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Twenty percent of patients with high-tumor-burden (HTB) follicular lymphoma (FL) develop progression/relapse of disease (POD) within 24 months of frontline immunochemotherapy. Unfortunately, about 50% of these patients die within 5 years since POD event. Rituximab maintenance was proven to reduce relapse rate in responding FL, but its role on preventing POD was not defined. We analyzed 1360 HTB-FL patients from the Czech Lymphoma Study Group registry treated with frontline rituximab-containing regimen. Of those, 950 cases received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and achieved complete or partial remission: 712 patients received rituximab maintenance (MAINT) and 238 were a historical observational cohort (OBS). We have proposed a modified POD24 (mPOD24) endpoint for the chemosensitive patients calculated from the end-of-induction (EOI). Survival rates since EOI were as follows: 5-year overall survival (OS) 86.2% versus 94.5% in the OBS and MAINT groups, respectively (

Relapsing diffuse large B cell lymphomas (rDLBCL) represent a heterogeneous disease. This heterogeneity should be recognized and reflected, because it can deform the interpretation of clinical trial results. DLBCL patients with the first relapse and without CNS involvement were identified in the Czech Lymphoma Study Group (CLSG) database. Interval-to-therapy (ITT) was defined as the time between the first manifestation of rDLBCL and the start of any treatment. The overall survival (OS) of different ITT cohorts ( 7 vs. 7-21 vs. 21 days) was compared. In total, 587 rDLBCLs (51.8% males) progressed with a median of 12.8 months (range 1.6 to 152.3) since the initial diagnosis (2000-2017). At the time of relapse, the median age was 67 years (range 22-95). First-line therapy was administered in 99.3% of the patients; CHOP and anti-CD20 were given to 69.2% and 84.7% of the patients, respectively. The salvage immune/chemotherapy was administered in 88.1% of the patients (39.2% platinum-based regimen). The median ITT was 20 days (range 1-851), but 23.2% of patients initiated therapy within 7 days. The 5-year OS was 17.4% (range 10-24.5%) vs. 20.5% (range 13.5-27.4%) vs. 42.2% (range 35.5-48.8%) for ITT 7 vs. 7-21 vs. 21 days (p 0.001). ITT was associated with B symptoms (p 0.004), ECOG (p 0.001), stage (p 0.002), bulky disease (p 0.005), elevated LDH (p 0.001), and IPI (p 0.001). The ITT mirrors the real clinical behavior of rDLBCL. There are patients (ITT 7 days) with aggressive disease and a poor outcome. Conversely, there are rDLBCLs with ITT ≥ 21 days who survive for a long time.

The aim of this study is to assess the incidence, risk factors, and outcome of biopsy-proven transformation in follicular lymphoma (FL) patients in the rituximab era. Transformation was analyzed in 1233 patients with initially diagnosed FL grades 1–3A, identified between 2002 and 2012 in the prospectively maintained Czech Lymphoma Study Group database. Only patients with histologically proven transformation (HT) were included. HT occurred in 58 cases at a median of 3.0 years from the initial FL diagnosis; the HT rate was 4% at 5 years. Transformation occurred most frequently at the first relapse (84% patients). Median OS from the HT was 2.5 years (95% CI 0.4–4.6) and 6-year OS with HT was shorter compared to all FLs (60 vs. 83.9%; 95% CI). A bulky tumor (≥ 10 cm), increased lactate dehydrogenase, age ≥ 60 years, and International Prognostic Index (intermediate/high risk), but not Follicular Lymphoma International Prognostic Index, were associated with transformation (p

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.

Rituximab maintenance (RM) improves time to progression (PFS) in advanced follicular lymphoma (FL), but the impact of various RM schedules remains unknown. This study performed a retrospective evaluation of RM given for up to 2 years vs observation in 319 untreated FL patients (stage II-IV; grade 1-3A) responding to RCHOP induction and a comparison of two different RM schedules (RM8=eight doses given every 3 months and RM12=12 doses given every 2 months). A total of 183 patients received RM and 136 patients were observed; 5-year PFS was better in the RM arm, 74.1% vs 52.3% (p

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.

