ALBERT

Description: Introduction: Given the critical role of BCR–ABL kinase activity in chronic myeloid leukemia (CML), tyrosine kinase inhibitors (TKIs) are currently considered the cornerstone of CML treatment. Previous studies have suggested that TKIs may influence anti-tumor immunity through off-target modulation of different immune effectors. Natural killer (NK) cells, as well as T cells in the context of adaptive immunity, are a key component of the innate immune system, providing first-line defense against virally infected cells and tumors. The activity of NK cells is modulated by a finely-tuned balance between signals received from inhibitory and activating cell surface receptors. Aims: We sought to evaluate the impact of first and second generation TKIs on modulating different NK cell receptors patterns; secondly we studied the effect of a TKIs driven NK subpopulations selection on treatment response. Finally, we analyzed the T cells Vβ-TCR repertoire to identify any restrictions. Materials and Methods: Peripheral blood samples from 25, 9 and 8 chronic phase CML patients treated with imatinib frontline, nilotinib and dasatinib as first or second line therapy, respectively, were collected. Patients characteristics are described below (see table 1). After separation of mononuclear cells (PBMC), the expression of several NK cell receptors (Killer Immunoglobulin-like Receptors, KIR: p70, p140, p58/p50; Killer Lectin-like Receptors, KLR: CD94, NKG2A, NKG2C/A, NKG2D; Natural Cytotoxicity Receptors, NCR: NKp30, NKp44, NKp46, NKp80; Co-receptors: 2B4; LIR1/ILT2, GPR56) and Vβ TCR-repertoire were analized by flow cytometry analysis. Treatment response was assessed with standardized real quantitative polymerase chain reaction and cytogenetics according to ELN recommendations. Results: The leukocyte count was not statistically different between groups (WBC = 5.5 x 109 / L vs. 6.8 x 109 / L vs. 5.6 x 109 / L, p = 0.09, respectively); also lymphocytes, considered either in percentage or absolute number, were comparable (32% vs 26% vs 35%, p = 0.08), as well as the percentage and absolute number of NK cells (20%; 0.37 x 109 / L vs. 15%; 0.26 x 109 / L vs. 24%; 0.54 x 109 / L (p = 0.17, p = 0.10).The analysis of NK receptors expression showed that patients treated with Imatinib exhibited a preferential selection of NK cells subpopulations harboring activating receptors (NKp30, NKp46, NKp80 and NKG2D), while in Dasatinib treated patients an increased expression of KIR (KIR2DL1) receptors was observed (figure 1). Interestingly, these effects were documented also in the absence of lymphocytosis. 44.4% (4 of 9 patients) of patients treated with nilotinib showed preferential expression of Vβ chains, compared with 87.5% of patients treated with dasatinib; no TCR-repertoire restriction was documented in the sole TKI primary resistant patient. 8 out of 17 patients showed a preferential expression of more than oneVβ chain (figure 2). No specific NK receptors profiles were found to be associated with different degrees of treatment response. Conclusions: These preliminary data suggest the existence of a different NKRs and T cell receptor repertoire modulation, mediated by Tyrosine-Kinase Inhibitors. Since no significant correlation between response and specific NK receptor profiles has been demonstrated, TKIs immunomodulatory effect seems secondary compared to direct inhibition of BCR-ABL kinase. However, it's conceivable that NK and T cells subpopulations selection, induced by TKIs, may become relevant in the immunological control of leukemic disease at the time of drug discontinuation. These observations are currently being investigated on a larger series of patients. Figure 1 NK cell receptors differentially expressed between imatinib, nilotinib and dasatinib treated patients. Figure 1. NK cell receptors differentially expressed between imatinib, nilotinib and dasatinib treated patients. Figure 2 Figure 2. Figure 3 T cell receptor repertoire in nilotinib (A) and dasatinib (B) treated CML patients Figure 3. T cell receptor repertoire in nilotinib (A) and dasatinib (B) treated CML patients Disclosures No relevant conflicts of interest to declare.

