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Obesity is a well-known risk factor for the development of cancer, but its influence on the course of disease is still controversial. We investigated the influence of body mass index (BMI) on overall survival (OS) in 502 patients with indolent non-Hodgkin’s lymphoma or mantle cell lymphoma in a subgroup analysis of the StiL (Study Group Indolent Lymphomas) NHL1 trial. We defined a cut-off of 22.55 kg/m2 by ROC calculation and Youden Index analysis and stratified patients into “low BMI” and “high BMI”. Five-year OS was significantly longer in the high BMI group (82.2%) when compared to that of the low BMI group (66.2%) (HR 0.597; 95%CI 0.370–0.963; p = 0.034). BMI was also an independent prognostic factor for OS in multivariate analysis (HR 0.541; 95%CI 0.332–0.883; p = 0.014). Of note, patients had a significantly lower BMI in the presence than patients in the absence of B-symptoms (p = 0.025). BMI significantly impacts on OS in indolent non-Hodgkin’s lymphoma and mantle cell lymphoma, which may be influenced by the effect of B-symptoms on BMI. Electronic supplementary material The online version of this article (doi:10.1007/s00277-017-3003-0) contains supplementary material, which is available to authorized users.

Bcl-2/IgH rearrangements can be quantified in follicular lymphoma (FL) from peripheral blood (PB) by polymerase chain reaction (PCR). The prognostic value of Bcl-2/IgH levels in FL remains controversial. We therefore prospectively studied PB Bcl-2/IgH levels from 173 first-line FL patients who were consecutively enrolled, randomized, and treated within the multicenter phase 3 clinical trial NHL1-2003 comparing bendamustine-rituximab (B-R) with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone. From April 2005 to August 2008, 783 pre- and posttreatment PB samples were quantified by quantitative PCR. At inclusion, 114 patients (66%) tested positive and 59 (34%) were negative for Bcl-2/IgH. High pretreatment Bcl-2/IgH levels had an adverse effect on progression-free survival (PFS) compared with intermediate or low levels (high vs intermediate: hazard [HR], 4.28; 95% confidence interval [CI], 1.70-10.77; P = .002; high vs low: HR, 3.02; 95% CI, 1.55-5.86; P = .001). No PFS difference between treatment arms was observed in Bcl-2/IgH-positive patients. A positive posttreatment Bcl-2/IgH status was associated with shorter PFS (8.7 months vs not reached; HR, 3.15; 95% CI, 1.51-6.58; P = .002). By multivariate analysis, the pretreatment Bcl-2/IgH level was the strongest predictor for PFS. Our data suggest that pre- and posttreatment Bcl-2/IgH levels from PB have significant prognostic value for PFS in FL patients receiving first-line immunochemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT00991211 and at the German Federal Institute for Drugs and Medical Devices as #BfArM-4021335.

Previous meta-analyses of psychotherapies for child and adolescent depression were limited because of the small number of trials with direct comparisons between two treatments. A network meta-analysis, a novel approach that integrates direct and indirect evidence from randomized controlled studies, was undertaken to investigate the comparative efficacy and acceptability of psychotherapies for depression in children and adolescents. Systematic searches resulted in 52 studies (total N=3805) of nine psychotherapies and four control conditions. We assessed the efficacy at post-treatment and at follow-up, as well as the acceptability (all-cause discontinuation) of psychotherapies and control conditions. At post-treatment, only interpersonal therapy (IPT) and cognitive-behavioral therapy (CBT) were significantly more effective than most control conditions (standardized mean differences, SMDs ranged from -0.47 to -0.96). Also, IPT and CBT were more beneficial than play therapy. Only psychodynamic therapy and play therapy were not significantly superior to waitlist. At follow-up, IPT and CBT were significantly more effective than most control conditions (SMDs ranged from -0.26 to -1.05), although only IPT retained this superiority at both short-term and long-term follow-up. In addition, IPT and CBT were more beneficial than problem-solving therapy. Waitlist was significantly inferior to other control conditions. With regard to acceptability, IPT and problem-solving therapy had significantly fewer all-cause discontinuations than cognitive therapy and CBT (ORs ranged from 0.06 to 0.33). These data suggest that IPT and CBT should be considered as the best available psychotherapies for depression in children and adolescents. However, several alternative psychotherapies are understudied in this age group. Waitlist may inflate the effect of psychotherapies, so that psychological placebo or treatment-as-usual may be preferable as a control condition in psychotherapy trials.

