bluuebunny/crossref_metadata_2025_split huggingface dataset:
PF765 RESULTS OF AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) IN PATIENTS ABOVE THE AGE OF 70 ARE COMPARABLE TO THE RESULTS IN YOUNGER PATIENTS
Authors: Mamat K. , Murray J. , Bloor A. , Cavet J. , Dennis M. , Castleton A. , Wiseman D. , Somervaille T. , Kulkarni S. 
Published: June 2019

Background:High dose chemotherapy and autologous stem cell transplant is an important therapeutic procedure for select solid tumours and haematological malignancies providing chance of durable remission following induction therapy and in some patient potential cure. Increasing numbers of patients above the age of 70 are offered high dose chemotherapy and Auto‐PBSCT. This retrospective analysis compares the outcomes, morbidity and mortality of Auto‐PBSCT in patients above the age of 70 to those in the age group of 65‐69.Aims:To evaluate the results of ASCT in patients with lymphoma or myeloma who were above the age of 70 yrs to the reults in matched group in the age group of 65 to 70 yr. with the aim to compare engraftment data, morbidity, mortality and overall survival.Methods:Retrospective evaluation using case notes, electonic patient records and haematology database.Results:We analysed 54 patients, ages 70 and over, and 56 patients, ages between 65 and 69 years, who received AutoPSCT from 1990 to 2018 in Haematology and Transplant Unit, The Christie NHS Foundation Trust, Manchester, UK. Median age was 71yr(70–75) and 67yr(65–69). Male to female ratio are 38:16 (>70yr) and 41:15 (65–69). The two indications for transplants are Myeloma and lymphoma. The proportions are similar for both age groups, Myeloma:Lymphoma 37(68.5%):17(31.5%) in >70yrs and 40(71.4%):16(28.6%) in 65–69yr The numbers of patients undergoing second Auto‐PBSCT are 9(17%) in >70yr and 11(20%) in 65–69yrs. The follow up period was 2 years (43d‐14.1years) in >70yrs and 4 years (41d‐16.3years) in the 65–69yrs. Median time to neutrophil engraftment (ANC>0.5) was 12 days(9–19days) and 12 days(9–21days). Median platelet recovery (>25) was 21days(10–195days) and 29 days (10–694 days). Median hospitalisation was 27 days (14–91days) and 21days (14–60days). In terms of morbidity during transplant, patients needing intensive or high dependency care was 8 (15%) in >70yr and 5(9%) in 65–69yrs). Patients requiring readmission post discharge was 14(26%) in >70yrs and 9 (16%) in younger age group.here was no difference in treatment related mortality and less than 3% in both groups.Summary/Conclusion:It is feasible to offer ASCT to patients above the age of 70 yr. Patient selection is crucial and should be based not only on the objective organ function evaluation but also the subjective assessment of transplant physician about appropriateness to undergo the ASCT therapy. The decision should be based on the individualised risk benefit ratio, risk of morbidity and expected survival benefit.image
PF777 IMMUNOLOGICAL RECONSTITUTION AS A BASIS FOR THE EARLY INITIATION OF PNEUMOCOCCAL VACCINATION AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Stoma I. , Iskrov I. , Smolnikova V. , Lendina I. , Milanovich N. , Uss A. 
