A B S T R A C T PurposeAlthough rituximab (R) is commonly used for patients with advanced follicular lymphoma (FL) requiring treatment, the optimal associated chemotherapy regimen has yet to be clarified. Patients and MethodsWe conducted an open-label, multicenter, randomized trial among adult patients with previously untreated stages II to IV FL to compare efficacy of eight doses of R associated with eight cycles of cyclophosphamide, vincristine, and prednisone (CVP) or six cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or six cycles of fludarabine and mitoxantrone (FM). The principal end point of the study was time to treatment failure (TTF). ResultsThere were 534 patients enrolled onto the study. Overall response rates were 88%, 93%, and 91% for R-CVP, R-CHOP, and R-FM, respectively (P ϭ .247). After a median follow-up of 34 months, 3-year TTFs were 46%, 62%, and 59% for the respective treatment groups (R-CHOP v R-CVP, P ϭ .003; R-FM v R-CVP, P ϭ .006; R-FM v R-CHOP, P ϭ .763). Three-year progression-free survival (PFS) rates were 52%, 68%, and 63% (overall P ϭ .011), respectively, and 3-year overall survival was 95% for the whole series. R-FM resulted in higher rates of grade 3 to 4 neutropenia (64%) compared with R-CVP (28%) and R-CHOP (50%; P Ͻ .001). Overall, 23 second malignancies were registered during follow-up: four in R-CVP, five in R-CHOP, and 14 in R-FM. ConclusionIn this study, R-CHOP and R-FM were superior to R-CVP in terms of 3-year TTF and PFS. In addition, R-CHOP had a better risk-benefit ratio compared with R-FM. Oncol 31:1506Oncol 31: -1513 J Clin

Purpose To compare doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) versus bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) versus cyclophosphamide, lomustine, vindesine, melphalan, prednisone, epidoxirubicin, vincristine, procarbazine, vinblastine, and bleomycin (COPPEBVCAD; CEC) for advanced Hodgkin's lymphoma (HL). Patients and Methods Three hundred seven patients with advanced HL (stage IIB, III, and IV) were randomly assigned to receive six courses of ABVD, four escalated plus two standard courses of BEACOPP, or six courses of CEC, plus a limited radiation therapy program. Results After a median follow-up of 41 months, BEACOPP resulted in a superior progression-free survival (PFS), with a significant reduction in risk of progression (hazard ratio [HR] = 0.50) compared with ABVD. No differences between BEACOPP and CEC, or CEC and ABVD were observed. The 5-year PFS was 68% (95% CI, 56% to 78%), 81% (95% CI, 70% to 89%), and 78% (95% CI, 68% to 86%), for ABVD, BEACOPP, and CEC, respectively (BEACOPP v ABVD, P = .038; CEC v ABVD and BEACOPP v CEC, P = not significant [NS]). The 5-year overall survival was 84% (95% CI, 69% to 92%), 92% (95% CI, 84% to 96%), and 91% (95% CI, 81% to 96%) for ABVD, BEACOPP, and CEC, respectively (P = NS). BEACOPP and CEC resulted in higher rates of grade 3-4 neutropenia than ABVD (P = .016); BEACOPP was associated with higher rates of severe infections than ABVD and CEC (P = .003). Conclusion As adopted in this study BEACOPP is associated with a significantly improved PFS compared with ABVD, with a predictable higher acute toxicity.

We performed a multicenter study in order to validate the concept that a simple CGA can identify elderly DLBCL non-fit patients in whom curative treatment is not better then palliation and to analyse potential benefits of treatment modulation after further subdividing the non-fit category by CGA criteria.One-hundred-seventy-three patients aged > 69 treated with curative or palliative intent by clinical judgment only were grouped according to CGA in fit (46%), unfit (16%) and frail (38%) categories. Two-yr OS was significantly better in fit than in non-fit patients (84% vs 47%; P <.0001). Survival in unfit and frail patients was not significantly different. Curative treatment slightly improved 2-yr OS in unfit (75% vs 44%), but not in frail patients (45% vs 39%).CGA was confirmed as very efficient in identifying elderly DLBCL patients who can benefit from a curative approach. Further efforts are needed to better tailor therapies in non-fit patients.3

