ALBERT

Description: Abstract 3528 Allogeneic stem cells transplant (allo-SCT) is currently the preferred therapeutic option for young adults with Ph- ALL in first CR. However, the results of different studies suggested that pediatric-inspired therapy have markedly improved the outcome of these patients. In our monocentric study, we analyzed the impact of the allo-SCT on outcome in adults treated within these pediatric-inspired trials. Between April 2002 and March 2010, 75 young adult patients with Ph- ALL were treated in our clinical unit. 70 patients (49 men and 21 women) were in complete remission (CR) (93%) after induction chemotherapy (4 after two courses), 2 died before evaluation (3%) and 3 patients were refractory and died with progressive disease (4%). The median age of the population was 33 years (range, 16–59). Among the 70 patients in CR, 54 (77%) were considered at high-risk ALL and therefore eligible for allo-SCT after 1 or 2 consolidation courses. Baseline high-risk factors were: WBC count of ≥ 30 × 109/L for B-lineage ALL, clinical and/or morphologic CNS involvement, t(4;11) and/or MLL-AF4 fusion transcript, t(1;19) and/or E2A-PBX1 fusion transcript and low hypodiploidy and/or near-triploidy. Fourteen patients with low-risk ALL received chemotherapy alone with late intensification followed by maintenance therapy. With a median follow-up of 36.5 months, median overall survival (OS) for the entire population was not reached and the estimated OS at five years was 75% (70-80%). The high-risk factors as previously defined could separate two different groups with statistically different outcome. In the low-risk (LR) group, none patient died or relapsed during this study. While, in the high-risk (HR) group, 11 of 54 patients (20%) relapsed and 14 patients (26%) died. For the LR group and the HR group, the estimated OS at five years was respectively 100% and 69% (64-74%) (p=0.04) and the estimated disease free survival (DFS) was respectively 100% and 61% (56-66%) (p=0.02). In the HR group, 30 of the 54 patients (55.5%) had donor and had received allogeneic SCT, 28 of 30 patients after myeloablative conditioning regimen, 12 patients with related donor and 18 patients with unrelated donor. The 24 other patients without donor had received the same chemotherapy than patients in the LR group with late intensification and maintenance therapy. There was no difference between the two subgroups for death: 6 patients with donor (D+) and 8 without donor (D-). Nevertheless, there was more relapses in the subgroup D- (8 relapses) than in the subgroup D+ (3 relapses) (p=0.006). At five years, in the subgroup D+, the estimated OS and DFS were respectively 75 % (68-82) and 72 % (66-78). In the subgroup D-, the estimated OS and DFS were respectively 62 % (55-69) and 48 % (41-55). There was no difference between two subgroups D+ and D- for OS (p=0.4) and DFS (p=0.19). In addition, there was no difference for age, sex, risk factor and initial characteristic of the disease. These results suggest that allograft might not improve the outcome of patient with high-risk Ph- ALL. One explanation is that pediatric-inspired induction chemotherapy improves the outcome of the whole population (75% of overall survival) and this advantage decreases the impact of the allo-SCT. Nevertheless, allo-SCT decreased the risk of relapse but did not modify OS and DFS. However, more patients are necessary to confirm these results in a multicentric study. Disclosures: No relevant conflicts of interest to declare.

