ALBERT

Description: Introduction: Insufficient yield of Peripheral Blood Progenitor Cells (PBPC) from healthy donors can result in higher mortality after allogeneic transplantation. Plerixafor (Mozobil®) is approved for the mobilization of PBPC in combination with G-CSF for collection and subsequent autologous transplantation in patients with non-Hodgkin lymphoma and multiple myeloma. Clinical data on G-CSF and Plerixafor in healthy donors are still limited. In a prospective single arm phase 2 trial we investigated the safety and efficacy of a single dose of Plerixafor as a salvage regimen in poor mobilizing allogeneic PBPC donors (NCT01954914). Methods: We enrolled healthy unrelated PBPC donors who had received G-CSF (Lenograstim) at a targed dose of 10 µg/kg bodyweight (bw) for five days but donated less than 2x 106 CD34+ cells/kg recipient bw during the 1st apheresis on day 5 of the mobilization regimen. Plerixafor was injected subcutaneously at a dose of 240µg/kg once on day 5 in the evening before the second leukapheresis. The target for the processed blood volume during each apheresis procedure was 3x donor blood volume +/- 25%. Mobilization success was defined by a donation of more than 4.5x 106CD34+ cells/kg recipient bw. Primary endpoint was the number of mobilization successes. The null hypothesis (success rate of less than 50%) was tested with an exact single sample binomial test at a one-sided significance level of 5%. Results : Between 1/2014 and 12/2015 37 allogeneic unrelated PBPC donors (54% women, 46% men, median age 34 years) were enrolled into the study. The median donor bw was 69 kg (IQR, 61 kg to 76 kg) and the median recipient bw was 85 kg (IQR, 74 kg to 102 kg). Application of Plerixafor was well tolerated in most donors with only moderate side effects such as nausea, diarrhea and occasional vomiting. The median CD34+ count in peripheral blood was 15.4/µl (IQR, 12.0-18.3) on day 5 after G-CSF alone and 44.0/µl (IQR, 38.0-60.5) on day 6 after G-CSF plus Plerixafor. The collected total nucleated cell count was 187 x 106 (IQR, 159.9-223.4) cells per ml volume of the apheresis product on day 5 and 289 x 106 (IQR, 248.0-348.0) cells per ml volume of the apheresis product on day 6. The yield of CD34+ cells in the apheresis products was 1.05 x 108 (range, 0.21-1.80) on day 5 and 2.8 x108(range, 0.93-5.26) on day 6. The percentage of CD3+ cells per TNC was 31% (IQR 27%-40%) and 31% (IQR, 23% - 35%) on days 5 and 6, respectively. In total, a median number of 5.16 x 106 CD34+ cells (IQR 3.06-6.10) per kg recipient weight were collected during both aphereses. Twenty-one out of 37 donors reached the target cell count (56.8%, 95% confidence interval (CI) 39.5% - 72.9%) by donating a CD34+ cell dose of 〉4.5x 106 CD34+ cells per kg recipient bw. Nine donors had donated ≤0.8 106 CD34+ cells per kg recipient bw during their first leukaphersis after stimulation with G-CSF alone. Notably, only one out of these nine very poor mobilizing donors failed to donate at least 2.0 x 106CD 34+ cells per kg recipient bw after salvage mobilization with Plerixafor. Nevertheless, the null hypothesis (H0: rate of mobilization success 4.5x 106 CD34+ cells per kg recipient bw) was 56.8% (95%-CI 39.5% - 72.9%) after a single dose of Plerixafor on day 5 of G-CSF administration. After injection of Plerixafor the CD34+count in the peripheral blood and the yield of CD34+ cells in the leukapheresis product increased by more than factor 2. The application of G-CSF and Plerixafor was well tolerated by most of the donors. Like for autologous donors, the administration of Plerixafor appears promising to optimize PBPC mobilization in allogeneic poor mobilizing donors. Disclosures Hoelig: Janssen Cilag GmbH: Honoraria; Therakos: Honoraria, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schetelig:Sanofi: Honoraria.

