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The Elderly Prognostic Index (EPI) is based on the integration of a simplified geriatric assessment, hemoglobin levels and International Prognostic Index and has been validated to predict overall survival in older patients with diffuse large B-cell lymphoma (DLBCL). In this study, we evaluated the ability of EPI to predict the risk of early mortality. This study included all patients registered in the Elderly Project for whom treatment details and a minimum follow-up of 3 months were available. Three main treatment groups were identified based on the anthracycline amount administered: cases receiving70% of the theoretical anthracyclines dose (Full Dose [FD] group), ≤70% (Reduced Dose [RD]) and palliative therapy (PT; no anthracyclines). The primary endpoint was early mortality rate, defined as death for any cause occurring within 90 days from diagnosis. We identified 1150 patients with a median age of 76 years (range 65-94). Overall, 69 early deaths were observed, accounting for 19% of all reported deaths. The cumulative rate of early mortality at 90 days was 6.0%. Comparing early with delayed deaths, we observed a lower frequency of deaths due to lymphoma progression (42% vs. 75%; p 0.001) and a higher frequency due to toxicity and infections (22% vs. 4%, p 0.001, and 22% vs. 3%, p 0.001, respectively) for early events. A multivariable logistic analysis on 931 patients (excluding PT) confirmed an independent association of high-risk EPI (odds ratio [OR] 3.60; 95% confidence interval [CI] 1.15-11.2) and bulky disease (OR 2.08; 95% CI 1.09-3.97) with the risk of early mortality. The cumulative incidence of early mortality for older patients with DLBCL is not negligible and is mainly associated with non-lymphoma related events. For patients receiving anthracyclines, high-risk EPI and bulky disease are associated with a higher probability of early mortality.

The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added with CHOP. We designed a study combining romidepsin and CHOEP as induction before HDT + auto-SCT in untreated PTCLs (PTCL-NOS, AITL/THF, ALK-ALCL), aged 18–65 years. A phase Ib/II trial was conducted to define the maximum tolerated dose (MTD) of Ro-CHOEP, and to assess efficacy and safety of 6 Ro-CHOEP as induction before HDT. The study hypothesis was to achieve a 18-month PFS of 70%. Twenty-one patients were enrolled into phase Ib; 7 dose-limiting toxicities were observed, that led to define the MTD at 14 mg/ms. Eighty-six patients were included in the phase II. At a median follow-up of 28 months, the 18-month PFS was 46.2% (95%CI:35.0–56.7), and the 18-month overall survival was 73.1% (95%CI:61.6–81.7). The overall response after induction was 71%, with 62% CRs. No unexpected toxicities were reported. The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients.

PURPOSE To prospectively validate the use of a simplified geriatric assessment (sGA) at diagnosis and to integrate it into a prognostic score for older patients with diffuse large B-cell lymphoma (DLBCL). METHODS We conducted the prospective Elderly Project study on patients with DLBCL older than 64 years who underwent our Fondazione Italiana Linfomi original geriatric assessment (oGA) (age, Cumulative Illness Rating Scale for Geriatrics, activities of daily living, and instrumental activities of daily living) before treatment. Treatment choice was left to the physician's discretion. The primary end point was overall survival (OS) (ClinicalTrials.gov identifier: NCT02364050 ). RESULTS We analyzed 1,163 patients (median age 76 years), with a 3-year OS of 65% (95% CI, 62 to 68). Because at multivariate analysis on oGA, age > 80 years retained an independent correlation with OS, we also developed a new, simplified version of the GA (sGA) that classifies patients as fit (55%), unfit (28%), and frail (18%) with significantly different 3-year OS of 75%, 58%, and 43%, respectively. The sGA groups, International Prognostic Index, and hemoglobin levels were independent predictors of OS and were used to build the Elderly Prognostic Index (EPI). Three risk groups were identified: low (23%), intermediate (48%), and high (29%), with an estimated 3-year OS of 87% (95% CI, 81 to 91), 69% (95% CI, 63 to 73), and 42% (95% CI, 36 to 49), respectively. The EPI was validated using an independent external series of 328 cases. CONCLUSION The Elderly Project validates sGA as an objective tool to assess fitness status and defines the new EPI to predict OS of older patients with DLBCL.