Description: Umbilical cord blood transplantation (UCBT) is an alternative in the absence of related or unrelated HLA-matched donor. Defects in the mechanisms of immuno-surveillance, due to the absence of antigen-experienced lymphoid subsets transferred in the cord blood unit (CBU), render recipients more prone to viral infections. Our center conducted a clinical trial testing the benefit of ex vivo amplification of the CD34+ fraction (using SCF, FLT3L, TPO and GCSF) enriched from one CBU on hematopoietic reconstitution, while the CD34- fraction was infused at the same time as the expanded fraction (NCT01034449). We intended to simultaneously evaluate the potential impact of such a procedure on the immune reconstitution following freeze-thaw cycle for the CD34- fraction and on the expansion potential of lymphoid progenitors from CD34+ fraction. We prospectively analyzed fresh patient samples from the clinical trial (called the EVEX), at different time points (Day 42, D100, D180, D360), and, in parallel, from patients receiving one or two un-manipulated CBU during the same period (Control group - CTRL). Immune monitoring included flow cytometry analysis of T-cells (CD3+, CD4+, CD8+) and sub-compartments, B-cells (CD19+), NK cells (CD3-CD16+CD56+) and Dendritic cells (DC). Sixteen patients were included in EVEX, of which 12 were analyzed (4 excluded: 1 not grafted, 1 graft infection, 2 primary rejections before Day 42) and 12 patients in CTRL. In the EVEX group, all patients received reduced intensity conditioning, compared to 6 out of 12 in the CTRL group. GVHD prophylaxis was similar. EVEX showed a shorter duration of neutropenia compared to the CTRL (8.5 versus 17 days, p=0.02). NK and B-cell subsets recovered earlier than T-cells, reaching median normal values at 3 and 6 months, respectively. NK cell count tended to be lower in EVEX, starting at 3 months until 1 year. B-cell counts were lower for EVEX at D360. Both groups recovered T-cells within 12 months, but, interestingly, EVEX recovered earlier, reaching Healthy Donor (HD) median values as soon as D180. The CD4+ T-cells (CD4+T) recovered within 12 months for both groups, with EVEX values tending to plateau at low normal values (Fig 1). CD8+ T-cells (CD8+T) reached HD values within 12 months with an earlier recovery for EVEX (Fig 1). We characterized CD4+T and CD8+T compartments with CD45RA and CD27 delineating: naïve (TN: CD45RA+CD27+), central memory (TCM: CD45RA-CD27+), effector memory (TEM: CD45RA-CD27-) and late effector (TEMRA: CD45RA+CD27-) T-cells. Among the CD4+T, TN and TCM gradually increased until D360 for CTRL, while EVEX reached a plateau at D180. EVEX showed a higher TEMRA CD4+T count at D360. Thus, the plateau observed in the whole CD4+T at D180 in EVEX suggested an altered capacity to induce new CD4+T (thymic output or peripheral expansion), or an exhaustion phenomenon. To this end, we evaluated thymic function via CD31 expression among TN CD4+T and TREC analysis by qPCR. Both methods showed a decreased thymic function in EVEX after D180, probably related to the age difference observed (median: 52 vs. 26 years old for EVEX and CTRL, respectively). TEM and TEMRA CD8+T subsets were higher starting at D180 for the EVEX group. There was no difference between groups for myeloid or plasmacytoid DC. Group outcomes differed in terms of chronic GVHD (cGVHD) (1 vs. 6 patients for EVEX and CTRL respectively, p=0.024). Among the subsets playing a role in cGVHD pathogeny, no difference was found in Treg/Tcon ratio (Treg = CD25hiCD127lo CD4+T, Tcon = non-Treg CD4+T), but memory B-cell subset tended to be greater in CTRL from D42 to D180 (median time of cGVHD onset = 186.5 days). CMV reactivation rate was similar in both groups, occurring around 42 days post transplant. Vdelta-2 negative γd T-cells were greater in EVEX early after infection (D42), suggesting a comparable anti-CMV innate function. However, when looking at adaptive anti-CMV immunity with ELISpot, we found reduced IFNg-secreting cells in EVEX, although group size was small. In conclusion, patients receiving ex vivo expanded CBU showed faster hematopoietic reconstitution than un-manipulated CBU and comparable recovery of the main immune subsets. Baseline clinical differences observed between groups may have impacted on some of the immune findings. A prospective and randomized trial would help to better analyze if the expansion procedure has an impact on immune reconstitution. Disclosures Milpied: Celgene: Honoraria, Research Funding.

