bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB1972 RIBOCICLIB INDUCES MACROCYTOSIS IN THERAPEUTIC DOSES: CHARACTERIZATION OF OUTCOME
Authors: Alves S. , Alves S. 
Published: June 2019

Background:Ribociclib is a small molecule that selectively inhibits cyclin‐dependent kinases 4 and 6, blocking the phosphorylation of retinoblastoma protein and inducing of G1 phase arrest hence having an important role in the regulation and prevention of cell‐cycle progression. The project OncoDynamics aims to explore possible correlations between therapeutic doses of ribociclib for treatment of breast cancer and other therapies with several analytic biomarkers and clinical data. Adverse events of CDK 4/6 inhibitors are mostly hematologic being neutropenia the most frequent followed by anemia and thrombocytopenia as it is the case of palbociclib which has been recently described as associated with macrocytic, dysplastic anemia.Aims:This study aims to characterize the outcome of macrocytosis evident in our patients treated with ribociclib in therapeutic doses for treatment of breast cancer.Methods:This study is integrated in the OncoDynamics project and is a prospective, unicentric cohort study with patients treated for metastatic breast cancer with ribociclib plus letrozole, each patient registered as digital case report form and evaluated data of mean corpuscular volume (MCV), hemoglobin (Hg) and red cell distribution width (RCDW) for descriptive analyses.Results:Of the 7 patients with breast cancer treated with ribociclib (14,8%) with a follow up period ranging from 3 to 18 months, 4 patients (57,1%) had a sustained rise of the mean corpuscular volume (MCV > 97 fL), Hg ranging from 8,8 to 13,5 g/dL and RCDW from 12,7 to 20,9 CV%.Summary/Conclusion:We found this macrocytosis to be related to the treatment with ribociclib in therapeutic doses and in literature the correlation between CDK 4/6 inhibitors and macrocytosis has been described in relation to palbociclib. Clinical evolution of these patients is under evaluation. We aim to extend this study and to explore the inherent mechanism of action of ribociclib regarding anemia and macrocytosis.
PB1973 CONTRIBUTION OF NGS IN THE DIAGNOSIS OF HEREDITARY SPHEROCYTOSIS: CASE REPORT
Authors: Verstraete G. , Graux C. , Collinge E. , Depaus J. , Vellemans H. , Bianchi P. , Gulbis B. 
Published: June 2019

Background:Hereditary spherocytosis (HS) is the most frequent cause of non‐immune haemolytic anaemia (HA) among individuals of Northern European ancestry; its estimated prevalence is 1:2000. HS results from various molecular defects leading to decreased production or abnormality of one or more red blood cell (RBC) membrane proteins i.e., ankyrin, protein 4.2, band 3 and spectrin. The majority of HS cases (75%) are inherited in an autosomal dominant manner. Especially because of the spherical shape, RBCs are trapped in the spleen and have a shortened life span. Among other factors, according to the importance of the deficiency or protein abnormality it conducts to a clinical expression that may range from asymptomatic to severe chronic HA. Most often a phenotypic diagnosis can be made but next‐generation gene sequencing (NGS) has a place in difficult cases i.e. unsolved cases of HA, transfusion prior to diagnosis and discrepancy between clinical phenotype and diagnosis.Aims:We report here the case of a 18‐year‐old patient with a suspected HS, prominent splenomegaly and unknown personal or family history.Methods:Case report:The patient complained of fatigue for several months and grade 2 dyspnea. In the past, he repeatedly presented with biliary colic pain. He apparently had no personal or family medical history. Two years ago, he nevertheless had jaundice secondary to haemolytic anaemia. The evolution was spontaneously favourable and no further investigation was undertaken. He has a twin brother and a 20‐year‐old sister, both in good health. The clinical examination found a prominent splenomegaly. Haemoglobinopathy and most frequent RBC enzyme deficiencies were excluded. Given the high clinical suspicion of HS, his parents and siblings (although asymptomatic) were screened for HS.Results:The main biological data are reported in the Table 1.Molecular genetic analyses were performed: NGS targeted sequencing panel, containing panel 40 genes associated to haemolytic anemia, and confirmation by Sanger identified a nonsense mutation on the cytoplasmic domain of Band3. The mutation is novel and drastic; it causes a stop codon at 75 residues. The mutation is transmitted by the mother. NGS targeted sequencing analysis did not demonstrate any other abnormalities that could explain the phenotypic variability observed in the propositus and his mother.Given the profound anaemia associated to the voluminous spleen (main diameter of 25 cm by CT‐scan evaluation) and given the presence of symptomatic gallstones, the patient underwent a splenectomy and a cholecystectomy. After the procedure, he recovered from fatigue and the haemoglobin level returned to normal with no signs of residual haemolysis.Summary/Conclusion:This case reports a HS related to a new nonsense mutation in SLC4A1. The transmission is autosomal dominant but the penetrance is heterogeneous within the same family.image
PB1974 PYRUVATE KINASE DEFICIENCY IN FOUR CHILDREN WITH TWO UNPUBLISHED MUTATIONS
Authors: Unal E. , Gok V. , Roy N.B.A. , Hipkiss R. , Howard K. , Ozcan A. , Yilmaz E. , Karakukcu M. , Henderson S. , Patıroglu T. 
Published: June 2019