The R-BAC regimen is considered among standard first-line treatment for elderly fit patients with mantle cell lymphoma (MCL). In the previous R-BAC500 FIL trial, patients with the blastoid variant and/or high Ki67 proliferative index (High Risk - HR-) had a significantly higher risk of progression (2-years PFS of 40%), as compared to classical histologies and low proliferative index (Low Risk -LR-). When treated with R-BAC, LR patients had excellent outcome (median PFS not reached after 7 years), although no maintenance therapy was delivered. For this reason we designed a phase 2 trial that enrolled patients from 35 centers of the Fondazione Italiana Linfomi (FIL). At study entry, patients were centrally reviewed and stratified as "low risk (LR)", or "high risk (HR)", depending on morphology (blastoid versus others), Ki67 expression (≥30% versus others), TP53 mutation/TP53 deletions (present versus not). Patients with any of the three risk factors were classified as HR. The primary endpoint was 2-years progression-free survival (PFS) for the HR patients. Patients had to be aged ≥65 years and fit according to the geriatric CGA assessment, or age ≤64 years if not eliglible to high-dose chemotherapy plus transplantation. Asymptomatic patients with non-nodal disease were excluded. Treatment consisted of 6 cycles of R-BAC (rituximab 375 mg/m2 d 1; bendamustine 70 mg/m2 d 1,2; cytarabine 500 mg/m2 d 1,2,3) for LR patients. HR patients received abbreviated induction with a maximum of 4 R-BAC followed by consolidation (4 months, 800 mg/d), and maintenance (20 months, 400 mg/d) with venetoclax. First patient was included on the 3rd of september, 2018, and last patient on the 20th of july, 2021. Overall, 140 patients were enrolled, of whom 52 were HR (37%). Median age was 72 (range 57-79), and 75% were males. The prevalence of TP53 mutations and deletions in the whole series was 21%, and 13%, respectively; Ki67 was ≥30% in 24%, and the blastoid variant was diagnosed in 9%. Demographic characteristics of HR versus LR patients (127 patients with available data at the present time) are reported in Table 1A. Median follow-up was 9 months (range 0-34). The two groups (HR and LR) had similar age, gender, and MIPI, but differed for LDH, and SUVmax at diagnosis, both being significantly more elevated in the HR group. The VR-BAC trial represents the first prospective study that stratified patients with MCL to different frontline treatments according to centralized on-time evaluation of the risk profile. We have shown that almost 40% of elderly patients with MCL in need of treatment have HR features. Data on tolerance, and tumor response will be presented at the meeting. Figure 1 Figure 1. Disclosures Tisi: GILEAD: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; BWS: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Takeda: Other: travel expenses, accommodation; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau. Corradini: AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Honoraria; BMS: Other: Travel and accommodation; Novartis; Gilead; Celgene: Consultancy, Other: Travel and accommodations; Amgen; Takeda; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations; KiowaKirin; Incyte; Daiichi Sankyo; Janssen; F. Hoffman-La Roche; Kite; Servier: Consultancy; Sanofi: Consultancy, Honoraria; Incyte: Consultancy; AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Consultancy; Novartis, Janssen, Celgene, BMS, Takeda, Gilead/Kite, Amgen, AbbVie: Other: travel and accomodations. Musuraca: janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Puccini: Takeda: Membership on an entity's Board of Directors or advisory committees. Cavallo: Servier: Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees; Gilead: Speakers Bureau. Merli: EUSA Pharma: Other: Travel, Accomodations, Expenses; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; MSD: Membership on an entity's Board of Directors or advisory committees; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Celgene: Other: Travel, Accomodations, Expenses. Ferreri: PletixaPharm: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Beigene: Research Funding; Hutchison Medipharma: Research Funding; ADC Therapeutics: Research Funding; Adienne: Membership on an entity's Board of Directors or advisory committees; Genmab: Research Funding; Amgen: Research Funding; x Incyte: Membership on an entity's Board of Directors or advisory committees; Ospedale San Raffaele srl: Patents & Royalties; Pfizer: Research Funding. Santoro: AstraZeneca: Speakers Bureau; AbbVie: Speakers Bureau; Amgen: Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Speakers Bureau; Sandoz: Speakers Bureau; Eli-Lilly: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Eisai: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Speakers Bureau; Sanofi: Consultancy; Arqule: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zinzani: KYOWA KIRIN: Other, Speakers Bureau; SERVIER: Other: Advisory board, Speakers Bureau; SANDOZ: Other: Advisory board; TG Therapeutics: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; BMS: Other: Advisory board, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; MSD: Consultancy, Other: Advisory board, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; Beigene: Other, Speakers Bureau; ADC Therap.: Other; Incyte: Other, Speakers Bureau; JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; GILEAD: Other: Advisory board, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. OffLabel Disclosure: Venetoclax is off-label in Italy in mantle cell lymphoma

Background. Immunochemotherapy is effective in follicular lymphoma (FL), but most patients (pts) eventually relapse. MRD analysis, based on the detection of Bcl-2/IGH rearrangement by highly sensitive PCR-based tools, is effective in identifying pts at risk of relapse [Ladetto Blood 2012; Pott EHA23]. However, several issues are still unresolved, including: i) which is the best tissue source and the most reliable technique; ii) which are the most predictive time points; iii) which is the role of disease kinetics during the long natural history of FL. The FIL FOLL12 prospective, phase III randomized clinical trial (EudraCT: 2012-003170-60) included a systematic MRD analysis on both peripheral blood (PB) and bone marrow (BM) taken at eight different pre-planned time points, by both nested and real time quantitative (RQ)-PCR. Therefore, it allows addressing these unresolved issues. Methods. The FOLL12 compared conventional rituximab maintenance [Salles et al, Lancet 2010] vs a combined PET/MRD response-based post-induction approach in pts with advanced FL after first line chemo-immunotherapy. Clinical results have been already reported [Luminari et al, ICML16]. PB and BM samples were centralized at four Italian Euro-MRD certified laboratories. MRD was assessed with consensus primers on Bcl-2/IGH rearrangements (MBR, mcr and minor rearrangements) by both nested and RQ-PCR at eight time points: baseline, end of induction (EoI) and every six months thereafter till month 36. MRD data were treated as a time-varying covariate and analyzed by means of flexible parametric survival model (Parmar-Royston) with the log cumulative baseline hazard function. MRD data were modeled with restricted cubic spline as function of time. Effect of fixed covariates and landmark analysis were performed with the Cox PH regression. Any estimation was reported with its 95%CI. Results. Overall, 10,702 analytical results were generated, (3,000 for marker screening and 7,702 for MRD). 780 of 786 eligible pts (99%) were screened at baseline for the presence of a molecular marker. 