Description: INTRODUCTION. Resistance to carbapenems by Klebsiella pneumoniae (KP) isolates has become a significant problem in recent years in several countries, and has been recently highlighted as one of the major emerging causes of severe and fatal infections in patients suffering from hematological malignancies (HM). The aim of the present study was to identify risk factors for mortality in HM patients with concurrent bloodstream infections (BSIs) caused by KP. Particular attention was focused on defining the impact of carbapenem resistance by the bacterial isolates on mortality. METHODS. We conducted a prospective cohort study including all consecutive cases of BSIs caused by KP diagnosed in 13 Italian hematological units participating to HEMABIS registry-SEIFEM group. The outcome measured was death within 30 days of the first positive blood culture. Survivor and non-survivor subgroups were compared, and logistic regression analysis was conducted to identify independent predictors of mortality. RESULTS. A total of 278 episodes of KP BSI were included in the study between January 2010 and June 2014. One hundred-sixty-one (57.9%) KP isolates were carbapenem resistant (CRKP). The rate of carbapenem resistance among KP isolates significantly increased from 21.4% in 2010 to 75.9% in 2013 (P

Description: Introduction. In a modern context of improved management of acute lymphoblastic leukemia (ALL), central nervous system (CNS) involvement at diagnosis remains an obstacle towards long-term cure. We have previously reported that flow cytometry (FCM) is better than conventional cytology (CC) in demonstrating the presence of leukemic cells in patients' (pts) cerebrospinal fluid (CSF), especially in samples with low cell counts. In the framework of the national Campus ALL program aimed at improving the management of adult ALL patients enrolled in the GIMEMA protocols, we retrospectively evaluated the incidence of occult CNS positivity and its impact on outcome in 221 adult pts with newly diagnosed ALL from 11 centers. Methods. Ninety-four patients (42%) were females and 127 (58%) males, with a median age of 44 years (range 17-80), a median white blood cell (WBC) count of 10.6x109/L (range 0.1-457). One hundred and seventy pts (77%) had B-lineage ALL. Cytogenetic/genetic data were available in 167 (75%) pts: 58 (35%) had a BCR/ABL rearrangement, 14 (8%) a complex karyotype and 11 (6%) a MLL rearrangement. Pts were treated according to the GIMEMA/NILG ALL protocols or with the Hyper-CVAD program. Ninety-eight pts underwent an allogeneic stem cell transplant (ASCT). Median follow up was 26.8 months (range 1-136.6). All CSF samples were evaluated both by CC and FCM. The presence of ≥10 clonally restricted or phenotypically abnormal events was regarded as a FCM positivity. Based on the results of CSF examination, three different categories were recognized: manifest CNS+ (CC+FCM+), occult CNS+ (CC-FCM+) and CNS- (CC-FCM-). Results. Overall, 16 (7%) pts had manifest CNS+, 39 (17%) occult CNS+ and 166 (75%) were CNS-Median age, WBC count, B/T lineage, cytogenetic/genetic features did not differ significantly between the three categories. A complete remission (CR) was achieved in 178 (80%) pts, 9 (4%) died early in induction and 104/178 (58%) experienced a relapse. The frequency of CR rate did not vary significantly across the three identified categories. In univariate analysis, the CNS status correlated significantly with the incidence of relapse (p=.004) and with censor (45 years (RR:1.45, 95% CI 1.47-2.43, p=0.04)were independently associated with a lower OS. Conclusions. Our large, multicenter CAMPUS ALL study showed that i) in ALL adult pts, FCM allows to detect occult CNS disease, even in conditions of low spinal fluid leukemic count; ii) the presence of occult CNS disease is associated with an unfavorable outcome. Further prospective studies on larger series are needed to confirm these data. Figure. Figure. Disclosures Del Principe: Gilead: Membership on an entity's Board of Directors or advisory committees. Fracchiolla:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees. Foà:NOVARTIS: Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; CELTRION: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; INCYTE: Other: ADVISORY BOARD; ROCHE: Other: ADVISORY BOARD, Speakers Bureau.