Description: Abstract 502 Autologous stem cell transplantation with PBSC after high-dose chemotherapy remains standard therapy for patients with symptomatic Multiple Myeloma (MM). Strategies to minimize complications could significantly reduce the morbidity of that procedure. One possibility could be to shorten the duration of induced neutropenia through the injection of an ex-vivo expanded graft. Nineteen patients (pts) received EVEC after high-dose Melphalan (HDM) (200 mg/m2) as the only graft. The ex-vivo expanded procedure has been described elsewhere (Boiron et al. Transfusion 2006 and Ivanovic et al. Transfusion 2006). Briefly, thawed peripheral blood CD 34+ cells collected after G-CSF mobilisation and selected with immunomagnetic devices were incubated for 10 days in a serum free medium (Maco Biotech HP01) with Stem Cell Factor (Amgen), G-CSF (Amgen) and TPO (Amgen: 7 pts; Cellgenix:12 pts). The expanded cells were then thoroughly washed and injected 48h after the HDM injection. The ex-vivo expansion lead to a median fold of 5,4 for CD34+ cells (1,3-11,8); 118 for CD33+ (1-703880); 3386 for CD14+ (4-101075); 28,5 for CD13+ (10-703880) and 13 for CFUs (6-21). The median N° of CD34+ cells injected was 14×10e6/kg (5,3-48). The results of these transplants were compared to those achieved in 38 pts who received unmanipulated PBSC after HDM. Pts and controls were matched for age, sex, stage of the disease, first line chemotherapy ( VAD or VD) status of the disease at time of transplant, year of transplant, time between diagnosis and transplant, CD34+ mobilisation technique (HD cytoxan + G-CSF or G-CSF alone) and the median N° of total nucleated cells and of CD34+ collected. The results are summarized on the table: There was no secondary neutropenia in the patients who received EVEC. With a median FU of the entire cohort of 30 m, the median OS for pts who received their first transplant with EVEC and with PBSC is 69 m and not reached respectively (p=NS), the median PFS is 18 m and 27 m (p = NS) and the median time to progression is 14 m and 15 m (p=NS). Conclusion: EVEC is feasible, safe and reduce significantly the morbidity of autologous stem cell transplantation after HDM for multiple myeloma. Disclosures: Milpied: Amgen France: Honoraria.

Description: Abstract 486 CBU is a widely used source of stem cells for allogeneic transplantation (SCT). Engraftment rate and speed of a single CBU in adults remains unsatisfactory. Transplantation of 2 CBU may overcome this problem to the expense of an increased incidence of GVHD. Until now, attempts at using ex-vivo expanded CBU have been unsuccessful to promote long term engraftment of the expanded product. We report the results achieved in the first 8 Pts included in a PCT of transplantation of a single ex-vivo expanded allogeneic CBU. Eudract 2008–006665–81, Clinicaltrials.gov NCT 01034449. Methods: Adults patients with an indication for SCT and unable to tolerate MAC (age〉45, comorbidities, previous high-dose therapy) were included after inform consent if no Id sibling, no MUD 9 (C or DQ mismatch accepted) to 10/10 HLA matches and no CBU fulfilling the HLA matching (≥ 4/6) and richness (≥ 3 to 4 × 107 TNC/kg before thawing) criteria were available. RIC consisted of Flu (40 mg/m2/d × 5d), Cyclophosphamide (50 mg/kg × 1d) ICT 2 Gy. GVHD prevention consisted of MMF (d-3 to d28) and CSA from d-3. Graft engineering: 1 CBU with 〉 2 TNC/kg 〈 3 and 4 to 6 HLA compatibilities was thawed, CD34+ cells were selected through magnetic device (Miltenyi) and submitted to ex-vivo expansion in SF medium ( HPO1-Macopharma) supplemented with SCF, Flt3l, G-CSF and TPO during 12 days, starting d-12 of the transplantation (Ivanovic, Cell Transplant 