Peripheral T cell lymphomas (PTLs) have a globally poor prognosis. The CHOP regimen shows insufficient efficacy; first-line consolidation with autologous stem cell transplantation (auto-SCT) is a promising strategy but has never been confirmed by randomized data. We analyzed retrospectively 906 patients diagnosed with PTL between 1999 and 2015. Chemotherapy was given to 862 patients, and 412 of them were

The rituximab maintenance (RM) therapy for follicular lymphoma is effective and clinically well tolerated, however there is limited data regarding this from the elderly segment of the population. This analysis was performed to evaluate the efficacy of RM in elderly patients 65 years of age and older and to assess the influence of the induction therapy with immunochemotherapy (R-CHEMO) on the treatment outcome in a real world setting. A total of 232 consecutive patients treated with first-line R-CHEMO and RM (RM1 group; n = 158) or observation (RM0 group; n = 74) were analyzed. The effect of which induction therapy (R-CHOP vs. R-CVP) and the response of the patients to the first-line therapy were also evaluated. The addition of RM improved the treatment results in elderly patients. The 5- year overall survival rate in patients receiving R-CHEMO + RM1 compared to patients receiving R-CHEMO + RM0, was 83.7% (95% CI 76.1–89%) and 64.3% (95% CI 51.8–74.3%), respectively, p = 0.0012. The induction therapy with R-CHOP was found to be more effective than R-CVP but it is necessary to point out higher age of patients in the R-CVP arm. The 5- year overall survival rate in patients using R-CHOP ± RM and R-CVP ± RM was 84.9% (95% CI 77.5–90%), and 65.0% (95% CI 50.1–76.4%), respectively, p = 0.0008. The patients who achieved CR + uCR after having received first-line therapy had better outcomes compared to patients in PR. The 5- year overall survival rate in uCR + CR patients treated with R-CHEMO + RM1 and PR patients treated with R-CHEMO + RM1 was 90.6% and 68.3%, respectively, p = 0.0019. Rituximab maintenance treatment in patients 65 years and older yielded improved survival rates in a real world clinical setting. The R-CHOP regimen seems to be a more effective induction agent than R-CVP but the outcome of less intensively treated patients with R-CVP + RM is also acceptable. The achievement of uCR + CR after first-line therapy is associated with a better outcome.

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.

Early-stage follicular lymphoma (FL) has traditionally been treated with involved-field radiotherapy (RT). Rituximab (R) is a low-toxic, efficient systemic therapy for FL, but there are no data about its clinical impact in early FL. We retrospectively analyzed 93 patients with stage I–II indolent FL treated with RT (n = 65) or RT + R (n = 14) or R alone (n = 14). Median follow-up was 5.0 years for patients with RT, 2.8 years for the RT + R subgroup and 2.5 years for patients treated with R. The complete response rate was 92%, 100% and 86% (not significant) and the median PFS was 3.3 years, not reached and 4.9 years (p = 0.035) for the RT, RT + R and R arms, with no impact on overall survival. R combined with RT seems to give better results in terms of global FL control, but longer follow-up and prospective comparison are needed to verify these results.

We have studied the feasibility and efficacy of intensified R-MegaCHOP-ESHAP-BEAM therapy in high-risk aggressive B-cell lymphomas. Altogether 105 patients (19-64 years) with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBL) or follicular lymphoma grade 3 (FL3) with an age-adjusted International Prognostic Index of 2-3 were recruited. Treatment consisted of three cycles of high-dose R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), followed by three cycles of R-ESHAP (rituximab, etoposide, methylprednisolone, cytarabine, cisplatin) and high-dose consolidation with BEAM (BCNU, etoposide, cytarabine, melphalan) and autologous stem cell transplant. The 5-year progression-free survival (PFS) was 72% (DLBCL 60%, PMBL 89%) and overall survival (OS) was 74% (DLBCL 61%, PMBL 89%) after a median follow-up of 85 months. However, an independent prognostic factor was age only, with patients ≤ 45 years having 5-year PFS 90% and patients45 years having PFS 54%. PMBL had better prognosis than DLBCL/FL3 in patients45 years (PFS, 88% vs. 48%), but not in younger patients (PFS, 91% vs. 94%).

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.

Although a prognostic model (MIPI, Mantle Cell Lymphoma International Prognostic Index) for patients with mantle cell lymphoma (MCL) has been established, its clinical significance for daily practice in the rituximab era remains controversial. Data of 235 unselected patients with MCL from the Czech Lymphoma Project Database were analyzed. MIPI, simplified MIPI (s-MIPI) and Ki-67 proliferation index were assessed for all patients and for a subgroup of 155 rituximab-treated (RT) patients. MIPI divided all patients into subgroups of low-risk (22%), intermediate-risk (29%) and high-risk (49%), with median overall survival 105.8 vs. 54.1 vs. 24.6 months, respectively (p < 0.001). s-MIPI revealed similar results. The validity of both indexes was confirmed in RT patients. We confirmed the Ki-67 index to be a powerful single prognostic factor for overall survival (64.4 vs. 20.1 months, p < 0.001) for all patients and for the RT subset. Our results confirm the clinical relevance of MIPI, s-MIPI and Ki-67 for risk stratification in MCL also in the rituximab era.

