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Cancer‐associated cachexia (CAC) is a debilitating syndrome associated with poor quality of life and reduced life expectancy of cancer patients. CAC is characterized by unintended body weight reduction due to muscle and adipose tissue loss. A major hallmark of CAC is systemic inflammation. Several non‐steroidal anti‐inflammatory drugs (NSAIDs) have been suggested for CAC treatment, yet no single medication has proven reliable. R‐ketorolac (RK) is the R‐enantiomer of a commonly used NSAID. The effect of RK on CAC has not yet been evaluated. Ten‐ to 11‐week‐old mice were inoculated with C26 or CHX207 cancer cells or vehicle control (phosphate‐buffered saline [PBS]). After cachexia onset, 2 mg/kg RK or PBS was administered daily by oral gavage. Body weight, food intake and tumour size were continuously measured. At study endpoints, blood was drawn, mice were sacrificed and tissues were excised. Immune cell abundance was analysed using a Cytek® Aurora spectral flow cytometer. Cyclooxygenase (COX) activity was determined in lung homogenates using a fluorometric kit. Muscle tissues were analysed for mRNA and protein expression by quantitative real‐time PCR and western blotting analysis, respectively. Muscle fibre size was determined on histological slides after haematoxylin/eosin staining. Ten‐day survival rate of C26‐bearing animals was 10% while RK treatment resulted in a 100% survival rate (P= 0.0009). Chemotherapy resulted in a 10% survival rate 14 days after treatment initiation, but all mice survived upon co‐medication with RK and cyclophosphamide (P= 0.0001). Increased survival was associated with a protection from body weight loss in C26 (−0.61 ± 1.82 vs. −4.48 ± 2.0 g, P= 0.0004) and CHX207 (−0.49 ± 0.33 vs. −2.49 ± 0.93 g, P= 0.0003) tumour‐bearing mice treated with RK, compared with untreated mice. RK ameliorated musculus quadriceps (−1.7 ± 7.1% vs. −27.8 ± 8.3%, P= 0.0007) and gonadal white adipose tissue (−18.8 ± 49% vs. −69 ± 15.6%, P= 0.094) loss in tumour‐bearing mice, compared with untreated mice. Mechanistically, RK reduced circulating interleukin‐6 (IL‐6) concentrations from 334 ± 151 to 164 ± 123 pg/mL (P= 0.047) in C26 and from 93 ± 39 to 35 ± 6 pg/mL (P= 0.0053) in CHX207 tumour‐bearing mice. Moreover, RK protected mice from cancer‐induced T‐lymphopenia (+1.8 ± 42% vs. −49.2 ± 12.1% in treated vs. untreated mice, respectively). RK was ineffective in ameliorating CAC in thymus‐deficient nude mice, indicating that the beneficial effect of RK depends on T‐cells. RK improved T‐lymphopenia and decreased systemic IL‐6 concentrations, resulting in alleviation of cachexia and increased survival of cachexigenic tumour‐bearing mice, even under chemotherapy and independent of COX inhibition. Considering its potential, we propose that the use of RK should be investigated in patients suffering from CAC.

Vladimer: Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Jaeger:Karyopharm: Honoraria; Amgen: Honoraria; Gilead: Honoraria, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; True North: Honoraria, Research Funding; Miltenyi: Consultancy, Honoraria; CDR Life AG: Consultancy, Research Funding; F. Hoffmann-La Roche: Honoraria, Research Funding; Infinity: Honoraria; Takeda: Honoraria; Novartis: Consultancy, Honoraria, Research Funding; AbbVie: Honoraria. Krall:Allcyte GmbH: Current Employment, Current equity holder in private company, Other: Founder. Valent:Allcyte GmbH: Research Funding; Cellgene: Honoraria, Research Funding; Pfizer: Honoraria. Wolf:Celgene: Honoraria, Research Funding. Zielinski:MSD: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; Imugene: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Merrimack: Consultancy, Honoraria, Speakers Bureau; Merck KGaA: Consultancy, Honoraria, Speakers Bureau; Fibrogen: Consultancy, Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Speakers Bureau; Tesaro: Consultancy, Honoraria, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, Speakers Bureau; Shire: Consultancy, Honoraria, Speakers Bureau; Eli Lilly: Consultancy, Honoraria, Speakers Bureau; Athenex: Consultancy, Honoraria, Speakers Bureau. Superti-Furga:Allcyte GmbH: Current equity holder in private company, Other: Founder. Snijder:Allcyte GmbH: Current equity holder in private company, Other: Founder. Staber:Roche: Consultancy, Honoraria, Research Funding; Astra Zeneca: Consultancy, Honoraria; Celgene/ BMS: Consultancy, Honoraria; msd: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria.

