bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS1321 INHIBITION OF NOTCH SIGNALING RESTORES SENSITIVITY TO IMMUNOCHEMOTHERAPY IN AN IN VITRO MODEL OF ACQUIRED RESISTANCE TO R‐CHOP
Authors: Di Pinto G. , Masiero M. , Li D. , Banham A.H. , Lawrie C.H. 
Published: June 2019

Background:Diffuse large B‐cell lymphoma (DLBCL) accounts for almost 40% of all lymphomas. One‐third of DLBCL patients either initially fail to respond to Rituximab plus anthracycline based therapy CHOP (R‐CHOP) or suffer a relapse (i.e. acquired resistance). The Notch pathway is involved in cell proliferation, differentiation and survival in a wide range of cancers.Aims:We investigated the role of Notch signaling in an in vitro model of acquired resistance to R‐CHOP treatment.Methods:We developed an in vitro model of acquired R‐CHOP resistance using different DLBCL cell lines (SU‐DHL‐4, SU‐DHL‐10 for GCB‐like subtype; RIVA and U2938 for ABC‐like subtype). Using gene expression microarrays, we screened parental and R‐CHOP resistant cell lines to identify putative genes responsible for acquired resistance. Notch1/2 and JAG1 expression levels were validated by qPCR and flow cytometry in R‐CHOP resistant U2932 cells. We treated U2932 cells with a neutralising anti‐JAG1 antibody (clone J1–65D, 10ug/ml) or with the γ‐secretase inhibitor dibenzazepine (DBZ, 100 nM). We then evaluated cell viability after 72 h of R‐CHOP treatment at 400 ng/ml (corresponding to the GI50 of the resistant clones).Results:Our microarray analysis showed many genes were differentially expressed. We focused particularly on the U2932 cell line, where overexpression of NOTCH1, NOTCH2 and JAG1 were independently confirmed by qPCR and flow cytometry. We evaluated the viability of U2932 after 72 h treatment with R‐CHOP and we found that the treatment of the resistant clones with DBZ or anti‐JAG1 restored sensitivity to RCHOP, compared to DMSO (vehicle) or IgG controls.Summary/Conclusion:We have demonstrated that blocking of Notch signaling, either by preventing JAG1 ligand binding or impeding the cleavage of the intracellular Notch domain, can restore sensitivity to R‐CHOP at levels comparable to the parental control. These preliminary results may suggest Notch signaling as new therapeutic target for resistant DLBCL.
PS1387 CARFILZOMIB IN RELAPSED AND REFRACTORY MULTIPLE MYELOMA (RRMM): FRAILTY SUBGROUP ANALYSIS FROM PHASE 3 ASPIRE AND ENDEAVOR
Authors: Facon T. , Niesvizky R. , Weisel K. , Bringhen S. , Ho P.J. , Obreja M. , Yang Z. , Klippel Z. , Blaedel J. , Mezzi K. , Siegel D. 
Published: June 2019

Background:Carfilzomib (K)‐based regimens improved progression‐free survival (PFS) and overall survival (OS) in relapsed and refractory multiple myeloma (RRMM) patients (pts) in ASPIRE (K [27 mg/m2]‐lenalidomide‐dexamethasone [KRd] vs Rd) and ENDEAVOR (K [56 mg/m2]‐dexamethasone [Kd56] vs bortezomib‐dexamethasone [Vd]), regardless of age. Frailty scores have been developed based on age, comorbidities, and functional status (Palumbo Blood 2015;125:2068–74; Facon Blood 2015;126:4239).Aims:We assessed post‐hoc pt outcomes by frailty status.Methods:PFS, OS, and safety were assessed by treatment arm and frailty score (based on age, medical history‐derived Charlson Comorbidity Index, and ECOG performance status); frailty scores: 0 = fit, 1 = intermediate (int), and ≥2 = frail.Results:Pt frailty status was balanced between treatment arms in ASPIRE and ENDEAVOR. Median PFS and OS were longer with K‐based regimens vs controls in ASPIRE and ENDEAVOR across frailty subgroups (Table). Rates of treatment‐emergent adverse events are summarized in the Table.Summary/Conclusion:Kd56 and KRd consistently improved outcomes vs Vd and Rd, respectively, in all frailty subgroups as defined by the algorithm above. These findings support the favorable benefit‐risk profile of KRd and Kd56 regardless of frailty score.image
PS1471 MYELOPROLIFERATIVE NEOPLASMS IN KOREAN CHILDREN AND YOUNG ADULTS
Authors: Choi H.S. , Hong J. , Lee J.H. , Bang S.M. 
Published: June 2019

