Abstract: Background. Ara-c based chemo-immunotherapy followed by autologous stem cell transplantation (ASCT) is the most effective approach in young mantle cell lymphoma (MCL) patients, though few if any patients are cured. Recent data indicate that subsequent Rituximab maintenance (RM) prolongs PFS and OS (Le Gouill NEJM 2017). Lenalidomide is an oral agent effective in MCL, considered suitable for prolonged maintenance programs, but has never been tested in this setting. The FIL MCL0208 trial (NCT02354313) is a prospective, international randomized, phase III trial, comparing Lenalidomide maintenance (LM) vs observation (OBS) after an intensive Ara-c containing chemo-immunotherapy (R-HDS) program, followed by ASCT in previously untreated MCL patients. Patients and Methods. Adult patients aged 18-65 years, with advanced stage MCL without clinically significant comorbidities were enrolled. Patients received 3 R-CHOP-21, followed by R-HDS i.e. R-high-dose Cyclophosphamide (R-HD-CTX) (4g/m2), 2 cycles of R-high-dose Ara-C (R-HDAC) (2g/m2 q12x3 d). CD34+ cells were collected after the first course of R-HDAC. The conditioning regimen for ASCT was BEAM. After ASCT, responding patients were randomized between LM (15 mg days 1-21 every 28 days) for 24 months or observation. Primary endpoint analysis was scheduled at the occurrence of the 60th PFS event in the randomized population, which occurred on June 20th, 2017 and data were analyzed for the present abstract on March 3rd 2018. Results. Three-hundred three patients were enrolled from May 2008 to August 2015 by 48 Italian and 1 Portuguese Center. Three patients were excluded after central histological review. Median age was 57 years (IQR 51-62), M/F ratio 3.6/1. Ninety-two percent of patients had stage IV, 33% bulky disease ( 〉 5 cm), 33% elevated LDH, and 75% BM infiltration. Ki67 ≥30% was observed in 32%, MIPI was low (L) in 54%, intermediate in 31% and high (H) in 15% of patients. MIPI-c was L in 49%, low-intermediate (LI) in 29%, high-intermediate (HI) in 14%, H in 9%. Nine percent had blastoid variant. Fifty-two (17%) patients interrupted treatment before randomization (8 toxic deaths, 1 death for car accident, 24 progressions and 19 toxicity/refusals). On an ITT basis, the R-HDS + ASCT program induced 78% of CR, 7% of PRs, 10% of PD, 3% of toxic deaths (TRM) and 2% NA. Median follow-up (mFU) from inclusion was 51 months. Three years PFS and OS for the enrolled population were 67% and 84%, respectively. Of 248 patients who received ASCT, 205 were randomized either to LM (n=104) or OBS (n=101) and 43 (17%) were not because of: lack of response (8), refusal/PI decision/delay (8), unresolved infections (3) and inadequate hematopoietic recovery (24). Feasibility and efficacy were assessed on an ITT basis while toxicity was analyzed on subjects receiving at least one Lenalidomide dose. In the LM arm, 53 out of 104 patients did not start or complete the planned maintenance because of death (2), AE (26), PD (7), still ongoing (2), other causes (16). In the OBS arm 32 patients did not complete the observation phase because of death (1), AE (1), PD (20), still ongoing (10), other causes (1). Overall 28% of patients received less than 25% of the planned Lenalidomide dose. Despite suboptimal exposure to study drug, with a mFU from randomization of 35 months, 22 PFS events were recorded in the LM cohort vs 38 in the OBS arm, resulting in a 3y-PFS of 80% (95% CI; 70%-87%) in the LM arm vs. 64% in the OBS arm (95% CI; 53%-73%), stratified HR 0.51; 95% CI 0.30-0.87; p=0.013 (Fig 1A). OS was superimposable in the two arms: 93% vs 86%, stratified HR 0.96, 95% CI 0.44-2.11, p= 0.91 (Fig1B). Two deaths were observed in the LM arm due to pneumonia and thrombotic thrombocytopenic purpura and one in the OBS arm due to pneumonia. Grade 3-4 hematological toxicity was seen in 63% of patients in LM vs 11% in the OBS arm with 59% vs 10% of patients experiencing granulocytopenia. Non-hematological grade 3 toxicity was comparable in the two arms except grade 3-4 infections (11% vs. 4%; Fisher's p=0.10). Second cancers occurred in 7 patients in the LM and 3 in the OBS arm (Fisher's p=0.20). Conclusions. Results from the MCL0208 trial indicate that LM has a clinically meaningful anti-lymphoma activity in MCL. However, the applicability of LM has some limitations in the context of patients undergoing intensified chemoimmunotherapy. Overall these data support the use of a maintenance regimen after ASCT in young MCL patients. Disclosures Ladetto: Roche: Honoraria; Celgene: Honoraria; Acerta: Honoraria; Jannsen: Honoraria; Abbvie: Honoraria; Sandoz: Honoraria. Di