CR. There was no difference in the CR rate between the patients treated with CMC5 (30%) and CMC3 (28.6%) (P = 0.9), nor in the OR rate (55.0% and 69.0%, respectively, P = 0.3). Residual disease was identified in seven out of 18 (38.9%) patients who were in CR, including two treated with CMC5 and five treated with CMC3 protocols. CMC-induced grade III or IV thrombocytopenia occurred in 12 (19.4%) of patients, including four (20%) CMC5-treated and eight (19%) CMC3-treated patients (P = 0.8). Neutropenia grade III or IV was observed in seven (35%) and 11 (26.2%) patients, respectively (P = 0.8). Severe infections, including pneumonia and sepsis, occurred more frequently after CMC5 (11 patients, 55.0%) than CMC3 (10 patients, 28.6%) (P = 0.03) Fourteen patients died, including six treated with CMC5 and eight treated with CMC3 (30% and 19%, respectively). Infections were the cause of death in nine patients, including four in the CMC5 group and five in the CMC3 group. In conclusion, our results indicate that the CMC programme is an active combined regimen in previously untreated B-CLL patients; its efficiency seems to be similar to that observed earlier in B-CLL patients treated with 2-CdA as a single agent. However, toxicity, especially after CMC5 administration, is significant. Therefore, we recommend the CMC3 but not the CMC5 programme for further evaluation. Leukemia (2001Leukemia ( ) 15, 1510Leukemia ( -1516

Cladribine alone and in combination with cyclophosphamide or cyclophosphamide plus mitoxantrone in the treatment of progressive chronic lymphocytic leukemia: report of a prospective, multicenter, randomized trial of the Polish Adult Leukemia Group (PALG CLL2)

“…The doses and schedule of treatment were based on previous studies in CLL or low-grade lymphoma patients, performed earlier by our group. 11,16,17 Regarding CMC, 3-day protocol was selected for this study based on our previous results. 17 We showed that a 3-day schedule (previously referenced as CMC3) has similar efficacy and lower toxicity than a 5-day CMC (CMC5).…”

“…In our previous phase 2 studies, we showed that combined treatment with 2-CdA and CY (CC regimen) or with 2-CdA, CY, and MIT (CMC regimen) gave high ORRs and CRs and acceptable toxicity in previously untreated patients with CLL. 16,17 In this report, we present the results of a prospective, randomized multicenter trial comparing the efficacy and toxicity of CC and CMC combination regimens to 2-CdA alone.…”

Significance of the levels of bone marrow lymphoid infiltrate in chronic lymphocytic leukemia patients with nodular partial remission

“…[5][6][7][8][9][10][11][12][13][14][15][16] Despite the fact that CLL is an incurable hematologic malignancy, complete remission can be achieved with conventional chemotherapy. [14][15][16][17][18][19] In 1996, The National Cancer Institute-sponsored Working Group (NCI-WG) on CLL defined patients with complete remission (CR) and persistent bone marrow nodules as nPR. 20 The main goal of this study is to investigate the significance of the levels of the lymphoid infiltrate in nPR CLL patients and its correlation with clinical progression and overall survival.…”

Alkylating agents and nucleoside analogues in the treatment of B cell chronic lymphocytic leukemia

“…56,[93][94][95][96] Combined treatment with NA, mitoxantrone and CY has been undertaken both in previously treated and untreated patients with B-CLL. 93,97,98 However, the efficacy of these regimens seem to be similar to that observed after treatment with FAMP or 2-CdA alone. In addition, the toxicity, especially myelosuppression and infections of such combined therapy is high and reduction of NA doses is essential.…”