443/780 (57%) had a detectable Bcl-2/IGH rearrangement, as expected. High rates of MRD negativity were observed at EoI, with similar results by both techniques (87% in BM and 95% in PB by nested-PCR, 90% in BM and 95% in PB with RQ-PCR). Overall, the presence of one MRD positive result was associated during the entire follow-up period with an increased risk of relapse in the subsequent six months interval (HR for PFS 2.82, 95% CI 1.84-4.34, p Conclusions. This comprehensive MRD study in FL clearly indicates that: i) punctual MRD analysis is predictive of poor outcome at multiple pre-planned time points taken over a 36 months period; ii) both nested and RQ-PCR performed adequately, the latter being preferable as broadly used and internationally standardized; iii) BM allows better prediction at the early time points but, starting from month 12 after EoI PB is superimposable to BM, allowing effective and reliable long-term non-invasive MRD monitoring; iv) the high predictive value of punctual time point analysis is further improved by a kinetic approach to the interpretation of MRD results. Figure 1 Figure 1. Disclosures Ladetto: AbbVie, Jazz, Gentili, Incyte, ADC Therapeutics, Acerta, Pfizer: Honoraria; Roche, J&J, Celgene, Novartis, Amgen, Gilead, Beigene, GSK: Honoraria. Ferrero: Servier: Speakers Bureau; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Morphosys: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees; Gilead: Research Funding, Speakers Bureau; Clinigen: Membership on an entity's Board of Directors or advisory committees. Del Giudice: Tolero: Membership on an entity's Board of Directors or advisory committees; Astrazeneca: Membership on an entity's Board of Directors or advisory committees. Galimberti: Incyte: Speakers Bureau; AbbVie, Janssen: Honoraria, Other: Travel grants. Gattei: abbVie: Research Funding; Janssen: Research Funding; Menarini: Research Funding. Mannina: Janssen,Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Falini: Rasna Therapeutics: Honoraria. Luminari: Roche, Celgene, Teva Pharmaceuticals, Gilead Sciences, and Takeda Pharmaceuticals: Honoraria.

Introduction: Peripheral T-cell lymphomas (PTCL) have a 40-50% cure rate when treated with cyclophosphamide-doxorubicin-etoposide-vincristine-prednisone (CHOEP) and hematopoietic stem cell transplantation (HSCT). Romidepsin, a histone deacetylase inhibitor, showed promising activity in relapsed or refractory PTCLs. Methods: On these premises, we designed a phase I/II trial (PTCL13 NCT02223208) to evaluate whether the addition of romidepsin to CHOEP improves the outcome of newly diagnosed PTCLs. In the phase Ib part of the study, we defined 14 mg/ms as the maximum tolerated dose of romidepsin when administered in combination with CHOEP (Ro-CHOEP). Thus, in the phase II part of the study we evaluated the efficacy of Ro-CHOEP followed by HSCT in young patients. The primary objective of the study was to demonstrate a 15% increase in 18-months progression-free survival (PFS) for the combination Ro-CHOEP plus HSCT (from 55% to 70%, planned sample size=110), compared to the previous Italian trial (Corradini P et al, Leukemia 2014). Patients aged 18-65 years with stage II-IV PTCL-NOS, angioimmunoblastic/T follicular helper (AITL/THF) and ALK negative anaplastic large cell lymphoma, were eligible. Treatment plan consisted of 6 courses of Ro-CHOEP every 21 days (14 mg/ms Ro day 1 and 8), followed by cisplatin-cytarabine-dexamethasone (DHAP) with stem cell harvest and HSCT. Patients in complete response (CR) after induction proceeded to autoHSCT, while those in partial response (PR), with an available HLA-matched donor, proceeded to alloHSCT upfront. Results: From September 2017 to October 2020, 86 patients were enrolled into the phase II part of the study; median age was 55 years (IQR 49;60); 78 (91%) had stage III-IV and 31 (36%) IPI score >2. Pathological materials were collected at the time of diagnosis, and centrally reviewed by expert hemo-pathologists; subgroups were: 33 PTCL-NOS, 21 ALK negative, 31 AITL/THF, and one case not classified due to inadequate material. According to the statistical plan, an interim analysis was performed on the first 75 patients. At a median follow-up of 26 months, the 18-months PFS was 48% (95% CI: 0.36-0.58) and the OS was 75% (95% CI: 0.64-0.83). The 18-months PFS for PTCL-NOS versus ALK negative vs AITL/THF was 