ALBERT

Description: 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.

Description: Background: Follicular lymphoma (FL) is an indolent lymphoma with chronically relapsing disease course. Treatment of relapses with 2nd line regimens such as salvage and autologous stem cell transplant (ASCT) is considered successful, i.e. the relapse itself does not shorten life expectancy. However, LymphoCare registry study (Casulo et al., JCO 2015) identified an early progression of the disease (POD24, i.e. progression within 24 months after R-CHOP commencement) to be a strong unfavorable event. Early progressors experienced only 50% 5-year OS compared to 90% in the control group) irrespective of the salvage treatment delivered. It is unclear whether post R-CHOP maintenance immunotherapy (MAINT) decreases POD24 incidence. Potential predictors identifying patients at risk of POD24 have not been analyzed yet. Aims: (1) To analyze the impact of MAINT on POD24 occurrence, (2) to find clinically applicable predictors of POD24 at the time of FL diagnosis. Methods: The Czech Lymphoma Study Group (CLSG) database was searched using the LymfoCare (LC) study methodology for previously untreated FL grade I-IIIa patients (pts), CS II-IV (Ann Arbor), no watch-and-wait before R-CHOP. Early progressors were defined as pts with progression or relapse within 24 months after FL diagnosis. OS was calculated both from diagnosis and from the Risk-defining event (rdOS) - it means from the date of early progression (POD group) or 24 months after diagnosis (non POD group). We have identified 821 FL pts, who met the inclusion criteria above and were diagnosed before DEC-2014. Median age of the CLSG group (58 years; range 26-82 years) was identical to the LC group (58 years; 22-88). Fifty-eight percent were females (46% in LC) and 50.5 % had high risk FLIPI (44% in LC). 80.8% of our pts had FL grade I-II and 19.2% had FL grade IIIa (62% and 38% in LC, respectively) Results: Treatment response was available in all but 15 pts (99.9%): CR/CRu, PR and SD/PD was achieved in 70.0%, 25.5% and 4.5%, respectively. After median follow up of 5.02 years 244 (29.7%) pts relapsed or progressed and 101 (12.3%) of the pts died. Five year OS and progression-free survival (PFS) was 90.1% (95% CI 0.88-0.92) and 63.7% (95% CI 0.60-0.68), respectively. In total, 99 POD24 (12.3%) were identified in the whole cohort of 821 patients. Five-year OS without POD24 (93.8%) was superior to 5-year OS in the POD24 group (64.3%, p

Description: Abstract 2882 Absolute lymphocyte count (ALC) at time of diagnosis has been documented as an independent predictor of survival in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The optimal cut-off values of ALC are still a matter of debate. An extensive analysis of the prognostic impact of ALC in the elderly population treated with rituximab has not yet been carried out. Thus, we assessed the prognostic significance of different ALCs in unselected, newly diagnosed elderly patients with DLBCL in the population of the Central European region (the Czech Lymphoma Project registry). We analyzed data of 651 patients with confirmed DLBCL older than 59 years. Those with CNS involvement were excluded. The median age at diagnosis was 69 years (range, 60–97); the Ann Arbor stages were as follows: I (16.5%), II (26.1%), III (15.9%), and IV (41.5%). The IPI scores were: low (L) 19.8%, low-intermediate (LI) 26.6%, intermediate-high (IH) 24.3%, and high (H) 29.3%. We analyzed the prognostic value of lymphopenia with 3 different cut-off values. Values of ALC 〈 1.0 × 109/L and ALC 〈 0.84 × 109/L were chosen according to the previously published data, the third value was the median ALC at diagnosis (ALC 1.35 × 109/L). ALC 〈 1.0 × 109/L was observed in 201 (31%) and ALC 〈 0.84 × 109/L in 159 (24%) patients. ALCs below predefined levels were associated with higher (IH, H) IPI scores: ALC 〈 0.84 × 109/L (78% vs 46%, p 〈 0.001), ALC 〈 1.0 × 109/L (77% vs 43%, p 〈 0.001), and ALC 〈 1.35 × 109/L (68% vs 38%, p 〈 0.001); advanced disease (stages III/IV): ALC 