7515Background: Rituximab (R) maintenance is part of a standard treatment for follicular lymphoma. In MZL, however, it is not yet common practice. In this study we compared the effect of 2 years of...

7501 Background: This multicenter, randomized, phase III study compared B-R and CHOP-R as first-line treatment in patients (pts) with indolent lymphomas or mantle cell lymphoma and was first published in The Lancet in 2013. The final analysis demonstrated a significantly prolonged progression-free survival (PFS) in the B-R group compared to the CHOP-R group, with a median PFS of 69.5 vs. 31.2 months, respectively. In the current analysis, we present updated results for overall survival (OS), time-to-next-treatment (TTNT), and secondary malignancies (sNPL) with a median follow-up of 113 months for patients with indolent lymphomas (excluding MCL). Methods: 447 pts with indolent lymphomas were randomized to receive B-R or CHOP-R for a maximum of 6 cycles. The primary endpoint was PFS; secondary endpoints included OS, TTNT, and sNPL. Results: Patient characteristics were well balanced between arms; median age was 64 years. The difference in OS between the two treatment arms was not statistically significant, with 60 deaths in the B-R group vs 68 deaths with CHOP-R (HR 0.82, 95% CI 0.58 – 1.15, p = 0.249). The estimated 10-year survival rates were 71% for B-R and 66% for CHOP-R. TTNT was significantly prolonged with B-R compared with CHOP-R (HR 0.52, 95% CI 0.38 – 0.69, p < 0.001). Median TTNT was not yet reached in the B-R group (95% CI 124.9 – n.y.r) vs. 56 months in the CHOP-R group (95% CI 39.1 – 82.0). Patients treated initially with B-R needed fewer second-line treatments due to disease progression compared to CHOP-R treated pts: 73 pts (34%) in the B-R group received salvage treatment compared with 106 pts (52%) in the CHOP-R group. For B-R pts, CHOP-R was used as second-line therapy 26 times (36%), whereas B-R was used for pts initially treated with CHOP-R 49 times (46%). 36 pts with sNPL were observed in the B-R group compared with 39 in the CHOP-R group, with 7 hematological malignancies in both groups to date. Conclusions: In pts with previously untreated indolent lymphomas, B-R demonstrates a PFS and TTNT benefit over CHOP-R. Clinical trial information: NCT00991211.

Background Due to the heterogeneous nature of chronic low back pain (CLBP), it is necessary to identify patient groups and evaluate treatments within these groups. We aimed to identify groups of patients with CLBP in the primary care setting. Methods We performed a k-means cluster analysis on a large data set (n = 634) of primary care patients with CLBP. Variables of sociodemographic data, pain characteristics, psychological status (i.e., depression, anxiety, somatization), and the patient resources of resilience and coping strategies were included. Results We found three clusters that can be characterized as “pensioners with age-associated pain caused by degenerative diseases”, “middle-aged patients with high mental distress and poor coping resources”, and “middle-aged patients who are less pain-affected and better positioned with regard to their mental health”. Conclusions Our results supported current knowledge concerning groups of CLBP patients in primary care. In particular, we identified a group that was most disabled and distressed, and which was mainly characterized by psychological variables. As shown in our study, pain-related coping strategies and resilience were low in these patients and might be addressed in differentiating treatment strategies. Future studies should focus on the identification of this group in order to achieve effective treatment allocation. Trial registration German Clinical Trial Register DRKS00003123