Rocco:Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Rossi:Novartis: Honoraria; Jazz: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Teva: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses; Janssen: Membership on an entity's Board of Directors or advisory committees, Travel expenses; Roche: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Mundipharma: Honoraria; Sandoz: Honoraria; Seattle Genetics: Research Funding; Alexion: Other: Travel expenses. Chiappella:Janssen: Membership on an entity's Board of Directors or advisory committees, Other: lecture fees; Roche: Other: lecture fees; Teva: Other: lecture fees; Nanostring: Other: lecture fees; Amgen: Other: lecture fees; Celgene: Membership on an entity's Board of Directors or advisory committees, Other: lecture fees. Rusconi:Celgene: Research Funding. Gomes da Silva:Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: lecture fees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: lecture fees, Institution's payment for consultancy, Travelling support; Celgene: Other: Travelling support; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: lecture fees; Roche: Other: Institution's payment for consultancy, Travelling support; Gilead Sciences: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: lecture fees, Research Funding. Vitolo:Takeda: Speakers Bureau; Sandoz: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gilead: Speakers Bureau. Martelli:Sandoz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; F. Hoffman-La Roche: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Abstract: INTRODUCTION We retrospectively analyzed the impact on post-relapse survival of selected prognostic factors and salvage therapy (finalized to perform an allo-SCT) in 145 patients (pts) with non-APL AML who had been initially treated with standard induction and risk-adapted consolidation. The aim was to identify factors associated with a better outcome at first relapse. METHODS All pts were at first recurrence following consolidation of CR1 with (i) high-dose Ara-C (HiDAC) multicycle therapy supported by blood stem cells (standard risk, as defined by mixed clinico-cytogenetic criteria) or (ii) allo-SCT in case of high-risk prognostic profile. Median pt age was 55 y (range 21–68). CR1 duration was ≤ 6 months in 49 pts (34%), ranging from 0.6 to 6 mo (median 3.7). 25/68 pts (37%) had an unfavourable cytogenetics (CG), and 8.2 % had MDS-related AML. 96 pts (66%) had received HiDAC and 21 (15%) an allo-SCT according to study design. RESULTS 105 pts (72%) received salvage chemotherapy, 10 pts (7%) underwent directly allo-SCT, while the remaining 30 (21%) received palliation and all of them died. Salvage therapy consisted again of HiDAC alone or in combination with fludarabine or anthracyclines. After reinduction, 52/105 pts (49.5%) achieved CR2 and 15 (14%) died of complications. Altogether, 42 pts (29%, group 1) received an allo-SCT following relapse, 27 (64%) in CR2, 5 beyond CR2 and 10 soon after relapse. Of 20 more pts (14%, group 2) in CR2 but without HLA identical donor, 13 could be given further intensive consolidation therapy. Both groups were comparable regarding adverse prognostic features such as age 〉 55 y, WBC count 〉 50,000/μL, unfavourable CG, presence of FLT-3 ITD, prior allo-SCT and 1st CR lasting ≤ 6 mo. At the end of treatment, 37/42 pts (88%) receiving SCT and all 20 pts (100%) given only chemotherapy were in CR2. Logistic regression analysis showed that intensive treatment without HiDAC at induction (p=0.04) as well as CR1 lasting 〈 6 mo (p=0.01) negatively affected CR2 rate. Median duration of CR2 was 7.5 mo (range 1–49) in group 1 compared to 4 mo (range 1–15) in group 2. Day 100 non-relapse mortality in the 2 groups was 7% and 10%. After a median follow-up of 9.4 mo in group 1 (range 3–49) and 10 mo in group 2 (range 2–65), 2-y OS was 24% and 15.5%, respectively. Notably, 2-y OS in allo-SCT group ranged from 42% in pts ≤ 45 years to 14% in older ones. Moreover, survival was affected by risk category. In fact 2-y OS of 14/37 (38%) standard risk pts undergoing allo-SCT at salvage was 41% vs 17% in 28/108 (26%) comparable high risk pts. Cox regression analysis revealed achievement of CR2 being the only independent prognostic factor related to overall survival (p=0.0001). CONCLUSIONS AML patients receiving intensive chemotherapy including HiDAC at 1st relapse reached a high CR2 rate, regardless of type of prior risk-adapted consolidation. Further intensification with allo-SCT may offer substantial salvage rates to younger standard risk patients, thus adding value to the underlying concept of a risk-oriented first-line therapy.