37% (95% CI: 0.20-0.54) vs. 51% (95% CI: 0.28-0.70) vs. 58% (95% CI: 0.36-0.74), p 0.118; the 18-months OS for PTCL-NOS vs. ALK negative vs. AITL/THF was 72% (95% CI: 0.51-0.85) vs. 76% (95% CI: 0.51-0.89) vs. 81% (95% CI: 0.60-0.92), p 0.957. All 86 patients completed the induction phase and were evaluable for response after 6 Ro-CHOEP: the overall response rate (ORR) was 71% (61 patients), with 62% (53 patients) CR. Four patients with ongoing treatment are not evaluable for response at the end of therapy, at the time of the analysis. Only 39 of 82 patients (48%) underwent HSCT and 43 did not: 28 due to progressive disease, 8 for poor mobilization, 7 for adverse events (1 sepsis, 2 cardiological events, 4 others). Among the 82 patients evaluable for response at the end of treatment, the final ORR after HSCT was 40% (33 patients), with 39% CR (32 patents). The most frequent toxicities during Ro-CHOEP treatment were hematological, with grade 3-4 neutropenia and thrombocytopenia in 33% and 34% of all the 459 cycles, respectively; severe febrile neutropenia was reported in only 4% of Ro-CHOEP courses. Severe non-hematological toxicities were observed in 35 (41%) of patients: cardiological in 5 patients (6%), gastrointestinal in 9 (10%), infections in 10 (12%), others in 11 (13%). Twenty-four deaths were recorded: 22 due to lymphoma progression, 1 due to transplant related mortality for a septic shock after alloSCT, 1 due to secondary malignancy. Conclusions: In the PTCL13 phase I part of the study we demonstrated the feasibility of the combination Ro 14 mg/ms plus CHOEP followed by high-dose chemotherapy and HSCT; in the phase 2 part of the study, the primary objective was not achieved, with a 18-months PFS of 48%. Based on these results, the enrollment of the trial was stopped due to inefficacy of the experimental combination. The benefit of adding romidepsin to chemotherapy was not observed neither in PTCL-NOS nor in AITL/THF. In conclusion, the addition of romidepsin to CHOEP did not ameliorate prognosis in newly diagnosis PTCLs eligible to HSCT. Disclosures Chiappella: Roche: Other: lecture fee, advisory board; Incyte: Other: lecture fee; Takeda: Other: advisory board; Celgene Bristol Myers Squibb: Other: lecture fee, advisory board; Clinigen: Other: lecture fee, advisory board; Novartis: Other: lecture fee; Janssen: Other: lecture fee, advisory board; Gilead Sciences: Other: lecture fee, advisory board; Astrazeneca: Other: lecture fee; Servier: Other: lecture fee. Flenghi: Roche: Other: Travel, Accomodations, Expenses; Janssen: Other: Travel, Accomodations, Expenses. Zilioli: Gentilli: Consultancy, Speakers Bureau; Takeda: Consultancy, Other, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; MSD: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Italfarmaco: Consultancy. Cavallo: Servier: Speakers Bureau; Gilead: Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees. Musuraca: roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Varettoni: janssen: Membership on an entity's Board of Directors or advisory committees; beigene: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; roche: Membership on an entity's Board of Directors or advisory committees. Corradini: Incyte: Consultancy; Novartis, Janssen, Celgene, BMS, Takeda, Gilead/Kite, Amgen, AbbVie: Other: travel and accomodations; BMS: Other: Travel and accommodation; Sanofi: Consultancy, Honoraria; Novartis; Gilead; Celgene: Consultancy, Other: Travel and accommodations; Amgen; Takeda; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations; KiowaKirin; Incyte; Daiichi Sankyo; Janssen; F. Hoffman-La Roche; Kite; Servier: Consultancy; AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Honoraria; AbbVie, ADC Theraputics, Amgen, Celgene, Daiichi Sankyo, Gilead/Kite, GSK, Incyte, Janssen, KyowaKirin, Nerviano Medical Science, Novartis, Roche, Sanofi, Takeda: Consultancy. OffLabel Disclosure: Romidepsin is not registered in first line treatment. Romidepsin was provided free for the clinical trial.