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.

Background. According to the gene expression profiling studies, mediastinal variant of DLBCL is closely related to classical Hodgkins lymphoma (HL). As dose-intensive chemotherapy markedly improves survival in advanced HL, we investigated whether the same is true for high-risk mediastinal DLBCL. Methods. Since 1998, three studies utilising dose-intensive chemotherapy with ASCT for high-risk DLBCL (aaIPI 2–3) were conducted by Czech Lymphoma Study Group. From 1998–1999, patients were induced with 3–4 cycles of MegaCHOP every 3 weeks (Cyclophosphamide, 3 g/m2 d 1, Vincristin 2 mg d 1, Doxorubicin 75 mg/m2 d 1, Prednison 60 mg/m2 d 1–5, G-CSF 5 ug/kg from day 6) and consolidated with BEAM and ASCT (Protocol 1). From 2000–2002, patients received 3 cycles of MegaCHOP, followed by 3 cycles of ESHAP and BEAM with ASCT (Protocol 2). From 2002, 4–6 doses of Rituximab 375 mg/m2 were added to the previous regimen (Protocol 3). Outcome of patients with mediastinal DLBCL was compared with outcome of other DLBCL patients treated by the same protocols with log-rank test. Results. 24 patients with mediastinal DLBCL with at least 12 months follow-up were identified. Their median age was 26 years (range, 21–59) and 15 of them were women (62%). 88% of patients had stage IV disease based on extensive pulmonary, pleural or pericardial involvement and 25% of patients had subfrenic disease. LDH was elevated in 88% of cases. Nine patients were aaIPI 2 (38%) and 14 patients aaIPI 3 (58%). Five patients were treated with Protocol 1 (21%), 9 with Protocol 2 (37%) and 10 with Protocol 3 (42%). 22 patients (92%) were successfully mobilized after one of the induction cycles with median 8.03x106 CD34+ cells/kg collected and 21 of them were transplanted as a part of primary treatment (88%). After chemotherapy and ASCT, there were 18 CR (75%) and 4 PR (17%). Twenty patients (84%) were further consolidated by mediastinal radiotherapy because not being in CR or because of bulky disease at diagnosis. Overall, 21 patients achieved CR and one achieved PR at the end of the treatment (ORR, 92%). Two patients progressed on treatment and two other relapsed; three of these were salvaged by additional therapy. After median follow-up of 31 months (12–70), the 3-year FFS is 87% and OS is 95%. Compared with other DLBCL patients, patients with mediastinal DLBCL had significantly better 3-year survival (95% v. 64%, p = 0.007). Conclusion. Dose-intensive chemotherapy in high-risk mediastinal DLBCL patients leads to equally good results as in advanced Hodgkins lymphoma patients. Further studies are needed with aim to reduce the treatment burden while maintaining the efficacy of the therapy.

Background: MCL is a distinct lymphoma entity with improved outcome achieved by the introduction of rituximab, high dose Ara-C and autologous stem cell transplantation (ASCT) into the first line therapy. The outcome of the relapsed patients (pts) remain however poor and there is little data on the outcome after subsequent relapses and there is no information on secondary MIPI prognostic value. Aim: To analyze the outcome of the MCL patients after first line treatment failure and to evaluate the prognostic role of the sec MIPI which is MIPI calculated at the time of relapse/progression. Methods: This analysis is a part of the Lymphoma project in which consecutive lymphoma patients are registered since the year 1999. Altogether 519 newly diagnosed MCL patients were registered in 5 university centers and 9 regional departments between 1999 and 2011. Patients who were treated with rituximab as part of the first line treatment (n=388) were included into the analysis. The diagnoses were confirmed according to WHO classification in the reference pathology centers. The median follow up is 4.5 years. Results: The whole cohort consists of 261 males and 127 females (2.1:1) with median age 65 y (28-87), the majority of pts had advanced disease (CS IV in 81.6% pts), PS ECOG ≥ 2 in 23.6% pts, elevated LDH in 52.5% of pts. The MIPI risk profile was as follows: low risk 21.7%, intermediate risk 27.2% and high risk in 51.1%. All pts received rituximab as part of the induction, 48.7% pts received CHOP, 5.7% alternation of CHOP and HD Ara-C, 26.2% intensive induction with HD Ara-C, 10.3% CVP, 6.4% FC. High dose therapy with ASCT was performed in 23.9% of pts. The ORR was 89.0% with 63.8 CR/CRu, 6.3% had stable disease and 4.9% were primary progressive. The PFS and OS were 2.9 y and 5.5 y with significant impact of MIPI risk (p Conclusions: Our analysis of relapsed MCL patients shows that 1: Median PFS from the Dg was 2.9 y but each subsequent relapse resulted in significantly shorter PFS median 12.1, 6.8 and 4.9 months resp. 2: The median OS from Dg was 5.5y but after each relapse it became shorter - 15.7 m, 7.4 m and 5.5 months resp. 3: The sec MIPI at the time of relapse discriminates the groups with significantly different prognosis. Disclosures No relevant conflicts of interest to declare.