2011) CD34 neg cells were cryopreserved. On d0, expanded cells were washed and resuspended in HSA 4% and upon viability and sterility were injected to the pt. Cd34 neg cells were thawed and injected to the pt 3 h later. Results: From 03/2010 to 06./2011 8 pts have been included, med age 55y.o. (26–64) with AL: 3, Hodgkin's: 2, MDS: 3. Pts had received 1 to 3 lines of Tx (med:2). For 1 pt the expanded product was contaminated and this pt then received a back-up unmanipulated CBU. He engrafted correctly and is AW at 14 m with full donor chimerism. For the 7 other pts, the ex-vivo median fold expansion of CD34+ cells and TNC was 39 (29–75) and 390 (127–526) respectively, leading to a graft that contained 1.3 to 13 × 106 CD34+ cells/kg (med: 2 × 106/kg). The CD34 neg counterpart contained 3 × 106 CD3+/kg (1–5) and 0,9 × 106 CD19+ cells/kg (0,3–1,5). At d42, 6/7 pts who received the expanded graft engrafted with ≥99% donors cells. A 2d RIC was performed followed by a double CBU transplant in the patient who did not engraft. That 2d graft again failed to engraft. However the patient remains alive at 9m. For the 6 pts who engrafted with the expanded product the time to reach 500, 1000 PMN's and 20 000 plts/mm3 was 7d (6–19), 8d (6–21) and 24d (0–39) respectively. The chimerism on WBC and CD3+cells (evaluated on d 15, 42, 60, 100, 180, 365) remains full donor up to 1 year + after transplant (1y+: 2 pts; 6m+: 1pt; 180d+: 1 pt; 60d+: 1pt) or to relapse (at 1y) in the one pt who relapsed. Five pts experienced an AGVHd (grade III-IV: 1 pt). With a median FU of 10m (2 to 18m) 7 pts are alive, 6 wo disease. One pt died 1y after transplant from relapse. Conclusion: Ex-vivo expansion of a single CBU is feasible and reproducible. Transplantation of the expanded product together with the CD34 neg counterpart of the same CBU produces rapid, complete and sustained donor engraftment after RIC in adults. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction CPX-351 is a liposomal formulation of cytarabine and daunorubicin packaged at a 5:1 molar ratio. This drug has recently been approved by FDA and EMEA for patients with therapy-related acute myeloid leukemia (t-AML) or AML with myelodysplasia-related changes (MRC-AML). The primary objective of this study was to analyze the efficacy of CPX-351 in a real-life setting, evaluating the impact of mutations on response and minimal residual disease (MRD) in responding patients. Methods We retrospectively collected data from patients treated by CPX-351 in eleven centers in France. Clinical, biological and treatment information were available for all patients. NGS (19 genes or more) was performed in 67 patients (84%) at diagnosis. Overall response rate (ORR) was defined by complete remission (CR) and CR with incomplete haematological recovery (CRi). Among the patients in CR or CRi, 25 (56%) had MRD evaluation assessed by NGS or flow cytometry. Overall survival (OS) was calculated from the date of AML diagnosis to the date of death or last follow-up. All statistical analyses were performed using SPSS v.22 software (IBM SPSS Statistics). Results Between April 2018 and July 2019, 80 patients treated with CPX-351 were included in this study. Sex ratio M/F was 43/37 and median age was 66 years old (range 20-83). AML subtypes were MRC-AML (61%) including AML with prior myelodysplastic syndrome (MDS-AML) (33%), prior chronic myelomonocytic leukemia (CMML-AML) (7%), or t-AML (29%). Sixteen patients (20%) had received prior treatment by hypomethylating agents (HMA), at the time of MDS diagnosis, before AML evolution. According to ELN 2017 classification, genetic risk was favorable, intermediate and adverse in 1 (1%), 31 (38%) and 47 (58%), respectively. 