Introduction Non-pegylated liposomal doxorubicin (NPLD) is considered a good alternative to conventional doxorubicin for the treatment of older patients (pts) with aggressive lymphomas and/or at high risk for cardiological toxicity. The use of R-COMP for the treatment of older pts with DLBCL has been supported by several small retrospective studies . In this report we describe the characteristics and outcomes of pts who were prospectively enrolled in the Elderly Project (EP) and who were treated with R-COMP and compared them with pts treated with conventional R-CHOP. Methods. This analysis was conducted starting from the dataset of the EP study. The use of NPLD was allowed according to 648/96 law, treatment decision was left to physician discretion and was independent of frailty status. For the purposes of this analysis, we included all pts who were treated with full doses of R-CHOP and R-COMP. The study endpoint were progression free survival (PFS) and overall survival (OS). A propensity score analysis was conducted to account for the main confounding factors. Results Overall 691 out of 1163 pts of the EP were treated with R-CHOP (383; 55%) or R-COMP (308; 45%); median age was 71 and 76 years for R-CHOP and R-COMP, respectively (p < 0.001) (Table 1). Pts were similarly distributed among different IPI groups for R-COMP or R-CHOP. Based on simplified Geriatric Assessment (sGA) 88%, 11% and Conclusions Data from the prospective observational EP study did not show significant differences in terms of efficacy comparing R-COMP to standard R-CHOP. The higher frequency of UNFIT and FRAIL pts among those treated with NPLD suggests R-COMP is a good strategy to offer a curative treatment to these groups of pts. Figure 1 Figure 1. Disclosures Merli: EUSA Pharma: Other: Travel, Accomodations, Expenses; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; MSD: Membership on an entity's Board of Directors or advisory committees; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Celgene: Other: Travel, Accomodations, Expenses. Tucci: janssen: Membership on an entity's Board of Directors or advisory committees; Gentili: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Rigacci: Merck: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Gilead Science: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Menarini: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cavallo: ROCHE: Membership on an entity's Board of Directors or advisory committees; Servier: Speakers Bureau; Gilead: Speakers Bureau. Fabbri: Servier/Pfizer: Honoraria; Takeda: Other: Travel, Accomodations, Expenses; Takeda: Honoraria. Puccini: Takeda: Membership on an entity's Board of Directors or advisory committees. Ferrero: Incyte: Membership on an entity's Board of Directors or advisory committees; Morphosys: Research Funding; Gilead: Research Funding, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; EUSA Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Speakers Bureau; Clinigen: Membership on an entity's Board of Directors or advisory committees. Zilioli: Roche, Italfarmaco: Consultancy, Honoraria; MSD, Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations; Gentili, Takeda, Gilead, Servier: Consultancy, Speakers Bureau; Takeda: Other: travel expenses, accommodation. Nassi: Takeda: Consultancy; Kyowa Kirin: Consultancy; Incyte: Consultancy; Roche: Consultancy. Musuraca: Janssen, Incyte, Roche: Consultancy; Janssen, Roche, Incyte: Membership on an entity's Board of Directors or advisory committees; Janssen, Roche, Incyte: Honoraria. Flenghi: Janssen: Other: Travel, Accomodations, Expenses; Roche: Other: Travel, Accomodations, Expenses. Marcheselli: sandoz: Membership on an entity's Board of Directors or advisory committees. Luminari: Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accomodations, Expenses; Janssen: Other: Travel, Accomodations, Expenses; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy; GENELAB SRL: Consultancy.