Description: Abstract 4571 Background. The accumulation of CD19+/CD5+/CD23+ B cells with a prolonged lifespan in peripheral blood, secondary lymphoid organs and bone marrow (BM) is a peculiar feature of B-cell chronic lymphocytic leukemia (B-CLL). Since CLL cells removed from the in vivo microenvironment and in vitro cultured rapidly undergo spontaneous apoptosis, bidirectional interactions between malignant and by-stander cells may lead to an abnormal microenvironment that confers growth advantages to neoplastic clone. Mesenchymal Stromal Cells (MSCs) are the dominant marrow stromal population in indolent subtype of CLL/small lymphocytic leukemia (SLL) and follicular lymphoma (FL), rather than other aggressive B-cell lymphomas, and are involved in B-CLL cell survival. Despite the phenotypic and cytologic homogeneity, CLL is characterized by extremely variable clinical courses, suggesting that malignant B-cells hold variable degrees of dependency on pro-survival signals coming from the microenvironment. The aim of this study was to assess the role of MSCs in CLL B-cell localization and survival, defining the degree of dependency of leukemic B-cells from external pro-survival signals, with the ultimate goal of identifying patients that mostly benefit microenvironment-targeted therapies. Methods. MSCs isolated from the BM of 47 B-CLL patients were expanded ex vivo and characterized through flow cytometry analysis and differentiation cultures. Fresh isolated CLL peripheral blood mononuclear cells were co-cultured with CLL-MSCs or stromal cells and apoptosis were measured by Annexin V test and western blotting analysis (PARP-1 detection). Chemotactic assays were performed. Results. The survival of neoplastic cells ranged from 13.3% (±13.2) in leukemic cells cultured in medium alone to 58.5% (±17.2) when leukemic cells were cultured in presence of CLL-MSCs (p

Description: Background Invasive fungal infections (IFI) are serious and life-threatening complications of hematological malignancies particularly in patients affected by acute myeloid leukemia and following hematopoietic stem cell transplantation. However, only few epidemiological data concerning fungal infections in chroniclymphoproliferativedisorders are available. In this work we aimed to identify the clinical and biological features of patients with chronic lymphocytic leukemia (CLL) affected by IFI. Methods We performed a single-center retrospective study based on the CLL patients referred to the Hematology Unit of University of Padua from 1983 to 2015. IFI were defined as infective events caused by yeasts ormouldsthat required inpatient management and/or intravenous antifungal therapies. We included only proven and probable IFI. Time to IFI (TIFI) and overall survival (OS) were calculated from the date of CLL diagnosis to IFI development or death (event), respectively, or last available follow-up (censored). Diagnostic work-up of fungal infection included blood cultures, serumgalactomannanantigen test for 3 consecutive days (cut-off 0.5), β-1,3-(D)-glucanand high resolution chest computed tomography andbronchoalveolarlavages when clinically indicated. We also collected the closest immunoglobulin (IG) levels data before the onset of each IFI or serious bacterial infective events. IGs measured during infections were not included in the analysis, because they could have been influenced by the infectious event. The last available serum IG levels were considered for patients who did not suffer from any IFI. Results 795 patients with CLL were recruited in this study. 60% were male and the median age at diagnosis and at IFI onset were 65 and 68 years, respectively. The median follow-up was 8.5 years and 316 patients required treatment during the follow-up. 11 out of 795 (1.4%) patients developed IFI during the follow-up. Among them, 7 patients (64%) had probable Aspergillosisand 4 had proven IFI (3 Aspergillusspp and 1 Candida kruseii) based on histological confirmation and/or microbiological isolation of the specific fungal agent. 9 patients wereBinet stage A, 2Binet B and noneBinet C at CLL diagnosis. The median lines of treatment were 5 ranging from 2 to 9. Six out of 11 (55%) patients showed high-risk cytogenetic by FISH analysis (11q or 17p deletion), 2 harbored complex karyotypes, 62% (5/8) hadunmutated IGVH gene. By Kaplan-Meyer analysis we showed that IFI occurred in 2.1% and 7.0% of the cohort after 10 and 20 years of follow-up, respectively (Figure 1A). However, considering the number of chemotherapy regimens, the estimated cumulative incidence of IFI was higher in patients who were treated with at least 4 lines of chemo-immunotherapy (10-year TIFI were 9.0% and 0.3%, p