Rituximab plus chemotherapy, most often CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), is the first-line standard of care for patients with advanced indolent lymphoma, and for elderly patients with mantle-cell lymphoma. Bendamustine plus rituximab is effective for relapsed or refractory disease. We compared bendamustine plus rituximab with CHOP plus rituximab (R-CHOP) as first-line treatment for patients with indolent and mantle-cell lymphomas.We did a prospective, multicentre, randomised, open-label, non-inferiority trial at 81 centres in Germany between Sept 1, 2003, and Aug 31, 2008. Patients aged 18 years or older with a WHO performance status of 2 or less were eligible if they had newly diagnosed stage III or IV indolent or mantle-cell lymphoma. Patients were stratified by histological lymphoma subtype, then randomly assigned according to a prespecified randomisation list to receive either intravenous bendamustine (90 mg/m(2) on days 1 and 2 of a 4-week cycle) or CHOP (cycles every 3 weeks of cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) on day 1, and prednisone 100 mg/day for 5 days) for a maximum of six cycles. Patients in both groups received rituximab 375 mg/m(2) on day 1 of each cycle. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival, with a non-inferiority margin of 10%. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00991211, and the Federal Institute for Drugs and Medical Devices of Germany, BfArM 4021335.274 patients were assigned to bendamustine plus rituximab (261 assessed) and 275 to R-CHOP (253 assessed). At median follow-up of 45 months (IQR 25-57), median progression-free survival was significantly longer in the bendamustine plus rituximab group than in the R-CHOP group (69.5 months [26.1 to not yet reached] vs 31.2 months [15.2-65.7]; hazard ratio 0.58, 95% CI 0.44-0.74; p0.0001). Bendamustine plus rituximab was better tolerated than R-CHOP, with lower rates of alopecia (0 patients vs 245 (100%) of 245 patients who recieved ≥3 cycles; p0.0001), haematological toxicity (77 [30%] vs 173 [68%]; p0.0001), infections (96 [37%] vs 127 [50%]); p=0.0025), peripheral neuropathy (18 [7%] vs 73 [29%]; p0.0001), and stomatitis (16 [6%] vs 47 [19%]; p0.0001). Erythematous skin reactions were more common in patients in the bendamustine plus rituximab group than in those in the R-CHOP group (42 [16%] vs 23 [9%]; p=0.024).In patients with previously untreated indolent lymphoma, bendamustine plus rituximab can be considered as a preferred first-line treatment approach to R-CHOP because of increased progression-free survival and fewer toxic effects.Roche Pharma AG, Ribosepharm/Mundipharma GmbH.

OBJECTIVES Systematic reviews on prevalence estimates of child sexual abuse (CSA) worldwide included studies with adult participants referring on a period of abuse of about 50 years. Therefore we aimed to describe the current prevalence of CSA, taking into account geographical region, type of abuse, level of country development and research methods. METHODS We included studies published between 2002 and 2009 that reported CSA in children below 18 years. We performed a random effects meta-analysis and analyzed moderator variables by meta-regression. RESULTS Fifty-five studies from 24 countries were included. According to four predefined types of sexual abuse, prevalence estimates ranged from 8 to 31 % for girls and 3 to 17 % for boys. Nine girls and 3 boys out of 100 are victims of forced intercourse. Heterogeneity between primary studies was high in all analyses. CONCLUSIONS Our results based on most recent data confirm results from previous reviews with adults. Surveys in children offer most recent estimates of CSA. Reducing heterogeneity between studies might be possible by standardized measures to make data more meaningful in international comparisons.

BACKGROUND: Chronic pain is a common reason for consultation in general practice. Current research distinguishes between chronic localized pain (CLP) and chronic widespread pain (CWP). The aim of this study was to identify differences between CWP and chronic low back pain (CLBP), a common type of CLP, in primary care settings. METHODS: Fifty-eight German general practitioners (GPs) consecutively recruited all eligible patients who consulted for chronic low back pain during a 5-month period. All patients received a questionnaire on sociodemographic data, pain characteristics, comorbidities, psychosomatic symptoms, and previous therapies. RESULTS: GPs recruited 647 eligible patients where of a quarter (n = 163, 25.2%) met the CWP criteria according to the American College of Rheumatology. CWP patients had significantly more comorbidities and psychosomatic symptoms, showed longer pain duration, and suffered predominantly from permanent pain instead of distinguishable pain attacks. CWP patients were more often females, are less working and reported a current pension application or a state-approved grade of disability more frequently. We found no other differences in demographic parameters such as age, nationality, marital status, number of persons in household, education, health insurance status, or in health care utilization data. CONCLUSIONS: This project is the largest study performed to date which analyzes differences between CLBP and CWP in primary care settings. Our results showed that CWP is a frequent and particularly severe pain syndrome. TRIAL REGISTRATION: German Clinical Trial Register, DRKS00003123. &nbsp

7503Background: Rituximab maintenance is part of a standard treatment approach for follicular lymphoma. In mantle cell lymphoma (MCL), however, it is not yet common practice. In this study we compa...