The basis of allogeneic hemopoietic stem cell (HSC) transplantation in thalassemia consists in substituting the ineffective thalassemic erythropoiesis with and allogeneic effective one. This approach is an efficient way to obtain a long lasting, probably permanent, clinical effective correction of the anaemia avoiding transfusion requirement and subsequent complications like iron overload. The first HSC transplant for thalassemia was performed in Seattle on Dec 2, 1981. In the early eighties transplantation procedure was limited to very few centres worldwide. Subsequently between 17 December 1981 and 31 January 2003, over 1000 consecutive patients, aged from 1 to 35 years, underwent transplantation in Pesaro. After the pioneering work by the Seattle and Peasaro groups, this therapeutic approach is now widely applied worldwide. Medical therapy of thalassemia is one of the most spectacular successes of the medical practice in the last decades. In recent years advances in knowledge of iron overload patho-physiopathology, improvement and diffusion of diagnostic capability together with the development of new effective and safe oral chelators promise to further increase success of medical therapy. Nevertheless situation is dramatically different in non-industrialized countries were the very large majority of patients live today . Transplantation technologies have improved substantially during the last years and transplantation outcome is likely to be much better today than in the ‘80s. Recent data indicated a probability of overall survival and thalassemia free survival of 97% and 89% for patients with no advanced disease and of 87% and 80% for patients with advanced disease. Thus the central role of HSC in thalassemia has now been fully established. Thalassemia remains the only definitive curative therapy for thalassemia and other hemoblobinopathies. The development of oral chelators has not changed this position. However this has not settled the controversy on how this curative but potentially lethal treatment stands in front of medical therapy for adults and advanced disease patients. In sickle cell disease HSC transplantation currently is reserved almost exclusively for patients with clinical features that indicate a poor outcome or significant sickle-related morbidity.

Background. Autologous stem cell transplant is a consolidation treatment for standard risk acute myeloid leukemia (AML). Traditional preparative regimens, most of all Busulphan (Bu) based, have been widely used, but the relapse risk is high and extra hematologic toxicity is a concern. Even if the combination of Busulphan intravenous formulation in association with cyclophosphamide has shown lower toxicity and suggests favorable safety and efficacy, new drugs associations are continuously explored. Methods. Since April 2004 to January 2013, 39 consecutive patients (20 males, 19 females ) entered this study. Median age at transplant was 51 years (range 21-79). Cytogenetic risk classification at diagnosis was good in 4, intermediate in 29 and poor in 6. At transplant time thirty-six patients were in first complete remission, one in partial remission and two in second complete remissions. Mean number of induction chemotherapy courses received was 2.2. Conditioning consisted of oral Busulfan/Cyclophosphamide in 13, intravenous once-daily infusion Busulphan/Cyclophosphamide in 11, intravenous Busulfan/Fludarabine in 8, intravenous Busulphan /Melphalan in 3, Treosulfan/Cyclophosphamide in 3 and Treosulfan /Melphalan in 1. In all patients aged less than 70 years an extended patient and family HLA typing was performed at diagnosis to eventually plane a salvage allogeneic transplant since the beginning of the therapy course. Cytogenetic risk, status of disease, age, number of chemotherapy courses, conditioning regimens have been analyzed. Primary objective was evaluation of overall survival, disease free survival, transplant related mortality and relapse. Comparison analyses were performed with chi square test. All analyses were intention to treat. Results: Of the 39 patients studied one patient (2.5%) died for intracranial haemorrhage during the period of aplasia. All the other engrafted. Of the latter all but one had sustained long-term engraftment. Fourteen patients (36%) did not relapse; all but one are alive and well in continuous complete remission. The only patient who died in remission had lethal infection after salvage allogeneic transplant performed for persistent cytopenias. Twenty-four patients (61%) relapsed Of the 24 relapsed patients eleven (46%) received a second allogeneic transplant after re-induction chemotherapy (all but one from alternative donors: 8 from a matched unrelated donor, 1 from an aplo-identical family member and one from an unrelated cord blood donor). Of them six have died by transplant related mortality and 5 are alive (4 in complete remission). Overall nineteen over 39 patients (49%) are alive after a median follow up of 60 months (range 18-120); seventeen (44% of the entire cohort) in complete remission and two with persistent disease. As regard the 13 patients who didn’t relapse all were transplanted in first complete remission; cytogenetic risk was good in 2, intermediate in 10 and poor in 1; leukemia chemotherapy induction was standard Daunoblastina- Cytarabine (3+7 schedule) in all; transplant conditioning regimens were oral Busulphan/Cyclophosphamide in 6 and intravenous once-daily dose Busulphan in association with cyclophosphamide or Fludarabine in 7. In our analyses the only risk factor impacting on patients’ outcome was patient age at transplant time. Age impacted overall survival and disease free survival. Median age was 61years (range 21-79 ) in patients who died versus 36 years (range21-68) in patients alive (P = 0.03 ) and 64 years ( 21-79) in patients with relapse versus 36 years (21-60) in patients who didn’t relapse (P = 0.04). No other factor had impact on outcome. Conclusion. This limited, single centre experience, confirms that autologous hematopoietic stem cell transplant is an efficient consolidation treatment for AML in remission. Relapse still remains the major problem even if some selective patients may be rescued by allogeneic transplant after a re-induction strategy. A complete HLA family study and preliminary unrelated research should be early performed in all patients for optimal treatment plan and decision. Disclosures No relevant conflicts of interest to declare.

