Using the combination of R-CHOP leads to significant improvement of the outcome of elderly patients with diffuse large B-cell lymphoma, with significant survival benefit maintained during a 5-year follow-up. This combination should become the standard for treating these patients.

Lymphopenia is frequent in advanced cancers and predicts the toxicity of chemotherapy. Its effect on relapse and survival is uncertain. Its prognostic value for survival was analyzed in three databases of previously reported prospective multicenter studies: (a) FEC chemotherapy in metastatic breast carcinoma; (b) CYVADIC in advanced soft tissue sarcoma (European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group 62791); and (c) prospective, consecutive phase III studies of aggressive diffuse large-cell non-Hodgkin's lymphomas conducted at Centre Léon Bérard between 1987 and 1993. Univariate and multivariate analyses of prognostic factors for survival were performed. The incidence of lymphopenia of <1,000/ML before treatment was constant among the series: 25%, 24%, and 27%, respectively. Lymphopenia was significantly more frequent (P < 0.05) in metastatic breast cancer patients with performance status (PS) of >1, non-Hodgkin's lymphoma patients with international prognostic index (IPI) of > 0, and advanced soft tissue sarcoma and metastatic breast cancer patients with bone metastases. In univariate analysis, lymphopenia of <1,000/ML significantly correlated to overall survival in patients with metastatic breast cancer (median, 10 versus 14 mo; P < 0.0001), advanced soft tissue sarcoma (median, 5 versus 10 months; P < 0.01), and nonHodgkin lymphoma (median, 11 versus 94 months; P < 0.0001). In multivariate analysis (Cox model), lymphopenia was an independent prognostic factor for overall survival in metastatic breast cancer [RR (relative risk), 1.8; 95% CI (confidence interval), 1.3-2.4] along with liver metastases and PS; in advanced soft tissue sarcoma (RR, 1.46; 95% CI, 1.0-2.1) along with liver metastases, lung metastases, and PS; and in nonHodgkin's lymphoma (RR, 1.48; 95% CI, 1.03-2.1) along with IPI. Our findings show that lymphopenia is an independent prognostic factor for overall and progression-free survival in several cancers. [Cancer Res 2009;69(13):5383-91]

On the basis of the final analysis of this prospectively treated series of patients, retrospectively analyzed on the basis of the International Prognostic Index, we hypothesize that HDT benefits patients at higher risk who achieve complete remission after induction treatment.

Transformation is an early event in the course of the disease and is mainly observed in patients with known adverse prognostic factors or those who do not achieve CR after initial treatment. These findings may be useful to select follicular lymphoma patients for intensive therapeutic approaches.

The Intergroupe Francophone du Myelome conducted a randomized trial to compare bortezomib-dexamethasone (VD) as induction before high-dose therapy (HDT) and autologous stem cell transplantation (ASCT) to a combination consisting of reduced doses of bortezomib and thalidomide plus dexamethasone (vtD) in patients with multiple myeloma. Overall, a total of 199 patients were centrally randomly assigned to receive VD or vtD. After 4 cycles, the complete response (CR) rate was the same in both groups (13% in the vtD arm, 12% in the VD arm, P ‫؍‬ .74). However, the CR plus very good partial response (VGPR) rate was significantly higher in the vtD arm (49% vs 36%, P ‫؍‬ .05). After ASCT, the CR plus VGPR rate was significantly higher in the vtD arm (74% vs 58%, P ‫؍‬ .02). The reduced doses of bortezomib and thalidomide translated into a reduced incidence of peripheral neu- Continuing Medical Education onlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 5982. Disclosures

Recent advances in follicular lymphoma (FL) have resulted in prolongation of overall survival (OS). Here assessed if early events as defined by event-free survival (EFS) at 12 and 24 months from diagnosis (EFS12/EFS24) can inform subsequent OS in FL. 920 newly diagnosed grade 1–3a FL patients enrolled on the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002–2012 were initially evaluated. EFS was defined as time from diagnosis to progression, relapse, re-treatment, or death due to any cause. OS was compared to age-and-sex-matched survival in the general US population using standardized mortality ratios (SMR) and 95% confidence intervals (CI). We used a cohort of 412 FL patients from two Lyon, France hospital registries for independent replication. Patients who failed to achieve EFS12 had poor subsequent OS (MER SMR=3.72, 95%CI: 2.78–4.88; Lyon SMR=8.74, 95%CI: 5.41–13.36). Conversely, patients achieving EFS12 had no added mortality beyond the background population (MER SMR=0.73, 95%CI: 0.56–0.94, Lyon SMR=1.02, 95%CI: 0.58–1.65). Patients with early events after immunochemotherapy had especially poor outcomes (EFS12 failure: MER SMR=17.63, 95%CI:11.97–25.02, Lyon SMR=19.10, 95%CI:9.86–33.36; EFS24 failure: MER SMR=13.02, 95%CI:9.31–17.74, Lyon SMR=7.22, 95%CI:4.13–11.74). In a combined dataset of all patients from both cohorts, baseline FLIPI was no longer informative in EFS12 achievers. Reassessment of patient status at 12 months from diagnosis in follicular lymphoma patients, or at 24 months in patients treated with immunochemotherapy, is a strong predictor of subsequent overall survival in FL. Early event status provides a simple, clinically relevant endpoint for studies assessing outcome in FL.

Both treatments were active; the better response rate and EFS obtained with the addition of rituximab did not translate into improved OS.

There is no consensus on the optimal systemic treatment of patients with extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. The IELSG-19 phase III study, to our knowledge, was the first such study to address the question of first-line treatment in a randomized trial. Patients and MethodsEligible patients were initially randomly assigned (1:1 ratio) to receive either chlorambucil monotherapy (6 mg/m 2 /d orally on weeks 1 to 6, 9 to 10, 13 to 14, 17 to 18, and 21 to 22) or a combination of chlorambucil (same schedule as above) and rituximab (375 mg/m 2 intravenously on day 1 of weeks 1, 2, 3, 4, 9, 13, 17, and 21). After the planned enrollment of 252 patients, the protocol was amended to continue with a three-arm design (1:1:6 ratio), with a new arm that included rituximab alone (same schedule as the combination arm) and with a final sample size of 454 patients. The main end point was event-free survival (EFS). Analysis of chlorambucil versus the combination arm was performed and reported separately before any analysis of the third arm. ResultsAt a median follow-up of 7.4 years, addition of rituximab to chlorambucil led to significantly better EFS (hazard ratio, 0.54; 95% CI, 0.38 to 0.77). EFS at 5 years was 51% (95% CI, 42 to 60) with chlorambucil alone, 50% (95% CI, 42 to 59) with rituximab alone, and 68% (95% CI, 60 to 76) with the combination (P = .0009). Progression-free survival was also significantly better with the combination (P = .0119). Five-year overall survival was approximately 90% in each arm. All treatments were well tolerated. No unexpected toxicities were recorded. ConclusionRituximab in combination with chlorambucil demonstrated superior efficacy in mucosa-associated lymphoid tissue lymphoma; however, improvements in EFS and progression-free survival did not translate into longer overall survival.