Description: Background Graft versus host disease (GVHD) is the principal cause of non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo HCT) and is associated with intestinal microbial dysbiosis. Administration of microbial metabolite butyrate or microbial cocktails of butyrogenic bacteria reduce the severity of acute GVHD in mice. Furthermore, this intestinal microbiome-metabolome axis can be manipulated via dietary intervention in healthy humans with supplementation by defined quantities of resistant potato starch (RPS), an indigestible carbohydrate that is metabolized by intestinal anaerobic commensal bacteria to produce butyrate1. Hereon we aimed to study the feasibility and tolerability of RPS in allo HCT recipients to test the hypothesis that the patients' intestinal microbiome and butyrate levels could be rationally modified by administration of defined quantities of RPS. Methods Between May 8, 2017 and September 30, 2018, we performed a single-center prospective, single arm, pilot study. We recruited adults who were undergoing human leukocyte antigen-matched, related-donor myeloablative allo HCT. Participants received RPS (Bob's Red Mill®) 20 g package orally, once/day for the first 3 days followed by twice daily, from day -7 through day 100 after allo HCT. Feasibility was defined as adherence to ≥ 70 % of scheduled doses in ≥ 60 % of patients. The primary objective was to test adherence to scheduled doses of RPS. Secondary endpoints included assessing tolerability of RPS and its ability to alter representation of RPS-degrading and butyrate-producing bacteria as well as butyrate levels in the intestines of allo HCT recipients. Stool samples were collected in the OMNIgene-Gut® (DNA Genotek) collection kit at baseline before intake of RPS, at time of nadir (day 7-10), engraftment (day 12-18), at day 100, and additional samples were also collected. Fecal microbiome was determined by 16S rRNA gene sequencing and butyrate by liquid chromatography. Results Ten subjects were enrolled. The median age was 57 years (range 52-62 years). All subjects received GVHD prophylaxis with tacrolimus and methotrexate as well as antibiotic prophylaxis with levaquin, and were treated for neutropenic fever with IV cefepime (90%) or IV vancomycin along with IV aztreonam (10%). One patient developed biopsy proven stage I acute GI GVHD with overall grade II acute GVHD (10%). Feasibility exceeded the preset goal of ≥ 70% adherence to scheduled dosages in ≥ 60 % of patients as 8 of the 10 patients (80%) received ≥ 70 % of scheduled doses (Figure 1A). No adverse effects/toxicities attributed to RPS were observed and longitudinal specimens were collected successfully. There was greater abundance of intestinal RPS-degraders such as Ruminococcus bromii, R. lactaris, R. gnavus, and Bifidobacterium spp and butyrate-producers such as Roseburia spp, Faecalibacterium prausnitzii, Eubacterium rectale, and Anaerostipes spp in the 10 patients receiving RPS compared to 15 historical controls after allo HCT (Figure 1B). Butyrate levels were significantly higher in the participants when they were on RPS as compared to pre RPS intake [median (interquartile range): 10.76 (7.62, 19.05) vs. 3.06 (2.32, 6.21) mmoL/kg, p

Description: Key Points MYD88 mutation analysis significantly improves the detection rate of vitreoretinal B-cell lymphoma. The high frequency of MYD88 mutations in primary VRL provides further evidence that VRL and primary CNS lymphoma represent the same entity.