Published: June 2019

Background:In the context of significant advances in the treatment of hematological diseases using the method of autologous hematopoietic stem cell transplantation (auto‐HSCT), the number of patients requiring early vaccination against pneumococcal infection increases worldwide. Current guidelines indicate the early initiation of pneumococcal vaccination starting from 3 months after HSCT. Still, the topical issue is the determination of the earliest optimal dates for the start of vaccination after transplantation, taking into account the dynamics of immunological recovery.Aims:The aim of this study was to determine the optimal timeline for the onset of vaccination with conjugated pneumococcal vaccine in patients with multiple myeloma after auto‐HSCT.Methods:The immune response to the conjugated pneumococcal vaccine is based on the T‐dependent (CD4+) activation of B‐cells, what was taken into account when estimating the timing of immune reconstitution after auto‐HSCT in candidates for vaccination.An immunological study using flow cytometry was performed in 37 adult patients with multiple myeloma prior to the auto‐HSCT procedure, as well as on days +30, +60, +90, +180 after transplantation.Results:After auto‐HSCT, the level of naive B‐cells returns to its original value by the 60th day from transplantation (Kruskal‐Wallis test 41.97; P < 0.001), shown on Fig. 1. At the same time, the level of CD4 + cells did not fall below 200 cells/μl starting from day +30, what indicates the effectiveness of early vaccination with T‐dependent vaccines in this category of patients with immunosuppression. Dendritic cells (DC1 and DC2) are restored in parallel by the 30th day from auto‐HSCT (Kruskal‐Wallis test 25.78; P <0.001 for DC‐1 cells and Kruskal‐Wallis test 11,17; P <0.025, respectively), what confirms the basis for the early vaccination with conjugated pneumococcal vaccines in this category of patients.Summary/Conclusion:The obtained data allows planning the introduction of the first dose of the conjugated pneumococcal vaccine 60 days after autologous HSCT, with the perspective of introducing an individualized vaccination calendar based on immunological parameters. It is also necessary to further implement immunization programs for immunocompromised patients, especially in hematology and cancer setting with the participation of a multidisciplinary team of specialists.image
PF792 IDENTIFICATION OF REFERENCE GENES IN HUMAN TUMORS FOR TUMOR EDUCATED PLATELETS (TEPS) STUDY BASED ON RNA‐SEQ DATA
Authors: LUO L. , Luo H. 
Published: June 2019

Background:The previous studies have shown that Tumor Educated Platelets (TEPs) RNA may complement currently used biosources and biomolecules employed for liquid biopsy diagnosis. RT‐PCR is a regular method to measure gene expression levels to stage the patients and evaluate their prognosis. As there are little research on reference mRNA in platelets, especially in cancer.Aims:Our study is to find the proper internal controls for RT‐PCR in platelet study.Methods:Firstly, based on dataset GSE68086, we found 285 genes with relatively equal expression in 4 kinds of high incidence cancer (non‐small cell lung cancer (NSCLC), colorectal cancer (CC), breast cancer (BC) and liver cancer (LC)) and healthy control (HC). 95 genes left after screening with the criteria of mean>1 and coefficient of variation (cv) <1. Secondly, we gained 73 common reference genes from previous reported studies. Thirdly, we obtained 7 candidate reference genes (ACTB, B2 M, GAPDH, GNAS, OAZ1, PTMA and YWHAZ) after intersected the 95 genes and 73 genes. At last, we extracted total RNA from 1.5 ml blood in 30 unselected persons, including 6 NSCLC, 6 CC, 6 LC, 6 BC, and 6 HC, and performed RT‐PCR with equal quantity of RNA to measure the expression levels of the candidate reference genes.Results:All of 7 candidate reference genes performed well in 5 tested groups with a cv<0.1. Both B2 M and GAPDH were the most stably expressed with a cv<0.05, but the expression of B2 M was much higher than GAPDH in platelets.Summary/Conclusion:We have found 7 platelets mRNA with relatively same expression levels among several solid tumors and healthy people, which can be used as reference genes for mRNA measuring of platelets. Among them, B2 M may be the best reference control gene.image
PF814 KNOWLEDGE, ATTITUDES AND PRACTICES ON BLOOD TRANSFUSION OF MEDICAL RESIDENTS IN A TERTIARY HOSPITAL: A QUESTIONNAIRE‐BASED STUDY
Authors: Miranda R.S. , Dumagay T. 
