ALBERT

Description: Background. Similar probabilities of survival have been reported for patients transplanted from Matched Unrelated Donor (MUD), Umbilical Cord Blood (UCB) or Haploidentical (Haplo) donors as alternative hematopoietic stem cell sources. However, few studies have compared these results with those obtained in patients transplanted from HLA Id-siblings (Id-sib). Moreover, all reported studies are retrospective and the criteria of donor selection were not predefined. We report the intention to treat (ITT) analysis results on 238 patients with high-risk acute myeloid leukemia (AML) prospectively transplanted according to the policy of the Rome Transplant Network (RTN), a metropolitan transplant program established in Rome in 2006. Patients and Methods. For AML patients eligible to an allogeneic transplant, the RTN policy consists of an algorithm of donor choice based on a hierarchy according to the following criteria: 1) HLA identical sibling; 2) MUD ≥8/10 HLA 3) UCB as single unit selected on the base of cell dose and number of HLA disparities (0-1/6 HLA: TNC ≥2.5x107/kg and CD34 ≥1x105/kg; 2/6 HLA: TNC ≥3.5x107/kg and CD34 ≥2x105/kg); 4) G-CSF primed, unmanipulated bone marrow Haplo donor. Myeloablative (MAC) or reduced intensity (RIC) TBF (Tiothepa, Busulfan, Fludarabine) conditioning regimen was identical for all patients, GVHD prophylaxis was uniform for each categories. of transplant Results. From January 2006 to December 2014, 238(89%) out of 303 adult patients candidates to an allogeneic transplant for high-risk AML were considered eligible. Overall, a donor was available for 205 (86%) of 238 eligible patients. At time of the analysis, 17 of these 205 patients (8%) had lost the transplant eligibility and 4 (2%) were still scheduled for transplant, therefore 184/205 (90%) patients with an available donor were finally transplanted from Id-sib (n=76), MUD (n=38), UCB (n=17) or Haplo (n=53) donors. The 8-yrs overall survival (OS) of the 238 eligible patients from time of HLA typing and of the 184 transplanted patients from time of the graft was 40±4%and 43±4%, respectively. By excluding the low number of UCB recipients (n=17), the OS was particularly dismal for the 34 patients transplanted in advanced disease phase (7±4% at 4 yrs), whereas for the 132 patients transplanted in early (CR1+ CR2) phase the 8-yr OS was 56±5%: 58±7% for 61 HLA Id-sib, 50±8% for 40 Haplo and 63±10% for 27 MUD recipients (P=NS). The OS of patients transplanted in early phase was 63±5% for 97 patients receiving MAC and 33±9% for RIC recipients. For these 97 patients, the survival by type of donor was 62±10% either for 47 Id-sib or 28 Haplo and 70±10% for 22 MUD recipients (P=NS). The results were analyzed by various donor/recipient (D/R) combinations such as age, sex and CMV status. The median donor age was 39 years (range, 18-70) and the median patient age was 43 years (range, 16-59): the 8-yr OS of patients (n=30) with younger D/R combination (D

Description: Abstract 4995 Background. AL systemic amyloidosis is the most common and lethal form of amyloidosis. Macrophage inflammatory protein-1 alpha (MIP-1α) is a member of the CC chemokine family which is primarily associated with cell adhesion and migration. Adrenomedullin, and more the mid-regional fragment of proadrenomedullin (MR-proADM), comprising amino acids 45–92, have immune modulating, metabolic and vascular actions. Aims and Methods. Aim of the study was to evaluate MIP-1α and MR-proADM serum levels in patients with systemic AL λ amyloidosis at presentation to find out potential differences useful to define a characteristic inflammatory pattern. Blood samples were collected from 7 patients with systemic AL amyloidosis (median age 68 yrs) and from 10 age-matched healthy control individuals referred to our Unit and analyzed for serum MIP-1 α and MR-proADM levels. For every patient 1 sample of peripheral blood have been obtained. The blood was separated into plasma at the time of blood draw and frozen to −80°C. Two-group comparisons were performed using the Mann-Whitney U test and paired t test. Correlation analyses were performed using Spearman rank correlation. All statistical tests were two tailed and p 〈 0. 05 was considered statistically significant. Results. Serum MIP-1α levels were significantly higher in AL amyloidosis patients (median 25. 04 pg/mL; IQR 12. 77) compared to the control group (median 2. 54 pg/mL; IQR 0. 34; p=0. 0007). Also serum MR-proADM levels were significantly increased in AL amyloidosis patients (median 1. 15 nmol/L, IQR 0. 6 vs median 0. 