Background Chronic localized pain syndromes, especially chronic low back pain (CLBP), are common reasons for consultation in general practice. In some cases chronic localized pain syndromes can appear in combination with chronic widespread pain (CWP). Numerous studies have shown a strong association between CWP and several physical and psychological factors. These studies are population-based cross-sectional and do not allow for assessing chronology. There are very few prospective studies that explore the predictors for the onset of CWP, where the main focus is identifying risk factors for the CWP incidence. Until now there have been no studies focusing on preventive factors keeping patients from developing CWP. Our aim is to perform a cross sectional study on the epidemiology of CLBP and CWP in general practice and to look for distinctive features regarding resources like resilience, self-efficacy and coping strategies. A subsequent cohort study is designed to identify the risk and protective factors of pain generalization (development of CWP) in primary care for CLBP patients. Methods/Design Fifty-nine general practitioners recruit consecutively, during a 5 month period, all patients who are consulting their family doctor because of chronic low back pain (where the pain is lasted for 3 months). Patients are asked to fill out a questionnaire on pain anamnesis, pain-perception, co-morbidities, therapy course, medication, socio demographic data and psychosomatic symptoms. We assess resilience, coping resources, stress management and self-efficacy as potential protective factors for pain generalization. Furthermore, we raise risk factors for pain generalization like anxiety, depression, trauma and critical life events. During a twelve months follow up period a cohort of CLBP patients without CWP will be screened on a regular basis (3 monthly) for pain generalization (outcome: incident CWP). Discussion This cohort study will be the largest study which prospectively analyzes predictors for transition from CLBP to CWP in primary care setting. In contrast to the typically researched risk factors, which increase the probability of pain generalization, this study also focus intensively on protective factors, which decrease the probability of pain generalization. Trial registration German Clinical Trial Register DRKS00003123

Abstract 2739 Background: Bendamustine-rituximab (B-R) has demonstrated substantial efficacy in the primary treatment of indolent lymphomas. A multicenter prospective randomized trial was initiated to investigate the impact of adding rituximab maintenance following B-R first-line induction. The trial included patients (pts) with Waldenström's Macroglobulinemia (WM), marginal zone, small lymphocytic and mantle cell lymphomas. Here we present first and preliminary results for pts with WM. Methods: Treatment consisted of a maximum of 6 cycles of B-R (bendamustine 90 mg/m2, rituximab 375 mg/m2) administered every 28 days plus 2 cycles of rituximab every 4 weeks. Responding pts (≥ PR) were eligible for further treatment and were randomized to observation or 2 years of rituximab maintenance every two months. The primary endpoint is PFS. Results: From April 2009 to July 2012, 57 centers included a total of 162 pts with newly diagnosed WM with a median age of 67 years (31% < 60 years, 69% > 60 years). At baseline/inclusion/screening, the median values for b2-microglobulin (b2M), hemoglobin and IgM were 3.3 mg/L, 10.1 g/dL and 2110 mg/dL (max. 13400 mg/dL), respectively. To date (Aug 2012) 116 pts are evaluable for response (43 women [37%] and 73 men [63%]). 100 pts have responded to B-R leading to an overall response rate (ORR) of 86%. At the time of response evaluation, the median Hb was 12.6 g/dl and the median IgM was 380 mg/dl. 90 pts have undergone randomization to date, 43 to observation and 47 to maintenance. Randomization is ongoing. No results can be reported from that ongoing part of the trial. No uncommon toxicities were observed during B-R induction. Conclusion: Initial results of our trial confirm that for patients with Waldenström's macroglobulinemia, treatment with B-R is an efficacious treatment with a manageable safety profile. The role of rituximab maintenance in this disease is under investigation. Disclosures: No relevant conflicts of interest to declare.