Published: June 2019

Background:Blood transfusion remains to be one of the most common procedures performed in hospitals. It is an extremely efficient and perhaps life‐saving procedure which is very much an essential part in the management of hematologic and non‐hematologic cases. The knowledge of doctors on blood transfusion has a substantial influence on the rational utilization of blood products.Aims:We aim to assess the knowledge, attitudes and practices on transfusion of internal medicine (IM) residents at the Philippine General Hospital, using the BEST‐TEST, a validated questionnaire on transfusion medicine (TM).Methods:This is a descriptive cross‐sectional study design, which included all 63 internal medicine residents undergoing training at the Philippine General Hospital for the year 2016. General data on demographics were collected, after which the participants were asked to answer the BEST‐TEST validated questionnaire on transfusion medicineResults:A total of 63 internal medicine residents with a mean age 27.9 ± 1.6 ranging from 25 to 33 years old and majority (61.9%) were between 28 to 30 years old were included in this study. Gender distribution is almost even (50.8% males). In terms of number of hours of training on transfusion medicine in medical school, a third had 4+ hours and a little more than half (50.8%) had 3+ hours. Majority (58.7%) of the internal medicine residents appraised their knowledge of transfusion medicine as intermediate, and almost all (98.4%) rated it as beginner to intermediate. BEST‐TEST mean scores were 39.1%, 40.0%, and 41.0% for the first, second, and third year residents, respectively. There is no significant correlation between test scores of the residents and number of hours of training in transfusion medicine in medical school (p = 0.694) and in residency (p = 0.927). On the other hand, there is a significant correlation between the quality (perceived helpfulness) of residency training on transfusion medicine and test scores with the scores increasing as the year level increases.Summary/Conclusion:Indeed, the results of this study has shown inadeqacy in the knowledge on transfusion medicine among internal medicine residents. Therefore, further training on transfusion medicine, maybe in the form of lecture series and seminars, may help strengthen the knowledge of the residents.
S849 TNF‐α BLOCKADE CORRECTS THE MONOCYTE/MACROPHAGE IMBALANCE IN PRIMARY IMMUNE THROMBOCYTOPENIA (ITP)
Authors: Zhao Y. , Liu X. , Li G. , Peng J. , Hou M. 
Published: June 2019

Background:Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder. Deviation of monocyte/macrophage subsets plays an important role in the pathogenesis of ITP. TNF‐α blockade is widely used in many autoimmune diseases with satisfactory effects. However, the effect of TNF‐α blockade on monocyte/macrophage system in ITP remains unknown.Aims:Our study aimed to investigate whether TNF‐α could restore the disturbed balance of monocyte/macrophage subsets and be a potential therapeutic strategy for ITP.Methods:Plasma TNF‐α was detected by ELISA. The monocyte/macrophage subsets were analyzed using flow cytometry and immune fluorescence. Macrophage polarization was analyzed using western blot, q‐PCR, and flow cytometry. Phagocytic capacity of macrophages was measured by the engulfment of opsonized platelets. T‐cell priming ability of macrophages was determined through co‐culturing with CD4+ T cells and CD8+ T cells. We established a passive model of murine ITP. Platelet count was measured every other day. The retention of platelets in liver and spleen was assessed by the fluorescence intensity detected using the in vivo imaging system.Results:ITP patients manifested with an increased TNF‐α expression which was inversely correlated with platelet count. Moreover, the numbers of TNF‐α‐expressing macrophages in spleen and CD16+ monocytes were more than that of healthy controls. TNF‐α blockade inhibited M1 macrophage polarization by suppressing the NF‐κB signaling pathway, and dampened the phagocytic capacity and T‐cell priming ability of macrophages. Moreover, anti‐TNF‐α therapy reduced the number of non‐classical monocytes and M1 macrophages, ameliorated the retention of platelets in spleen and liver, and significantly increased the platelet count of ITP mice.Summary/Conclusion:Our study demonstrated that TNF‐α blockade could decrease the number and functions of pro‐inflammatory subsets of monocytes/macrophages by inhibiting NF‐κB signaling pathway, leading to remarkable attenuation of antibody‐mediated platelet destruction both in vitro and in vivo, thus might be a promising therapeutic strategy for the management of ITP.image
S870 SINTILIMAB FOR RELAPSED/REFRACTORY (R/R) EXTRANODAL NK/T CELL LYMPHOMA (ENKTL): A MULTICENTER, SINGLE‐ARM, PHASE 2 TRIAL (ORIENT‐4)
Authors: Tao R. , Fan L. , Song Y. , Hu Y. , Zhang W. , Wang Y. , Xu L. , Zhou H. , Li J. 