42 nmol/L, IQR 0. 18; p=0. 0008). In addition, a positive correlation between MIP-1α and MR-proADM has been observed in the group of patients with systemic amyloidosis (r2=0. 82, p=0. 034). Conclusions. The increase of MIP-1α and MR-proADM serum levels in patients with systemic AL amyloidosis at presentation is indicative of active basal inflammation which can contribute to organ damage, in particular heart and kidneys, due to microvascular impairment. On the basis of our results, MIP-1α and MR-proADM could be used as new serum markers of inflammation in AL amyloidosis patients, with possible role in monitoring of organ damage. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2653 Background The impact of tumor presence on the immune competence of the host may be of particular relevance in the case of B cell neoplasia, as the tumor itself derives from immune system components; moreover, immune effector mechanisms are directly involved in determining the efficacy of chemioimmunoterapies. It has been previously noted that alterations of the absolute number of circulating monocytes and lymphocytes (peripheral blood monuclear cells, PBMC) are a of prognostic relevance in diffuse large B cell lymphoma (DLBCL). Aims To analyze the phenotypic and functional asset of PBMC in DLBCL at diagnosis, and to evaluate possible correlations of the immunological profile with tumor biological traits and patient's clinical features. Patients and Methods We compared 30 consecutive newly diagnosed DLBCL patients with 21 healthy, age- and sex-matched controls for: 1) absolute number (/μL) and percentage (over PBMC) of monocytes, B cells, T cell (CD4+, CD8+, CD4+CD8+ double positive, CD4-CD8- double negative, CD56+ T cells, and FOXP3+CD25bright regulatory T cells), and Natural Killer (NK) cell subsets (CD56dim, CD56bright, CD16+), measured by cell blood count and multi-parameter flow cytometric (FACS) analysis; 2) functional capability of individual T and NK cell subsets, by assessing the frequency of Interferon-gamma (IFN-γ) expressing cells and cytotoxic granule-containing cells; 3) natural and CD16-dependent NK cytotoxic activity, by 51Cr release assay, and 4) plasma concentration of selected cytokines, as evaluated with Bioplex. Results DLBCL patients showed several quantitative and functional alterations of the PBMC compartment. DLBCL patients showed a higher absolute monocyte number (p=.001), and a lower lymphocyte count (p=.001), thus resulting in a strongly reduced lymphocyte/monocyte ratio (p

Description: Abstract 2659 Background: Gene-expression-profiling defined at least two main groups within Diffuse-large-B-cell Lymphoma (DLBCL) patients who have substantially different outcomes: Activated-B-cell (ABC-type) and Germinal-Center-B-cell (GCB-type). The translation of gene-expression-profiling arrays into robust algorithm useful for clinical purposes is still in progress. The detection of IgM monoclonal component (IgM MC) in DLBCL has been previously described in a few reports, mainly because it was associated with autoimmune hemolytic anaemia. To our knowledge this is the first report describing the incidence and prognosis of a series of DLBCL with IgM MC. Aims: In this report we compared clinical and biological features of DLBCL patients with and without secretory IgM MC . Patients & Methods: Within a consecutive series of 132 patients, diagnosed between September 2004 and April 2012 with conventional DLBCL, 16 cases (12%) with a IgM MC were identified. We selected a set of 95 consecutive DLBCL patients, treated with 6–8 cycles of RCHOP-like for comparison of histological features and survival. Only cases with a follow up time 〉24 months were included, unless a DLBCL–related event (i.e. primary refractoriness or relapse) had occurred earlier. Biological material was obtained after receiving patient's consent. This study was approved by our Institutional-Review-Board. Immunohistochemistry and FISH: Paraffin sections were immunostained for CD3, CD5, CD20, CD10, CD30, CD79a, CD138, ALK-1, MUM1, BCL2, BCL6, IgM, Kappa and Lambda immunoglobulin light chains, using an automated immunostainer (DAKO, Denmark). The Hans algorithm was used in order to classify cases as GCB-type and non GCB-type. FISH with Vysis break-apart probe was used to assess c-MYC gene abnormalities in tissue sections (Abbott Molecular Inc. US). Statistics: univariate comparisons between groups were carried out with appropriate non parametric test. Survival analyses were done by the Kaplan-Meier method, the analyses of factor predicting survival were carried out by the log-rank