Abstract 2724 Background: The NHL 1 study, a prospective, multicenter, randomized, phase 3 study which compared B-R and CHOP-R as first-line treatment in indolent lymphomas and mantle cell lymphoma (MCL), demonstrated a significant benefit in progression-free survival (PFS) as well as improved tolerability for B-R compared with CHOP-R. Here we present an analysis of the impact of response quality on outcome. Methods: 514 patients (pts) with indolent or MCL were randomized to receive B-R or CHOP-R for a maximum of 6 cycles. Results: The overall response rate in the 514 pts (261 B-R; 253 CHOP-R) was 92.7% and 91.3% in the B-R and CHOP-R arms, respectively (as presented at the last ASCO meeting, J Clin Oncol 30, 2012 (suppl; abstr 3). A complete response (CR) was observed in 39.8% in the B-R arm and in 30% in the CHOP-R arm (p=0.021). The achievement of CR was associated with a significantly prolonged PFS and overall survival (OS) (Table 1). Analysis by treatment arm revealed a trend for superior PFS and a significantly improved OS for patients achieving CR following treatment with B-R. In the CHOP-R arm, patients in CR had a significantly superior PFS compared to those in PR with a trend to superior OS. Regardless of the quality of response, PFS was superior with B-R versus CHOP-R: For patients in CR, the median PFS was not reached with B-R, whereas for CHOP-R it was 53.7 months (p=0.0204). In patients achieving PR, treatment with B-R resulted in a median PFS of 57.2 months, and this was 30.9 months with CHOP-R (p=0.0002). We noted a statistically significant difference in CR rates between male (n=272, median age 63 years) and female (n=242, median age 64 years) patients. The CR rate was 28.6% in male patients and 42.1% in female patients (p=0.0016). Female patients had a longer median PFS (51.4 months) compared to male patients (38.6 months), however, this difference was not statistically significant (p=0.0866). Conclusions: Patients in CR following first-line treatment in our study had a significantly longer PFS and OS compared to those achieving a PR. Therefore, our results strongly suggest an association between quality of response and outcome. Disclosures: No relevant conflicts of interest to declare.

3 Background: This multicenter, randomized, phase III study compared B-R and CHOP-R as first-line treatment in indolent lymphoma and MCL and was presented at ASH 2009 including a comprehensive safety analysis. Here we present an updated analysis with a cut-off date for 31 Oct 2011. Methods: 549 patients (pts) with indolent or MCL were randomized to receive B-R or CHOP-R for a max of 6 cycles. The primary endpoint was PFS. Results: 514 pts randomized pts were evaluable (261 B-R; 253 CHOP-R). Patient characteristics were well balanced between arms; median age was 64 years. At a median follow-up of 45 months, PFS was significantly prolonged with B-R compared with CHOP-R (HR 0.58, 95% CI 0.44–0.74; P 60 years (n=315). In pts with...

Abstract 856 Introduction: Promising results have been observed in two phase II studies evaluating the combination of bendamustine plus rituximab (B-R) in patients (pts) with relapsed/refractory follicular, other indolent or mantle cell lymphomas (MCL) (Rummel et al. JCO 2005; Robinson et al. JCO 2008). Fludarabine plus rituximab (F-R) is an established treatment option in this setting. Therefore, we initiated in 2003 a multicenter, randomized phase III study to compare the efficacy and safety of B-R versus F-R for pts with relapsed follicular (FL), indolent or MCL. Patients and methods: 219 pts with relapsed FL, indolent or MCL in need of treatment were randomized to rituximab 375 mg/m2 (day 1) plus either bendamustine 90 mg/m2 (days 1+2) or fludarabine 25 mg/m2 (days 1–3) q 28 days for a maximum of 6 cycles. Prophylactic use of antibiotics or granulocyte-colony stimulating factor (G-CSF) was not generally recommended; however in cases of severe granulocytopenia, G-CSF use was permitted. The primary endpoint was progression-free survival (PFS). The protocol was amended in 2006 to allow rituximab maintenance therapy (rituximab 375 mg/m2 q 3 months for up to 2 years) in both arms, following regulatory approvals in this setting. Results: 11 pts were not evaluable due to protocol violations, and were not followed further. A total of 208 pts were evaluable for the final analysis (109 B-R; 99 F-R). There were no significant differences between arms for patient characteristics, including age, stage, LDH, International Prognostic Index (IPI), follicular IPI (FLIPI), bone marrow infiltration and extranodal involvement. Most pts had stage IV (71.6% B-R; 60.6% F-R) or stage III disease (21.1% B-R and 25.3% F-R, respectively). Median patient age was 68 yrs (range 38–87). Patients had received a median of 1 prior therapy (range 1–7). Histological subtypes were distributed equally between the B-R and F-R arms: follicular 45.9 % and 47.5%, respectively; immunocytoma 11.9% and 11.1%; MCL 20.2% and 21.2%; other indolent lymphomas 23% and 20.2%. A median number of 6 cycles were given in both treatment arms, with 75.2% of B-R pts and 53.4% of F-R pts receiving 6 cycles, respectively. At the time of this analysis (June 2010), the median observation time was 33 months. Median PFS was significantly prolonged with B-R compared with F-R (30 vs 11 months; hazard ratio [HR] 0.51, 95 % confidence interval [CI] 0.34–0.67; p There were no significant differences in the rates of alopecia, stomatitis, erythema, allergic reactions, peripheral neuropathy or infectious episodes between groups. Hematologic toxicities were also similar between arms: 8.9% grade 3/4 neutropenia with B-R vs 9.1% with F-R; 11.8% grade 3/4 leukocytopenia with B-R vs 12.4% with F-R. The overall incidence of serious adverse events was similar for the B-R and F-R groups (17.4 and 22.2%, respectively). An unplanned subanalysis showed that rituximab maintenance therapy significantly prolonged overall survival (HR 0.21, 95% CI 0.22–0.67; p=0.0008) and PFS (HR 0.27, 95% CI 0.27–0.59; p< 0.0001) in the small group of 40 pts who received this treatment (23 B-R, 17 F-R), compared with those who did not. Although the numbers are too small in this non-randomized comparison to draw some validated conclusions, these results appear to confirm the favorable role of rituximab maintenance. Conclusions: These data confirm the efficacy of B-R in pts with relapsed FL, indolent or MCL, and, in this setting, demonstrate a superior PFS benefit for this regimen in comparison with F-R. Disclosures: No relevant conflicts of interest to declare.