Published: June 2019

Background:ENKTL account for more than 20% of the peripheral T‐cell lymphoma in Asia. Patients with r/r ENKTL have a poor prognosis after failing an L‐asparaginase based regimen, and the median overall survival is less than 6 months. The overexpression of PD‐L1 induced by EBV infection is a potential mechanism for ENKTL to avert immune surveillance, and recent studies of PD‐1 antibodies in pts with r/r ENKTL have demonstrated potential efficacy. Sintilimab, a fully human anti‐PD‐1 monoclonal antibody, has a safety profile consistent with other approved PD‐1 antibodies and was approved for r/r classical Hodgkin lymphoma in China in 2018.Aims:This multicenter, single‐arm, phase 2 study aims to validate the efficacy and safety of sintilimab monotherapy in patients with r/r ENKTL in China.Methods:Patients with pathologically confirmed r/r ENKTL were enrolled. Sintilimab was given 200 mg IV Q3W, until PD, death, unacceptable toxicity, or withdrawal from the study. Treatment beyond PD is allowed. Tumor response evaluation was performed by both PET‐CT and CT/MRI with contrast. The primary endpoint was objective response rate based on LUGANO 2014 criteria. Data cut‐off date for this analysis was Feb 2, 2019.Results:From Aug 31, 2017 to Feb 7, 2018, a total of 28 patients were enrolled: 60.7% male and the median age was 37 (range: 19∼65) yr. Sixty‐eight percent of patients were stage IV and 89.3% were ECOG PS ≥ 1. All patients had failed an L‐asparaginase based regimen, the median lines of previous therapy were 3 (range: 1∼13), 78.6% patients received prior radiotherapy and 7.1% had failed HSCT. Median duration of therapy was 14.04 (range: 1.4∼17.3) months and 19 patients are still receiving sintilimab. Sixty‐eight percent (19/28, 95%CI: 47.6%∼84.1%) of patients achieved response (CR+PR), including 4 pts who experienced PD prior to having a response. DCR was 85.7%, including 5 pts who experienced PD before SD or response. The 1‐year OS rate was 82.1% and the median OS has not been reached. Most TRAEs were G1∼2 (67.9%) and no patients discontinued treatment due to AEs. The most common TRAE was decreased lymphocyte count (46.4%) and 84.6% were grade 1∼2. SAEs occurred in 21.4% of patients and none were related to sintilimab. No patients died from AEs.Summary/Conclusion:Sintilimab is effective and well tolerated in r/r ENKTL and could be a promising treatment option for these patients. Early disease progression observed by PET scan in this study could be pseudo‐progression as it did not correlate with poor outcome, which warrants further investigation. NCT03228836
S890 NEW WHOLE GENOME ASSOCIATION SCANNING APPROACH FOR THE DISCOVERY OF HLA CLASS I‐RESTRICTED MINOR HISTOCOMPATIBILITY ANTIGENS
Authors: Fuchs K. , Adriaans A. , Honders W. , van der Lee D. , van der Meijden E. , Pont M. , Monajemi R. , Kielbasa S. , ’t Hoen P. , van Bergen C. , Falkenburg F. , Griffioen M. 