Description: Background: Histone acetylation plays a key role in regulating gene expression and in control of cellular activities in multiple pathways involved in normal and cancer cell growth.Panobinostat (pano) is a pan histone de-acetylase inhibitor (HDAC-i) approved by the FDA on February 23, 2015 for use withbortezomib (btz) and dexamethasone (dex) for patients with multiple myeloma (MM) who have had at least 2 prior lines of therapy including bothbtz and an immunomodulatory agent (IMiD). The combination ofpano withIMiDs and proteasome inhibitors (PIs) has been found to demonstrate enhanced anti-myeloma activity in clinical trials (Berdeja JG et al, 2015,Haematologica;Mateos M et al, 2010, ASCO Abstract 8030, JCO 28:15s). The goal of this retrospective study is to evaluate the real world experience on efficacy and safety ofpano in combination with a variety of FDA approved agents including a PI, anIMiD or a monoclonal antibody-based regimen in patients with relapsed/refractory MM. Methods: Between February 23, 2015 and July 1, 2016, 34 consecutive patients with relapsed/refractory MM who were treated with commercialpano were identified from the JohnTheurer Cancer Center. Charts were analyzed for response and safety data. The study was approved by the institutional review board. Results: Median age was 63 (range 27-78), with 58% percent men. Thirty-one patients (91.2%) wereDurie-Salmon stage II or III. Ten (30%) had high-risk FISH as defined byt(14;16), t(4;14), del p53, and gain 1q21. Median number of prior lines was 5 (range 2-9). All patients were relapsed/refractory to their last line of therapy, and 18 (53%) werebtz-refractory, 25 (74%) werelenalidomide-refractory, 27 (79%) werepomalidomide-refractory, and 29 (85%) were carfilzomib-refractory. Twenty-five (74%) were refractory to the combination of carfilzomib with anIMiD. Five patients (14.7%) had priordaratumumab, and 4 (12%) had prior HDAC-i therapy. Median number of cycles withpano was 1 (range 1-5). The overall response rate (≥ partial response (PR)) was 23.5% and the clinical benefit rate (≥ minor response (MR)) was 67.6%. The median duration of response (≥ stable disease (SD)) was 3 months. The median progression-free survival (PFS) for all patients was 2.3 months (95% CI: [1.27 - 4.07]). See Figure 1. Median overall survival (OS) from initiation ofpano through 7/27/16 was 5.5 months (95% CI: [3.93, NA]). See Figure 2. Of the 4 patients who were refractory to a prior HDAC-i, 1 achieved PR (4 cycles), 1 achieved MR (5 cycles) and 2 had disease progression. Only 1 patient discontinuedpano due to toxicities. Grade 3 and 4 non-hematologic toxicities were diarrhea (N=1), and hypoxia/respiratory failure (N=1). Grade 3 and 4 hematologic toxicities occurred in 11 (32%) patients, with 5 (15%) anemia, 9 neutropenia (26%), and 8 (24%) thrombocytopenia. Serious adverse events included acute kidney injury, GI bleed, and febrile neutropenia in 3 patients, respectively. Conclusions: These observations demonstrate that real-world use ofpano outside of the FDA indication in combination with PI andIMiD-based regimens has activity and is well tolerated in heavily pretreated patients with relapsed/refractory MM, even those who have exhausted conventional treatments. Further assessment in a larger prospective study is warranted. Figure 1 PFS of all patients receivingpanobinostat-based regimens Figure 1. PFS of all patients receivingpanobinostat-based regimens Figure 2 OS of all patients receivingpanobinostat-based regimens from time of initiatingpanobinostat Figure 2. OS of all patients receivingpanobinostat-based regimens from time of initiatingpanobinostat Disclosures Biran: Takeda: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; Amgen: Speakers Bureau. Vesole:Janssen: Speakers Bureau; Novartis: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau; Amgen: Speakers Bureau. Richter:Celgene: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Jannsen: Speakers Bureau. Siegel:Celgene: Honoraria, Speakers Bureau; Merck: Honoraria; Takeda: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau.