Background:Myeloproliferative neoplasms (MPNs) are a rare, heterogeneous group of clonal hematopoietic stem cell disorders, characterized by aberrant proliferation of one or more myeloid lineages leading to an overproduction of both mature and immature cells. Three major components of classical BCR‐ABL‐negative MPNs are polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (pMF). They may be transformed to either secondary MF (sMF) or secondary acute myeloid leukemia (sAML). In addition, they can have second cancers during follow up (FU). These classical MPNs primarily occur in middle and advanced age adults, and are exceptionally rare in pediatric age.Aims:We conducted an epidemiologic study to elucidate clinical course of MPNs in children and young adults under 30 years of age focusing on disease transformation as well as thromembolism and second cancers.Methods:We analyzing data from the Health Insurance Review and Assessment Service (HIRA) database which includes almost all hospital‐based patients’ information in Korea.Results:A total of 352 patients who were diagnosed as one of the three kinds of MPNs from Jan. 2008 to Dec. 2016 (242 patients for ET, 104 for PV, and 6 for pMF) were included. Six pMF patients were excluded from further analysis. The incidence was 0.148 per 100,000 for ET and 0.064 per 100,000 for PV. Among 242 ET patients, the male‐female ratio was 119 to 123, and median age at diagnosis was 22 years (range 13–29). Four ET patients (1.65%) underwent any transformation during the study period (median FU duration 49.5 months); ET→PV (i.e., initially diagnosed ET but changed to PV later; N = 2), and ET→sMF (N = 2). Among 104 PV patients, the male‐female ratio was 96 to 8, and median age at diagnosis was 24 years (range 11–29). No PV patients were transformed into sMF during the FU period (median 45.9 months). sAML did not develop in both ET and PV patients. Solid cancers occurred in 5 ET patients and 3 PV patients. Cumulative incidence of arterial and venous thromboembolism were 6.98% and 1.71% in ET, 16.69% and 4.77% in PV, respectively. Five‐year overall survival and transformation‐free survival (to PV, MF and cancer) were 98% and 96.12% in ET, 100% and 97.29% in PV, respectively.Summary/Conclusion:This is the first population‐based epidemiologic study in Korean children and young adults with MPNs. The incidence of MPNs is very low in this age group. ET is more common than PV, whereas pMF is very rare. Transformations of ET to PV or MF occurred in a small number of patients. Considering long latency to transformation in MPNs, continuous observation is needed. In addition, second solid tumors should also be carefully observed. Further research is necessary in this patient group, including studies involving other complications such as bleeding.
PS1552 THE INCIDENCE RATES AND RISK FACTORS OF ATYPICAL INFECTIONS IN PATIENTS WITH LYMPHOMA WHO RECEIVED AUTOLOGOUS STEM CELL TRANSPLANTATION
Authors: Lee H.S. , Kim D.J. , Jung S.M. , Lee H. , Jeong S. , Kong S.G. , Lee S. 
Published: June 2019

Background:Autologous stem cell transplantation (ASCT) is an intermediate risk group for infections according to National Comprehensive Cancer Network (NCCN) guideline. Based on the risk of infection, experts recommend prophylaxis for fungal infections with fluconazole or micafungin if mucositis is accompanied, and prophylaxis for Pneumocystitis jirovecii (P. jirovecii) infection with trimethoprim‐sulfamethoxazole (TMP‐SMX) for 3 to 6 months after transplantation. For varicella zoster virus (VZV) reactivation, acyclovir or famcyclovir or valacyclovir is recommended as prophylaxis for 6 to 12 months after ASCT. However, there is a lack of evidence to support this guideline.Aims:In this study we performed a nationwide population‐based study to provide information regarding the incidence and risk factors of atypical infections such as fungal, viral or PJP in patients were performed ASCT in the South Korea.Methods:Using the Korean Health Insurance Review and Assessment Service database, the patients with lymphoma who received ASCT from 2003 to 2016 were retrospectively analyzed. Atypical infection is identified by international classification of disease (ICD) codes of each infection or ATC(Anatomical Therapeutic Chemical) codes of medicines for treatment. Oral Candidiasis, Herpes simplex virus (HSV), and Epstein‐Barr virus (EBV) infection were excluded because these are considered to non‐pathogenic in clinical field. The patients undergoing allogenic stem cell transplantation (AlloSCT) were excluded.Results:The total number of patients with lymphoma undergoing ASCT was 2147, median age was 48 years (range 2–70). The cumulative incidence of fungal infection is 10.4%, viral is 20.0% and PJP is 5.5% in lymphoma. In multivariate analysis, TBI (HR 1.702, p = 0.0390), and previous fungal infection (HR 1.701, p = 0.0398) were independent significant risk factors for fungal infection. The multivariate analysis showed that TBI (HR 2.524, p < 0.0001), previous infection history (HR 1.351, p = 0.0046) and prophylaxis (HR 1.633, p = 0.0001) were independent risk factors for viral infection. The multivariate analysis showed that prophylaxis (HR 2.647, p = 0.0002) were independent risk factors for PJP infection.Summary/Conclusion:In this study, patients with lymphoma who underwent ASCT showed relative high risk of viral infection (CIR 20.0%) and previous viral infection, TBI conditioning and non‐prophylaxis were independent risk factors for viral infection. So patients with lymphoma who planed ASCT should be considered prophylaxis for 2years after ASCT. Especially, patient who treated with TBI conditioning and have previous viral infection should receive prophylactic anti‐viral agents.
PB1662 INTEGRATION OF GENOME‐WIDE ANALYSIS INTO CLINICAL DIAGNOSIS OF ACUTE LYMPHOBLASTIC LEUKEMIA: HOW MUCH CAN WE IMPROVE CYTOGENETIC TESTING?
Authors: Othman M. , Melo J. , Carreira I. , Grygalewicz B. , Silva M. , Liehr T. 
Published: June 2019