Background:

Fibroblast growth factor 21 (FGF21) is a PPARα-regulated gene elucidated in the liver of PPARα-deficient mice or PPARα agonist-treated mice. Mice globally lacking adipose triglyceride lipase (ATGL) exhibit a marked defect in TG catabolism associated with impaired PPARα-activated gene expression in the heart and liver, including a drastic reduction in hepatic FGF21 mRNA expression. Here we show that FGF21 mRNA expression is markedly increased in the heart of ATGL-deficient mice accompanied by elevated expression of endoplasmic reticulum (ER) stress markers, which can be reversed by reconstitution of ATGL expression in cardiac muscle. In line with this assumption, the induction of ER stress increases FGF21 mRNA expression in H9C2 cardiomyotubes. Cardiac FGF21 expression was also induced upon fasting of healthy mice, implicating a role of FGF21 in cardiac energy metabolism. To address this question, we generated and characterized mice with cardiac-specific overexpression of FGF21 (CM-Fgf21). FGF21 was efficiently secreted from cardiomyocytes of CM-Fgf21 mice, which moderately affected cardiac TG homeostasis, indicating a role for FGF21 in cardiac energy metabolism. Together, our results show that FGF21 expression is activated upon cardiac ER stress linked to defective lipolysis and that a persistent increase in circulating FGF21 levels interferes with cardiac and whole body energy homeostasis.

Manifestations of chronic graft-versus-host disease (cGVHD) can resemble those seen in immunodeficiency states and autoimmune disorders. Reports by us and others suggest an involvement of B cells in the pathogenesis of cGVHD. We investigated B-lymphocyte subpopulations in cGVHD cohorts defined by serum immunoglobulin G (IgG) levels to characterize novel biomarkers for impairment of humoral immunity after allogeneic hematopoietic stem cell transplantation. Seventy-six patients were enrolled a median of 46 months after hematopoietic stem cell transplantation. The hypogammaglobulinemia group had significantly diminished CD19+ B cells (165 vs 454 vs 417 × 106/L) with elevated CD19+CD21low immature (16.5%, 7.7%, and 9.1%) and CD19+CD21int-highCD38highIgMhigh transitional (10.5% vs 4.2% vs 6.3%) B-cell proportions compared with the normogammaglobulinemia and hypergammaglobulinemia groups. CD19+CD10−CD27−CD21high naive B cells were highly elevated in all patients with cGVHD. CD19+CD27+IgD+ non–class-switched (4 vs 12 vs 11 × 106/L) and class-switched (7 vs 35 vs 42 × 106/L) memory B cells were significantly lower in the hypogammaglobulinemia group compared with the others. Besides significantly higher B-cell activation factor/B-cell ratios, significantly more cGVHD patients with hypergammaglobulinemia had autoantibodies compared with the hypogammaglobulinemia subgroup (68% vs 24%, P = .024). In conclusion, B-cell subpopulations can serve as novel cellular biomarkers for immunodeficiency and autoimmunity indicating different pathogenetic mechanisms of cGVHD and encouraging future prospective longitudinal studies.

Manifestations of chronic graft-versus-host disease (cGVHD) can resemble those seen in immunodeficiency states and autoimmune disorders. Reports by us and others suggest an involvement of B cells in the pathogenesis of cGVHD. We investigated B-lymphocyte subpopulations in cGVHD cohorts defined by serum immunoglobulin G (IgG) levels to characterize novel biomarkers for impairment of humoral immunity after allogeneic hematopoietic stem cell transplantation. Seventy-six patients were enrolled a median of 46 months after hematopoietic stem cell transplantation. The hypogammaglobulinemia group had significantly diminished CD19+B cells (165 vs 454 vs 417 × 106/L) with elevated CD19+CD21lowimmature (16.5%, 7.7%, and 9.1%) and CD19+CD21int-highCD38highIgMhightransitional (10.5% vs 4.2% vs 6.3%) B-cell proportions compared with the normogammaglobulinemia and hypergammaglobulinemia groups. CD19+CD10−CD27−CD21highnaive B cells were highly elevated in all patients with cGVHD. CD19+CD27+IgD+non–class-switched (4 vs 12 vs 11 × 106/L) and class-switched (7 vs 35 vs 42 × 106/L) memory B cells were significantly lower in the hypogammaglobulinemia group compared with the others. Besides significantly higher B-cell activation factor/B-cell ratios, significantly more cGVHD patients with hypergammaglobulinemia had autoantibodies compared with the hypogammaglobulinemia subgroup (68% vs 24%, P= .024). In conclusion, B-cell subpopulations can serve as novel cellular biomarkers for immunodeficiency and autoimmunity indicating different pathogenetic mechanisms of cGVHD and encouraging future prospective longitudinal studies.