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

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.

Introduction: Mantle cell lymphoma (MCL) is considered to be an incurable disease with a poor prognosis, but the prognosis can be significantly different among the patients. The new prognostic index MIPI (MCL International Prognostic Index) has been proposed recently (Hoster ASH 2006, Blood 2008). Three prognostic groups with different survival (low-risk, intermediate-risk and high-risk) can been identified, based on four variables: WBC count, ECOG performance status, LDH and age. Aim: To validate MIPI on an independent unselected cohort of newly diagnosed patients with MCL in the Czech Lymphoma Study Group (CLSG) registry. Methods and patients: Out of 293 patients with MCL diagnosed and registered in the period 1999–2007, 149 patients had central pathology review and confirmation of MCL diagnosis and were eligible for the analysis. The age median was 65 year (24–86), 63% were male (M:F ratio 1,7:1). Most of patients were diagnosed in advanced Ann Arbor stage IV (82%), limited stages I+II formed only 10,5%. The bone marrow was involved in 75% of cases. B-symptoms were present in 45% patients, LDH level elevated in 51%, poor performance status (ECOG 2–4) in 21% and the median leukocyte count was 7,9 ×109/L. A chemotherapy was used as a first line treatment in 144 patients, the combination with rituximab (R) in 106 ones (73%). The most used regimens were hyperCVAD/MTX-HDaraC (30x), R-CHOP (30x), CHOP (19x), R-FC (13x), then R-maxiCHOP/HDaraC (12x), R-CHOP/HDaraC (9x), COP (8x) and others. A consolidation of the first remission with high-dose chemotherapy and autologous stem cell transplantation was used in 12 patients, and an allogeneic transplantation in 2 patients. A first-line radiotherapy was used in 14 patients. Median follow-up is 31 months. Results: Median overall survival (OS) in the whole group of confirmed MCL patients was 58 months, median progression-free survival (PFS) was 24 months. The MIPI index can be calculated for 148 patients, 28% of them belong to low-risk (LR), 35% to intermediate-risk (IR) and 37% to high risk (HR) group. All clinical stages were included. Our comparison of survival curves according to MIPI risk groups confirms a different prognosis – the median OS in the LR group was not reached, in the IR group is the median OS 58 months, and in the HR group 25 months (p < 0,0001). The 3-year OS probability for LR, IR and HR group is 82%, 62% and 31%, resp. Similarly, median PFS in the LR, IR and HR group is 45, 24 and 13 months, resp. (p < 0,0001). The analysis of rituximab-treated subgroup was performed as well, with a significant difference between the three groups regarding to OS and PFS. The 3y OS probability for LR, IR and HR group is 82%, 63% and 37%, the median OS for LR and IR was not reached, for HR is 31 months (p Conclusion: Our retrospective analysis confirms a validity of the MIPI prognostic model even in a non-selected population of patients with MCL. This prognostic index seems to be valid also in the era of rituximab. Figure Figure

