ALBERT

Description: Beside the rare true leukemic forms of follicular lymphoma (FL), low levels of circulating tumor cells (CTC) are detected by PCR in the vast majority of FL patients at diagnosis. By a regular recirculating process, those CTC could reflect the total solid tumor mass. Alternatively, they could represent a subpopulation of tumor cells with distinct molecular profile including adhesion molecules and, as such, could add to the prognostic value of solid tumoral mass previously reported in FL (Dupuis, JCO 2013). In order to address these issues, we retrospectively selected FL patients treated in our institution between 2007 and 2014 who were simultaneously evaluated for both t(14;18) cells in peripheral blood (PB) and FDG-PET/CT tumor mass at diagnosis or at relapse. Absolute quantification of t(14;18) positive cells was performed using quantitative droplet digital PCR (ddPCR). Total metabolic tumor volume (TMTV) and total lesion glycolysis (TLG) were calculated from FDG-PET/CT, and baseline clinical characteristics and outcomes were collected. One hundred fourteen patients fulfilled the inclusion criteria. Using a routine 10-4 sensitive biomed 2 t(14;18) PCR assay, 75 had a positive PCR, either in peripheral blood alone (n=37), in peripheral blood and tumor biopsy (n=27) or in tumor biopsy but not PB (n= 11). Absolute quantitative ddPCR was performed for the 56 t(14;18) MBR+ patients. Clinical characteristics are given in Table 1. Median CTC value (number of t(14;18) positive cells out of total peripheral blood nucleated cells) was 1.6 10-3 (range 0-0.96), with only 5 CTC (-) patients and 13 patients with 〉10% CTC . Median TMTV was 267 cm3 (range 4.61-1900) and median TLG was 1473 (range 10.24-5912). A positive correlation was found between number of CTC and TMTV (R2 = 0.49; P 432 cm3 and TLG 〉 2717 tend to be associated with poorer OS (Fig. 2). The combined presence of 〉 6% CTC and TLG 〉 2717 allowed to identify a group of patients with 3-year OS of 71%, compared with 100% when both criteria were negative or dissociated (P= 0.01) (Fig. 2). In the subset of 42 patients with an untreated and untransformed FL, incremental prognostic value of circulating mass and metabolic tumor burden remained significant (P=0.03). Disclosures Dupuis: ABBVIE: Membership on an entity's Board of Directors or advisory committees; ROCHE: Speakers Bureau.

Description: Background: The prognostic value of COO classification by immunohistochemistry (IHC) for de novo untreated advanced DLBCL remains controversial after Rituximab-based frontline therapy. Other biomarkers such as BCL2 or MYC protein expression have been proposed to predict survival. IHC characteristics were investigated in a large multicenter randomized study. Methods: Three hundred twenty-three patients (pts) younger than 60 years with de novo untreated advanced DLBCL were randomized in the french prospective multicenter trial GOELAMS-075 to receive either 8 courses of RCHOP14 (n=161) or 2 courses of RCEEP (Rituximab, Cyclophosphamide, Eldisine, Epirubicine, Prednisone) and 1 course of Rituximab-Methotrexate-Cytarabine (RMC) followed by intensive BEAM conditionning with autologous transplant (ASCT) (n=162) upon negative interim PET-CT (visual analysis). In case of positivity, salvage regimen followed by ASCT was applied. Three years Event-free-survival (3y-EFS) was the primary endpoint. Event was defined by interim PET-CT positivity, progression or relapse, or death from any cause. Central pathology review confirmed de novo DLBCL diagnosis for 300 pts (93%). COO determination using Hans algorithm, BCL2 protein expression (clone 124, Dako) and MYC protein expression (clone Y69, Abcam) were recorded. Cut-off values were 70% for BCL2, and 40% for MYC. Results: COO analysis could be performed for 125/161 pts in RCHOP arm and 134/162 pts in intensive regimen arm including 36 and 34 Primary-Mediastinal-B-Cell subtype (PMBL) respectively. Repartition of non-PMBL was: 33/89 (37%) Germinal-Center subtype (GC), 56/89 (63%) Non-Germinal-Center subtype (NGC) in R-CHOP arm; 48/100 (48%) GC, 52/100 (52%) NGC in intensive regimen arm. Of 70 PMBL there were 50 NGC, 4 GC and 16 NE equally distributed in both arms. Clinical characteristics were similar in both GC and NGC subtypes, whereas PMBL presented with more frequent bulky disease and predominantly female gender. BCL2 ≥70% and MYC ≥40% were found in 147/285 (55%) and 85/185 (46%) of available samples, without difference between two arms. No correlation was found between BCL2 or MYC protein expression and GC or NGC subtype, however there were seen in a significantly lower proportion of PMBL (34% and 17% respectively). Coexpression of BCL2≥70% and MYC≥40% (MYC+/BCL2+) occurred in 52/184 (28%) cases, without difference between two arms or COO subtypes. By contrast, PMBL subtype displayed an extremely low rate of MYC+/BCL2+ cases (1/49, 2%). 