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Background: Twenty percent of patients (pts) with high-tumor burden follicular lymphoma (FL) develop progression/relapse of disease within 24 months of frontline immune-chemotherapy (POD24). Those ultra-high-risk cases are at 50% risk of dying within 5-years since the POD event. Unmet need is to identify such pts at the time of initial treatment. The traditional approach used for building predictive scores (such as FLIPI, PRIMA-PI) is multivariable logistic regression (LR). LR is the tool of choice in case of many predictors (continuous or categorical) and a single binary (yes/no) outcome. Bayesian network (BN) offer an alternative strategy which may overcome several drawbacks of LR (risk of overfitting, missing data handling, problems of odds ratio interpretation), brings more insight into the complex relations among the variables, and offer an individualized prediction. Aim: The goal was to build a model to predict the risk of POD24 from the parameters known at diagnosis and compare LR to BN approach. Methods: The study (ClinicalTrials.gov No NCT03199066) comprised 1394 FL (grade I-IIIA) patients from the Czech Lymphoma Study Group registry treated with frontline rituximab-containing regimen and diagnosed between 10. 4. 2000 and 28. 12. 2016. The following parameters were analyzed: gender, age at diagnosis, clinical stage, lymphoma grade, no. of LNs regions, bone marrow involvement, no. of extranodal localizations, longest tumor diameter, systemic symptoms, performance status, LDH, beta-2-microglobulin, hemoglobin, and leucocyte, lymphocyte, and thrombocyte counts, induction regime, radiotherapy, ASCT, maintenance application, response to treatment, and OS, PFS and POD24 as outcome parameters. POD24 was defined as relapse, progression, change of therapy for 24 months since the induction started. Only parameters known at diagnosis were used for the prediction of POD24. Results: The median age was 59 yrs (range 26-89 yrs) with female predominance (59.2%), advanced disease stage (III/IV) was seen in 85.9% of the cases and FLIPI risk groups distribution was as follows: low (18.8%), intermediate (30.9%) and high (50.3%). The most frequent regime used was R-CHOP (76.8%), followed by R-CVP (12.4%), R-bendamustine (4.7%), intensive protocols (3.3), and fludarabine-based (2.8%). Consolidative IF-radiotherapy was applied in 5.1% and up-front ASCT in 2.9% of the pts. Maintenance immunotherapy was given in 67.1% of the pts. Response to therapy was known in all but 28 pts (98%) with CR/CRu 67.9%, PR 26.6%, SD 1.8%, and PD in 3.2% of the cases. After a median follow-up of 7.64 yrs, 484 (34.7%) of the pts progressed or relapsed and 316 (22.6%) have died. POD24 was recorded in 266 (19.0%) of the pts. The 5-year OS reached 86.4% and 5-year PFS 64.2%. LR model (PFS) building strategy included testing for significance as this model performed better than the model with all parameters. Overfitting was prevented by splitting the data into training (75%) and testing (25%) set. The performance of the model was assessed using the AUC criterion computed on the ROC curve. The LR model reached AUC of 0.69, and at 80% specificity, it reached about 51% sensitivity. Next, the BN (Augmented Naïve Bayes Classifier) was trained. Links of all predictors to POD24 were forced and all links to age and gender were forbidden, otherwise the network structure was inferred from the data. The performance of the BN was similar to the LR - AUC of 0.67 and about 50% sensitivity at the specificity of 80%. Both these models were compared to the standard PRIMA-PI risk classifier and were found to better stratify the population into risk groups (Table 1). An example of a patient is presented who was low-risk according to PRIMA-PI but actually experienced the POD24 event. The BN estimated the probability of the event to 91% (Figure 1). Conclusion: Lymphoma-related death following POD24 remains the most frequent cause of mortality in FL patients. BN modelling is a non-inferior prognostic tool compared to LR in term of POD24 prediction. Unlike LR, it also allows visualisation of complex relations among the predictors and individualized prediction of the patient's POD24 risk, even if some of the predictors are unknown. Both "ad hoc" trained LR and BN were found to better stratify the population into risk groups with respect to POD24 event than the traditional PRIMA-PI score. Acknowledgement: MZ Czech Republic DRO grant (FNOL, 00098892). Disclosures Procházka: F. Hoffmann-La Roche AG: Consultancy, Honoraria; Takeda Pharmaceuticals, Inc: Consultancy, Research Funding. Belada:Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding; Celgene: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Research Funding. Trněný:Janssen: Consultancy, Honoraria, Other: Travel Expenses; Gilead: Consultancy, Honoraria, Other: Travel Expenses; Takeda: Consultancy, Honoraria, Other: Travel Expenses; Bristol-Myers Squibb Company: Consultancy, Honoraria, Other: Travel Expenses; Amgen: Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel Expenses; Roche: Consultancy, Honoraria, Other: Travel Expenses; MorphoSys: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Celgene: Consultancy.