Background:Acute lymphoblastic leukemia (ALL) is a heterogeneous, aggressive disease, and most common in children. It is a leading cause of cancer death in young and adult, too. However, about 30% of pediatric and 50% of adult ALL patients still lack defined genetic hallmarks of biological and clinical significance. In addition, complex karyotype‐ALL (CX‐ALL) promoting a wide spectrum of diverse genetic alterations with striking genomic instability, are overall often neglected by research.Aims:The overall goal of this study was to characterize karyotypes and genetic content of 25 ALL cases and to rule out if one single molecular approach may be sufficient to detect genomic aberrations in these patients.Methods:ALL cases were retrospectively studied by multitude multicolor banding (mMCB), fluorescence in situ hybridization (FISH) using selected locus‐specific probes and array‐comparative genomic hybridization (aCGH).Results:Most strikingly, 13 of the studied 25 ALLs (∼55%) revealed abnormal karyotypes, applying mMCB: structural abnormalities were present in 12 and even numerical ones were identified in 2 cases. Overall, 123 copy number alterations (CNAs) were identified as loss (∼80%) or as gains (∼20%). Furthermore, highly complex karyotypes were detected by aCGH and mMCB in 4 out of the 13 aberrant cases. The latter four patients had either deletions or amplifications in genes involved in lymphoid development, cell cycle, Hematopoietic stem cells development and/or DNA repair (IKZF1, CDKN2A/B, PAX5, BIRC3, ATM, RB1, RUNX1), as shown by FISH, and also presented acquired marker chromosomes.Summary/Conclusion:Molecular approaches are suited to identify cryptic aberrations and potential target genes involved in leukemogenesis and progression of the disease. The present work demonstrated that aCGH is a highly efficient tool for detection of CNAs in ALL. However, while aCGH provide data on imbalanced genomic alterations, molecular cytogenetics additionally detects different leukemic subclones within one sample, as well as balanced translocations leading to tumor‐specific fusion genes. Thus, still no single approach is sufficient to comprehensively characterize all acquired aberrations in ALL.
PB1673 FEASIBILITY AND OUTCOME OF ALLOGENEIC BONE MARROW TRANSPLANTATION IN ADULT PHI NEGATIVE ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: Fakhfakh Y. , Frikha I. , Abdeljlil N. Ben , Tojmen L. , Hdiji S. , Mdhaffar M. , Ladab S. , Kassar O. , Ghorbel M. , Benothmen T. , Elloumi M. 
Published: June 2019