Description: Background and Aims: Myelodysplastic syndromes (MDS) are mainly diagnosed in the elderly with an increasing burden on healthcare systems. As a consequence, population-based studies are important in order to estimate the evolution of this emerging disease in different countries. Objectives: The objective of this study was to provide trends ofannual case frequency, morphological subtypes, incidence, mortality and survival of patients diagnosed with MDS in Switzerland between 2001 and 2012. Methods: A retrospective, population-based, epidemiological study was carried out on MDS cases reported to the Swiss Cantonal Cancer Registries and aggregated by the National Institute for Epidemiology and Cancer Registration. The Swiss Federal Statistical Office provided mid-year population estimates and cause of death statistics. Due to changes in the WHO classification of MDS, data was stratified for two time periods 2001-2007 and 2008-2012, respectively. 56 million person-years (py) were observed, covering 60%-65% of the Swiss population, during a time period of 12 years. Results: 2138 MDS cases were reported with a median age of 77 years (range of means: 75-78 years). The estimated annual case frequency increased from 263 to 316 (+20%) but the overall age-standardized (adjusted) incidence-rate did not change between the time periods (Table 1). A substantial increase in incidence was only visible for men aged 80-84 (+57.7%), men aged 85+ (+29.3%) and women aged 85+ (+13.4%). With respect to mortality rates, a 10% decline was observed for men aged 85+. Incidence and mortality were very low below the age of 60 years but the rates steeply increased thereafter (Figure 1a). Irrespective of time period, incidence- and mortality-rates were almost twice as high among men compared to women (Figure 1b). Classification in MDS subtypes was poor and improved only modestly from 20% to 39% with a higher awareness for diagnosis of higher-risk diseases. Relative survival at 5 years (RS at 5y) for all patients was 37% in 2008-2012 with better survival for younger patients 〈 65 years (61%) compared to older patients 〉 65 years (24-37%). No differences in survival could be observed between the two time periods (Figure 2). Conclusions: In this study we provide the first population-based, epidemiologic data from MDS patients in Switzerland. The analysis showed a 20% increase of annual incidence mainly due to population aging and not explained by increase in age-specific risk. This observation will impact on the future prevalence of the disease and its burden on healthcare systems.The age-specific incidence-ratesin patients 〉 75 years increased markedlyconsistent with the general increase of cancer-incidence in the elderly population. An increased diagnostic awareness of higher-risk disease seems to shift the population-based data for MDS sub-classification. We observed that younger patients without classified MDS subtypes have a similar survival like lower-risk disease, indicating that lower-risk MDS is underreported. Unsurprisingly, our data showed that younger patients have a better survival than elderly patients. This is most likelyrelated to higher frequency of lower-risk diseases in younger patients and their eligibility for allogeneic HSCT. However,the lack of a survival benefit observed in elderly patients on population-based level, after introduction of hypomethylating agents as standard treatment for transplant ineligible patients, is intriguing. The underlying reasons require further health-service research investigations. Relevance: The currently available data from CCRs in Switzerland is insufficient for detailed health service research on MDS patients, since important data is lacking on treatment, side effects and outcomes. A new cancer registration law with mandatory notification of cancer cases will be implemented in Switzerland by 2018. Moreover, the Swiss MDS Study Group has launched a Swiss MDS Registry that has started recruitment in 2016. Both initiatives will be of great value to improve data collection in order to foster future health service research of MDS patients in Switzerland with international collaborators. Table 1 Incidence and Mortality of MDS in Switzerland in 2001-2007 and 2008-2012 Table 1. Incidence and Mortality of MDS in Switzerland in 2001-2007 and 2008-2012 Figure 1 Incidence and mortality of MDS in Switzerland in 2001-2007 and 2008-2012 Figure 1. Incidence and mortality of MDS in Switzerland in 2001-2007 and 2008-2012 Figure 2 Age-specific relative survival of MDS patients diagnosed in 2001-2007 and 2008-2012 Figure 2. Age-specific relative survival of MDS patients diagnosed in 2001-2007 and 2008-2012 Disclosures Bonadies: Bristol-Myers Squibb: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Ruefer:Novartis: Consultancy; Celgene: Consultancy, Research Funding. Gerber:Celgene: Consultancy. Benz:Celgene: Consultancy. Lehmann:Novartis: Consultancy.