Description: Background and objectives. Bendamustine in combination with rituximab has demonstrated a relevant clinical activity and a good toxicity profile in patients with mantle cell lymphoma (MCL). Cytosine arabinoside (Ara-C) is a key drug in induction chemotherapy regimens of young patients with MCL. In vitro studies have shown that bendamustine increases the cytotoxic effect of Ara‐C in leukemic blasts and lymphoma cells, and the two drugs display high synergistic activity when used in consecutive combinations. Clinically, it has recently been demonstrated that rituximab + bendamustine + Ara‐C (R-BAC) combination has a remarkable activity and is well tolerated both in untreated and in relapsed/refractory patients with MCL (Visco C et al. J Clin Oncol 2013 31:1442-1449). In the present study, we report data from an Italian single-center experience evaluating the efficacy and tolerability of R-BAC association in previously untreated MCL patients both eligible and ineligible for transplantation. Design and methods. From January 2009 to November 2014, 25 newly diagnosed patients with MCL (median 67 years; range 57-83 years) were treated with immunochemotherapy according to R-BAC schedule (Rituximab 375 mg/mq day 1; Bendamustine 70 mg/mq days 2, 3; Ara-C 500 mg/mq days 2-4) x 4 or 6 28-day cycles. All patients received G-CSF prophylaxis. Ninety-six percent of patients had stage III/IV disease; MIPI score was high in 24%, intermediate in 60% and low in 12%; in one patient it was not evaluable. Results. Twenty-two patients (88%) completed the scheduled treatment (4 or 6 cycles). The ORR was 88%: CR 84% (21 patients); PR 4% (1 patient); 1 patient was in SD, but he received only 1 cycle due to toxicity and died still in SD about three years later. Seven patients (28%) underwent autologous stem cell transplantation (ASCT); seven patients (28%) received rituximab maintenance for two years. Two patients (8%) experienced disease progression during first line therapy, both had intermediate MIPI score. After a median follow up of 33 months (range 4-65 months), the OS was 80% (one patient died for unrelated causes) and the PFS was 80%. At this time point, 19 (76%) and 1 (4%) patient were in CR and in PD, respectively. The latter patient is currently undergoing salvage chemotherapy. Patients who received either maintenance immunotherapy with rituximab or consolidation with ASCT after R-BAC (overall 56%) seemed to experience longer PFS and OS. In the ASCT group the OS was 100% at a median follow up of 23 months; in the rituximab maintenance group the OS was 71% at a median follow up of 41 months. In the group of patients that received R-BAC induction therapy only, the OS was 61% at a median follow up of 26 months (p=0.14, likely due to the low number). The most common adverse events (AEs) during R-BAC were hematological: grade 3-4 neutropenia (88%), grade 3-4 thrombocytopenia (64%) and grade 3-4 anemia (36%). The numbers of common grade 3/4 non hematological AEs in the study included: febrile neutropenia (28%), acute coronary syndrome (4%), lung infection (4%) and hyperglycemia (4%). No treatment-related mortality was observed, one patient died of secondary acute myeloid leukemia four years later from induction therapy. Conclusions. The present retrospective study confirms that R-BAC as frontline regimen in MCL is well tolerated and highly effective in ASCT ineligible patients and that it can be administered also in ASCT eligible patients as induction therapy. Moreover, our data suggest that a consolidation therapy (ASCT or maintenance immunotherapy) after R-BAC induction could improve the outcome. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Incidence of fungal infections is reducing in the last years due to wider use of effective antifungal prophylaxis. On this basis, we evaluated clinical characteristics and outcome of patients (pts) with hematological malignancies (HMs) and fungal bloodstream infections (FBSI). Patient and Methods: This retrospective/prospective study gathered consecutive documented FBSI observed among HMs diagnosed between January 2011 and June 2015 in 19 Italian Hematology Departments that refer to SEIFEM (Sorveglianza Epidemiologica Infezioni Fungine Emopatie Maligne) group. Results: We collected overall 100 patients including retrospective pts and those observed in the first six months of the prospective study with FBSI among 16 centers; further 3 centers reported no cases of FBSI. Regarding patients' characteristics male/female ratio was 1, median age was 55 yeras. (IQR 18-88). Two-third of FBSI were detected in AML (43 - 43%) and NHL (27 - 27%); the remaining pts were affected by ALL (9 - 9%), MM (6 - 6%), MDS (5 - 5%), MDS/MPN (5 - 5%), CLL (3 - 3%) and HL (2 - 2%). Thirty-five pts had FBSI at the onset of HM or after the first induction, 47 after treatment for refractory/relapsed disease, 13 when in remission, 28 pts during transplant procedures (17 from allogeneic donor, 11 from autologous cells). Fifty-nine pts were receiving antifungal prophylaxis at FBSI breakthrough: 26 posaconazole, 16 fluconazole, 6 itraconazole, 3 amphotericin