Abstract: Background. Mantle Cell Lymphoma (MCL)represents an aggressive lymphoma for which an effective treatment has still to be determined. The FIL-MCL0208 phase III trial (EudraCTNumber: 2009-012807-25) is exploring R-CHOP followed byi) high-dose cytarabine, autologous stem cell transplantation, and ii) randomization between lenalidomide maintenance vs observation (Cortelazzo et al, EHA 2015). We performed genome-wide DNA profiling to identify unbalanced copy number variations (CNVs) with a clinical significance in patients enrolled in the FIL-MCL0208 phase III trial. Patients and Methods. The study included untreated, advanced stage MCL patients ( 〈 65 years) enrolled into the MCL0208 trial. Clinical results of the first interim analysis (without random unblinding) have been already reported and are the basis of the present analysis: median follow-up of alive patients was 26 months, and at 2-years, 79% of patients were progression free and 91% alive (Cortelazzo et al EHA 2015). DNA profiling with the Illumina HumanOmni2.5 arrays was performed on 174 DNA samples derived from baseline bone marrow CD19+ purified tumor cells. Genomic profiles were segmented with the Fast First-derivative Segmentation Algorithm (Rinaldi et al, BJH 2013; Kwee et al, bioRxiv 2016). Recurrent CNVs were defined applying both the minimal common regions and the GISTIC algorithms (Lenz et al, PNAS 2008; Mermel et al, Genome Biol 2011). CNVs were integrated with somatic mutational data obtained for 8 genes recurrently affected in MCL (ATM, BIRC3, CCND1, KMT2D, TP53, TRAF2, WHSC1, NOTCH1) (Rossi et al, ASH 2015). Progression free survival (PFS) was the primary endpoint of the analysis. Results. 161 patients were currently evaluable for CNVs and clinical outcome. Patients had an intermediate/high-risk MIPI and a Ki67 ³ 30% in 43% and 42% of the cases, respectively. Twenty-five recurrent unbalanced CNVs were defined (Table 1). By multiple test corrected univariate analysis, seven CNVs had a negative impact on PFS: +3, 7p gain, 9p loss (CDKN2A), 17p loss (TP53), 8p loss, and 2 losses at 22q (Table 1). MIPI (intermediate/high vs low risk), Ki67+ and the TP53/KMT2D model (Rossi et al, ASH 2015) were also statistically significant. Combining CNVs and mutations, TP53 was inactivated in 27/147 cases (18%): mutated/deleted in 7/147 (5%), deleted but not mutated in 14/147 (10%), and mutated but not deleted in 6/147 (4%). The negative prognostic impact was equal for all the 3 inactivation modalities, which were then considered as a single group for further analyses. ATM was inactive in 69/147 (47%): mutated/deleted in 24/147 (16.3%), deleted in 12/147 (8%), and mutated in 33/147 (22.4%). KMT2D (MLL2) was inactive in 18/147 (12%): mutated/deleted in 1/147 ( 〈 1%), deleted in 1/147 ( 〈 1%), and mutated in 16/147 (11%). The lesions with a significant impact at univariate were included in a multivariate analysis alongside MIPI, KMT2D inactivation and Ki67+ as continuous variable. Only TP53 inactivation by deletion and/or mutation, 7p22.2-p12.1 gain and KMT2D inactivation maintained their independent prognostic significance. Conclusions. Genome wide DNA profiling in the FIL-MCL0208 phase III trial identified lesions, namely TP53 and KMT2D inactivation and gains at 7p, which maintain a poor outcome significance in young MCL patients even following high-dose cytarabine and autologous stem cell transplantation. Disclosures Rossi: Gilead: Honoraria, Research Funding; Abbvie: Honoraria; Janseen: Honoraria. Stelitano:Azienda Ospedaliera: Employment. Gaidano:Janssen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Morphosys: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria.