36% and 28% patients had complex and monosomal karyotypes, respectively. Assessed by NGS the most frequent mutated gene were : RUNX1 (n=17, 25%), TP53 (n=15, 22%), ASXL1 (n=14, 21%), TET2 (n=13, 19%), DNMT3A (n=11, 16%), srsf2 (n=9, 13%), FLT3-ITD (n=8, 12%), CBL (n=7, 10%), WT1 (n=7, 10%), and EZH2 (n=7, 10%). According to a genetic ontogeny-based classifier (Lindsley et al., Blood 2015), 23 patients (34%), 29 (43%), 15 (22%) had de novo/pan-AML, secondary type mutations AML, and TP53 mutated AML, respectively. Only 4 patients discontinuing treatment due to prolonged haematological toxicity. Early death rate was 5% and 8.75% through day 30 and day 60, respectively. Median time to neutrophil recovery (〉0,5 G/L) and platelet recovery (〉20G/L) after induction was 29 days (range 19-78) and 28 days (range 12-77), respectively. Seventy-five patients (95%) had at least one grade 3 or more AEs, including 69 (86%) febrile neutropenia. We observed gastrointestinal toxicity 32 patients (40%) (nausea/vomiting (30%/11%), mucositis (15%)) including 4% with grade 3 or more and alopecia in only 12%. ORR was 45/80 (56%) after induction 1 including 53% CR and 3% CRi. ORR increased to 58% after induction 2. Among the 45 CR/CRi patients, 25 were evaluable for MRD at the time of the 1st consolidation. 72% had MRD below 10-3 (64% below 10-4). Prior treatment by HMA and presence of monosomal karyotype were identified as factors predicting a lower rate of CR/CRi (P=0.001 and P=0.002, respectively). Lindsley's classifier predicted significantly a better chemosensitivity in de novo/pan-AML mutations (P= 0.037). Poor molecular prognosis subgroups defined by 2017 ELN risk stratification (n = 53) as TP53, ASXL1, RUNX1 and EVI1 mutations were not associated with a lower response rate with CPX-351 (Table 1). Twenty-one (26%) patients underwent an allogeneic haematopoietic stem cell transplant (HSCT) with an improved median OS compared to non-transplanted patients (non reached vs 8 months, P= 0.004). With a median follow up of 8.5 months, median OS was not reached. Survival analysis in subgroups will be available for the ASH meeting. Conclusion These data confirmed the efficacy and safety of CPX-351 in poor risk AML (t-AML and MRC-AML). The high rate of CR with low MRD compares favorably with previous report using 7+3 in elderly unfavorable AML (Sylvie D. Freeman et al., JCO 2013) and may explain the favorable outcome observed in patients after HSCT. Moreover, CPX-351 erases the poor prognosis associated with unfavorable mutations defined in 2017 ELN risk stratification. Lindsley's classifier was the best prognostic scoring system in patients treated by CPX-351. Disclosures Bertoli: Daiichi Sankyo: Consultancy; Astellas: Consultancy, Honoraria; Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria. Peterlin:Jazz Pharma: Consultancy; AbbVie Inc: Consultancy; Astellas: Consultancy; Daiichi-Sankyo: Consultancy. Chevallier:Incyte: Consultancy, Honoraria; Daiichi Sankyo: Honoraria; Jazz Pharmaceuticals: Honoraria. Thomas:INCYTE: Honoraria; DAICHI: Honoraria; PFIZER: Honoraria; ABBVIE: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Pigneux:Daichi: Honoraria; Abbvie: Honoraria; Jazz: Honoraria; Astellas: Honoraria; Roche: Honoraria; Pfizer: Honoraria; F. Hoffmann-La Roche Ltd: Honoraria; Amgen: Honoraria; Novartis: Honoraria. Recher:Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Macrogenics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ades:Amgen: Research Funding; Helsinn Healthcare: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Silence Therapeutics: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Cluzeau:Abbvie: Consultancy; Jazz Pharma: Consultancy; Menarini: Consultancy.