FAs are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGL-ko) exhibit defective lipolysis and accumulate TG in adipose tissue and muscle, suggesting that ATGL deficiency affects energy availability and substrate utilization in working muscle. In this study, we investigated the effect of moderate treadmill exercise on blood energy metabolites and liver glycogen stores in mice lacking ATGL. Because ATGL-ko mice exhibit massive accumulation of TG in the heart and cardiomyopathy, we also investigated a mouse model lacking ATGL in all tissues except cardiac muscle (ATGL-ko/CM). In contrast to ATGL-ko mice, these mice did not accumulate TG in the heart and had normal life expectancy. Exercise experiments revealed that ATGL-ko and ATGL-ko/CM mice are unable to increase circulating FA levels during exercise. The reduced availability of FA for energy conversion led to rapid depletion of liver glycogen stores and hypoglycemia. Together, our studies suggest that ATGL-ko mice cannot adjust circulating FA levels to the increased energy requirements of the working muscle, resulting in an increased use of carbohydrates for energy conversion. Thus, ATGL activity is required for proper energy supply of the skeletal muscle during exercise.

FAs are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGL-ko) exhibit defective lipolysis and accumulate TG in adipose tissue and muscle, suggesting that ATGL deficiency affects energy availability and substrate utilization in working muscle. In this study, we investigated the effect of moderate treadmill exercise on blood energy metabolites and liver glycogen stores in mice lacking ATGL. Because ATGL-ko mice exhibit massive accumulation of TG in the heart and cardiomyopathy, we also investigated a mouse model lacking ATGL in all tissues except cardiac muscle (ATGL-ko/CM). In contrast to ATGL-ko mice, these mice did not accumulate TG in the heart and had normal life expectancy. Exercise experiments revealed that ATGL-ko and ATGL-ko/CM mice are unable to increase circulating FA levels during exercise. The reduced availability of FA for energy conversion led to rapid depletion of liver glycogen stores and hypoglycemia. Together, our studies suggest that ATGL-ko mice cannot adjust circulating FA levels to the increased energy requirements of the working muscle, resulting in an increased use of carbohydrates for energy conversion. Thus, ATGL activity is required for proper energy supply of the skeletal muscle during exercise.

The Saccharomyces cerevisiae ALR1(YOL130w) gene product Alr1p is the first known candidate for a Mg2+transport system in eukaryotic cells and is distantly related to the bacterial CorA Mg2+transporter family. Here we provide the first experimental evidence for the location of Alr1p in the yeast plasma membrane and for the tight control of its expression and turnover by Mg2+. Using well characterizednpi1and end3mutants deficient in the endocytic pathway, we demonstrate that Alr1 protein turnover is dependent on ubiquitination and endocytosis. Furthermore, cells lacking the vacuolar protease Pep4p accumulated Alr1p in the vacuole. Mutants lacking Alr1p (Δalr1) showed a 60% reduction of total intracellular Mg2+compared with the wild type and failed to grow in standard media. When starved of Mg2+, mutant and wild-type cells had similar low levels of intracellular Mg2+; but upon addition of Mg2+, wild-type cells replenished the intracellular Mg2+pool within a few hours, whereasΔalr1mutant cells did not. Expression of the bacterial Mg2+transporter CorA in the yeastΔalr1mutant partially restored growth in standard media. The results are discussed in terms of Alr1p being a plasma membrane transporter with high selectivity for Mg2+.