Description: Background β-globin gene transfer into hematopoietic stem cells (HSCs) could reduce or eliminate sickle cell disease (SCD)-related manifestations. LentiGlobin for SCD gene therapy contains autologous CD34+ cells transduced with the BB305 lentiviral vector (LVV), encoding a human β-globin gene with the anti-sickling T87Q mutation (βA-T87Q). The safety and efficacy of LentiGlobin for SCD is being evaluated in the ongoing Phase 1/2 HGB-206 Study (NCT02140554). The initial 7 patients (Group A) were treated with LentiGlobin made from bone marrow harvested HSCs. The protocol was modified to improve HbAT87Q production by including pre-harvest red blood cell (RBC) transfusions, increasing the total busulfan exposure, and using a refined LentiGlobin manufacturing process (Group B, n=2). An additional modification was made for Group C patients where HSC collection by plerixafor mobilization followed by apheresis was instituted. Data from these Group C patients are discussed here. Results from patients in Groups A and B are reported separately. Methods Patients (≥ 18 years) with severe SCD (including those with recurrent vaso-occlusive crisis [VOC] and acute chest syndrome [ACS]) were screened for eligibility. Patients received 240 µg/kg of plerixafor 4-6 hours prior to HSC collection via apheresis. CD34+ cells were transduced with BB305 LVV. Patients underwent myeloablative busulfan conditioning and subsequent LentiGlobin drug product (DP) infusion. Patients were monitored for adverse events (AEs), engraftment, vector copy number (VCN), total hemoglobin (Hb) and HbAT87Q expression, hemolysis markers, and SCD clinical manifestations. Data are presented as median (min-max). Results: As of 7 March 2019, 19 Group C patients, aged 26 (18-36) years, had initiated mobilization/apheresis and 13 patients were treated with LentiGlobin for SCD gene therapy. Median DP VCN, % transduced cells, and CD34+ cell dose in the 13 treated patients were: 3.8 (2.8-5.6) copies/diploid genome (c/dg), 80 (71-88) %, and 4.5 (3.0-8.0) x 106 CD34+ cells/kg, respectively. The median follow-up was 9.0 (1.0-15.2) months. Twelve patients achieved neutrophil and platelet engraftments at a median of 19 (15-24) days and 28 (19-136) days, respectively. As of the data cut-off, engraftment was not yet evaluable in 1 patient at 1-month post-infusion. All patients stopped red blood cell (RBC) transfusions within about 3 months post-LentiGlobin gene therapy. Median total hemoglobin (Hb) and Hb fractions in patients at various time points are shown in Figure 1. Median HbS levels were at or below 50% in all patients with at least 6 months follow-up. The median total Hb at last visit in 8 patients with at least 6 months of follow-up, was 11.5 (10.2-15.0) g/dL, with a corresponding HbAT87Q median contribution of 5.3 (4.5-8.8) g/dL and a median HbS 5.7 (4.8-8.0) g/dL. Of these 8 patients, 6 had a history of VOCs or ACS. The median annualized VOC+ACS rate in these patients was 5.3 (3-14) pre-treatment and decreased to 0 (0-2) post-treatment. One Grade 2 VOC was observed 3.5 months post-treatment. No ACS or serious VOCs were observed in Group C patients' post- treatment. Lactate dehydrogenase, reticulocyte count, and total bilirubin at last visit post-LentiGlobin infusion were 225.0 (130.0-337.0) U/L, 150.0 (42.1-283.0) 109/L, 22.2 (3.42-39.3) µmol/L, respectively, trending towards normalization. The most common non-hematologic Grade ≥ 3 AEs were febrile neutropenia (n=10) and stomatitis (n=7) post-DP infusion. Serious AEs were reported in 6 patients post-LentiGlobin treatment, most common being nausea and vomiting. To date, there have been no DP-related AEs or graft failure, vector-mediated replication competent lentivirus detected, or clonal dominance reported. Longer follow-up and additional patient data will be presented. Summary The safety profile of LentiGlobin gene therapy for SCD remains consistent with single-agent busulfan conditioning and underlying disease. Patients in HGB-206 Group C experienced high-level, sustained expression of gene-therapy derived hemoglobin, with median HbS levels reduced to ~50% and median total Hb levels of 11.5 g/dL at 6 months. The