B, 3 caspofungin, 1 voriconazole, and 4 combination of amphotericin B/azoles; 4 pts were treated with secondary prophylaxis after previous fungal infection. Eighty-nine pts had a central venous catheter. Eighty-four pts presented a neutrophils count 〈 500/mmc for a median time of 7 days before FBI onset (0-70 d); 50 pts received steroids and other 17 immunosuppressive treatment for allo-HSCT. Yeasts were the most common agent detected. Candida spp. represent the most represented yeast, counting for 77% of all infections; (21 albicans and 56 non albicans); 8% of FBI were due to 8% Geotrichum, 3% Trichosporon and 2% Rhodotorula, Molds were rare but not infrequent: 8% were caused by Fusarium and 1% by Scedosporium. Three patients died before starting any antifungal. Fifty-two received echinocandins (49 caspofungin and 3 anidulafungin), 22 liposomal amphotericin B (L-AmB), 15 azoles (7 fluconazole, 3 posaconazole, 3 voriconazole and 2 itraconazole) and 8 pts combo therapy (5 posa+L-AmB, 2 Caspo+L-AmB, 1 vori+caspo). Thirty-eight pts died within 30 days from FBSI diagnosis, 28 (74%) of whom due to infection. Among these 12 (43%) suffered from AML (1 in induction, 1 in CR, 10 had refractory/relapsed disease), 2 (7.2%) from ALL (all with refractory/relapsed disease), 7 (25%) from NHL (2 in induction, 2 in CR, 3 with refractory/relapsed disease), 4 (14%) from refractory/relapsed MM, 1 (3.6%) from MDS in remission, 2 (7.2%) from newly diagnosed MDS/MPN. In 8 pts (21%) for whom we cannot discriminate if death was subsequent to FBSI only or to uncontrolled HMs, fungal isolates were all rare yeast or molds except 2. Mortality was related only with advanced phase of underlying HM (p

Description: Introduction: in the last 5 years new "target drugs" to treat lymphoproliferative disorders have been introduced in clinical practice, such as monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab), BTK inhibitors (ibrutinib) and PI3K inhibitors (idelalisib). Efficacy and safety of these drugs were assessed in registrative trials and data regarding infectious complications in the "real life" experience are currently unavailable. We aimed to assess the incidence of major infections in patients treated with the above mentioned drugs. Methods: 555 patients were treated, for registered indications, with idelalisib, ibrutinib, brentuximab, ofatumumab and obinutuzumab (single agents or in combination as licensed) in 13 hematology centres in Italy, from time of their commercial availability to December 2016. The observation period was one year after study entry. Patients in clinical trials or treated within patient named programs were excluded as well as patients with active infections at beginning of treatment. Results: in 132/555 patients (24%) infections occurred for a total number of 187 events, 56% of whom were of grade 3. The median age was 64 years (range 20-86), 46,2% (61/132) of patients were treated with 3 or more previous lines of therapy, 55/132 (42%) experienced 2 or more infective episodes. A bacterial cause of infection was reported in 35% of cases, viral in 22% and an invasive fungal infection (IFI) in 9% (17/187). In 2% of cases the infection was of mixed origin (bacterial/viral or bacterial/fungal) while in 32% of cases there was not microbiological documentation. The lower respiratory tract was the most frequent site of infection in 39% of cases (73/187) while the upper respiratory tract was involved in 30% of events (39/187). The urinary tract infections were 13% (24/187). Other sites involved were skin and soft tissue 7%, sepsis 7%, gastrointestinal site 5%, central nervous system 2% and fever of unknown origin 6%. Patients treated with idelalisib were 106 (80% affected by chronic lymphocytic leukemia - CLL- and 20% follicular lymphoma) and 35 (33%) experienced one ore more infections for a total of 49 episodes. The incidence of bacterial infections was 37%, of viral infections 37% and of IFI 6%. In 235 patients treated with ibrutinib, 70 (30%) had one ore more events for a total of 102 infective episodes. 60/70 (86%) patients had CLL and 10/70 (14%) had indolent or mantle cell lymphoma The incidence of bacterial infections was 50%, viral 20% and IFI 16%. Focusing on IFI, 17 events were reported in 15 patients. According to the EORTC criteria, 11 cases (4 possible, 1 probable, 6 proven) were reported in patients treated with ibrutinib, 3 cases of possible IFI in patients treated with idelalisib and 3 cases of proven IFI in patients treated with brentuximab. The incidence of IFI in patients treated with ibrutinib (11/102 events) and idelalisib (3/49 events) was not different (11% vs. 6% respectively; p-value = 0.55) even considering proven/probable cases only (3% in ibrutinib vs. 0% in idelalisib p-value = 0.11). The incidence of bacterial infections in patients treated with ibrutinib (35/102) was not statistically different compared to