Background:Pyruvate kinase is a key enzyme of anaerobic glycolysis which helps keeping the energy level of red blood cells and their viability in circulation. The genetic heterogeneity of pyruvate kinase deficiency (PKD) is high and, to this day, over 250 different mutations have been identified.Aims:We aimed to emphasize the importance of genetic testing in patients with unexplained non‐immune hemolytic anemia.Methods:Four patients who had been followed because of non‐spherocytic hemolytic anemia and in whom no causative enzyme deficiencies were identified were referred for targeted next‐generation sequencing using the Oxford Red Cell Panel, a 50‐gene panel for inherited anemias.Results:We studied four patients (2 females, and 2 males) with evidence of chronic hemolytic anemia aged between 4 years and 24 years. Three of the four patients had jaundice, pallor and hepatosplenomegaly, while one patient had growth retardation and hypotonicity. One patient had gallstones and also undergone splenectomy at the age of two. While homozygous mutation was detected in three of four patients, only one patient had a compound heterozygous mutations (c.602G > A, c.1675C > G). The five identified mutations are single nucleotide gene changes. Two of the five mutations (c.602G > A, and c.172C > T) are previously unpublished.Summary/Conclusion:The clinical presentation of PKD ranges from frequent transfusion in neonates to mild jaundice in adulthood. Total pyruvate kinase in liver and red cell (PKLR) gene sequencing is necessary for the characterization of all patients with PKD and for genetic counselling. We also report two previously unpublished mutations in PKLR.
PB1990 THE CHANGE OF BONE MARROW MICROENVIRONMENT OF SECONDARY POOR GRAFT FUNCTION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION AND ITS EFFECT ON PROGNOSIS
Authors: Liu S. , Ran C. , Li J. , Peng X. , Zhang X. , Liu Y. 
Published: June 2019

Background:Secondary poor graft functionis a serious life‐threatening complication after allogeneic hematopoietic stem cell transplantation, which pathogenesis, evolution and prognosis are still unclear.Aims:To explore the role of adhesion related indicators in secondary poor graft functionafter allogeneic hematopoietic stem cell transplantationMethods:In this study, clinical data and post‐transplantation status of 106 patients with hematological tumour who were enrolled in our center and underwent allo‐HSCT from Jan. 1, 2016 to Jan. 31, 2017 was counted.The patients were divided into good graft function (GGF) group and secondary poor graft function (sPGF) group according to the implantation status after transplantation. The differences of age, primary disease, stem cell source, HLA matching, sex matching, ABO blood group matching, degree of bone marrow hyperplasia before transplantation, recurrence rate and mortality between the two groups were compared.29 patients with sPGF after transplantation were selected as the experimental group while 29 patients with GGF were selected as the control group.Results:The changes of adhesion related indicators in the two groups were detected.There were no significant differences in age, primary disease, stem cell origin, HLA matching, sex matching, ABO blood group matching and the degree of bone marrow proliferation before transplantation between the two groups (P > 0.05). The infection rate of CMV in sPGF group was significantly higher than that in GGF group, and the remission rate before transplantation in sPGF group was significantly lower than that in GGF group (P < 0.05).Cox regression analysis showed that the survival rate of patients with sPGF after allo‐HSCT was significantly lower than that of patients without sPGF (P < 0.05, HR = 3.598).The expression of CD44, CD29, ICAM‐1 and VCAM‐1 in sPGF group was not significantly different from that in control group (P > 0.05), but the expression of CD105 was higher than that in control group, and the expression of Cx43 was lower than that in control group (P < 0.05).Summary/Conclusion:We believe that the survival rate of patients with sPGF after allo‐HSCT will decrease significantly, and the occurrence of sPGF after transplantation may be related to the increase of CD105 expression and the decrease of Cx43 expression in bone marrow stromal cells before transplantation.
PB1995 THE EFFECTS OF ANTITUMOR THERAPY ON BONE REMODELING IN PATIENTS WITH HODGKIN'S LYMPHOMA
Authors: Voytko M. , Pospelova T. , Klimontov V. , Fazullina O. 
Published: June 2019

