[Preliminary results of a multicenter randomized study on the treatment of acute promyelocytic leukemias]. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. Consolidation with alemtuzumab in patients with chronic lymphocytic leukemia (CLL) in first remission--experience on safety and efficacy within a randomized multicenter phase III trial of the German CLL Study Group (GCLLSG). A randomized phase II trial of fludarabine, cyclophosphamide and mitoxantrone (FCM) with or without rituximab in previously treated chronic lymphocytic leukaemia.
To study efficacy of maintenance therapy of patients with acute promyelocytic leukemia (APL) in the APL treatment Russian multicenter trial.
                The trial was made with participation of 18 hematological departments of clinics in Russia. A total of 68 APL patients entered the trial. The maintenance therapy consisted of 5-day courses of cytostatic drugs which alternated or did not alternate with 5-day courses of ATRA. Cytogenetic tests were made in 31 patients, t(15;17) was detected in 26 of them. Molecular examination conducted in 28 patients discovered chimeric transcript PML/RARa in 26 of them. Of 20 patients examined in Hematological Research Center, 7 (35%) had a bcr 1/2 variant of the transcript PML/RARa, 13 (65%)--bcr 3 variant.
                65 patients were eligible for assessment. A complete remission was achieved in 90% cases. No resistance was observed. In follow-up within 30 months the recurrence rate was similar on both treatments. The results of the induction therapy and survival in patients with different variants of the transcripts were also similar. Overall 2.5 year survival for all the patients was 77%, recurrence-free--80%. The survival analysis in patients with leukocytosis higher and lower 10 x 10(9)/l found no statistical differences by the survival. Patients with hyperleukocytosis had higher early lethality than patients with leukocytes under 10 x 10(9)/l (25% vs 5.3%, p = 0.03).
                The APL 06.01 protocol showed high efficacy of the relevant maintenance which provides a complete molecular remission in the majority of patients with probable recurrence-free 2.5 year survival 80%. Rituximab, a monoclonal antibody that targets the CD20 cell surface antigen, has clinical activity in patients with non-Hodgkin's lymphoma and other B-lymphocyte disorders when administered alone or in combination with chemotherapy. Promising results have previously been reported in nonrandomized studies in patients with chronic lymphocytic leukemia (CLL). This trial was designed to compare chemoimmunotherapy with chemotherapy alone in patients with previously treated CLL.
                This international, multicenter, randomized trial compared six cycles of rituximab plus fludarabine and cyclophosphamide (R-FC) with six cycles of fludarabine and cyclophosphamide alone (FC) in patients with previously treated CLL. A total of 552 patients with Binet stage A (1%), B (59%), or C (31%) disease entered the study and were randomly assigned to receive R-FC (n = 276) or FC (n = 276).
                After a median follow-up time of 25 months, rituximab significantly improved progression-free survival in patients with previously treated CLL (hazard ratio = 0.65; P < .001; median, 30.6 months for R-FC v 20.6 months for FC). Event-free survival, response rate, complete response rate, duration of response, and time to new CLL treatment or death were also significantly improved. Although the rates of adverse events, grade 3 or 4 events, and serious adverse events were slightly higher in the R-FC arm, R-FC was generally well tolerated, with no new safety findings and no detrimental effect on quality of life.
                R-FC significantly improved the outcome of patients with previously treated CLL. Patients with CLL responding to initial chemotherapy with fludarabine alone (F) or in combination with cyclophosphamide (FC) were randomized for treatment with alemtuzumab (30 mg i.v. TIW, 12 weeks) or observation. Of 21 evaluable patients, 11 were randomized to alemtuzumab before the study was stopped due to severe infections in seven of 11 patients. These infections (one life-threatening pulmonary aspergillosis IV; four CMV reactivations III requiring i.v. ganciclovir; one pulmonary tuberculosis III; one herpes zoster III) were successfully treated and not associated with cumulative dose of alemtuzumab. In the observation arm, one herpes zoster infection II and one sinusitis I were documented. At 6 months after randomization, two patients in the alemtuzumab arm converted to CR, while three patients in the observation arm progressed. After alemtuzumab treatment, five of six patients achieved a molecular remission in peripheral blood while all patients in the observation arm remained MRD-positive (P=0.048). At 21.4 months median follow-up, patients receiving alemtuzumab showed a significant longer progression-free survival (no progression vs mean 24.7 months; P=0.036). In conclusion, a consolidation therapy with alemtuzumab is able to achieve molecular remissions and longer survival in CLL, but a safe treatment regimen needs to be determined. Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic. A randomized, two-stage, Phase II trial of FCM and FCM-R was conducted in relapsed CLL. The primary endpoint was response rate 2 months after therapy, assessed according to the 2008 International Workshop CLL criteria. In addition, minimal residual disease (MRD) in the marrow was studied 2 months after therapy, with MRD negativity defined as <0·01% CLL cells. Fifty-two patients were entered, 26 in each arm. The overall response rates to FCM and FCM-R were 58% and 65% respectively. Combined complete response (CR) and CR with incomplete marrow recovery [CR(i)] was 15% (95% confidence interval [CI]:4-35%) for FCM and 42% (95%CI:23-63%) for FCM-R, with eight patients achieving MRD negativity (3 FCM; 5 FCM-R). The toxicity of both regimens was acceptable. In conclusion, the addition of rituximab to FCM improves the response rates in relapsed CLL, resulting in more complete remissions and without additional safety concerns. Efficacy and safety should be fully tested in a randomized Phase III trial.
                © 2011 Blackwell Publishing Ltd.
Despite significantly increased overall response and complete remission rates and longer progression-free survival with first-line treatment of B-CLL patients with single-agent purine antagonists, we were not able to detect a statistically significant improvement of overall survival compared to alkylator-based regimens. Furthermore, the use of purine antagonists also augments the risk for grade III/IV infections and haemolytic anaemia.