patients treated with idelalisib (18/49) (34% vs. 37% respectively p-value =0.87). Noteworthy, the incidence of viral infections in patients treated with idelalisib (18/49) was significantly higher compared to patients treated with ibrutinib (14/102) (37% vs. 14% respectively; p-value =0.015). Brentuximab was used in 175 patients, 70% of cases for Hodgkin Lymphoma and 30% for T cell lymphoma. The rate of infections was 11% for a total of 27 infection episodes. The incidence of bacterial, viral and fungal infections was 37%, 30% and 11% respectively. In 22% of cases the cause of infection could not be established. Patients treated with ofatumumab or obinutuzumab were 39 and in 7/39 (18%) an infective episode was reported (four of bacterial origin, one viral and four undetermined). All patients were affected by CLL. Conclusions: this "real life" experience confirm that the incidence of infections in patients treated with "target drugs" is not negligible. Ongoing analysis that take into account patient's clinical and demographical characteristics, may give insights on risk factors that will contribute to better characterizing patients at different risk levels. Figure. Figure. Disclosures Cattaneo: GILEAD: Other: Advisory Board. Candoni:Pfizer: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Merck SD: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau. Fanci:Gilead: Honoraria; Pfizer Pharmaceuticals: Honoraria; Merck: Consultancy, Honoraria, Speakers Bureau. Del Principe:Gilead: Membership on an entity's Board of Directors or advisory committees. Busca:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merk: Honoraria, Speakers Bureau; Pfizer Pharmaceuticals: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria; Novartis: Speakers Bureau.

Description: Abstract 5027 Background: LCDD is a rare plasma cell dyscrasia characterized by deposition of immunoglobulin light chain in kidneys and, occasionally, in other organs such as liver and heart. Most patients present with rapidly deteriorating renal function and nephrotic proteinuria. There is no standard treatment for LCDD. High dose dexametasone (HDD) with or without alkylating agents and high dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) have been used, the latter with better results. Recently the combination therapy with Bortezomib-Dexametasone (BD) has been used in small series of patients and has shown promising results. Here we report on four patients with LCDD treated in our center from September 2010 to September 2011 with BD as induction therapy. Patients and Methods: The characteristics of the patients are shown in Table 1. Three patients were male; the median age was 44. 5 years (range 37–64 years). Two patients had more than 20% bone marrow plasma cell count with no evidence of active multiple myeloma (MM) defined by osteolytic bone disease, hypercalcemia or myeloma cast nephropaty. All patients had renal biopsy with histologic and immunofluorescence studies. In all patients except one, the diagnosis was confirmed by electron microscopy examination. One patient was therapy naive and three patients were refractory to HDD. All patients but one presented with impaired renal function and all of them showed nephrotic albuminuria. Serum free light chains values (sFLC) were high in all patients, with abnormal kappa to lambda ratio (R k/λ). Noteworthy, in three patients serum immunofixation electrophoresis did not succeed in detecting the circulating monoclonal light chain. Patients were given Bortezomib (1. 3 mg/m2days 1, 4, 8 and 11) and Dexamethasone (40 mg days 1–4) every 21 days, for three to six cycles. Results: Two patients achieved normalization of R k/λ. One patient achieved reduction of more than 50% of involved sFLC and reduction of more than 50% of the M protein after three cycles. One patient had progressive disease. None of the responding patients with renal impairment achieved improvement of the renal function, but all responding patients showed reduction of more than 50% of initial albuminuria. After BD one patient achieved hematological CR, one VGPR and one PR (Gertz MA et al., Amyloid 2010). All responding patients were eligible for ASCT. Two patients underwent stem cell mobilization with cyclophosphamide 4 g/m2; one patient was mobilized with G-CSF alone. Melphalan dose was reduced to 140 mg/m2in the only patient undergoing hemodyalisis. There were no complications related to stem cell harvest and engraftment (only one patient showed a late platelet engraftment). After ASCT two patients achieved at least VGPR; one patient achieved a PR and he underwent second ASCT achieving again a PR. Dose reduction of Bortezomib was required in two patients because of grade 2 neuropathy. Conclusions: BD is feasible and effective in LCDD patients, and it can be used as an induction regimen before ASCT. Disclosures: Off Label Use: Bortezomib for light chain deposition disease.