Background: Early events within 24 months (POD24) of initial immunochemotherapy (IC) were repeatedly confirmed to be associated with poor survival in follicular lymphoma (FL). Rituximab maintenance (RM) given to responding patients after IC is effective strategy to reduce relapse incidence and improve survival (Salles, Lancet 2011; Hill, BJH 2019). There is little known about the POD24 incidence pattern in chemosensitive patients, and the impact of subsequent RM application for POD24 reduction has not been studied yet. Aim: To (1) analyze the role of POD24 events in patients with responding FL and (2) describe whether post-induction RM changes the pattern of POD24 incidence and possibly post-POD24 outcome of the patients. Methods: The study comprised patients prospectively enrolled in the Czech Lymphoma Study Group network (ClinicalTrials.gov: NCT03199066) in 2000-2015, with grade 1-3A FL and treated with frontline R-CHOP/R-CHOP-like or R-bendamustine or R-CVP IC. Cases with previous WaW were not enrolled. No frontline stem cell (auto/allo) transplant was allowed. Only patients who achieved complete (CR/CRu) or partial remission (PR) at the end of induction (EOI) and were thus potential candidates for RM were included. Early event was defined as progression, relapse or death within 24 months after the date of EOI response assessment. Overall (OS) and progression-free survival (PFS) were calculated from the date of diagnosis and date of EOI response (OS-EOI). Patients who experienced an event before the median time to RM initiation were excluded from POD24 survival analyses to avoid overestimation of the RM group results. Results: A total of 1089 patients were identified, of whom 729 (67%) received RM (maintenance group) and 360 (33%) were followed without RM (observation group; OBS). When comparing both groups, we found no differences in age (median age 59 yrs for both; P=0.54), sex distribution (males 39% vs. 41% in OBS vs. RM, respectively; P=0.37) and ECOG 0-1 (90% vs. 93% in OBS vs. RM; P=0.10). There was a slightly lower proportion of advanced FL (Ann Arbor III-IV) in OBS (80%) as compared to RM (87%, P=0.01), which translated into a lower proportion of high FLIPI patients (46% vs. 52% in OBS vs. RM, respectively; P=0.003). The induction regimens were as follows: R-CHOP in 70% and 83%, R-COP in 18.6% and 10.7%, R-bendamustine 1% and 4%, R-fludarabine-based in 4% and 1% and others in 5% and 1% in RM and OBS, respectively. The EOI remission status was assessed 61 days (median) after the last IC dose with CR/CRu/PR rates of 65%/9%/26% and 65%/6%/29% in OBS and RM, respectively (P=0.14). The median time from EOI response to the first RM dose was 48 days (range 0-371 days), 89% of the pts have started RM within 120 days. The median number of RM doses given was 8 (range, 1-36), with 85% of patients receiving 8-12 doses of RM. After a median follow-up of 10.4 yrs (OBS) vs. 6.0 yrs (RM); P Conclusion: Early progression of the disease significantly increases the risk of death even in pts who respond well to the initial IC. Application of RM significantly prolonged both OS and PFS and reduced POD-24 incidence by half. However, once patients developed an early event on RM, their outcome remained poor. On the other hand, in the POD-24-free group, RM brought survival benefit that lasted beyond its termination. Large independent validation may enhance the validity of these data since the observation group was mainly of a historical nature. Acknowledgement: Supported by IGA_LF_2019_001, MH CZ - DRO (FNOL, 00098892), and AZV 16-31092A grants. Figure 1 Disclosures Prochazka: Roche: Consultancy; Takeda: Research Funding. Trneny:Morphosys: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Gilead sciences: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria.