Published: June 2019

Background:Patients that undergo allogeneic stem cell transplantation (SCT) as treatment for hematological diseases face the risk of relapse as well as Graft‐versus‐Host Disease (GvHD). GvHD as well as the favorable Graft‐versus‐Leukemia effect are mediated by donor T cells. These T cells recognize minor histocompatibility antigens: polymorphic peptides, which are presented on the cell surface by HLA molecules and are caused by genetic differences in single nucleotide polymorphisms (SNPs) between patient and donor. Knowledge about mismatched minor histocompatibility antigens may enable a more directed donor search as well as better prediction and measurement of the Graft‐versus‐Leukemia effect and GvHD for personalized treatment after transplantation, thereby contributing to a better outcome for patients treated with allogeneic SCT.Aims:Identification of minor histocompatibility antigens has been a laborious process in the past. Therefore, whole genome association scanning was developed in our laboratory. However, this method was restricted to two HLAs and screening of one million SNPs. The aim of this study is to develop and use an optimized method to identify the dominant repertoire of minor histocompatibility antigens in common HLA class I alleles.Methods:Donor T‐cells isolated from patients after allogeneic SCT are tested for recognition of a new panel of 191 selected B‐cell lines, which are sequenced in the 1000 Genome Project. This panel enables the inclusion of seven common HLAs and increases SNP coverage to 12 million (MAF > 0.01). SNPs that strongly associate with T‐cell recognition are subsequently validated to encode minor histocompatibility antigens.Results:A total of 19 novel minor histocompatibility antigens have been identified that are presented in seven common HLA class I alleles, showing the potential of this optimized approach. Besides conventional antigens, cryptic peptides were found as well as peptides restricted to HLAs that were not primarily targeted.Summary/Conclusion:This improved approach for whole genome association scanning has been successfully applied in rapidly discovering new minor histocompatibility antigens. The new method surpasses previous methods in its rapidness and coverage of HLAs and SNPs across the human genome, which additionally allows for identification of cryptic peptides. With the increasing number of patients that are analyzed in this study, T‐cells recognizing known minor histocompatibility antigens are more often isolated, indicating that the repertoire of minor histocompatibility antigens is limited. Our optimized method is expected to discover the majority of unknown antigens in this repertoire, thereby contributing essential knowledge for new strategies to improve clinical outcome after allogeneic SCT.
S906 PRECLINICAL EVALUATION OF THE PRESERVATION OF RED BLOOD CELL CONCENTRATES IN HYPOXIA BY HYPOXIC STORAGE TECHNOLOGY FOR TRANSFUSION IN SICKLE CELL DISEASE.
Authors: Bencheikh L. , Nguyen K.‐A. , Chadebech P. , Kiger L. , Bodivit G. , Jouard A. , Pakdaman S. , Adypagavane S. , Audureau E. , Tebbakha K. , Hebert N. , Pirenne F. , Sowemimo‐Coker S. , Dunham A. , Bartolucci P. 
Published: June 2019

Background:Sickle cell disease (SCD) is the most common genetic disease, due to a mutation of the sixth amino acid of gene coding for the Hemoglobin (Hb) beta chain. The mutated Hb, called HbS, is able to polymerize which entails red blood cell (RBC) sickling, leading to chronic hemolysis and painful vaso‐occlusive crisis. Transfusion exchange is one of the therapeutic strategies used for this pathology since it allows the replacement of sickle RBCs. The quality of the transfused RBCs is essential, both to improve the transfusion yield but also to limit the pathological interactions between RBCs and endothelial cells, damaged by hemolysis. RBC concentrates can be stored up to 42 days at 4°c, however, during their hypothermic storage, the quality of RBCs decreases, mainly because of oxidative damage. Hypoxic storage technology helps to keep RBC in hypoxia, improving the concentration of ATP, 2‐3DPG, hemolysis and deformability of RBCs.Aims:The purpose of our study was to compare the quality of conventionally conserved RBCs with those conserved with hypoxic storage technology.Methods:We assessed several parameters including sickle RBC flow adhesion to HUVEC (human umbilical vein endothelial cells), previously exposed to hemolysate, to mimic endothelial damage present in patients. We also evaluated hypoxic RBC senescence parameters by flow cytometry. In that purpose, we measured intracellular calcium and reactive oxygen species (ROS) concentration as well as phosphatidylserine exposure by annexin V staining in hypoxic RBCs and control RBCs, after incubation 24 h in plasma from healthy donors and SCD patients. RBC adherence on thrombospondin (TSP) under flow was also quantified, since RBC adhesion to TSP was shown to increase during storage and since TSP concentration is elevated in sickle cell disease patients during acute chest syndrome (ACS) or at risk of ACS. In addition, we assessed hemolysis in the bags by measuring free hemoglobin concentration in the supernatant by spectroscopy.Results:We found a reduction in the concentration of free Hb (produced by RBC lysis) in hypoxic storage bag, a decrease in RBC senescence (ROS and calcium intracellular concentrations) in hypoxic RBCs and a reduced adherence to thrombospondin when hypoxic RBCs are incubated during 24 h in plasma from healthy donors or SCD patients. There was no difference of RBC adhesion to endothelial cells.Summary/Conclusion:These results suggest that hypoxic storage technology meets the safety criteria for transfusion in SCD patients and may provide significant clinical benefits.