Background. Aggressive lymphomas with high-intermediate to high risk according to IPI or age-adjusted IPI (aaIPI) have approximately 50% probability of disease progression in two years. Previous studies of CLSG have shown that intensive induction chemotherapy combined with high-dose chemotherapy and autologous stem cell transplant (ASCT) might be benefitial in these patients (Trneny, Blood98(11) 682a, 2001). In current study, we have explored the efficacy and tolerability of this regimen in combination with antiCD20 antibody rituximab (R) for DLBCL with 2 or 3 risk factors according to aaIPI. Methods. DLBCL patients of age 18–65 years and aaIPI 2 or 3 were eligible for the study. Treatment protocol consisted of three cycles of high-dose CHOP (MegaCHOP, cytoxan 3 g/m2, doxorubicin 75 mg/m2, vincristin 2 mg, and prednison 300 mg/m2 every 21 days with G-CSF support), followed by three cycles of ESHAP and BEAM with ASCT. Peripheral progenitor cells were collected after first cycle of ESHAP. Four to six doses of R 375 mg/m2 were given on day 1 of induction chemotherapy. As four treatment-related deaths occured in first twenty patients, prephase consisting of AOP (MegaCHOP without cytoxan) was incorporated into the treatment regimen from mid-2003. Results were analysed with intend-to treat approach. Kaplan-Meier curves were constructed for survival analyses. Results. 57 patients were treated from 2002–2004. Median age was 42 years (range, 21–64), and 34 patients were males (60%). 39 patients (67%) had aaIPI 2 and 18 patients (33%) had aaIPI 3. 17 patients had mediastinal variant of DLBCL (30%), and 40 patients (70%) had DLBCL-other. Of 54 evaluable patients, 47 achieved CR or CRu (87%), 5 achieved PR (9%) and two progressed less than three months after treatment completion (4%). Six patients died due to treatment related toxicity (11%), four of them treated without prephase. Three other patients have life-threathening complications (6%). Only one patient (2%) progressed more than one year after study entry. Both 2-year actuarial overall survival (OS) and 2-year event-free survival (EFS) are 79% after median follow-up of 13 months and are not different for aaIPI 2 or 3 patients. Conclusion. Intensive induction chemotherapy combined with rituximab and ASCT is an effective strategy for treatment of young and high risk patients with CD20 positive DLBCLs. The two-year survival rates are higher than expected especially for aaIPI 3 patients. However, the toxicity is quite severe and the advantage of this regimen is to be proven in randomized trials.

Objectives. Both high-dose induction and front-line ASCT have been tested for improvement of treatment results in younger patients with aggressive lymphomas. Since 1998, Czech Lymphoma Study Group is testing these approaches in Phase II prospective studies. We present mature data from two studies conducted in the pre-Rituximab era. Methods. In 1998–1999, patients up to 65 years of age with all types of aggressive lymphomas except Burkitt and lymphoblastic lymphoma and age-adjusted (aa)IPI 2 or 3 were recruited to MegaCHOP-BEAM protocol, which consisted of 3–4 cycles of high-dose CHOP (cyclophosphamide, 3 g/m2, adriamycine, 75 mg/m2, vincristine, 2 mg and prednisolone 300 mg/m2 + G-CSF every two weeks) followed with BEAM and ASCT. From 2000, 3 cycles of MegaCHOP were followed with 3 cycles of ESHAP and BEAM consolidation. Peripheral blood progenitor cells were collected after 2nd or 3rd MegaCHOP in first and after 1st ESHAP in the second protocol. Analyses were performed on intention to treat principle. Results. 21 patients were recruited to MegaCHOP-BEAM and 30 patients to MegaCHOP-ESHAP-BEAM protocol, respectively. Median age was 41 years (range, 21–66 years), 29 patients were males (57%). 47% of patients had diffuse large B-cell lymphoma (DLBCL), 33% primary mediastinal B-cell lymphoma (PMBCL), 16% peripheral T-cell lymphoma and 4% grade 3 follicular lymphoma. 53 % of patients had aaIPI 2 and 47% of patients had IPI 3. Overall response rate was 93% and 70% of patients achieved complete remission. Treatment related mortality was 4% (2 patients). 67% of patients proceeded to transplant and in 21%, protocol was changed because of toxicity. Median follow up is 63 months (range, 32–96) for living patients. Median overall survival or progression-free survival have not been reached and actuarial overall survival is 66 ± 13% in three years with no differences between the two protocols. Patients with PMBCL had better outcome than patients with DLBCL and patients of other histologies (3-year survival 94% v. 60% v. 30%, p = 0,001). Interestingly, patients with aaIPI 3 apparently benefited from addition of ESHAP (3-year survival 77% in MegaCHOP-ESHAP-BEAM v. 30% in MegaCHOP-BEAM, p = 0,03) while aaIPI 2 patients had the same survival with both protocols. Omission of ASCT or protocol change because of toxicity did not seem to influence patients outcome. Conclusions. Full-lenght intensified induction improved treatment results in high-risk patients with aggressive B-cell lymphomas, particularly with aaIPI 3, while ASCT did not seem to have an impact. For T-cell lymphomas, other treatment strategies have to be sought.