Background:Cures have been achieved in a significant proportion of patients with Hodgkin lymphoma (HL) for many years. Treatment for HL has been associated with adverse late effects. One of those consequences of antitumor therapy may be a change in bone mineral density (BMD). Hemoblastosis is considered as a strong risk factor for secondary osteoporosis and major low‐energy fractures. The decrease in BMD can be associated with polychemotherapy, including various combinations of cytostatic drugs and glucocorticoids, as well as with hypogonadism caused by toxic effects of radiotherapy and chemotherapy, tumor process, low physical activity and other factors.Aims:To assess the bone mineral density (BMD) in patients with HL.Methods:The study included 103 patients with HL from the City Hematology Center of Novosibirsk, from 19 to 72 years of age (median 49 years [33;55]). The disease was staged according to the Ann Arbor staging system: 55 patients had early stage disease and 48 patients had advanced stage disease (stage III to IV). All subjects received first‐line regimens (ABVD, BEACOPP‐14, et al.). Eighteen patients with advanced stages and unfavorable prognosis obtained second‐line regimens (DHAP, ESHAP). Radiotherapy was performed in 57 (55,3%) individuals. Complete remission was achieved in 60 of 103 patients (58,2%), and partial remission was recorded in 32 ones (31%). The BMD was assessed by dual‐energy X‐ray absorptiometry with GE Lunar Prodigy densitometer (USA). The assessed variables were BMD and T‐ or Z‐criterion (when appropriate) at the lumbar spine (L1–L4), proximal femur, femoral neck and forearm of a non‐dominant arm. Fracture Risk Assessment Tool (WHO FRAX, web version 3.8, adjusted for Russia) was used to determine the risk of major osteoporotic fractures.Results:The decreased BMD was revealed in 47 observed HL subjects (45,6%), 30 of them diagnosed osteoporosis. The decline in BMD was more frequent in patients aged ≥50 years as compared to younger ones (χ2 = 5,75; p = 0,02). More patients with radiotherapy in anamnesis had decreased BMD compared to patients who received chemotherapy only (χ2 = 8,82; p = 0,003) More than half of the patients (60 %) receiving regimens containing glucocorticosteroids had BMD decrease. Based on FRAX assessment, the 10‐year risk of major low‐energy fractures and the hip fractures was expectedly higher in patients with osteoporosis and osteopenia as compared to subjects with normal BMD (p < 0,05). A comparative analysis revealed that patients younger than 50 years old had more often lower values of BMD and Z‐score of the lumbar spine. In turn, the femoral neck was the most frequent localization of osteoporosis in patients older 50 years and postmenopausal women.Summary/Conclusion:The study demonstrates high prevalence of decreased BMD in patients with HL. The decrease in BMD is associated with radiotherapy and chemotherapy with glucocorticoids.
PB2031 INVASIVE ASPERGILLOSIS IN ELDERLY ONCOHEMATOLOGICAL PATIENTS
Authors: Shadrivova O. , Desyatik E. , Volkova A. , Popova M. , Uspenskaya O. , Shneyder T. , Melekhina J. , Bogomolova T. , Ignatyeva S. , Zubarovskaya L. , Afanasyev B. , Klimko N. 
Published: June 2019