test. Cox's regression was used for multivariate analyses. The SPSS19 package (SPSS Inc.Chicago IL) was used for elaborations. Histology, immunohistochemistry and FISH Results: In 14 out of 16 cases (87.5%) the IgM MC was related to the DLBCL clone. This was ascertained by immunostaining of cytoplasm for IgM, Kappa and Lambda immunoglobulin light chains. All the 14 cases were classified as non GCB-type. FISH analysis detected no c-MYC gene rearrangements in all the cases. Clinical Results: The incidence of bone marrow involvement, two or more extranodal sites, female sex, IPI score 3–5 and failure to achieve CR on RCHOP treatment were significantly more frequent in the IgM MC group. Noteworthy four out of 14 patients had central nervous system involvement at diagnosis or at relapse. All but one, with a previous diagnosis of marginal zone lymphoma, were de novo DLBCL. Twelve patients (85.7%) presented a DLBCL related event compared to 35 patients (37%) without IgM MC (p=.001). Seven patients (50%) died with primary refractory or relapsed-chemoresistant disease, another one died of an adverse event during chemotherapy. Two are alive on salvage treatment, two are in PFS at +30 and +13 months after salvage treatment with Bortezomib-RDHAP followed by high dose therapy. Only two patients are in PFS after first line RCHOP at +56 and +29 months respectively. Survival analysis: The estimated two-year EFS, PFS and OS were significantly worst for IgM MC group (22% Vs 70%, p

Description: From November 2012 to July 2014, brentuximab vedotin (BV) was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma (ALCL) outside a clinical trial context based on a local disposition of the Italian Drug Agency (AIFA) issued according to a national law (Law 648/96: "medicinal products that are provided free of charge on the national health service"). A large Italian observational retrospective study was conducted on the use of BV in the everyday clinical practice to check if clinical trial results are confirmed even in a real life context. Primary endpoint was the best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and the safety profile. BV was infused intravenously at the dose of 1.8 mg/kg every 3 weeks for a maximum of 16 cycles. A total of 40 ALCL (18 anaplastic lymphoma kinase [ALK] negative and 22 ALK-positive status) patients were treated with BV in 40 Hematology Centers. All patients had histologically documented CD30+ ALCL; 16 (40%) had relapsed and 24 (60%) had refractory disease. Patients were heavily pretreated with a median of 2 previous therapies (including autologous transplant in the 32.5% of cases). Best response was observed after a median of 4 cycles in 31 patients (77.5%): 19 (47.5%) patients obtained a complete response (CR) and 12 (30%) achieved a partial response (PR); overall response rate at the end of the treatment was 62.5% (18 CR and 7 PR). The best response rate was higher in the elderly subset (〉60 years): 9 (64.2%) CR and 3 (21.4%) PR, achieving a total of 85.6%. At the latest follow up 15/18 patients are still in CR (3 with consolidative procedure). Global progression free survival was 39.1% at 29 months and disease free survival 54% at 23.9 months (median not reached). Median duration of response was 12 months (range 9-24 months). We identified 5 long term responders (patients with a response ≥ 12 months), all were still in CR at the latest follow up (1 underwent allogeneic transplant). Particularly, all the long term responders were aged

Description: Abstract 4970 Background. The natriuretic peptides are a family of different biomarkers including NT-proBNP and MR-proANP. As recommended by guidelines, they are important in heart failure diagnosis and monitoring. MR-proANP (1–98) is the mid-regional portion of the active atrial natriuretic peptide prohormone (99–126) and is considered a significant independent predictor of death, adding prognostic value to NT-proBNP. Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen with angiogenic and nonangiogenic role in several disorders including cardiovascular ones. Moreover, it regulates multiple cellular stress responses, including survival, proliferation, migration and differentiation. Systemic AL amyloidosis represents a peculiar disease with a clinical heart involvement that needs of a specific monitoring in order to avoid poor outcome. Aims and Methods. The study was devoted to evaluate treatment related changes in cardiovascular activity by MR-proANP and VEGF serum levels in systemic AL amyloidosis. Blood samples were collected from 8 patients with systemic AL amyloidosis (median age 72. 