Background: The outcome of DLBCL patients is improving, it however seems to be very poor for those who are refractory to the therapy. We have decided to analyze this group of patients. Methodology: As part of an observational clinical study NiHiL (GovTrial No NCT03199066) we identified the patients treated in the first line by R-CHOP like immunochemotherapy who met at least one criterium: 1. refractory (stable disease - SD or progression) on 1st line therapy (1st l- R), 2. refractory (SD or progression) on salvage (platinum based regimen) (Salv-R), 3. refractory to or relapse/progression within 12 months after ASCT (ASCT-R/R). There were 210 patients diagnosed in the period 2001-2017 who fulfilled the criteria. Progression-free survival (PSF) and overall survival (OS) were estimated from the time of determination of a refractory disease. Results: The cohort consisted of 163 patients primarily resistant to the first-line therapy, 31 patients were resistant to the salvage therapy and 16 patients progressed within 12 months after ASCT . At the time of the diagnosis, the median age was 65 years (22-91) (the same as at the refractory disease), 54% were males, 74% had advanced clinical stage (III+IV), 68% had IPI >3, 77% had above-normal LDH, and 45% had a tumor mass >10cm. The OS from the time of determination of refractory disease was 0.53 years, median PFS was 0.29 years. Patients under 65 years had median survival 0.8 years compared to 0.4 years in the group of patients above 65 years of age. The median PFS for 1st l-R, Salv-R and ASCT-R/R resp. was 0.3, 0.26 and 0.35 years resp. and 5y survival 22%, 0% and 6% resp. The median OS for 1st l-R, Salv-R and ASCT-R/R resp. was 0.55, 0.39 and 0.65 y resp. and 5y survival was 28%, 0% and 13% resp. Our results demonstrate that resistant DLBCL has an extremely poor prognosis, clearly new effective therapeutic strategies such as CAR-based therapies or others are required. This work was supported by a research program Progres Q28-9. Disclosures Belada: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

INTRODUCTION: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with usually poor prognosis. Age was identified as the independent risk factors in many studies. Elderly patients suffer from comorbidities, impaired organ functions, and poor performance status resulting in worse tolerance of therapy and its efficacy. Data on outcome, prognosis and treatment efficacy for elderly patients with PTCLs are sparse. METHODS: We used data of 941 newly diagnosed PTCLs registered into CLSG database between January 1999 and March 2015 with last follow-up in February 2016. CLSG database covers approximately 85% of all newly diagnosed NonHodgkin´s lymphomas (NHLs) in Czech Republic. For the analysis, 208 patients with age >70 years at diagnosis were selected. RESULTS: Totally, PTCLs accounted for about 8.7% (454/5210) patients of all NHLs in population younger 60 years, but only about 5.8% (208/3561) NHL patients older 70 years. Median age was 76ys (71-91ys), 94 (45%) were women, lactate dehydrogenase (LDH) was elevated in 130/208 (62.5%) pts., ECOG ≥2 had 80 (38%) pts., and advanced clinical stage III-IV presented 132/208 (63.5%) pts. We identified following PTCL subtypes: PTCL-NOS (Peripheral T-cell lymphoma not otherwise specified) 89/208 (43%), Anaplastic large cell lymphoma (ALCL) 34/208 (16.3%), Cutaneous Anaplastic large cell lymphoma (C-ALCL) 10/208 (4.8%), Mycosis fungoides/ Sézary syndrome (MF/SS) together 29/208 (14%), NK/T nasal lymphoma (NK/T) 2/208 (1%), Angioimmunoblastic lymphoma (AITL) 17/208 (8.1%), Cutaneous CD30+ T lymphoproliferative disease 1/208 (0.5%), T-lymphoblastic lymphoma/leukemia (T-LBL) 3/208 (1.4%), T-cell lymphoma without specification (T-NHL) 17/208 (8.1%). Distribution of PTCL subtypes changed significantly with age. There was higher proportion of PTCL-NOS (43% vs. 34%; p.001) and MF/SS (14% vs. 4.8%; p70ys) compared to younger cohort (≤70ys; n=725). Contrary, percentage of ALCL (16.3% vs. 27%; p For the whole cohort of PTCLs (>70ys), the 5-year overall survival (OS) was 30% and 5-year progression free survival (PFS) was 21% regardless of subtype or stage. Progression is fatal event in elderly patients with median survival about 8 months only. There were significant survival differences between patients (>70ys vs. ≤70ys) according to PTCL subtype; PTCL-NOS 5 yr-OS 23% vs. 43% (p.00001), ALCL ALK+ 5-yr OS not reached vs. 79% (p.01), ALCL ALK- 5 yr-OS 24% vs. 50% (p.001). Patients with AITL or EATL showed no age-related survival differences. First-line chemotherapy was administered in majority of cases (67%); CHOP-like regimen was given in 78 (37%) pts., COP-like in 44 (21%) pts., and other chemotherapy in 18 (9%) cases. Local therapy (surgery, radiotherapy) was administered in first line in 17 (8%) pts., no or palliative therapy (corticoids) was given in 34 (17%) pts., initial therapy was unknown in 17 (8%) cases. We compared two subgroups of patients according to first line chemotherapy CHOP (n=75) vs. COP (n=41). Median age was 74ys (71-84) vs. 79ys (71-89), high IPI was presented in 29% vs. 50% of patients (p.001). Complete response (CR) was achieved in 35/75 (47%) CHOP treated patients, and in 7/41 (17%) patients managed with COP (p.001). Contrary, there were 12/75 (16%) progression in CHOP arm compared to 10/41 (24%) COP treated pts. Five-year OS was 28% vs. 15% better in CHOP group (p.029) and 5-yr PFS 25% vs. 10%, respectively. CONCLUSIONS: In population-based analysis of adult Caucasian PTCL patients, we identified mild decreasing incidence with age. There were significant age-related distribution differences of PTCL subtypes with shift to preponderance of PTCL-NOS, Mycosis fungoides, and NK/T nasal lymphoma in elderly. Worse survival in elderly PTCLs in comparison to younger patients was evident especially for PTCL-NOS and ALCL subtypes. Despite the baseline differences (COP managed pts. had higher IPI), there is tendency that anthracycline-based chemotherapy (CHOP) brings better results with higher proportion of CR and lower progression/relapse rate projected in longer survival. Disclosures Belada: Seattle Genetics: Research Funding. Mayer:AOP Orphan Pharmaceuticals: Research Funding; Novartis: Research Funding.