Abstract 2679 Poster Board II-655 Introduction: Bendamustine, a hybrid alkylating agent, shows a unique mechanism of action with a good toxicity profile in various hematological malignancies, particularly in non-Hodgkin's lymphoma. Bendamustine (B) in combination with Rituximab (R) was demonstrated to be an effective regimen in first- or second-line treatment of patients (pts) with indolent lymphomas. So far, however, no data about the capacity of peripheral blood stem cell (PBSC) mobilization or a possible stem cell toxicity of B has been studied. It is still an open and clinically relevant question, if pts treated with B are able to mobilize enough stem cells for subsequent high dose therapy with autologous stem cell support. Objective: We performed a prospective randomized multicenter phase-III trial to compare the efficacy and safety of the combination of Bendamustine plus Rituximab (B-R) versus CHOP plus Rituximab (CHOP-R) as first-line therapy for follicular, indolent and mantle cell lymphomas. Chemotherapy was given in 6 cycles each (B: 90 mg/m2 d1+2). One of the secondary objectives (not mandatory) of this study was to evaluate the possibility to mobilize a sufficient number (at least 2.0 × 10E6 CD 34+ cells/kg) of PBSC and progenitor cells in younger pts after completing either B-R or CHOP-R and to compare both stem cells yields. Results: 549 pts have been randomized, 513 pts (B-R = 260, CHOP-R = 253) are evaluable. In each arm, 23 PBSC mobilizations have been performed. In the B-R as well as in the CHOP-R arm each 18 mobilizations were performed directly after completion of therapy, and in 5 pts stem cells were collected at the time of first relapse. Patient characteristics: initial bone marrow involvement was observed in 17 of 23 pts in the B-R arm and 14 of 23 pts in the CHOP-R arm, respectively. Median patient age was 51 years (B-R) and 53 years (CHOP-R). The mobilization regimen was either high dose cyclophosphamide + G-CSF (9 pts in each arm) or G-CSF alone in 7 pts after B-R and in 2 pts after CHOP-R, respectively. Alternative regimens such as Dexa-BEAM, DHAP, ICE and others were also used in the remaining patients. The median CD34+ cell-count/kg was not significantly different in the two arms with 4.55 × 10E6 CD34+ cells/kg (range 1.68 – 12.35) in the B-R group and 6.17 × 10E6 CD 34+ cells/kg (range 1.68 – 20.39) in the CHOP-R group, respectively. In both arms the medium number of apheresis to achieve these yields was not different (B-R: 1.85 vs. CHOP-R: 1.66). Only 3 pts were not able to mobilize at least 2.0 × 10E6 CD 34+ cells/kg: 1 patient after B-R (1.68 × 10E6 CD 34+ cells/kg), and 2 pts after CHOP-R (1.68 × 10E6 CD 34+ cells/kg, and in 1 patient no mobilization was possible). In patients who were mobilized directly after completion of first-line chemotherapy (18 pts in each arm), again, no differences (B-R: median 5.52 × 10E6 CD 34+ cells/kg vs. CHOP-R: median 7.35 × 10E6 CD 34+ cells/kg) were observed. The yield of stem cells in each 5 pts of both arms who were mobilized at the time of first relapse was also nearly the same (B-R: median 8.79 × 10E6 CD 34+ cells/kg vs. CHOP-R: median 7.3 × 10E6 CD 34+ cells/kg). Conclusions: Our results demonstrate that the collection of sufficient numbers of PBSC after B-R treatment is possible and appears to be comparable to the PBSC yield after prior treatment with CHOP-R. Disclosures: Rummel: Roche Pharma AG: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding.