8 yrs) admitted to our Unit and analyzed for serum MR-proANP (mean±SD) and VEGF levels (Kits Brahms MR-proANP Kryptor and Randox Evidence Biochips Arrays). According to age and disease risk stratification all patients were treated with upfront oral Mel-Dex association (Melphalan 9 mg/sm, Dexamethasone 20mg day 1–4 q28). From each patient 2 samples of peripheral blood were performed (T0: at exordium of disease and T1: at conclusion of the first course of treatment). The sera were frozen to −80°C until their use. The results were analyzed by paired t test and Person correlation, p values ≤ 0. 05 were considered statistically significant. Results. VEGF serum levels were significantly (p=0. 01) reduced at the end of the first course of treatment (M±SD: T0: 282. 3 ± 86. 23 pg/mL vs. T1: 189. 7 ± 64. 24 pg/mL). Also MR-proANP serum levels were significantly decreased (M±SD: T0: 204. 4 ± 28. 82 pmol/L vs. T1: 160. 2 ± 21. 05 pmol/L, p=0. 008; see figure). The decreases of VEGF and MR-proANP were significantly (r =0. 79; p=0. 02) related. Conclusions. MR-proANP serum levels reduction could be hypothized as related to the decrease of inflammatory activity of disease, including heart involvement and a consequent reduced probability of fatal events. Our hypothesis seems to be confirmed by VEGF serum level reduction suggesting an inhibition of new angiogenesis with reduced interactions between neoplastic plasma cells and bone marrow microenvironment. The effective role of treatment in reducing the disease activity is demonstrated by the significant correlation between VEGF and MR-proANP level decreases. MR-proANP and VEGF could be used to evaluate and select systemic AL amyloidosis patients with an early good response to treatment. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4951 Introduction. Azacitidine (AZA) has proven effective in myelodysplastic syndromes (MDS). The duration of haematological response is limited (median 13. 6 months) (Fenaux, 2009), although some patients (pts) show a prolonged response. The French Group (Itzykson 2011) identified some clinical and haematologic parameters (poor ECOG performance status, IPSS intermediate and poor risk cytogenetics, circulating blasts, high transfusion need) independently associated with a a poorer outcome, and these 4 criteria were integrated in a 3-group prognostic score, validated in other cohorts (van der Helm 2011; Breccia 2012). Moreover, a complex karyotype was also predictive of a shorter duration of response. However long term survival was also observed in some of the pts with poor risk features (Itzykson 2012). Methods. These data prompted us to retrospectively analyse our MDS pts treated with AZA who showed a favourable long-lasting response to AZA (i. e: duration of response ≥ 20 months), in order to enucleate the clinical and haematologic features of long-responder pts. The type of response was defined according to IWG criteria (Cheson 2006): Complete Remission (CR); Partial Remission (PR) and Hematologic Improvement (HI). The response duration was measured from the date of achievement of a first response (HI, PR or CR), (also in pts who subsequently achieved a higher response category) until the date of disease progression or death. Overall Survival (OS) was measured from the start of AZA treatment. Moreover, as some of us (Follo, 2009) demonstrated that phosphoinositide-phospholipase C (PI-PLC) beta1 may represent a target for AZA, in a subgroup of pts we quantified the degree of PI-PLCbeta1 methylation and gene expression before and during AZA administration. Results. Thirty-four pts (M/F: 20/14), from eight Institutions, with a median age of 72 (range 52–84) yrs, showed a response duration ≥ 20 months. At AZA onset, WHO diagnosis was: refractory anemia (RA): 1 pt; refractory cytopenia with multilineage dysplasia (RCMD): 1 pt; RCMD with ringed sideroblasts (RCMD-RS): 1 pt; refractory anemia with excess blasts (RAEB)-1: 8 pts; RAEB-2: 15 pts; cronic myelomonocytic leukemia(CMML): 4 pts; AML with 20–30% blasts: 3 pts, MDS with fibrosis (MDS-F): 1 pt. Four pts had therapy-related MDS. IPSS risk was: low: 3 pts; intermediate-1: 6 pts; intermediate-2: 20 pts, high: 5 pts. IPSS cytogenetic risk was: low: 21 pts (61. 8%); intermediate: 8 pts (23. 5%); high: 5 pts (14. 7%) (3 with complex karyotypes and 2 with isolated -7 or 7q-). ECOG-PS was poor (≥ 2) in 2 pts (5. 8%) and 〈 2 in the other 32 pts. Transfusion need was high (≥ 4 RBC units/8 weeks) in 17 pts (50%), and low or absent in the remaining 17 pts. Three pts (8. 