ABSTRACTand prednisone (CHOP), CHOP-like, or third-generation anthracycline-containing regimens, with or without rituximab; 521 patients (51%) received the above therapies with rituximab as part of the regimen. Statistical analysisSurvival was assessed by Kaplan-Meier estimates 14 and compared by risk groups using the log-rank test and Cox proportional hazard analysis. 15 The proportional hazard assumption was verified graphically by means of scaled Schoenfeld residuals. 16 The effect size was reported as a hazard ratio (HR) with the associated 95% confidence interval (95% CI).We 20 Thereafter we chose cut-off values with the best power in discriminating patients with either good or poor outcome, after adjusting for the IPI. The performance of the different cut-offs was checked by means of the hazard ratios and respective z-score (from Wald's test) and by comparing the discriminating power, expressed as Harrell's C index.21 The Harrell's C standard error and 95% confidence interval were estimated by means of a jackknife procedure. 22 We arbitrarily chose the cut-off on the basis of the compromise between the discriminative power of the factor and the size of the group at greatest risk. Whereas we analyzed different cut-off points for AMC and LMR, given the broad agreement regarding the definition of lymphopenia as an ALC<1000/mm 3 , we used this cut-off for ALC. 23,24The effect of rituximab on the prognostic power of AMC, ALC and LMR was evaluated by interacting prognostic factors with rituximab, after adjustment by IPI score. Results Patients' characteristicsWe analyzed data from 1191 patients with DLBCL diagnosed between 1993 and 2010. Patients with missing data on monocyte or lymphocyte counts or one of the IPI parameters before treatment were excluded, and the final cohort consisted of 1017 patients.The median age at diagnosis was 60 years (range, 25-81 years) and 47% of the patients were more than 60 years old; 53% were male and 54% of the patients had advanced, stage III-IV disease (Table 1); the clinical characteristics at diagnosis were comparable in the Israeli and Italian cohorts.A total of 496 patients (49%) were treated with chemotherapy alone, while 521 (51%) received immunochemotherapy including rituximab. The median follow-up of the entire cohort was 48 months (range, 0.2-180 months), and 64 months for patients still alive. Overall, 317 events were recorded with a death rate of 7.4x100 person-years (95% CI: 6.6-8.3x100 person-years) and a 5-year overall survival of 68% (95% CI: 65-71%). The overall survival at 5 years in patients treated with or without rituximab was 68% in both groups (HR 0.98, P=0.864). It is noteworthy that in our series there was an association between the use of rituximab and the IPI score; in the group of patients with IPI 0-2, only 43% of patients had been treated with rituximab compared to 70% of the patients with IPI 3-5. In a multivariate analysis, adjusted for IPI score, the risk of death in patients treated with rituximab was reduced by 30% (P=0.002). Absolute monocyt...

Single-center experiences have shown that intensified treatments with autologous transplantation are a promising therapeutic strategy for patients with high-risk follicle-center lymphoma (FCL) at diagnosis, whereas data from prospective multicenter trials are still lacking. This paper describes the results of a prospective multicenter study of an intensified purging-free high-dose sequential (i-HDS) chemotherapy schedule with peripheral blood progenitor cell (PBPC) autografting. The main feature of this program is harvesting stem cells after intensified chemotherapeutic debulking, with no ex vivo manipulation of PBPCs. Ninety-two previously untreated patients aged 60 or younger with advanced-stage FCL were enrolled by 20 Italian centers and evaluated on an intention-to-treat basis. i-HDS proved feasible with limited toxicity (87% patients completed the planned treatment schedule). i-HDS led to a complete remission rate of 88%. The projected overall survival and disease-free survival (DFS) were, respectively, 84% and 67% at 4 years. Centralized molecular analysis showed that polymerase chain reaction-negative harvests could be collected in 47% of cases. Following autograft, 65% of molecularly evaluable patients achieved clinical and molecular remission. The projected DFS at 4 years of this subgroup is 85%. This result emphasizes the importance of achieving maximal tumor reduction in these patients. In conclusion, our data show that highly effective intensified treatments can now be routinely offered to young patients with poor-risk FCL even at small institutions, with no need for sophisticated and expensive cell manipulation procedures. IntroductionSeveral studies have investigated the role of intensified chemotherapy followed by autologous transplantation in the management of relapsed follicle-center lymphoma (FCL). [1][2][3][4][5][6][7] Results were encouraging with high rates of complete remission (CR) and molecular remission. [1][2][3][4][5][6][7][8][9][10] The latest findings from the Dana Farber Cancer Institute show that molecular remission is associated with an extremely low relapse rate and a more than 80% projected freedom from relapse at 12 years. 7 Autologous transplantation may thus possess a curative potential in this otherwise incurable disease. 11,12 Similar approaches have been less frequently used at diagnosis. [13][14][15][16] In fact, a recent retrospective study from Stanford University showed that patients treated with autologous transplantation as first-line treatment have a better outcome compared to those treated with conventional chemotherapy. 16 Three important issues, however, still need to be addressed in evaluation of the real role of intensified approaches in FCL. First, there have been no multicenter prospective trials. A single-center trial carries the risk of overestimation of outcomes due to selection biases, and only highly qualified clinical teams may be able to achieve similar results with high-dose programs. Second, most autografting programs require ex vivo purging procedu...