3y-EFS rates were 52% ± 6% for GC, 58% ± 5% for NGC and 49% ± 6% for PMBL (p= 0,42) with no significant difference according to treatment arm. Of note, in PMBL, the majority of events was positive interim PET-CT. Worse EFS was seen in BCL2≥70% cases (3y-EFS: 47% ± 4% vs 60% ± 4%, p= 0,05) but this difference was erased in RCHOP arm (3y-EFS: 52% ± 6% vs 58% ± 6%). 3y-Progression Free Survival (PFS) rates were 73% ± 6% for GC, 76% ± 6% for NGC and 94% ± 4% for PMBL (p=0,03) with no difference between the two arms (Fig 1). There was no PFS difference in BCL2≥70% vs

Description: Background: Because of the disruption of BCNU (Carmustine) in France during several months, and based on the results reported by Visani and colleagues (Visaniet al, Blood 2011) Bendamustine has been used in combination with Etoposide, Cytarabine and Melphalan (BeEAM) in a new high dose conditioning regimen before autologous transplant in relapsed/refractory (R/R) lymphoma patients. We report our experience on the safety and efficacy of BeEAM compared to the classical BEAM regimen. Patients and methods: Ninety consecutive pts (BEAM = 60, BeEAM = 30) with R/R lymphoma were enrolled between December 2013 and September 2015 (BEAM from December 2013 to January 2015 and BeEAM from February to September 2015) in this retrospective study. Pts in complete or partial response after salvage therapy received high dose conditioning with Bendamustine (d-8 and d-7), Cytarabine (400 mg/m2 continuous infusion from d-6 to d-3), Etoposide (200 mg/m2 continuous infusion from d-6 to d-3) and Melphalan (200 mg/m2 d-2) followed by ASCT on d0. Bendamustine was given at 200 mg/m2/d for the first 4pts then 100 mg/m2/d for the 4 subsequentpts and finally at 120 mg/m2/d for the remaining pts (22 pts). Among the BEAM group, 68% had Non-Hodgkin's Lymphoma (NHL) and 32% Hodgkin's Lymphoma (HL) compared to 87% and 13% respectively in the BeEAM group (p = 0,014). HHV-6 detection was performed by PCR for symptomatic pts (fever, rash or prolonged cytopenia). Patients were housed in single bedrooms with air filtration and received the same supportive care. Results: Median age was 50 (18-66) and 56 (20-67) in the BEAM and BeEAM groups respectively and median of previous chemotherapy regimens was 2 (1-5). Fifty two out of 90 patients were male (37/60 in the BEAM group and 15/30 in the BeEAM group). Pts were in CR (46, 7% Vs 56, 7%) or PR (53, 3% Vs 43, 3%) at time of transplant. There was no difference in terms of hematologic recovery (median = 11 days (range: 7-22)), blood and platelets transfusion, mucositis toxicity. There was no statistical difference in the incidence of acute renal failure when comparing the two groups. However, there was a very striking difference when considering the highest dose of Bendamustine when compared as well to the two others doses of Bendamustine (p 〈 0.00001) as to the BEAM group (p=0.005). Additionally, we also observed a high incidence of symptomatic HHV-6 infections (53.3% vs 8.3%, p 〈 0.00001), digestive toxicity (36.6% vs 15%, p = 0.03) and a longer hospitalization duration (25 days (range: 18-59) vs 21 days (range: 18-32), p = 0.001) for patients in the BeEAM group overall. With a median follow up of 18.3 and 9.7 months for BEAM and BeEAM respectively, overall survival (93% vs 86%), transplant related mortality (0% vs 3%) and event free survival (83% vs 78%) were comparable. Conclusion: Overall, BeEAM regimen was associated with longer duration of hospitalization, higher rate of digestive toxicity and increased risk of symptomatic HHV-6 infection as compared to the BEAM regimen. In addition, higher doses of Bendamustine (200mg/m2/d for two consecutive days) were associated with unacceptable high rate of acute renal toxicity. With a still short follow-up, the absence of benefit on disease control together with higher short term toxicity does not allow to recommend the use of BeAM instead of classical BEAM. Should it be used, we suggest that pts should be carefully monitored for renal toxicity and for HHV-6 infection in case of symptoms. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4129 In patients with cytogenetically normal AML, the mutational status of FLT3, NPM1 and CEBPA are associated with the outcome (Schlenk, NEJM 2008). In that study, the benefit of ASCT was limited to the subgroup of pts with FLT3-ITD or the genotype consisting of WT NPM1 and CEBPA without FLT3-ITD (triple neg). In these pts, ASCT provided a better RFS not translating into a better overall survival. In that study, pts were under the age of 60 and were transplanted with an HLA matched related donor after a myeloablative conditioning. In an effort to further explore the role of ASCT in AML with FLT3-ITD or triple neg, we undertook a single centre retrospective analysis of de-novo AML with a cytogenetically intermediate-risk profile (Döhner, Blood 2010) treated at 1st CR with a RIC ASCT or conventional consolidation chemotherapy in the absence of a suitable donor. Methods: All pts age 18 up to 65 diagnosed with AML in our center between January 2001 and December 2010 were reviewed. Secondary AML and APL were excluded as were AML with favorable or unfavorable karyotypes (according to Döhner). Pts who never reached CR were also excluded. Furthermore, pts not genotypically defined at diagnosis with available frozen leukemic cells were retrospectively analyzed and only AML with FLT3-ITD or triple neg were included in the study. To avoid biases in favor of the donor group, pts excluded from ASCT because of a poor performance status were excluded as were pts deceased before the median time between CR1 and ASCT in the donor group. As a consequence, the only reason for not performing ASCT was the absence of an appropriate donor. The aim of our study was to compare RIC ASCT to conventional chemotherapy as the post-CR1 therapy. Results: 67 pts were included (30 treated with conventional chemotherapy, the “no donor” group and 37 treated with ASCT, the “donor” group). Both groups (donor vs no donor) were comparable with respect to med age at dg: 57 y (31–64) vs 54 y (19–63), WBC at dg, sex ratio, proportion of normal/abnormal karyotypes: 28/9 vs 23/7, proportion of FLT3-ITD/triple negative genotypes: 10/27 vs 14/16, median time between dg and CR1: 52 d (29–230) vs 45 d (32–75), and number of lines (n=1/ n=2/ n=3) to reach CR1: 23/12/2 vs 21/9/0. The med time between CR1 and ASCT was 114 days (24–295). Conditioning were fludarabine+busulfan+ATG (n=20), fludarabine+cyclophosphamide+TBI2Gy (n=3), fludarabine+TBI2Gy (n=11), fludarabine+treosulfan+ATG (n=3). The source of stem cells were PB (n=33), BM (n=1), or cord blood (n=3). Donors were matched-related or -unrelated, in 51% and 30% of patients, respectively. Med F.U after CR1 was 28 months (6 to 112) and 54 months (6–83) in the donor and no donor groups, respectively. In the donor group, 10 patients relapsed at a med time of 8 months (4–39) after CR1. In the no donor group, 19 patients relapsed at a med time of 8 months (1–44) after CR1. In the donor vs no donor groups, the 3-years relapse rate were 29% ±8% vs 65% ± 9%, p=0.007. The 3-years NRM were 25% ± 10% vs 6 % ± 6%, p=0.02. At the last follow-up, 18 patients have died in the donor group from the following causes: disease (n=9), infections (n=7), GvHD (n=1), suicide (n=1). Fifteen patients have died in the no donor group from disease (n=14) or infections (n=1). The 3-years OS were 51% ± 9% vs 41% ± 10%, p=0.9. Conclusion: in pts with intermediate-risk de-novo AML and FLT3-ITD genotype or WT NPM1 and CEBPA without FLT3-ITD, a RIC ASCT as post-remission therapy improves the PFS as compared to conventional chemotherapy, demonstrating a potent graft-versus-leukemia effect in these pts with AML at a high-risk of relapse. Efforts remain to be done to decrease RIC ASCT associated NRM. Disclosures: No relevant conflicts of interest to declare.