8%) presented circulating blasts. Following Itzykson's AZA prognostic scoring system, the risk was low in 12 pts (35. 3%), intermediate in 21 pts (61. 8%), and high in 1 pt (2. 9%), respectively. Time from diagnosis to AZA onset was 〈 6 months in 21 pts, and 〉 6 months in 13 pts. The pts received a median of 22 cycles of AZA (range: 8–52). The median number of cyles to any first response was 4 (range: 2–10). Twenty pts (58. 8%) showed an at least two-fold increase of platelets after the first cycle of AZA. The best response achieved was: CR in 23 pts (67. 7%), PR in 2 pts (5. 8%), and HI in 9 pts (26. 5%). Cytogenetic remission was achieved in 7 pts (20. 6%). The median duration of response was 24. 5 (range: 23–88) months. A significant toxicity (grade 〉 2) was observed in 5 (14. 7%) pts. Twenty-two pts (64. 8%) are still maintaining hematologic response, 6 pts (17. 6%) are still alive but discontinued treatment because of disease progression, and 6 pts died, for AML (2 pts), infection (1 pt), haemorrhage (1 pt), myocardial infarction (1 pt), cachexy (1 pt), respectively. Median OS from the start of AZA was 35. 5 (range: 22–120) months. In a subgroup of pts, we observed an increase in PI-PLCbeta1 expression, that was maintained along with the hematologic response. Moreover, PI-PLCbeta1 early increase (during the cycles 1 to 3) was significantly associated with a higher duration of response. Conclusions. Although our data confirm the finding of other Authors, as the majority of long-responder patients showed pre-treatment favourable prognostic factors, a long-lasting hematologic response can be achieved even in a significant fraction of pts presenting one or more poor risk features (IPSS intermediate or high risk cytogenetics, high transfusion need). Disclosures: Finelli: Celgene Corporation: Research Funding, Speakers Bureau; Novartis: Speakers Bureau.

Description: Abstract 4958 Erythropoietin (EPO) have been widely employed in the treatment of patients with low-risk Myelodysplastic Syndromes (MDS) and anemia, with response rates ranging from 30 to 60%. These data, however, have been derived only from controlled clinical trials or unicentric single-arm studies; it is still lacking a wider survey evaluating the use of EPO in the real-life clinical practice. To address this issue, the Gruppo Romano Mielodisplasie (GROM) revised retrospectively 394 MDS patients (M/F 225/169, median age at diagnosis 73. 9 yrs, IR 67. 0 – 79. 3) treated with EPO from 1/2002 to 12/2010 by 11 Hematological Centers (5 university hospitals and 6 community-based hospitals) in the metropolitan area of Rome. According to WHO classification, there were 81 (20. 6%) patients with RA, 7 (1. 8 %) with SA, 160 (40. 7%) with RCMD, 17 (4. 3%) with RCMD-S, 75(19. 0%) with RAEB-1, 27 (6. 8%) with RAEB-2 and 27 (6. 8%) with isolated del5q. The IPSS score was calculated in the 307 patients with an available karyotype: 145 (47. 2%) patients were low-risk, 135 (44. 0%) int-1, 24 (7. 8%) int-2 and 3 (1. 0%) high-risk. Median interval from diagnosis to EPO start was 3. 7 months (IR 0. 9 – 12. 1). At EPO start, median age was 74. 5 yrs (IR 68. 3 – 79. 9) with a median haemoglobin level of 8. 9 g/dl (IR 8. 2 – 9. 6). Creatinine level was elevated in 64 (16. 2%) cases: 138 patients (35. 3%) had a previous transfusion requirement. Median serum EPO level was 50. 0 mU/L (IR 26. 2 – 110. 0). The initial doses of EPO were ≤ 40. 000 UI/week in 259 patients (65. 7%) (standard doses, α-EPO in 104 patients, β-EPO in 143 patients, darbepoietin in 12 patients) and 80000 UI/week in 135 patients (34. 3%) (high doses, α-EPO in 130 patients, β-EPO in 5 patients). An erythroid response was observed in 228 (57. 9%) patients, with Hb increase 〉 1. 5 g/dl in 210 patients (53. 3%) and disappearance of transfusion requirement in 18 (4. 6%): patients receiving initial high doses had a higher response rate compared to patients receiving standard doses [94/135 (69. 6%) vs 134/259 (51. 7%), p=0. 002]. Only 5 thrombotic events (1. 2%) were reported during the treatment. Predicting factors for erythroid response were no previous transfusion requirement (p