〈 0.84 × 109/L (72% vs 53%, p 〈 0.001), ALC 〈 1.0 × 109/L (72% vs 51%, p 〈 0.001), and ALC 〈 1.35 × 109/L (66% vs 48%, p 〈 0.001); and low performance status (ECOG ≥ 2): ALC 〈 0.84 × 109/L (52% vs 27%, p 〈 0.001), ALC 〈 1.0 × 109/L (50% vs 25%, p 〈 0.001), and ALC 〈 1.35 × 109/L (43% vs 22%, p 〈 0.001). In 85% of patients, treatment was initiated with an anthracycline-containing regimen (CHOP), i.e. only 15% of patients recieved a non-anthracycline-based regimen (COP). The median number of chemotherapy cycles was 6. Chemotherapy was combined with rituximab in all patients (a median of 6 doses). Generally, treatment response was assessed in 544 (83.6%) patients. Complete remission (CR) or unconfirmed CR was achieved in 79.8% and partial remission in 12.5% of patients, with 7.7% of patients being classified as having stable disease or disease progression. CR rates were significantly higher in patients with higher lymphocyte counts: ALC 〉 0.84 × 109/L (82% vs 71%, p = 0.006), ALC 〉1.0 × 109/L (83.1% vs 71.7%, p = 0.008), and ALC 〉 1.35 × 109/L (85% vs 75%, p = 0.027). The overall survival (OS) and event-free survival (EFS) rates were superior in all subgroups of patients with higher ALC levels. The 3-year OS rates stratified by lymphocyte count: ALC 〉 0.84 × 109/L (67% vs 51%, p = 0.0002), ALC 〉 1.0 × 109/L (67% vs 52%, p = 0.0017), and ALC 〉 1.35 × 109/L (71% vs 55%, p = 0.0001). The 3-year EFS rates stratified by lymphocyte count: ALC 〉 0.84 × 109/L (61% vs 44%, p = 0.0002), ALC 〉 1.0 × 109/L (62% vs 44%, p = 0.0002), and ALC 〉 1.35 × 109/L (66% vs 47%, p 〈 0.0001). Only ALC 〈 1.35 × 109/L was found to be an independent negative prognostic factor for the OS (RR = 1.53, p = 0.006) and EFS (RR = 1.43, p = 0.013) in a multivariate analysis when compared with the LDH level, clinical stage, performance status and age (above median). In summary, the data support the hypothesis that host innate immunity is critical in tumor growth control and is a limiting factor for the efficacy of immunochemotherapy in elderly patients with DLBCL. The optimal cut-off levels of ALC may be different in various populations. This fact should be taken into account when designing new ALC-based prognostic schemes. Disclosures: Prochazka: ROCHE: Honoraria. Pytlik:ROCHE: Honoraria.

Description: Background Follicular lymphoma (FL) is a disease with very heterogeneous course ranging from the indolent forms to rapidly progressive cases with poor outcome. Optimal therapy in FL patients with high tumor burden is immunochemotherapy (R-CHOP is the most frequent regimen used), followed by maintenance treatment. Data from randomized prospective studies (PRIMA) showed poorer outcome in those with high risk disease in terms of lower CR rate, higher risk of relapse and lower efficacy of maintenance therapy. Data comparing up-front intensive approach in younger fit patients and R-CHOP are limited. Aim To analyze long term results of intensive treatment protocol (R-sequential chemotherapy) in comparison with age, FLIPI and maintenance delivery matched (R-CHOP) controls. Methods Here we analyzed data of 48 prospectively enrolled FL patients who were treated by sequential (R-SQ) chemotherapy with or without up-front autologous stem cell transplant (ASCT) as a part of stratified risk adapted treatment in one institution. For R-SQ regimen were indicated patients3mg/L and/or thymidine kinase〉15 IU/L) or HIGH-FLIPI patients (irrespective of additional risk factors). R-SQ protocol consists of alternating three cycles of etoposide-doxorubicine regimen (PACEBO), one methotrexate-ifosfamide regimen (IVAM), and one cycle of high dose cytarabine regimen (HAM). Remission was consolidated with 6th cycle of chemotherapy (PACEBO) in INT-FLIPI patients (n=22, 46%) or with ASCT with BEAM-200 conditioning (n=26, 54%) in HIGH-FLIPI patients. Maintenance immunotherapy was applied for historical reasons in 24 patients (50%). Controls were randomly selected from the Czech Lymphoma Study Group (CLSG) database from 626 cases with confirmed FL grade I to IIIa, treated with R-CHOP. Pair