Introduction Localized stages of follicular lymphoma (I-II) have been traditionally treated with involved field radiotherapy (IF-RT), which seems to be able to cure a significant proportion of patients. On the other hand, nearly half of patients relapse within 10 years. The late distant relapses remain the problem. Rituximab (anti CD20 antibody) is low-toxic, efficient systemic therapy for follicular lymphoma (FL). In vitro models bring the evidence of significant synergism between rituximab and radiotherapy. Up to now, there are no clinical data about clinical benefit of rituximab addition to the IF-RT. This study compares IF-RT alone vs. IF-RT with rituximab in early-stages of FL. Methods Between 2005-2012, through the prospectively maintained multicentric database (Czech Lymphoma Group; CLG), we identified patients with stage I-II FL treated with IF-RT (dose ≥ 24Gy) or IF-RT (dose ≥ 24Gy) with rituximab or rituximab alone. Patients receiving IF-RT with chemotherapy were not included. Complete staging including CT (neck, thorax, abdomen and pelvis) and bone marrow biopsy was performed at diagnosis. We compared EFS and OS between these three treatment arms. Rituximab (4 doses á 375mg/m2) was administered prior start of radiotherapy in combined arm. The total doses of rituximab varied between 4-8 doses á 375mg/m2 in rituximab monotherapy subgroup as well as in combined arm. Response to treatment was evaluated with CT 6-12 weeks after last dose of therapy. Results For the study period, approximately 1700 pts. of FL were identified in CLG database; 101pts with stage I-II FL (grade 1-3A) were included in the analysis. 65 patient were treated with radiotherapy alone (RT), 14 pts. with rituximab alone (R) and 14 pts. received rituximab and radiotherapy (R+RT), 8 pts. were excluded because of incomplete data. Median follow up was 4.57 (2.25- 12.6) years since diagnosis. There were no differences of age, performance status, FLIPI, proportion of bulky or extranodal tumor. In subgroup treated with R+RT was higher proportion of FL grade 3A in comparison with R or RT alone arms (35% vs. 1.5% vs. 7.5%; p.007). Complete response rate was 92% in RT arm, 100% in arm with R+RT and 86% in group treated with R alone, difference did not reach statistical significance. Median of event free survival was 3.35years in RT group, not reached in R+RT arm and 5.1 years in patients treated with R alone. EFS differences are statistically significant (p.035), but with no impact on overall survival. Conclusions In spite of fact, that RT is considered to be a good initial treatment for localized FL, rituximab alone or better in combination with RT seems to give better results in terms of long-term global control of disease. Our preliminary results should be confirmed with other studies and longer follow up is needed to verify or not the impact of rituximab on survival in early stages of FL. The work is support by research grant NT/12193-5 and MHCZ-DRO FNBr65269705. Disclosures: Mayer: Roche: Consultancy, Research Funding; Glaxo: Consultancy, Research Funding. Trneny:Roche: Honoraria, Research Funding.

Introduction Results of randomized studies showed benefit of maintenance therapy with monoclonal anti-CD20 antibody (rituximab) in terms of time to progression (PFS) and overall survival (OS) in follicular lymphoma (FL). General recommendation, based on large clinical trial, is to give 2 years of rituximab maintenance á 375mg/m2every 2 months (12 doses) in first line setting. On the other hand, there are various rituximab maintenance schedules; however, the clear comparison of clinical efficacy is missing. Our retrospective analysis compared two different schedule of rituximab maintenance in first-line treatment of FL used in university centers participating on CLG registry. Methods Data were recruited from 1702 FL patients registered in the prospectively maintained multicentric database (Czech Lymphoma Group; CLG). For the analysis, patients with stage II-IV of new diagnosed FL (grade 1-3a) responding (complete or partial remission) to 6-8 cycles first-line RCHOP (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone) followed with rituximab maintenance (RM) were included. Completed planned maintenance was inclusion criterion. Patients with previous watch and wait or additional first line therapy (radiotherapy, other chemotherapy, transplant therapy) were excluded. Results Totally, 168 evaluable FL patients with median age 57ys (range 28-82) including 70 (41.7%) men treated with RCHOP + RM were found in CLG database. 52/168 patients received totaly 8 doses of rituximab maintenance every 3 months for 2 years (RM8 arm), whereas 47/168 patients were treated with totaly 12 doses (RM12 arm) of rituximab maintenance every 2 months for 2 years. All patients in both subgroups completed planned RM therapy. There was no difference in distribution of age, gender, FLIPI, grade, B-symptoms, bone marrow involvement, performance status, LDH and beta2microglobuline level between both arms. Induction treatment in terms of administered cycles CHOP (6xCHOP in 41/52 and 35/45 pts., for RM8 and RM12 arm) and rituximab doses (8xR in 48/52 and 41/45 pts., for RM8 and RM12 arm) was similar between arms (ns). There were 4/52 (7.7%) and 5/47 (10.6%) relapses in subgroups RM8 and RM12, with no statistical significance. Median PFS was 3.8 (2.1-5.8) years vs. 3.9 (2.4-7.8) years in RM8 and RM12 arms (not significant), and median OS 3.91 (2.2-6.94) years vs. 3.1 (2.48-8.6) years also with no statistical significance. Conclusion Our results show, that rituximab maintenance given every 2 or every 3 months for two years in first line treatment brings similar benefit to the FL patients in terms of remission duration and overall survival. Despite the fact, that presented data are retrospective observation, this is the first report comparing two different rituximab maintenance regimens in FL. Further prospective study and longer follow up are needed to confirm our preliminary data. This work was supported by grant NT/12193-5 and MHCZ-DRO (FNBr 65269705) Disclosures: Mayer: Roche: Consultancy, Research Funding; Glaxo: Consultancy, Research Funding. Trneny:Roche: Honoraria, Research Funding.