cessation of clinical complications (no ACS or serious VOCs) and decreased hemolysis suggest a strong therapeutic effect after LentiGlobin gene therapy in patients with SCD. Disclosures Kanter: Peerview: Honoraria; NHLBI: Membership on an entity's Board of Directors or advisory committees; Rockpointe: Honoraria; SCDAA: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Imara: Consultancy; Jeffries: Consultancy; Modus: Consultancy; Guidepoint Global: Consultancy; GLG: Consultancy; Cowen: Consultancy; bluebird bio, Inc: Consultancy; Medscape: Honoraria; Sangamo: Consultancy. Kwiatkowski:Terumo: Research Funding; Novartis: Research Funding; Apopharma: Research Funding; Imara: Consultancy; Celgene: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Agios: Consultancy. Schmidt:German Cancer Research Center, Heidelberg, Germany: Employment; GeneWerk GmbH, Heidelberg, Gemrany: Equity Ownership. Miller:bluebird bio, Inc.: Employment, Equity Ownership. Pierciey:bluebird bio, Inc.: Employment, Equity Ownership. Huang:bluebird bio, Inc.: Employment, Equity Ownership. Ribeil:bluebird bio, Inc.: Employment, Equity Ownership. Thompson:Baxalta: Research Funding; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; bluebird bio, Inc.: Consultancy, Research Funding. Walters:AllCells, Inc: Consultancy; TruCode: Consultancy; Editas Medicine: Consultancy.

Description: Introduction An "ideal" marker to monitor MRD after allo-SCT should be informative in the majority of pts and facilitate the use of a method with high sensitivity and specificity in a standardized manner. In addition, to allow repeated monitoring in timely tight intervals but also ensuring patients' comfort such marker should ideally be measurable in peripheral blood (PB). Despite recent identification of several molecular aberrations AML and MDS, many of these do not fulfil the above-mentioned requirements, as they are present only in small patient groups, their potential instability during disease course, the absence of standardized assays and the need for BM as optimal sample source. A molecular marker which might provide these properties is the WT1 gene, as it is overexpressed in the majority of AML pts and in about 50% MDS pts and is measurable in PB by a standardized assay. To estimate its value after allo-SCT we compared serial WT1 measurement with other methods used to monitor MRD in a real-life situation. Patients and Methods For this retrospective analysis all AML and MDS pts who underwent allo-SCT at our center between 2012 and 2016 were screened for PB WT1 mRNA overexpression using the ELN certified Ipsogen® WT1 ProfileQuant® Kit. Pts with WT1 overexpression, as defined by an validated cut-off level of 50 copies/104 ABL copies, were routinely monitored after transplant. In addition, in all pts STR-based chimerism analysis was performed. In pts with chromosomal aberrations existing prior allo-SCT metaphase and FISH analysis was performed, while XY FISH was additionally conducted in pts with sex-mismatched donor-recipient constellation. Furthermore, pts with molecular markers were regularly monitored by NGS or qPCR. Results of WT1 monitoring were correlated with clinical course and compared with results obtained from the other methods. Results Of 104 screened pts 59 (57%) showed an WT1 overexpression at diagnosis and underwent an allo-SCT. This included 40 AML pts (WT1 overexpressed in 66%) and 19 MDS pts (WT1 overexpressed in 44%). Chimerism analysis was accessible in all 59 pts (100%), while 20 pts (34%) could also be monitored by XY-FISH. Additionally, in 40 pts (68%) cytogenetics and FISH were applicable, while 22 pts (37%) could be investigated by NGS or qPCR. Overall, in 5 pts MRD could be monitored by WT1 and chimerism only, while in 29 pts MRD could be monitored by 1, in 22 pts by 2 and in 3 pts by 3 additional methods. With a median follow up of 13 months (2 - 51) we analyzed a total of 472 WT1 samples reflecting a median of 8 samples per patient (2 - 19). One month after allo-SCT 57 pts (97%) showed complete remission and a rapid decrease of WT1 expression below threshold. Only 2 pts had persistant hematological disease with sustained WT1 overexpression. Twenty-four