matching was performed on 1:3 basis, controls were matched by age, FLIPI and rituximab maintenance application. In the end, we analyzed intensive SQ-group (n=44) and standard control R-CHOP-group (n=144). Maintenance therapy was delivered to 24 patients (50%) in R-SQ group and to 72 patients (50%) in R-CHOP-group (P=1.00). Results Median age of SQ-group was 47.6 years compared to 48.7 years in R-CHOP (P=0.44), FLIPI index was equally distributed: INT-FLIPI (43% vs 43%), HIGH-FLIPI (57% vs 57%, P=1.00). Treatment response quality was higher in SQ-group than in R-CHOP-group: CR/CRu 93.8% vs 70%, PR 6.2% vs 23% and SD/PD 0% vs 8% respectively (P=0.01). During the follow-up, (median 3.5 and 6.1 years in R-CHOP and SQ-group respectively, P

Description: Background: Frontline therapy of Hodgkin lymphoma (HL) is strictly stage-adapted. Staging systems used are based on historical variables which only indirectly reflects tumor load (Ann Arbor stage) or lymphoma cytokine activity (systemic symptoms, erytrocyte sedimentation rate). With new, abbreviated interim PET-tailored chemotherapy schemes (2+2) and reduced radiotherapy protocols, there is a clinical need for precise staging tools. Last years have brought new insight into the prognostic role of metabolic quantitative PET parameters and HL-associated biomarkers. Total metabolic tumor volume (TMTV) measured using fluoro-deoxyglucose PET (FDG-PET) was found to be a predictor of therapy failure after frontline treatment (Kanoun 2014). Interestingly, TMTV was found capable of identifying poor responders within one (intermediate) staging group (Akhtari, 2018; Cottereau 2018). Serum concentrations of thymus and activation-regulated chemokine (TARC) and other cytokines have been proved to have prognostic significance in the patients treated both in the frontline and relapse setting (Moskowitz, 2015; Guidetti 2017). A relationship between pretreatment TMTV, baseline cytokines levels, and current staging systems has not been analyzed yet. Aim: To analyzed quantitative metabolic PET parameters and selected soluble biomarkers in the context of the staging systems used in the U.S. and Europe Methods: We have analyzed a prospectively enrolled cohort of forty-eight patients with HL who were diagnosed in two large university medical centers from 5/2015 to 2/2018. All pts have undergone pretreatment FDG-PET/CT with quantitative analysis of TMTV, Total Lesion Glycolysis (TLG), Maximum Standardized Uptake Volume (SUVmax.) and the Largest Tumor Diameter (LD) and were sampled for cytokine analysis within 16 (median) days from the PET/CT. We have analyzed a set of four serum biomarkers: CD30 (sCD30), CD163 (sCD163), TARC, and interleukin 6 (sIL6), which were measured using ELISA assays. Results: A cohort consisted of 22 males and 26 females with median age of 42 years (range 21-75). Histology subtype was known in all but one case: nodular sclerosis in 23, mixed cellularity 15, lymphocyte-rich in 5 and nodular-lymphocyte predominant (NLPHL) in four. Ann Arbor stages were as follows: I in 5, II in 20, III in 13 and IV in 10 of the pts with systemic symptoms in 20 (42%) of them. All pts were classified according to the German Hodgkin Study Group (GHSG) and NCCN staging systems. GHSG stages - limited, intermediate and advanced were seen in 8 (17%), 10 (21%) and 30 (62%) pts, respectively. NCCN stages were distributed into early favorable in 8 (17%), early unfavorable in 17 (35%) and advanced in 23 (48%) of the pts. Chemotherapy was applied in all but four pts using: BEACOPPesc, combined BEACOPP+ABVD, ABVD and ABV/COPP protocols in 7, 15, 16 and six pts respectively. Of four pts without chemo one case was treated with local radiotherapy and three with WaW (all of them with NLPHL). Treatment response was known in 41 (85%) of the cases with CR, PR, and PD in 33 (80.5%), 6 (14.6%) and two (4.9%) pts, respectively. Relationships between disease stages and PET-parameters are summarized in Table 1. Briefly, metabolic tumor burden (TMTV, TLG) identified two markedly different groups: low and