Abstract: Primary cutaneous B-cell lymphomas (PCBCL) are a distinct group of primary cutaneous lymphomas with few and controversial reports on their treatment and prognostic factors. The aim of this retrospective study of a large international series of PCBCL patients was to analyze the patient and lymphoma characteristics as well as treatment-related variables associated with clinical outcome. From 1980 to 2006, 507 patients were referred to 19 cancer centers of 6 countries all over the world. The median age was 55 years (range,16–92 years) and the M/F ratio was 1.4. According to the WHO-EORTC classification indolent lymphomas included 341 FCL and 122 MZL, while aggressive NHL were represented by DLBCL, leg type (n=44). Sixty patients (12%) had stage II. The majority of cases was diagnosed in trunk/arms (52%), while in 29% in head/neck and in 13% in the legs; 7% of patients had a generalized disease ( 〉 1 site). The maximal lesion diameter was 〉 4 cm in 21% of cases and ≥2 lesions were recorded in 39%. The prevailing type of lesions were nodules (74%), while only a minority of patients (6%) were affected by tumors. Few patients had B symptoms (5%), poor ECOG-PS (9%) or elevated LDH (7%). Two hundred eighty-four out of 446 patients (64%) were treated only with surgery (n=86) or chemotherapy (n=95), mostly consisting of a short course of anthracyclin containing regimens, or radiotherapy (30–50 Gy) (n=103). One hundred sixty two cases (36%) received combined therapy, mostly including surgery or chemotherapy, followed by radiotherapy. A small subgroup of 35 patients were given rituximab alone (n=19) or in combination with other treatments. The remaining 26 patients did not receive any therapy. The response rate of 446 patients was the following: 402 achieved CR (86%), 38 PR and 6 were in SD. Neither histology nor treatment significantly influenced CR rate. Among 402 responders, 128 (32%) eventually relapsed, 86% in the skin, 10% in extracutaneous sites and 4% in both. The relapse rate varied according to histology, ranging from 52% in DLBCL leg-type to 29% in MZL and 28% in FL. Moreover, combined treatments significantly reduced relapse rate (24% vs. 37%; p=0.008). The achievement and maintenance of CR significantly influenced the long-term disease specific survival (at 20 year 99 % vs. 45%; p=0.0001). The CR rate of subgroup of 35 patients treated with rituximab, was 74%, while the relapse rate was 35%. These results were not influenced by the addition of other therapies to rituximab. After a median follow-up of 53 months (range, 2–333 months), 5 and 10-year estimate of OS, disease-specific survival, PFS and DFS were 91%, 92%, 61%, 65% and 82%, 88%, 49% and 56%, respectively. Cox multivariate analysis, stratified for age with a stepwise selection of the significant variables, identified DLBCL, leg-type histology, elevated LDH, type of lesion (nodules and tumors), B symptoms and female gender, as significant predictors of a poor OS. In conclusion this retrospective analysis confirms, on a large series of cases, that patients with PCBCL belong to different risk categories requiring a tailored treatment approach. These data can be usefully taken into account for an adequate management strategy of PCBCL patients.