PS941 ANTI‐CD19 CAR‐T THERAPY BRIDGING TO ALLO‐HSCT IMPROVES LONG‐TERM OUTCOME OF B‐ALL PATIENTS WITH HIGH LEUKEMIA BURDEN OR POOR PROGNOSTIC MARKERS
Authors: Mei H. , Hu Y. , Jiang H. , Zhou F. , Guo T. , Wu Y. , Liu L. , Ai L. , Shi W. , Li C. , Tang L. , Xiong W. , Xia L. , Jin R. 
Published: June 2019

Background:Anti‐CD19 chimeric antigen receptor T cell (CAR‐T) therapy was an effective treatment method for relapsed and/or refractory B‐cell acute lymphoblastic leukemia (r/r B‐ALL) patients, but its ability to maintain long‐term leukemia‐free survival was limited. New strategies that can help CAR‐T therapy achieve lasting effect are urgently warranted.Aims:Our study aimed to answer the question that whether subsequent allo‐HSCT could improve the long‐term prognosis of the minimal residual disease‐negative (MRD‐) CR patients after CAR‐T therapy.imageMethods:In the first stage, patients received split doses of CAR‐T cells after lymphodepleting chemotherapy, consisting of fludarabine and cyclophosphamide. In the second stage, MRD‐ CR patients who had no history of allo‐HSCT and had no contraindications or other restrictions would, on their own accord, receive allo‐HSCT from 1 to 3 months after CAR‐T therapy.Results:58 r/r B‐ALL patients were treated with anti‐CD19 CAR‐T cells, and 51 (87.9%) achieved complete remission (CR) (47 MRD‐ CR). The 6‐month and 12‐month overall survival (OS) rates were 68.9% and 61.1% respectively. During the follow‐up (median, 7.7 months), 21 of the 47 MRD‐ CR patients received consolidative allo‐HSCT and 17 remained leukemia‐free, while the other 26 patients received CAR‐T therapy alone and only 10 remained in CR. (Fig. 1A) There was no difference in OS between the MRD‐ CR patients who received allo‐HSCT and those who didn’t, but event‐free survival (EFS) and relapse‐free survival (RFS) were significantly prolonged by allo‐HSCT in the subgroups with either high pre‐infusion bone marrow MRD (≥ 5%) or poor prognostic markers (P < 0.05). (Fig.1B∼E) However, no difference was found in OS, EFS and RFS in subgroup with MRD < 5% and without poor prognostic markers.Summary/Conclusion:These data demonstrate that CAR‐T therapy bridging to allo‐HSCT is a safe and effective therapeutic strategy for r/r B‐ALL patients, and can achieve better efficacy in terms of maintaining long‐term EFS and RFS. Patients with high pre‐infusion MRD or with poor prognostic markers can benefit from the early consolidative allo‐HSCT after CAR‐T therapy. Trials were registered at www.clinicaltrials.gov as # NCT02965092 and #NCT03366350.