pts (41%) experienced hematologic (62%) or molecular (38%) relapse at a median of 126 d (28 - 938 ) after allo-SCT. In 20 (83%) of these at least one WT1 value wasabove the cut-off before relapse. Median time from first elevated WT1 to relapse was 2 weeks (0 - 27). Only 4 pts (17%) with molecular relapse showed WT1 expression below cut-off. In contrast, known molecular aberrations were found again in 63% and loss of complete donor-chimerism or a positive signal in XY-FISH analyses were only seen in 46% and 57% before relapse. Furthermore, cytogenetics or FISH detected known or new aberrations in 39% before relapse. From 35 pts remaining in CR for a median of 13 months, only 1 (3%) had a transient increase of WT1 expression above the cut-off, whereas WT1 levels of the other 34 pts persisted below. Three pts (9%) with ongoing remission showed a transient decrease of donor-chimerism, whereas even 31% of pts accessible for XY-FISH showed temporary conspicuous results. Conventional cytogenetics and FISH in pts with CR showed transient abnormalities in 18%, whereas in 14% with molecular aberrations these were temporary detectable. Conclusion Measurement of PB WT1 overexpression is an easy accessible method to monitor MRD after allo-SCT that can be employed by a standardized assay in the majority of AML and MDS pts independent from their individual leukemic genotype. Besides these advantages, the results from our real-life experience also suggest that WT1 overexpression allows sensitive detection of imminent relapse after allo-SCT. Taking into account the methodical restrictions of this retrospective analysis, our data requires confirmation in a prospective trial. Disclosures Gattermann: Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Other: travel, accomodation expenses, Research Funding. Kobbe:Jansen: Honoraria, Other: travel support; Celgene: Honoraria, Other: travel support, Research Funding.

Description: Background: High-dose chemotherapy (HDCT) followed by autologous transplantation of hematopoietic stem cells (auto-HSCT) is an important component of treatment in multiple myeloma (MM). There is a standard method of controlled cryopreservation of HSC suspension. We found that the storage of native HSC suspension with temperature fluctuations from +3 °C to +5 °C during 72 - 120 hours does not significantly affect the content of CD34+ cells in the product, the index 7AAD- (7-AAD (7-aminoactinomycin - D) is a fluorescent marker that penetrates damaged cell membranes and binds to double-stranded DNA. Through 7AAD does not penetrate intact membranes, so living cells are not stained 7AAD with flow cytometry), and colony-forming ability (CFA) of HSC, as well as the recovery time of hematopoiesis in MM patients after auto-HSCT. Aim: To evaluate the effectiveness and safety of the method of storage of non-cryopreserved peripheral blood stem cells. Methods: 39 patients with MM were included in this study(male/female ratio 1.36:1). All the patients get standard immunochemotherapy programs and were in remission at the time of auto-HSCT. Patients were divided into two groups depending on the method of stem cell storage: group 1 - non-cryopreserved (n=20), group 2 - cryopreserved (standard) (n=19). An effectivity and safety were evaluated in such parameters as the number of CD34+ and 7AAD- cells, CFA after apheresis and before reinfusion of HSC. Also, we evaluated the number of platelets concentrate transfusions, the timing of engraftment of granulocytic and megakaryocytic blood sprouts, the length of hospital stays after auto-HSCT. Results: The results are presented in the comparison table of the evaluated parameters. Our data showed significantly reduce of episodes febrile neutropenia and cases of enteropathy. Conclusion: Thus, the proposed method of storage of HSC is not inferior to the traditional method with cryopreservation on such parameters as CD34+, 7AAD-, CFA, the number of platelets concentrate transfusions, terms of hematopoiesis restoration, length of hospital stay after HSCT, the number of complications. Table. Disclosures Shuvaev: Fusion Pharma: Consultancy; BMS: Consultancy; Novartis: Consultancy; Pfize: Honoraria.