Description: The neutrophil/lymphocyte ratio (N/L) at diagnosis has been shown to be a prognostic factor for survival in solid tumors. An increase in the neutrophil count is a marker of inflammation which is an essential part of the neoplastic process. Conversely, a decrease of the peripheral lymphocyte count might reflect an impairment of the host defense mechanism associated with advanced and aggressive cancers. Since There are only few reports on the N/L ratio in non-Hodgkin lymphomas. We studied the prognostic role of the N/L ratio at diagnosis in 286 patients with diffuse-large-B-cell lymphoma (DLBCL) enrolled in a multicenter prospective registry of the Lazio region in Italy The median age at diagnosis was 69 years (27-91) and the female/male ratio was:141/145.First, we analyzed for associations between N/L ratio and patient characteristics. The optimal cut-off value for the N/L was obtained using the Receiver Operating Curve (ROC) and according to the published data in solid tumor. N/L ≥ 4 was significantly associated with presence of B-symptoms (p=0.01) and elevated LDH levels (p=0.007) at diagnosis. Most patients were treated with R-CHOP (rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone) or R-CHOP-like (90%). Complete Remission (CR) + Partial Remission (PR) were obtained in 210/286 (73%). The median follow up period was 15 months (range: 1-33 months): 27 patients died for lymphoma relapse/progression and 16 for other causes. Patients with N/L ≥ 4 experienced a higher rate of relapse, while N/L〈 4 was associated to a significantly better Overall (OS, P 〈 0.05) and Event Free Survival (EFS, P〈 0.01). (Figure 1, panel a and b).Furthermore, considering only patients with IPI score ≤ 3, those with N/L

Description: BACKGROUND: Elderly patients with Relapsed/Refractory (R/R) aggressive Large B-cell lymphoma (LBCL) and Peripheral T-cell lymphomas (PTCL), are commonly treated with intravenous conventional chemotherapies, which are often poorly tolerated and of short-lasting efficacy. Therefore only few fit-elderly patients might undergo intensive treatments with curative intent. Metronomic chemoterapy (MTN-CHT) is a new way of administering old drugs at low doses with only short chemotherapy free intervals. MTN-CHT may be combined with new targeted molecules, immunotherapies and radiotherapy. Although very few reports on MTN-CHT in LBCL and PTCL have been published existing data suggest that these lymphomas might respond to this approach. AIM: We aimed at demonstrating the efficacy and safety of MTN-CHT in a retrospective series of elderly patients with LBCL and PTCL, unfit for conventional treatments. PATIENTS AND TREATMENTS: From October 2008 up to May 2015 we treated elderly patients with R/R LBCL, Follicular Lymphoma(FL) and PTCL with MTN-CHT based regimen. Eligible patients should have given written informed consent, have a Performance Status=0-3, a life expection 〉2 months, be able to take oral therapy and have a care-giver. We used three different MTN schedules: 1] Provecip; 2] Vinblastine+Endoxan+Etoposide+Prednisone (VEED) and in the last two years an all-oral schedule 3] Navelbine+Endoxan+Etoposide+Prednisone (DE-VEC). All three schedules of MTN-CHT consisted of an induction phase of six months followed by a maintenance phase administered until progression or excessive toxicity. Rituximab was added to the induction phase for those patients characterized by CD20 expression. Thrombosis prophylaxis was carried out with aspirin or LMWH. RESULTS Patients features: LBCL=21; PTCL=7, FL=3; Age=77y (median, range 62-90), Previous CHT=2 (median, range 0-5) refractory to last CHT= 43%. MTN-CHT: 8 pts were treated with schedule 1], 8 pts with schedule 2] and 15 pts with schedule 3]. Outcome: in aggressive B and T-cell lymphomas (n=28pts) with all schedules Overall Response Rate = 62%, Complete Remission rate = 36%; Progression Free Survival = 8 months, Median Duration of Response (DOR)= 10 months. Overall Response Rate and Complete Remission in the subset treated with the all-oral DE-VEC schedule were 66% and 50% respectively. Serious adverse events: Extra hematologic toxicity grade 3-4: pulmonary embolism in 1pts; hematological toxicity of grade 3-4 and/or neutropenic infections in 6 patients 5 of whom had 〉2 previous conventional chemotherapies. The use of DE-VEC all-oral schedule reduced the number and the durations of day-hospital admissions. CONCLUSION Although our series is limited, these results suggest that MTN-CHT in elderly patients with R/R LBCL, PTCL and FL might achieve favorable results in terms of activity, toxicity and costs due to hospital admissions. With MTN-CHT most of the patients did not need G-CSF. Notably, patients who had had 〉2 lines of chemotherapies may be at very high risk of prolonged cytopenia and infections during MTN-CHT. Since the all-oral DE-VEC schedule was particularly manageable and active we believe that this combination deserve further investigation in aggressive lymphomas. Disclosures No relevant conflicts of interest to declare.