The TSC13/YDL015c gene was identified in a screen for suppressors of the calcium sensitivity of csg2Δ mutants that are defective in sphingolipid synthesis. The fatty acid moiety of sphingolipids in Saccharomyces cerevisiaeis a very long chain fatty acid (VLCFA) that is synthesized by a microsomal enzyme system that lengthens the palmitate produced by cytosolic fatty acid synthase by two carbon units in each cycle of elongation. TheTSC13gene encodes a protein required for elongation, possibly the enoyl reductase that catalyzes the last step in each cycle of elongation. The tsc13mutant accumulates high levels of long-chain bases as well as ceramides that harbor fatty acids with chain lengths shorter than 26 carbons. These phenotypes are exacerbated by the deletion of either the ELO2or ELO3gene, both of which have previously been shown to be required for VLCFA synthesis. Compromising the synthesis of malonyl coenzyme A (malonyl-CoA) by inactivating acetyl-CoA carboxylase in atsc13mutant is lethal, further supporting a role of Tsc13p in VLCFA synthesis. Tsc13p coimmunoprecipitates with Elo2p and Elo3p, suggesting that the elongating proteins are organized in a complex. Tsc13p localizes to the endoplasmic reticulum and is highly enriched in a novel structure marking nuclear-vacuolar junctions.

ABSTRACTThe TSC13/YDL015c gene was identified in a screen for suppressors of the calcium sensitivity of csg2? mutants that are defective in sphingolipid synthesis. The fatty acid moiety of sphingolipids in Saccharomyces cerevisiaeis a very long chain fatty acid (VLCFA) that is synthesized by a microsomal enzyme system that lengthens the palmitate produced by cytosolic fatty acid synthase by two carbon units in each cycle of elongation. TheTSC13gene encodes a protein required for elongation, possibly the enoyl reductase that catalyzes the last step in each cycle of elongation. The tsc13mutant accumulates high levels of long-chain bases as well as ceramides that harbor fatty acids with chain lengths shorter than 26 carbons. These phenotypes are exacerbated by the deletion of either the ELO2or ELO3gene, both of which have previously been shown to be required for VLCFA synthesis. Compromising the synthesis of malonyl coenzyme A (malonyl-CoA) by inactivating acetyl-CoA carboxylase in atsc13mutant is lethal, further supporting a role of Tsc13p in VLCFA synthesis. Tsc13p coimmunoprecipitates with Elo2p and Elo3p, suggesting that the elongating proteins are organized in a complex. Tsc13p localizes to the endoplasmic reticulum and is highly enriched in a novel structure marking nuclear-vacuolar junctions.

Mohty: Celgene: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau; MaaT Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers: Consultancy, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Molmed: Consultancy; Servier: Consultancy; Amgen: Consultancy, Honoraria.

Background.Extracorporeal photopheresis (ECP) is increasingly used in the treatment of acute and chronic graft versus host disease (aGVHD). It is recognized as an immunomodulatory therapy that can decrease inflammation and allow for immune tolerance. Interesting results have obtained using ECP as salvage therapy in patients with steroid-refractory GVHD after failure of one or more lines of immunosuppressive therapy. With this background, we hypothesized that incorporation of ECP as part of first line treatment for aGVHD may improve response rate and avoid the development of steroid-refractory or steroid-dependent aGVHD, mainly in cases of aGVHD with predominant skin involvement.

No relevant conflicts of interest to declare.

Introduction:Despite allogeneic hematopoietic stem cell transplantation (HSCT), prognosis of fms-like tyrosine kinase 3 (FLT3) mutated acute myeloid leukemia (AML) remains poor due to the high risk of relapse. Sorafenib, a multikinase inhibitor active on FLT3, has shown encouraging results in these patients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used in the treatment of a variety of hematologic diseases. However, allo-HSCT can be associated with many complications, including poor graft function early after transplant requiring long-lasting supportive care. In the literature, the incidence of poor graft function post allo-HSCT has been reported to range from 4 to 27%.

No relevant conflicts of interest to declare.

Mohty: Riemser: Honoraria, Research Funding.

Mohty: Janssen: Honoraria; Celgene: Honoraria.

Background

Background

Mohty: Riemser : Research Funding.