Background The management of high dose chemotherapy followed by autologous or allogeneic hemopoietic stem cell transplantation requires an intravenous line for administrations of high-dose chemotherapy, blood and platelet transfusions, antibiotics and parenteral nutrition. In this context a safe central venous access is a basic tool for patients management. The aim of our phase II prospective study is to evaluate feasibility, safety and cost of the use of peripherally inserted central catheters (PICC) for the management of hemopoietic stem cell transplantation. Methods Inclusion criteria included inpatient who needed program of autologous and allogenic hematopoietic stem cell transplantation regardless the underlined hematological disease or white cells and platelets counts. All patients were submitted to a preliminary evaluation of arms vascular anatomy by ultrasonography. All implantation procedures has been done under ultrasound guide with radiographic control after insertion. The PICC cost analysis was performed on the cost of devices, insertion and daily management and compared with a historical cohort of patients with short term central venous catheter (CVC). The study was approved by institutional review board. All patients provided a written informed consent. Results From March 2007 to July 2013 76 consecutive PICC have been implanted in 74 patients for autologous or allogenic stem cell transplantations. There were 37 male and 37 females. Median age was 55 years, range 22-70. With regard to disease, 11 patients (15%) had Hodgkin Lymphoma, 13 (17.5%) non Hodgkin lymphoma, 9 (12%) acute lymphoblastic leukemia, 35 (47%) multiple myeloma, 4 (5.5%) acute myelogenous leukemia, and 2 (3%) other hematological disease. Fifty-five PICC (72%) have been used for single autologous stem cell transplantation, 10 (13%) for double autologous stem cell transplantation and 11 (15%) for allogenic transplantation. Catheter insertion was successful in all instances. PICC median life was 119 days (1-457) for a total of 10877 days of implanted PICC. At the time of this analysis 4 out of 76 PICC (5%) are still “in situ” and in use and 72 (95%) have been removed. Reason for removal was end of therapy in 58 instances (80.5%), accidental withdrawal in 8 (11%), patient death in 1 (1.5%) and catheter related complication in 5 (7%). Catheter related complications were the following: 2 occlusions, 3 suspected PICC-related sepsis. Only 1 episode of confirmed PICC-related septicemia (0.1/1000 days/PICC) was recorded and S.Aureus was isolated. There were only 2 cases (2.6%) of symptomatic PICC-related thrombotic complications which has requested conservative management. Twenty-five of 76 PICC (33%) were power PICC. No patients presented the need for a additional central venous access. Regarding the economic aspect, the actual daily cost of PICC was 1.98 €/day versus 3.40 €/day of the short term CVC (45% lower). Conclusions These data encourage the use of PICC in the autologous and allogenic stem cell transplantation because of insertion easiness, duration of life, cost and low rate complication. Disclosures: Off Label Use: Bendamustine.