Abstract 441 Introduction: By means of standard chemotherapy advanced stage follicular lymphoma (FL) is an incurable disease. Clinical courses are characterized by a continuous tendency to relapse caused by residual neoplastic cells. Quantitative polymerase chain reaction (qPCR) to detect lymphoma cell that carry the t(14;18) translocation is a suitable method to measure minimal residual disease (MRD) in patients with FL. Despite several reports dealing with MRD qPCR in FL, its role in the clinical management of patients is still not clearly defined. Therefore, we carried out a multicenter study, to assess the prognostic value of sequential quantitative MRD detection in first-line treatment of FL using an improved version of a LightCycler based qPCR specific for the major breakpoint region (MBR) positive IgH/bcl2 translocation, provided by Roche Diagnostics® (Penzberg Germany). Patients and Methods: We analysed 718 blood (PB) samples of 179 patients with newly diagnosed FL treated within the multicenter randomized trial NHL1, conducted by the German StiL group (Study group indolent Lymphomas), comparing 6 cycles of R–CHOP versus R–Bendamustin (R-B). Samples were taken at diagnosis, after 6 cycles of either R–CHOP or R–B immuno-chemotherapy and every three months during follow-up. All samples were analyzed in the department of Hematology at Heinrich-Heine University in Duesseldorf. Results: At diagnosis, 112 out of 179 patients (62.6%) were positive for IgH/bcl2 within the MBR in the peripheral blood. Significantly higher amounts of bcl2/IgH positive cells were found in patients with bone marrow infiltration (p=0.012) and depending on the number of lymphatic nodes (LN) with disease involvement (>3 LN p=0.003; >5 LN p=0.0009; >7 LN p=0.022). Overall, a remarkable inter-individual variation of bcl2/IgH positive cells in the PB at diagnosis, reflected by ratios from 0.000281 to 81, was found. The estimated event free survival (EFS) at 2 years of patients who presented at diagnosis low to normal amounts of bcl2/IgH positive cells in the PB (ratio < 2, n=83) was 82% (SE 0.045), which was significantly better than the 47% (SE 0.11) observed in patients showing the highest amount of bcl2/IgH positive cells (ratio >2, n=24) in the PB (p=0.003). By univariate and multivariate analysis, we found that the amount of bcl2/IgH positive cells in the PB at diagnosis (p=0.001) as well as the achievement of a negative MRD status after therapy (p=0.0001) were significant predictors for relapse free survival. Monitoring of MRD levels before and after therapy revealed that 6 cycles of immuno-chemotherapy significantly reduced the amount of bcl2/IgH positive cells in the PB compared with pre-treatment MRD levels (p=0.0001; median bcl2/IgH/tPA ratio: before treatment 0.0734, range: 0.000281–81, after treatment negative, range: negative–0.17). After treatment, 86% of the patients (n=82) achieved a molecular remission in the PB defined as qPCR negative, whereas 14% (13 patients) remained PCR positive. Not reaching a molecular remission in the PB at the end of therapy had a significant negative influence on PFS. After a median follow-up of two years, patients who remained MRD positive in the first measurement after therapy had a significant lower PFS than MRD negative patients (p=0.0001; 9 months vs. not reached). There was no significant difference in the degree of tumor cell depletion in the PB induced by the two different regimens. So far, 539 follow-up samples from 3 up to 39 months after therapy were analyzed. Patients with a consistent negative MRD status throughout follow-up showed a trend towards longer PFS. After 38 months follow-up, MRD positive patients had a PFS of 54% compared to 78% in the group of MRD negative patients (p=0.066). Conclusion: QPCR for the t(14;18) performed at diagnosis and during follow-up on PB samples predicts treatment response and long-term clinical outcome of patients with FL. Disclosures: Zohren: Roche: Honoraria, Research Funding. Rummel:Roche Pharma AG: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Amgen: Honoraria. Kobbe:Roche: Research Funding.