Abstract: Abstract 1784 Introduction. The outcome of MCL is unfavourable, with continuous relapses. The MIPI, a clinical score, defined performance status, age, LDH and leucocyte counts as predictors of MCL outcome. Ki-67 as cell proliferation index was evaluated in biological-MIPI (MIPI-b). Aim of the study was to tested MIPI on a retrospective group of MCL patients treated with Rituximab-chemotherapy with or without High Dose Chemotherapy and autologous stem cell transplantation (R-HDC); secondary endpoints were: to evaluate the feasibility of MIPI-b on a retrospective population and to quantify the predictive discrimination of IPI, MIPI, MIPI-b on the outcome of MCL in the Rituximab era. Methods. Between 1999 and 2009, 206 MCL 〉 18 years at diagnosis consecutively treated in seven Italian institutions were included into the study. Histology was centrally reviewed and, if possible, Ki-67 evaluation was performed. Overall survival (OS) and failure-free survival (FFS) curves were estimated both overall and stratified by MIPI, MIPI-b and IPI score. Differences between curves were tested using the 2-tailed log-rank test. In order to quantify the predictive discrimination of MIPI, MIPI-b and IPI scores, a Cox's model analysis and univariate logistic models (with death and failure event as binary outcomes) were fitted and the area under the receiver operating characteristic (ROC) curves (c-index) was estimated in a subgroup of 120 patients that fulfilled MIPI, MIPI-b and IPI scores. Results. Clinical characteristics were: median age 61 (34-85) years, 78% stage IV, 73% with bone marrow involvement, 16% with blastoid variant; median leucocyte counts at diagnosis was 7.53×103 (2.38-175). First-line treatments were: R-HDC in 51%, Rituximab-Fludarabine based chemotherapy in 12%, Rituximab-CHOP in 32% and other Rituximab containing regimens in 5%. Ki-67 evaluation was performed in 135 patients; median Ki-67 value was 30%. Patients at high-risk (HR) were 29% according to MIPI, 18% according to MIPI-b and 33% to IPI. With a median follow-up of 48 months, 4-year OS was 72% (95% CI:65-78) and 4-year FFS was 49% (95%CI: 41–56). Four-year OS according to MIPI by risk groups was: LR 94% (95%CI: 85–97), IR 66% (95%CI: 47–80), HR 41% (95%CI: 26–55) and according to IPI: LR 87% (95%CI: 73–94), IR 88% (95%CI: 74–95), HR 41% (95%CI: 26–55) (Figure 1). In the subgroup of 120 patients that fulfilled MIPI, MIPI-b and IP scores an univariate logistic model and a Cox's model analysis were fitted. The c-index and Cox-index for death event were 76% and 75% for MIPI, 69% and 69% for MIPIb, 76% and 71% for IPI respectively; the c-index and Cox-index for failure event were 61% and 68% for MIPI, 59% and 64% for MIPIb, 68% and 66% for IPI respectively. A sub-analysis was conducted to validate the role of MIPI in R-HDC group; an univariate logistic model and a Cox's model analysis were fitted and the c-index and Cox-index for death event and for failure event were calculated (Table 1). Conclusions. MIPI score was confirmed as a good predictor of death event in MCL retrospective patients treated with Rituximab-chemotherapy regimens. MIPI score should be a good predictor of death event also in patients treated with R-HDC. The impact of MIPI-b score should be tested in prospective trials, with central histology review. New therapeutic strategies are warranted to improve the outcome of MCL namely in MIPI-HR group. Disclosures: No relevant conflicts of interest to declare.

Abstract: We compared clinical characteristics, prognostic factors and treatment outcome of primary thyroid DLBCL (PTL) with those of other locations of primary extranodal head and neck lymphomas (PEHNL) and we further analyzed somatic hypermutation in pts with PTL. From December 1990 to June 2004, 48 PTL out of 478 PEHNL patients (pts) (10%) were enrolled in this study, including 10 males and 38 females, with a median age of 73 years (range, 34–90 years). In comparison with other locations PTL cases had more frequently advanced age ( 〉 60 yrs), female sex, bulky disease, poor ECOG-PS, elevated LDH and 〉 1 adverse factors according to stage-modified IPI (MIPI). The commonest treatment was a short course of anthracycline-based chemotherapy (CHT) ± involved field radiotherapy (IFRT). Forty-two percent of PTL pts also underwent surgery. Clonal IGHVDJ rearrangements were analyzed in 17/48 cases. The CR rate of PTL pts (85%) was comparable to those of other locations. After a median follow-up of 41 months (range 1–154.months), 5-yr OS, EFS and DFS were 51%, 46% and 86%, respectively. The OS compared unfavourably with other locations (75%), while the disease-specific survival rate was similar in both groups (80%). Moreover, MIPI was not predictive of survival, probably due to a high mortality unrelated to disease (19% Vs 7%). Regarding treatment PTL pts seem to benefit more from surgery in combination with chemotherapy and/or IFRT than from other treatments not including partial or complete thyroid resection (p=0.04). Somatic hypermutation of IGHV genes was observed in the majority of PTL cases, suggesting that they derive from germinal center experienced B-cell, while the unmutated status in a fraction of pts indicates a different histogenetic and pathogenetic pathway. The significant clustering of S and R mutations in CDRs and FRs in a fraction of cases with high homologous CDR3 suggests that antigen stimulation may have an important role in the pathogenesis of these lymphomas. In conclusion, in spite of more adverse features at presentation PTL pts showed a favorable disease-specific survival, comparable to that of other PEHN. Biological study in PTL pts suggests different histogenetic and pathogenetic pathway. The comparison of thyroid biological profile with that of other PEHNL could help to clarify the different clinical behaviour of this uncommon malignancy.