intermediate/high risk. Similarly, cytokines levels were significantly lower in low-risk patients compared to those with intermediate-high risk (Table 2). Treatment outcome did not correlate either with GHSG nor NCCN stage. We found correlation of sIL-6 (p=0.03) but not sCD30 (p=0.09), sCD163 (p=0.14) and TARC (p=0.57) with CR achievement. In terms of PET-parameters the high TMTV〉104 cm3 (P=0.046) and TLG〉798 (P=0.003) were associated with not achieving of CR with NPV, PPV and test accuracy of 94.4, 22.0, 58.5 for TMTV and 100%, 36,4%, 66% for TLG, respectively. Conclusion: Adequate frontline treatment policy is vital for achieving an optimal balance between efficacy and toxicity. Current staging systems have a weak correlation with metabolic tumor burden: one-third of those recognized as advanced stage have the low burden, and vice versa about a half of intermediate-risk pts have high tumor burden. Combination of TMTV/TLG and cytokines can be currently used for decision making in borderline stage cases and probably could serve as a backbone for a new staging system in the future. Acknowledgment: IGA_LF_2018_004, MH CZ-DRO (FNOL, 00098892) Disclosures No relevant conflicts of interest to declare.

Description: 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

Description: Background: Classical Hodgkin lymphoma (cHL) is the most common lymphoid malignancy under the age of 30. Despite the relatively high curability, about 20-30% of patients relapse after front-line therapy. Since the International Prognostic Factors Project score became obsolete in the era of dose-intensive regimens (BEACOPP), a clinically applicable tool for outcome prediction is lacking. Recent years have brought much novel information about close Hodgkin/Reed-Sternberg (HRS) microenvironment cross-talk promoting tumor growth. Many studies have tested the predictive value of microenvironment cells using immunohistochemistry but none have been concerned with HRS cell density. Aim: To assess the prognostic role of HRS cell density in lymph node biopsies using a novel automated system for scanning large tumor sample areas in cHL patients. Methods: Thirty-eight high-quality tissue samples obtained at time of cHL diagnosis were analyzed. The median age at diagnosis was 35 (17.5-93) years; the male-to-female ratio was 0.66:1. The lymphoma subtypes were nodular sclerosis (NS) in 25 (66%) and mixed cellularity (MC) in 13 (34%) patients. At the time of analysis, detailed baseline clinical information was available in 35 (92%) patients. Ann Arbor stages I through IV were observed in 2, 18, 9 and 6 patients, respectively. Systemic symptoms were present in 26 (75%) cases and large lymphoma mass (≥5 cm) was detected in 19 (56%) patients. German Hodgkin Study Group stages were: limited in 4 (12%), intermediate in 8 (23%) and advanced in 23 (66%) patients. Chemotherapy was given to 35 patients (92%): BEACOPP in 20 (57.1%), ABVD in 6 (17.1%), Stanford V in 4 (11.4%) and other (COPP, COPP/ABV) in 5 (14.3%) cases. Involved-field radiotherapy was applied in 11 (29%) cases. Tissue array analyses were performed using the TissueFAXS (TissueGnostics, Austria) system combining detailed morphologic information offered by microscopy with the scientific accuracy of multi-channel flow cytometry. Data were analyzed with TissueQuest software. Paraffin-embedded biopsies were prepared from pre-selected diagnostic samples stained with hematoxylin-eosin for morphology analyses and using CD30 (HRS) for cell density analyses. Each sample was previewed by the scanning software and only significant tumor tissue was manually gated by an experienced pathologist for further analyses. Fibrotic (≥10%), necrotic or residual lymphatic structures were excluded. Results: After treatment, 31 (82%) patients achieved complete remission, three partial remission, one stable disease and three patients progressed. After a median follow-up of 64.3 months, 9 (24%) patients relapsed or progressed and 7 (18%) of them died. Five-year overall survival (5-y OS) reached 81.0% (95%CI 0.68-0.94); 5-year