Follicular lymphoma is considered to be incurable disease, although rituximab introduction into the first line therapy has changed the outcome of the patients. Repeated relapses are observed and it is accepted, that each subsequent remission in the same patient has significantly shorter duration compared to the previous one (Gallagher, JCO 1986). We have addressed this question in the group of patients diagnosed and treated in the rituximab era. The interval 1999 till 2002 was chosen because in this time rituximab was already labeled for relapse treatment, but not for the first line treatment. Patients and method: Patients diagnosed as FL gr I, II, IIIa (central pathology review) and reported in the 6 centers during the period 1999–2002 were included into the analysis. The cohort consisted out of 176 pts. Median age at the 57.5 y(22–93), B symptoms were observed in 40 pts (2 missing), clinical stage (CS) I had 16 pts, II 32 pts, III 28 pts and IV 95 pts, PS WHO ≥ 2 in 25 pts(four missing), elevated LDH >n 60 pts (8 missing). FLIPI was estimated as poor risk in 52, intermediate risk in 46 and good risk in 66 pts. (13 missing). Median follow up is 7.5 years. Results: Ninety eight (55%) pts experienced 1st progression and 9 deaths without progression, 36 pts 2nd progression and 14 deaths w/o progression, 15 pts 3 rd progression and 6 death w/o progression and 9 pts 4th progression, therefore 176 were evaluable for 1st response, 98 pts were evaluable for duration of 2nd response, 36 for 3rd resp, 15 for 4th response. Median age was 57.5y at dg, 59y at 1st, 64y at 2nd, 66y at 3rd and 77y at 4th progression. The treatment data for the first line: 175 pts evaluable, 3 pts watch and wait (WW), anthracyclin based chemotherapy (A-th) 76%, fludarabine based chemotherapy (F-th) 5.2%, rituximab (R) 28.5%, radiotherapy (RT) 19.1%, ASCT 9.3%. 2nd line therapy: 93 pts available, WW 5pts, A-th 26%, F-th 13.6%, R 70.5%, RT 8.0%, ASCT 20.5%, AlloSCT 2.3%, 3rd line therapy: 35 pts evaluable, WW 3 pts, A-th 9.4%, F-th 28%, R 65.6%, RT 31.3%, ASCT and AlloSCT both 3.1%, 4th line therapy: 10 pts evaluable, WW 1 pt, A-th 1 pt, F-th 3 pts, R 7 pts, RT 3 pts. The significant increase in the relative number of rituximab treated pts in the subsequent treatment lines was observed. Median survival for the all pts PFS was 40 months, median OS not reached (79 month at 7 y). The medians of the time to progression (TTP) in subsequent responses (deaths w/o progression were excluded) were as follows: TTP1 49m, TTP2 43 m, TTP3 52m and TTP4 11m. There was no signifiant difference observed between TTP1, TTP2 and TTP3, but due the the very short TTP4 the overall significance was 0.05. Comparison of the PFS of subsequent lines revealed median PFS1 40 months, PFS2 30 months, PFS3 14 m and PFS4 11m. The difference between PFS1 and PFS2 was not significant, the subsequent PFS were significantly shorter for PFS3 and PFS 4 compared to the previous ones (p

Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status >1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.