Description: Abstract 2586 Even when intensively treated within pediatric-inspired protocols, about 25 to 30% of adults with ALL eventually relapse. With standard 4-drug or Hyper-CVAD salvages, post-relapse outcome remains very poor. Clofarabine is one of the new agents approved in US and EU to treat relapsing B-cell precursor (BCP) and T-cell ALL in children and young adults (up to 21 at initial diagnosis). In these patients, clofarabine is associated with a salvage rate around 30% when used as single agent. Combining clofarabine with conventional drugs in an intensive schedule may provide a chance to improve results in this difficult to treat population. Methods: Fifty-five patients were treated between March 2008 and February 2011. Thirty-seven patients received the VANDEVOL chemotherapy combining dexamethasone 10 mg/m2/12h day 1–5, mitoxantrone 8 mg/m2/d day 3–4, etoposide 150 mg/m2/d day 3–5, Peg-asparaginase 2.500 UI/m2 day 7, and Clofarabine 30 mg/m2/day day 1–5 and eighteen patients received the ENDEVOL chemotherapy combining cyclophosphamide 300 mg/m2/d day 1–3 and clofarabine 30 mg/m2/d day 1–5. Median age was 34 (19–67) and 53 (18–78) years in the VANDEVOL and ENDEVOL cohort, respectively. The proportion of first relapsing patients was 68% in the VANDEVOL cohort and 39% in the ENDEVOL cohort. Fifty patients had BCP-ALL (including 8 Ph+ ALL) and 5 patient had T-ALL. Results: Complete remission was achieved in 15/37 (41%) VANDEVOL patients and in 9/18 (50%) ENDEVOL patients. Early death rate was 5/37 (14%) in patients treated with VANDEVOL and 1/18 (6%) in patients treated by ENDEVOL. Grade 3–4 infectious, neurological, GI, and liver toxicities were observed in 22, 5, 5, and 11 VANDEVOL patients and in 10, 0, 0, and 2 ENDEVOL patients, respectively. Thirteen patients in the VANDEVOL group and three in the ENDEVOL group received subsequent allogeneic stem cell transplantation (overall transplant rate, 29%). After a median follow-up of 6 months, the median OS was 6.5 months. Conclusion: Combination of clofarabine with standard chemotherapy seems to be a promising and relatively safe approach to treat adult patients with refractory/relapsing ALL. This approach may be considered as a bridge to transplant in patients eligible for subsequent allogeneic stem cell transplantation. Updated data will be presented. The GRAALL will soon initiate a large multicenter prospective Phase II study using the VANDEVOL regimen. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 685 Background: In 2004 we have shown that first-line intensive therapy plus transplantation of autologous hematopoietic stem cells lead to an improved EFS and OS over standard CHOP regimen in adults with disseminated aggressive lymphomas (NEJM 2004; 350: 1287). Then the rituximab era came. We have shown that the addition of R to the intensive therapy was feasible and might further improve the results (BBMT 2010; 16: 672). We present here the preliminary analysis of a multicenter randomized trial aiming at comparing the results of R- CHOP every 14 days to R- HDT in adults with untreated confirmed DLBCL (clinical trial.gov: NCT 00561379). Methods: The patients were 18 to 60 y.o. with CD20 + DLBCL Ann Arbor stage 1 or 2 with bulk 〉/= 7 cm or 3 and 4 were randomized at diagnosis (with a stratification according to age adjusted IPI) between R-CHOP every 14 days at standard doses (8 consecutive courses if a response was observed after the first 4 courses) and R-HDT. This program consisted of 2 courses of high-dose CHOP-like regimen, 15 days apart, with rituximab (375/mg/m2) on day 1 of each course, followed by rituximab on d 22, harvest of G-CSF mobilised peripheral blood stem cells on d 28,29, then rituximab on d 36 followed by a course of high-dose methotrexate with cytarabin. For patients who achieved at least a partial response after these 3 courses, a BEAM regimen started on d 66 to 80 followed by the infusion of stem cells. In each arm, the intermediate evaluation of response was assessed by means of standard CT Scan and PET. Patients not achieving a PR or a negative PET were proposed a salvage Tx followed in case of response by an autologous transplantation. The main objective of the study was the EFS with an event defined as insufficient intermediate response, progression, relapse or death. Analysis was performed on intent to treat basis. Results: 331 pts were included from 01/2005 to 05/2010. 305 patients were found eligible and 286 are fully evaluable at time of this abstract, 143 in each arm. The main characteristics of the pts in the 2 arms are strictly super imposable. Overall 56% had a bulk as defined, 72% had a 3 or 4 AA stage and 58% had an aa IPI 2 or 3. The treatment as scheduled in the protocol was completed in 71% in the R-CHOP arm and 60% in the R-HDT arm. The intermediate evaluation showed exactly the same rate of response with Standard CT scan (CR + CRu: 65% and 62% following 4 courses R-CHOP and first 3 courses of R-HDT respectively). PET remained significantly more often + after the first 3 courses of R-HDT (43% vs 30% following 4xR-CHOP; p=0.03). The ORR (CR + Cru) was 78% and 71% in the R-CHOP and R-HDT arms respectively (p=0.8). With a med FU of surviving patients of 25 m, the probability of survival for the whole group of patients is 88% and 74% at 2 and 5 years. There is no significant difference according to the treatment arm in any of the aaIPI strata. The EFS with the standard CT Scan as an intermediate evaluation is 74% and 66% at 2y and 5 y with no difference according to the treatment arm in any aaIPI strata. The EFS with PET scan as an intermediate evaluation is 49% and 45% at 2y and 5 y and is statistically worse with R-HDT for aaIPI 2 and 3 pts (p=0.01). Conclusion: Based on these results, one cannot recommend first-line R-HDT as performed in that trial for adult patients with DLBCL. R-CHOP 14 is as efficient, less toxic and spares resources. Disclosures: Milpied: Roche: Membership on an entity's Board of Directors or advisory committees.