Thiotepa (N,N'N'-triethylenethiophosphoramide), which is an alkylating compound, has an antineoplastic activity and has been used in oncology (e.g. breast-, ovarian- and bladder cancer) for decades. In the recent years, and because of its good safety profile, Thiotepa has been increasingly used both for autologous and allogeneic hematopoietic stem cell transplantation conditioning. Interestingly, this agent has a very active myeloablative activity but also its mechanism of action can mimick the effect of radiation.With this background, the aim of this study was to compare outcome of patients receiving a myeloablative conditioning consisting of either high dose TBI or Thiotepa-based chemotherapy.Inclusion criteria were adults with AML, first allograft in CR1 from an HLA-matched sibling donor (MSD) or an unrelated donor (UD) between 2000 and 2011 and myeloablative conditioning. We first compared patient and transplant characteristics between the two types of conditioning, and then performed a pair-matched analysis.The number of patients was 2833 in the TBI group and 102 in the Thiotepa group. Patients who received Thiotepa were older (49y vs 40y, p<10-4), transplanted more recently (2009 vs 2006, p<10-4) and later after the diagnosis of AML (183 days vs 143 days, p<10-4). The percentage of secondary AML was also higher in the Thiotepa group (14% vs 6%; p=0.0002). There was no difference regarding patient/donor gender, type of donor and source of stem cells.In this cohort, we were able to match 96 patients who received Thiotepa with 185 patients who received high dose TBI. Matching factors were: age at transplantation (10 years classes), year of transplant, interval from diagnosis to transplant (less or more than median day), secondary AML and type of donor (MSD/UD). The characteristics of the 2 groups are summarized in Table 1.Median dose of TBI was 12 Gy (range, 8-16). In this group, TBI was combined with Cyclophosphamide (84% of cases), Fludarabine (14%) or other compounds (2%). On the other hand, Thiotepa was administered with Cyclophosphamide (45%), Fludarabine (54%) with/without Busulfan and other combinations (1%).Engraftment occurred in 96% of patients using Thiotepa-based conditioning versus 99% after TBI (p=0.11). The interval from transplant to neutrophils count>500/µL was 16 days (range, 9-42) versus 17 days (range, 9-81) in the 2 groups, respectively (p=0.23). Acute GvHD grade II+ was observed in 25 patients (27%) after Thiotepa-containing regimen versus 42 patients (25%) after TBI (p=0.78). 2-years cumulative incidence of chronic GVHD was 48±4% and 41±6% in the 2 groups, respectively (p=0.15). The 2-year cumulative incidences of non-relapse mortality (NRM) was 21±4% versus 27±4% (p=0.57) and relapse incidence (RI) was 18±4% versus 21±3% (p=0.71) in the Thiopeta and TBI groups, respectively. The 2-year leukemia-free survival (LFS) and overall survival (OS) were 61±5% and 64±5% in the Thiotepa group versus 51±4% and 52±4% in the TBI group (LFS: p=0.40; OS: p=0.25).This pair-matched analysis suggests that a Thiotepa-based myeloablative conditioning regimen prior to allogeneic HSCT in AML in first CR, can allow achieving similar results to high-dose TBI-based myeloablative conditioning. Also, given the deleterious long term side effects of TBI, it is likely that a Thiotepa-based myeloablative conditioning would represent an attractive and valid alternative to TBI. Prospective trials are currently planned in this setting.Bacigalupo: ADIENNE : Speakers Bureau. Mohty:Riemser : Research Funding.

Thiotepa (N,N'N'-triethylenethiophosphoramide), which is an alkylating compound, has an antineoplastic activity and has been used in oncology (e.g. breast-, ovarian- and bladder cancer) for decades. In the recent years, and because of its good safety profile, Thiotepa has been increasingly used both for autologous and allogeneic hematopoietic stem cell transplantation conditioning. Interestingly, this agent has a very active myeloablative activity but also its mechanism of action can mimick the effect of radiation.

Jaeger: Emergent Product Development: Consultancy, Research Funding.