Description: BACKGROUND: Invasive fungal infections (IFIs) including invasive candidiasis(IC), pulmonary invasive aspergillosis (IA) and other fungal species as mucor mycosis (IM), remain a major clinical problem in neutropenic patients receiving intensive chemotherapy for acute myeloid leukemia (AML) due to their high morbidity and mortality. DESIGN: We performed a prospective observational study on antifungal (AF) prophylaxis used in a prospective clinical trial of intensive chemotherapy within the Acute Leukemia French Association (ALFA 0702 study, ClinicalTrials.gov Identifier: NCT00932412). A total of 677 AML patients from 34 different centers were included, 45% were males, and median age was 46 years (18-60). Prognosis according to cytogenetics was favorable in 23% of patients, intermediate in 53% and unfavorable in 18%. All patients received daunorubicine and aracytine intensive induction chemotherapy. The trial protocol recommended posaconazole suspension as AF prophylaxis at the dose of 200 mg three times a day from day 4 after induction chemotherapy and until neutrophils recovery. Patients were considered evaluable for this study if they received posaconazole for a minimum duration of 7 days and not later than 10 days after the beginning of the induction chemotherapy. IFI were classified by the local investigators and were reviewed later by an independent expert according to the EORTC classification (possible, probable and proven), scanner images were requested for further investigations when needed. The objective of this study was to describe the IFI prophylaxis strategies used in the different centers, to calculate the cumulative incidence of IFI according to different strategies, and to evaluate the overall survival and IFI related mortality. RESULTS: Among the 677 patients, 383 (57%) received posaconazole as AF prophylaxis for a median duration of 25 days (7-253). Posaconazole was introduced after a median time of 3 days after the beginning of the chemotherapy. We distinguished 4 groups, Group 1: patients without any prophylaxis (n = 203, 30%), Group 2: posaconazole alone (n=241, 36%), Group 3: posaconazole plus other prophylaxis (n=142, 21%), and Group 4: patients receiving other prophylaxis (n= 91, 13%). Overall, there were 72 IA [34 (47%) possible, 38 (53%) probable/proven], 17 IC (all probable/proven) and 7 IM [1 possible, 6 probable/proven]. The median delay between posaconazole prophylaxis and IFI occurrence was 22 days (7-50) for IA, 18 days (15-60) for IC and 26 days (13-28) for IM compared to 10 days (3-180), 8 days (3-32) and 21 days (10-32) in case of other prophylaxis. The cumulative incidence of IFI was 2.4% at 10 days (IA: 2.4%, IC : 0%, IM : 0%), 11,2% at 30 days (IA: 8.4%, IC: 2%, IM: 0.7%), 14.2% at 60 days ( IA: 10.6%, IC : 2.5%, IM : 1%), and 14.2% at 100 days (IA:10.6%, IC : 2.5%, IM : 1%). When considering the prophylaxis groups, the cumulative incidence of probable/proven IA at day 60 was 8.37% for Group 1; 4.7% for Groups 2 and 3 combined and 3.3% for Group 4 (Figure 1). After a median follow-up of 27.5 months (0.4- 73.4), 418 patients are alive and 259 (38.3%) died with 5.4% from IFI. Concerning the overall survival, the results were analyzed according to the presence or absence of IFI and AF prophylaxis (Figure 2) we observed a better survival without any IFI whatever the AF prophylaxis was and in case of AF prophylaxis there was an improvement of 2-years survival after chemotherapy induction. Concerning the global mortality and the IFI related mortality, the results were analyzed according to the prophylactic groups and the timing of prophylaxis, the multivariate analysis showed the negative impact of 2 factors on the mortality at day 100: Unfavorable cytogenetics: HR= 3.34 (1-11.20) p=0.05 and presence of IFI: HR = 5.63 (2.62-12.08) p

Description: Key Points Generation and functional analysis of FVIII-specific human CAR Tregs. Specific regulation of FVIII responses by engineered human CAR Tregs.