Description: In the era of novel drugs, the role of RIC AT for relapsed Multiple Myeloma (MM) remains to be determined. In this retrospective study we analyzed the results of RIC AT performed in 36 patients with relapsed MM in our institution between June 1999 and August 2007. At diagnostic our population consisted of 27 males and 9 females. Twenty-eight patients had stage III, 4 patients had stage II and 4 patients had stage I DS. B2-micoglobuline was ≤ 3 mg/l in 16 patients and 〉 3 mg/l in 11 patients. Del 13 was present in 7/18 patients evaluated. Nineteen received at least 2 HDM with autologous stem cell transplantation, 15 received only one and 2 didn’t received HDM as part of frontline treatment. The median age at time of AT was 56 years (range: 44–64). The “pre-AT” treatments consisted in “standard chemotherapy” for 13 patients and targeted treatments, represented by thalidomide or lenalidomide, or bortezomib w or wo dexamethasone in 23 patients. At the time of AT, 29 patients were responder (3 complete response (CR), 6 very good partial response (VGPR) and 20 partial response (PR)), and 7 patients were not responder (6 stable disease (SD) and 1 progressive disease (PD)). RIC regimen consisted of fludarabine associated with busulfan (n=22), treosulfan (n=2), total body irradiation (n=10), idarubicine and cytosine arabinoside (n=1) or melphalan (n=1). In addition, 25 patients received ATG as part of the conditioning. The donor was an HLA-identical sibling in 20 cases or an unrelated donor in 16 cases. GVH Prophylaxis consisted of CSA alone (n=16), CSA with MMF (n=7), or CSA with MTX (n=13). The median delay between AT and the first response evaluation was 3.8 months, 15 patients achieved CR, 3 patients achieved VGPR, 9 patients achieved PR, 2 patients were in SD and 4 in PD. Twenty one patients developed acute GVHD (grade 1–4) and 14 patients developed chronic GVHD. With a med FU of 42 months, 11 patients are alive. The 3-year event free survival (EFS) and overall survival (OS) from AT are 17, 5% (+/−7.2%) and 32% (+/− 8.3%) respectively. The causes of death were transplant-related complications in 11 patients, relapse or progression in 13 patients, and second malignancy in 1 patient. The TRM at Day 100 and Day 365 was 19 % (+/− 6.6 %) and 32 % (+/− 8%) respectively. Among the numerous factors that were evaluated for their prognostic influence, only two were significantly associated with a better OS and EFS (in univariate and multivariate analysis): the achievement of a CR or VGPR after AT (median OS: 31m vs 5; p

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: In elderly patients with acute myeloid leukemia (AML) treated intensively, no improvement has been shown in the last 20 years. We performed a retrospective study in 847 patients over 60 years old, prospectively enrolled in 3 trials conducted in France between 1995 and 2005, with the aim to investigate prognostic factors for complete remission (CR) achievement and survival. Induction therapy consisted in the association of Idarubicin 8mg/m2 d1-5 and Cytarabine 100mg/m2 d1-7 (Group I, 339 patients) or the same drugs with the addition of lomustine (10mgm2 orally at day 1)(Group II, 508 patients). Consolidation therapy consisted of anthracycline and cytarabine courses at lower doses, preceded or not by a first course with intermediate dose cytarabine. The patients’ characteristics were similar between the two groups concerning sex, WBC count, ECOG, and cytogenetics, yet patients were older in Group II versus Group I (55% versus 45% over 69 years of age, p