Abstract 2685

Novel agents like the proteasome inhibitor bortezomib (Btz) and immunomodulatory agents show activity in multiple myeloma (MM) as well as in primary AL amyloidosis (AL). Btz has emerged as a standard of care in the treatment of patients with MM and AL. The approved dose and schedule of Btz is 1.3mg/m2 administered on days 1, 4, 8, and 11 as an intravenous (i.v.) bolus injection. However, among several side effects, peripheral neuropathy (PN) has a particular negative impact on the quality of life of patients treated with Btz. A recent trial provided evidence for a similar efficacy of Btz administered subcutaneously (s.c.) compared to i.v. administration, but side effects including PN were significantly less frequent with s.c. application of Btz. Here we report our experience regarding efficacy and tolerability of treatment with Btz administered s.c. in patients with MM and AL.19 consecutive patients with MM (n = 17) or histologically proven AL (n = 2) were included in this analysis. For s.c. administration, Btz was prepared at a concentration of 2.5 mg/mL (as opposed to an i.v. concentration of 1.0 mg/mL). All patients received Btz at a dose of 1.3 mg/m2 on days 1, 4, 8, and 11. Btz was used in combination regimens with dexamethasone (n = 9), with thalidomide/dexamethasone prior to autologous transplantation (VDT; n = 6), or with melphalan/prednisolone in elderly patients (VMP; n = 4).Patients (male n=7; female n=12) were at a median age of 64 years (range 38–77), and 11 patients (58%) received the Btz-based regimen with Btz s.c. as their first line treatment. At the time of analysis, a median of 3 cycles bortezomib s.c. (range, 1–5) have been administered. Hematological toxicities were only at Grades 1+2 and included anemia (78%) and thrombocytopenia (33%). Only one patient developed a grade 3 PN, and this patient already had pre-existing PN due to prior i.v. administration of Btz. Other non-hematologic side effects were at grades 1+2 including fatigue (11%) and local skin reactions at the site of s.c. injection, which were self-limited. No notable gastrointestinal toxicity was observed, and therefore we stopped the routine use of i.v. hydration and antiemetics, which were previously administered as concomitant therapy with i.v. Btz. Of 14 MM patients so far evaluable for response, 12 (86%) had a PR or better including 5 patients (36%) achieving a CR. Both patients with AL achieved a very good partial remission (VGPR). More data on efficacy with longer follow-up will be presented at the meeting.Our observations confirm the improved toxicity profile of the s.c. administration of Btz in various standard Btz-based combination regimens. In addition, due to the ease of s.c. administration of Btz, patient management has been markedly facilitated at our centre.No relevant conflicts of interest to declare.

Multiple myeloma (MM) is still an incurable disease. Initial treatment depends on age, risk stratification and co-morbidities. High-dose therapy followed by autologous stem-cell transplantation (ASCT) is the standard of care in transplant eligible patients.In recent years, novel agents became a promising role in newly diagnosed, relapsed myeloma as well as in maintenance treatment. Bortezomib, a proteasome inhibitor, and thalidomide or lenalidomide, immunomodulatory agents have been found to be superior to chemotherapy regimens.121 adult patients (50 female, 71 male) with a median age of 53.5 years at diagnosis underwent autologous stem-cell transplantation at the Medical University of Vienna between June 1985 and September 2010. Median age at ASCT was 57.4 years.46 patients received novel therapeutic agents, such as VDT (bortezomib, dexamethasone, thalidomide), Rd (lenalidomide, low dose dexamethasone) and VD (bortezomib, dexamethasone), whereas 75 patients were treated on the basis of chemotherapy schedules, e.g. VAD-based (vincristine, doxorubicin, dexamethasone).Progression-free survival (PFS) after ASCT was 7.9 months (6,4 – 9,3, 95% CI) after treatment with chemotherapy, whereas it was increased to 21,6 months (5 – 38,1, 95% CI) after initial treatment with either bortezomib and/or thalidomide/lenalidomide (p= 0.001).Post-induction VGPR or better was superior with new agents compared to chemotherapy, 34,1% versus 11,9%, respectively. Post-transplant VGPR or better was as high as 68% after initial therapy with novel agents prior to transplant, whereas VGPR or better was reached in 48.6% in patients receiving chemotherapy.Novel agents significantly prolong relapse-free survival in patients eligible for autologous stem-cell transplantation. Previous studies showed improved remission duration with thalidomide or lenalidomide maintenance after ASCT. The data of maintenance therapy after ASCT at our department will be presented at the meeting.No relevant conflicts of interest to declare.

Abstract 5124

Abstract 4494

No relevant conflicts of interest to declare.

Abstract 2955

Off Label Use: Sirolimus and ECP for therapy of chronic GVHD. Greinix:Therakos: Consultancy, Speakers Bureau. Knobler:Therakos: Consultancy, Speakers Bureau.

Abstract 2226