Abstract 405 Introduction: Promising results have been observed in two phase-II studies evaluating the combination of Bendamustine plus Rituximab (B-R) in patients with relapsed/refractory indolent or mantle cell lymphomas (Rummel et al., JCO 2005; Robinson et al., JCO 2008). In order to further investigate the role of the combination B-R we initiated a multicenter randomized phase-III study in October 2003 to compare efficacy and safety of B-R versus CHOP plus Rituximab (CHOP-R) as first-line therapy for patients with follicular (FL), indolent and mantle cell lymphomas (MCL). Patients and Methods: 549 patients (pts) in need of treatment for their disease were randomized to receive Rituximab 375 mg/m2 (day 1) plus either Bendamustine 90 mg/m2 (days 1+2) every 28 days or the standard CHOP regimen every 21 days for a maximum of 6 cycles. The primary endpoint was progression-free survival (PFS). Patients characteristics, including age, stage, LDH, IPI, FLIPI, bone marrow infiltration and extranodal involvement did not statistically significant differ between both arms. The median patient age was 64 years (range 31-83) (64 yrs for B-R and 63 yrs for CHOP-R). Most patients were in stage IV (76,9% in BR and 77,5 in CHOP-R) and stage III (19,2% in B-R and 18,6% in CHOP-R). Histologies were distributed equally between B-R and CHOP-R: follicular 55% and 56%, mantle cell 18% and 19%, and other indolent lymphomas 27% and 24%, respectively. Prophylactic use of antibiotics or growth factors were not generally recommended in this protocol. Results: Of the 549 pts 36 pts were not evaluable: 10 did not receive any study medication, 9 due to withdrawal of consent, 13 due to incorrect diagnosis (4 × DLBCL, 3 × CLL, 2 × MM, 1 × HD, 3 × solid tumors), and 4 for other reasons. 513 randomized pts are evaluable for the final analysis (B-R: n=260; CHOP-R: n=253). Out of these 9 pts were not evaluable for response evaluation: 4 pts (3 × CHOP-R, 1 × B-R) due to early death in neutropenic sepsis, 3 pts due to a subsequent change of therapy after severe toxicity in 1st cycle of CHOP-R, 1 B-R pt due to progress of disease, and 1 B-R due to early death. All patients were counted for evaluation of PFS, overall survival (OS), event-free survival (EFS; an event was defined by a response less than a partial response, disease progression, relapse, or death from any cause), and for time to next treatment (TTNT). A median number of 6 cycles was given in both treatment arms each. 82% of B-R pts and 86% of CHOP-R pts received 6 cycles. At the time of analysis in August 2009, the median observation time was 32 months. Overall response rate for pts treated with B-R was similar to the CHOP-R group (93,8% vs 93,5%, respectively). The CR rate was significantly higher with 40,1% for B-R compared to 30,8% for CHOP-R (p=0.0323). The median PFS, EFS and TTNT were significantly longer after B-R compared to after CHOP-R: PFS 54,8 months for B-R versus (vs) 34,8 months for CHOP-R (p=0.0002), Hazard Ratio (HR) 0.5765 (95% confidence interval (CI) 0.4292 to 0.7683); EFS 54 months for B-R vs 31 months for CHOP-R (p=0.0002, HR 0.6014 (95% CI 0.4515 to 0.7845); and TTNT median not yet reached in the B-R group vs 40,7 months in the CHOP-R group (p=0.0002; HR 0.5416, 95% CI 0.3897 to 0.7491). OS did not differ between both groups at this point of time. Thus far, 67 deaths have been observed (B-R: 34; CHOP-R: 33). CHOP-R treatment was more frequently associated with serious adverse events (SAE) (n=49 in B-R vs n=74 in CHOP-R). Significant differences in hematologic toxicities were observed for neutropenia grade 3+4 (BR 10,7% vs CHOP-R 46,5%; p Conclusions: In this final analysis the combination of Bendamustine plus Rituximab improves PFS and CR rates while showing a better tolerability profile. These promising results suggest that B-R does have the potential to become a new standard first-line treatment option for patients with FL, MCL, and indolent lymphomas. Disclosures: Rummel: Roche Pharma AG: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding; Amgen: Honoraria. Maschmeyer:OrthoBiotech: .