Abstract: High-dose sequential (HDS) chemotherapy followed by ASCT proved to be an effective salvage therapy for patients (pts) with refractory or recurrent non-Hodgkin’s lymphoma (NHL) (Cortelazzo et al Br J Haematol, 2001). The addition of Rituximab to HDS (R-HDS) could enhance the sensitivity to rescue treatment improving the outcome of ASCT. We evaluated retrospectively clinical outcome of two consecutive cohorts of pts with low grade (LG) (n=55) or aggressive (LG-transformed=50, DLBCL=89) NHL treated with HDS chemotherapy with or without Rituximab. Regarding disease status at enrollment 135 pts (70%) were at high risk being primary refractory (n=84), early relapsed (≤12 months; n=21) or relapsed ≥2 (n=30). 86 pts were treated with HDS alone from 10/92 to 5/99 (group1), whereas 108 received R-HDS from 6/99 to 11/05 (group 2). Both groups were comparable regarding age, histology, disease status, B symptoms, bulky disease, bone marrow infiltration, median number of previous chemotherapies and IPI risk factors. After a debulking phase of 2–3 cycles of either doxorubicin- or cisplatin-containing chemotherapy pts received original HDS chemotherapy (n=91): high dose (HD)-cyclophosphamide (CTX) 7 gr/sqm, HD-methotrexate 8 gr/sqm, HD-etoposide 2 gr/sqm or a modified version (n=103) in which HD-methotrexate was replaced by HD-Ara-C (2 g/sqm every 12 hours for 6 days). Rituximab (375 mg/sqm) was given twice after HD-CTX and HD-Ara-C in 108 patients (56%). After HDS chemotherapy a BEAM or HD-mitoxantrone plus melphalan (60 and 180 mg/sqm) conditioning regimen with ASCT was planned. After HDS chemotherapy ORR was 84% in group 1 and 94% in group 2 with 29 and 81 pts achieving complete remission (CR) (34% vs. 75%; p=0.0001). Moreover, 76 pts (88%) in group 1 and 97 (90%) in group 2 underwent ASCT with a median number of 7.2 x 10^6 cells CD34+/kg (range, 3–27) transplanted. At the completion of treatment, 52 pts in group 1 and 94 in group 2 achieved CR (60% vs. 87%; p=0.0001). Regarding toxicity, 2 pts (2%) died in group 1 and one developed a bladder carcinoma, while in group 2 two pts (2%) died, one of secondary MDS and one developed a thyroid carcinoma. With a median follow-up of 36 months (range 3–154) in group 1 and 21 months (range 1–81 months) in group 2, the 5-year estimated OS, EFS and DFS were 47%, 33%, 49% and 75%, 60 %, 70% (p=0.0001). In Cox regression analysis LG histology (p=0.05), R-HDS therapy (p=0.04) and CR prior to ASCT (p=0.0001) emerged as favourable independent prognostic factors, while bulky disease (p=0.01) and ≥2 relapses (p=0.02) were adverse prognostic factors for EFS. This retrospective study shows that addition of Rituximab to HDS improves the CR rate increasing the number of transplant eligible subjects and prolongs survival of these high risk patients.