progression survival (PFS) was 68.3% (95%CI 0.53-0.83). Tissue data: The mean scanned area covered 27.2±13.5 mm2 with the mean (median) total number of cells 461,504±286,491 (466,138). The mean (median) total cell density and CD30+ HRS cell density were 17,886±7,884 (16,557) and 279±232 (181) cells per mm2, respectively. Total cell density was 1.28-fold higher (p=0.14) and HRS cell density 1.44-fold (p=0.19) higher in MC compared to NS. HRS cell density did not correlate with sex (p=0.46), systemic symptoms (p=0.38), tumor bulk (p=0.34) or Ann Arbor stage (p=0.59). There was a trend for older age among low HRS cell density (below the median) patients (p=0.19). Low HRS cell density was associated with inferior 5-y PFS (44.4% vs 90.0%, p=0.0024) and OS (57.5% vs 100%, p=0.002). Multivariate Cox regression identified low HRS cell density as an unfavorable prognostic factor for PFS (p=0.037, HR=5.50) independent of age and lymphoma subtype. Conclusions: This is the first evidence about the possible predictive role of HRS cell density in cHL patients. Low density at diagnosis was associated with 5.5-fold higher risk of lymphoma progression or death. Automated image analysis is a new tool overcoming technical limitations caused by small (microarray) samples in lymphomas with high intra-tumor heterogeneity. Further analyses will define the role of HRS cell analysis in cHL in the context of risk-adapted and CD30-targeted therapies. Acknowledgment - Supported by: Palacky University Olomouc (IGA-LF-2015-001), Takeda Restricted Educational Grant and J. W. Fulbright Commission. Figure 1. Figure 1. Disclosures Prochazka: Takeda: Research Funding.

Description: Background: It has been demonstrated that rituximab with chemotherapy improves the outcome of older pts with DLBCL (Coiffier 2000, 2002, Habermann 2003) regardless risk category as well as the outcome of young patients with low IPI risk (Pfreundschuh, 2004). There is a lack of data on the impact of rituximab in high risk young patients. We have analyzed the outcome of young patients with DLBCL registered in Czech Lymphoma Study Group registry. Patients: 422 pts with newly diagnosed DLBCL younger than 60y have been registered between Jan 1999- Aug 2004. Pts with primary CNS lymphoma, pts with missing data, without anthracyclin based therapy were excluded from the analysis. Total 376 pts were analyzed. All patients received anthracyclin based therapy, 120 received rituximab (R-CT) and 256 chemotherapy only (CT). There were no significant differences between both group, R-CT and CT resp. Age median was 47.5y and 49y. Advanced CS was found in 73 pts (60.8%) and in 137 (53.5%), higher LDH was in 72 pts (60%) and 133 pts (51.9%), extranodal involvement was found in 76 pts (63.3%) and in 66 (25.8%) pts. The aaIPI risk distribution was as follows (R-CT vs CT): low risk 31 (25.8%) and 96 (31.5%), low-intermed. 34 (28.3%) and 70 (27.3%), intermed.-high 38 (31.7%) and 55 (21.5%), high 17 (14.2%) and 35 (13.7%). CHOP reg was used in 79 (65.8%) and 186 (72.7%) resp., intensified CHOP or CHOP with other combination was used in 36 (30.0%) and 52 (20.3%), other CT was used in 1 (0.8%) and 18 (7.0%). HDT with ASCT was used in 38 (32.2%) and 55 (22.0%) (ns). The median follow up was 22 m for R-CT and 44 m for CT group. Results: The estimates for 2y PFS was 85.5 % for R-CT and 66.4% for CT group resp. (p 0.0001). The estimates for 2y OS was 90.7% and 77.6% resp. (0.0007). The differences were significant in low risk (L and LI) as well as high risk (IH and H) group. PFS at 2y was 93.4% and 80.2% resp (p 0.005) and OS was 96.9% and 88.8% resp. (0.02) for low risk group. PFS at 2y was 75.8% and 41.8% resp. (0.0003) and OS was 83.4% and 57.0% resp. (0.0007) for high risk group. Conclusion: We have demonstrated the significance of rituximab combination with CT in young pts with DLBCL in this comparison. Rituximab has significant impact both in low risk pts (consistent with MINT data) as well as in high risk young pts, which has not been described in any prospective trial yet. Figure Figure