Background:Invasive aspergillosis (IA) in elderly patients is not well understood.Aims:Analysis of underlying diseases, risk factors, etiology, clinical features, treatment and survival rates in elderly patients with IA.Methods:Retrospective analysis of the register data in 1998‐2018 yy. We included 646 adultpatients with proven and probable IA. For diagnosis of IA we used criteria EORTS/MSG, 2008.Results:In group I we included 137 patients with IA ≥ 60 years old, males – 60%. The control group consisted of 509 patients aged from 18 to 59 years, males – 53%. Oncohematological diseases were less frequent in elderly patients – 77% vs 87%, p = 0,002. In this patients non‐Hodgkin's lymphoma prevailed (35% vs 13%, p <0.05) among underlying diseases, whereas other hematologic diseases were less common: acute lymphoblastic leukemia (6% vs 13%, p < 0.05), Hodgkin's lymphoma (6% vs 13%, p < 0.05). Non‐hematological diseases were more frequent in elderly patients (23% vs 13%, p = 0.002). We identified differences in risk factors between the two groups: prolonged agranulocytosis was detected in 59% vs 75%, (p = 0.0003), lymphocytopenia ‐ 45% vs 60%, (p = 0.002).Significantly smaller numbers of elderly patientswere recipients of allogeneic stem cell transplants (3% vs 26%, p = 0.00001) and received immunosuppressive therapy (17% vs 31%, p = 0.0002). No significant differences were obtained in the localization of the fungal infection, as well as in clinical symptoms and results of galactomannan test. Aspergillusspp. were isolated more often in elderly patients (52% vs 40%, p = 0,01). The main etiological agents wereA. fumigatus (59% vs 45%) and A. niger (25% vs 34%). Mixed fungal infection was found in 9% vs 11% patients. Antifungal therapy was used in most of patients, the main drug used was voriconazole (73% vs 72%). Twelve weeks overall survival rate was 82% vs 79%.Summary/Conclusion:Oncohematological diseases were less frequent in elderly patients – 77%.The features of risk factors in elderly patients was less severe immunosuppression: prolonged agranulocytosis – 59%, lymphocytopenia – 45%, immunosuppressive therapy ‐ 17%, allogeneic stem cell transplants – 3%. The overall 12‐week survival in elderly patients with IA was not significantly different (82% vs 79%).
PB2032 BASELINE PREDICTORS INFLUENCING THE PROGNOSIS OF INVASIVE ASPERGILLOSIS IN ADULTS
Authors: Köhler P. , Salmanton Garcia J. , Gräfe S. , Koehler F. , Mellinghoff S. , Seidel D. , Steinbach A. , Cornely O. 
Published: June 2019

Please indicate where the abstract has been published before: Journal of Infection.Background:Invasive aspergillosis (IA) is a serious hazard to hematological and critical care patients.Aims:To understand prognostic variables we analyzed original articles identifying baseline factors that predict treatment outcome in patients with IA.Methods:PubMed database was searched for publications since database inception until May 2018. Inclusion criteria were published baseline prognostic factors present at the diagnosis of IA.Results:In total, 58 studies from 267 centers reported 7,320 patients with IA, and 40 different predictors. Unfavorable predictors in medical history were kidney (7.4%, 10/136) and liver failure (3.7%, 5/136), ICU admission (3.7%, 5/136), and uncontrolled underlying disease (3.7%, 5/136). Regarding state of immunosuppression, negative outcome predictors were prolonged neutropenia (12.5%, 17/136), corticosteroid treatment (8.1%, 11/136), and graft‐versus‐host disease (3.7%, 5/136). On the pathogen side, relevant predictors were galactomannan positivity (8.1%, 11/136), Aspergillus terreus infection (2.2%, 3/136), and lack of amphotericin B susceptibility (1.5%, 2/136). IA‐specific predictors were disseminated disease (5.1%, 7/136) and CNS involvement (2.9%, 4/136). Imaging results associated with negative outcome were multiple consolidations (2.9%, 4/136), bipulmonary lesions (2.2%, 3/136), and pleural effusion (2.2%, 3/136).Summary/Conclusion:At diagnosis of IA, most frequently identified predictors of outcome were neutropenia, corticosteroid use, elevated galactomannan, renal failure, and disseminated disease.
PB2050 USING A FUNCTIONAL SCREEN TO IDENTIFY NOVEL ANTI‐PROLIFERATIVE MIRNAS IN DIFFUSE LARGE B‐CELL LYMPHOMA (DLBCL)
Authors: Sole C. , Goicoechea I. , Lawrie C.H. 
Published: June 2019

