Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukaemia

Abstract

Summary. We evaluated the efficacy and toxicity of fludarabine combined with cyclophosphamide and mitoxantrone (FCM) in patients with relapsed or resistant chronic lymphocytic leukaemia (CLL). In total, 37 patients with recurrent or resistant CLL received FCM: fludarabine 25 mg/m2 intravenously (IV), d 1–3; cyclophosphamide 200 mg/m2 IV, d 1–3; and mitoxantrone 6 mg/m2 IV, d 1, at 4‐week intervals for up to six courses. Moreover, 23 patients received FCM with cyclophosphamide 600 mg/m2 i.v. and mitoxantrone 8 mg/m2 i.v. on d 1. In addition to clinical methods, response was assessed using cytofluorometric and molecular techniques. ‘In vitro’ sensitivity to the FCM regimen was also analysed in 20 samples. The median number of courses given was 3 (range: 1–6). Overall, 30 patients (50%) achieved complete response (CR), including 10 cases of negative minimal residual disease (MRD(–)) (17%), and 17 (28%) partial response (PR). The median duration of response was 19 months. ‘In vitro’ sensitivity also correlated with CR achievement (P = 0·04). Main toxicity consisted of neutropenia, infections (8% of courses), and nausea and vomiting. The treatment‐related mortality was 5%. FCM did not hamper stem cell harvesting in patients who were candidates for autologous stem cell transplantation. FCM induced a high CR rate, including an important number of MRD(–), in patients with previously treated CLL.

The combination of rituximab, bendamustine, and cytarabine for heavily pretreated relapsed/refractory cytogenetically high‐risk patients with chronic lymphocytic leukemia

“…The majority of patients treated with the FCR regimen [27] for relapsed CLL experienced grade III-IV neutropenia (89%), which was complicated by neutropenic fever in 12% of the patients. Because of the presence of adverse events, approximately 50% of refractory patients treated with fludarabine combination regimens need to have dose reductions, skip courses of treatment, or have delays in administration of therapy because of myelosuppression [30,31], while our patients completed the planned 4 R-BAC cycles in 69% of cases with only 9% of cycles that were delayed. The RB regimen was associated with severe infections in 12.8% of patients, in front of a Figure 1.…”

Induction of histone H1.2 cytosolic release in chronic lymphocytic leukemia cells after genotoxic and non-genotoxic treatment

“…Treatment of CLL, which had largely been based on the use of alkylating agents, is currently switching to purine analogs-based regimens with or without monoclonal antibodies. [2][3][4][5][6] These combinations induce higher response rates and a longer disease-free survival than alkylating agents or fludarabine alone. 3,4 However, a significant number of patients are refractory to therapy.…”

The role of fludarabine in the treatment of follicular and mantle cell lymphoma

“…29,37,60 In a number of studies, an FCM regimen (fludarabine 25 mg/m 2 per day for 3 days, cyclophosphamide 200 -300 mg/m 2 per day for 3 days, and mitoxantrone 6 -8 mg/m 2 per day for 1 day) yielded noteworthy results. 39,52,62,63 Montoto et al 63 reported an overall response rate of 95% (CR rate, 75%); in addition, 69% of all patients in that study achieved molecular remission, and the 1.5-year failure-free survival rate was 90%. These results were confirmed by Spriano et al, 39 who reported the occurrence of molecular remission in 74% of all patients.…”

“…The response rates associated with fludarabinecontaining regimens are slightly lower for patients with recurrent FL. 30,31,36,62,64 In a randomized trial conducted by the German Low-Grade Lymphoma Study Group (GLSG), Dreyling et al 52 compared the FCM regimen with combined immunochemotherapy (FCM plus rituximab) in patients with recurrent or refractory low-grade NHL; the chemotherapy-only regimen resulted in an overall response rate of 70% and a CR rate of 23%.…”