Background:Diffuse large B‐cell lymphoma (DLBCL) is the most common B‐cell lymphoma, accounting for around 40% of all newly diagnosed non‐Hodgkin lymphoma (NHL) malignancies worldwide. Thanks to R‐CHOP therapy, the majority of DLBCL patients survive their disease. However, around 15% of patients treated have refractory disease, and of the patients that do respond to therapy, an additional 20‐25% will relapse.Proliferation is an important hallmark of cancer and in DLBCL has been associated with poor prognostic outcome. Consequently, several studies have focused on targeting molecules responsible for DLBCL proliferation as a novel therapeutic approach. MicroRNAs (miRNAs) are small non‐coding RNA molecules that act as key regulators of many biological and pathological processes including lymphomagenesis. miRNAs have been shown to be involved in many aspects of DLBLCL pathogenesis including initialization and progression of the disease, as well as having prognostic value.Aims:Identify miRNAs responsible the sustainment of proliferative signaling in DLBCL with the goal to develop novel anti‐lymphoma therapies.Methods:DLBCL cell lines (RIVA, SU‐DHL‐10, SU‐DHL‐4 and Oci‐ly‐10) were infected with a lentiviral library encoding for 698 miRNAs. We used a pooled‐approach using a MOI of 50. An empty vector was used as the control. Stable cell lines were produced by puromycin selection and cells maintained in culture for 4 months in triplicate. Both DNA and RNA were extracted at time 0, 2 months and 4 months post‐infection and the resultant DNA sequenced by NGS (Ion Torrent PGM). Differentially expressed miRNAs were detected by differential expression analysis (P < 0.05). For validation, selected miRNAs were infected individually in cell lines and proliferation rate (CFSE assay) and apoptosis (AnnexinV/TO‐PRO‐3) were determined by flow cytometry.Results:More than eighty miRNAs were identified as being differentially expressed between time 0 and time 4 months in each cell and five of these were differentially expressed in all cell lines. We validated five miRNAs by infecting cell lines with individual lentiviral vectors.Summary/Conclusion:We have demonstrated that the use of functional miRNA screens is a reliable tool for elucidating the phenotype‐genotype interface of cancers such as DLBCL. From our experiments, we propose that miRNA over‐expression could be used to decrease cell proliferation in DLBCL.
PB2120 THE IMPACT OF DEPTH OF RESPONSE BEFORE AND AFTER AUTOLOGOUS STEM CELL TRANSPLANT FOR MULTIPLE MYELOMA PATIENTS
Authors: Durão S. , Vieira J. , Velosa F. , Neves M. , Infante J. , Alho A. , Espada E. , Martins H. , Valle S. , Lourenço F. , Moreno R. , Alves D. , Costa M. J. , Polo B. , Lopes C. , Martins C. , Lacerda J. Forjaz , Esteves G. , Raposo J. 
Published: June 2019

Background:Over the last decade there has been an improvement on the outcome of multiple myeloma (MM) patients. In patients eligible for high‐dose chemotherapy and autologous stem cell transplant (ASCT), the inclusion of bortezomib in induction chemotherapy (ICT) has significantly delayed disease progression. Several studies have shown that achieving a complete response (CR) after ASCT is a predictive factor for disease control, leading to improved progression‐free survival (PFS) and overall survival (OS).Aims:Assessing the impact of depth of response before and after ASCT on PFS in a population of MM patients treated with ICT including bortezomib and identifying predictive/protective factors for disease progression.MethodsRetrospective study of MM patients admitted for ASCT between January 2015 and December 2017 treated in first line with VCd (bortezomib, cyclophosphamide, and dexamethasone) or VTd (bortezomib, thalidomide and dexamethasone). Demographic (gender, age), clinical and biological variables at diagnosis were collected, as well as response obtained before and at D + 100 after ASCT, and time elapsed between ASCT and disease progression. Statistical analysis was performed using STATA software (V13).Results:A total of 53 MM patients in the first line setting were included in this study. 43.4% were male; median age at diagnosis was 60 years old (IQR, 40‐72). Both groups (VCd and VTd) had similar baseline characteristics. Median follow‐up after induction chemotherapy was 20.6 months. PFS of patients who achieved CR or very good partial response (VGPR) post‐induction was 73.7%, versus 60% in patients who achieved partial response (PR) or lower (log‐rank p = 0.07). Looking at different variables that could modify the time between ASCT and disease progression, we observed that ISS stage 3 is an independent predictive factor for disease progression (HR 3.1; p = 0.014), and obtaining CR/VGPR at D + 100 post‐ASCT is an independent protective factor against disease progression (HR 0.2; p = 0.004).Summary/Conclusion:Despite the relatively short follow‐up period, in this population of transplant‐eligible MM patients, we have demonstrated that the depth of response after induction chemotherapy (VGPR/CR) is critical for a greater PFS, and that a profound reduction in tumor burden (VGPR/CR) after ASCT allows for prolonged disease control. However, ISS stage 3 is a risk factor for disease progression regardless of the obtained response.