Background:Acute lymphoblastic leukemia (ALL) is a rare disease in adults. Despite the novels therapies, clinical outcomes remain unsatisfactory. Bone marrow allograft still holds its place as a consolidation treatment for patients in complete remission in order to improve the prognosis and lengthen survival.Aims:We study in this work the feasibility and outcome of bone marrow allograft for adult Philadelphia chromosome negative ALL.Methods:Our study is retrospective including the cases of high‐risk adult ALL (HR) diagnosed in the hematology department of Hédi Chaker Hospital of Sfax during the period from January 2004 to December 2015. These patients were treated according to protocols inspired by GRAALL 2003 and 2005. The indication of bone marrow allograft is systematic in patients whose age are <50 years and having a compatible intrafamilial donor. For our patients we studied the allograft indication, the search for a family compatible HLA donor, the feasibility of the allograft and finally the result of this one which was carried out at the national center of bone marrow transplantation in Tunis.Results:Among the 36 cases of adult phi negative ALL treated with the GRAALL 2003 and 2005 protocols, 28 patients were in complete remission (CR) and 22 patients (79%) were classified as HR. Twenty patients had indication of bone marrow allograft (2 were> 50 years of age). Of the 20 patients who had an HLA study, 14 patients (70%) had a compatible HLA family donor. Allogeneic bone marrow allograft could only be performed for 9 patients: 64% of patients with a compatible HLA donor and 45% of patients with CR. For the 5 others the transplant could not be done for: relapsed before allograft for 2 cases and severe comorbidities for the 3 others. The median time to completion of the allograft was 15 weeks. Among the allografts, 6 patients (67%) were living in CR after a follow‐up of 74 months, one patient relapsed at 6 months post‐transplant and 2 patients died of acute GVH. Of the 19 non‐allograft CR patients, 6 patients were living in CR (31%) and 1 died during consolidation therapy and 12 relapsed. The 5‐year DFS of both allografted and non‐allografted patients was 72% and 21%, respectively.Summary/Conclusion:Despite the cost‐effectiveness of the intra‐familial HLA study (70% donor) in our study, allografting could only be performed for a small number of patients (45%), hence the need to expand the indication of allograft for subjects over 50 years old or perform a mini allograft, do the same haplo transplant and even expand donor sources on files (pheno‐identical donors). Two‐thirds of the allografted patients in our series did not relapse, an interesting result and comparable to the literature.
PB1683 INCIDENCE AND DEMOGRAPHIC CHARACTERISTICS OF THE MAJOR SUBGROUPS OF PRECURSOR B‐CELL ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN – A BULGARIAN SINGLE CENTER STUDY
Authors: Yurukova N. , Balatzenko G. , Konstantinov D. , Jordanova M. , Avramova B. 
Published: June 2019

Background:The detection of genetic aberrations is used to risk‐stratify patients with acute lymphoblastic leukemia (ALL), decide on the treatment protocol, and to estimate therapeutic effect through the detection of minimal residual disease.Aims:The aim of this study was: 1) to determine the frequency of the most common and significant genetic anomalies in children with ALL ‐ t(12;21)(p13;q22)/TEL‐ AML1, t(1;19)(q23;p13)/E2A‐PBX1, t(4;11)(q21;q23)/ MLL‐AF4 и t(9:22)(q34;q11.2)/BCR‐ABL; 2) to compere the incidence with that described in other studies; 3) to describe the demographic characteristics of the different genetic subgroups.Methods:For a thirteen year period, in 271 patients with established ALL, molecular‐genetic studies (RT‐PCR) were performed to search for the most common fusion genes.Results:In the study population of 271 patients, the incidence of TEL‐AML1 (+) OLL was 21%, E2A‐PBX1 (+) ALL was 5%, BCR‐ABL (+) was 3%, and MLL‐AF4 2.5%. A tendency for a characteristic demographic profile emerges for each genetic subgroup.Summary/Conclusion:This study is the first in Bulgaria. The results obtained are comparable to those published by other authors.
PB1738 NUCLEOPHOSMIN‐1 GENE MUTATION DETECTION: COMPARATIVE IMMUNO‐STAINING STUDY FOR BONE MARROW (BM) BIOPSY VERSUS BM ASPIRATE & BM CLOT IN DE NOVO ADULT ACUTE MYELOID LEUKEMIA PATIENTS AMONG EGYPTIANS
Authors: Elgamal B. , El Gammal M. , Badawy R. , Abdelghaffar E. , Rasheed E. , Elkafoury M. , Hamdy M. 
Published: June 2019

Background:NPM1 gene mutation is a well‐known prognostic marker in AML, probably related to its cytoplasmic localization. NPM1 gene mutation detection could be done by either molecular genetics or its protein product by immunohistochemical staining of bone marrow (BM) biopsy.Aims:This study aimed to compare the detection rate of the immuno‐staining technique for mutated nucleophosmin‐1 gene when applied on the standard BM biopsy versus BM aspirate or BM clot biopsy in adult de novo patients of acute myeloid leukemia.Methods:Forty adult patients (18‐60 years) with newly diagnosed AML were enrolled into this study. Detection of nucleophosmin localization either nucleolar or cytoplasmic was performed using monoclonal mouse anti‐human nucleophosmin (clone 376) by conventional immunohistochemical technique on BM biopsy, BM aspirate & BM clot biopsy.Results:The study included 40 AML patients, 23 males, 17 females. The complete remission (CR) rate was 70%. Median overall survival (OS) was 2.5 month (0.1‐40 months). Median disease free survival was 6 month (0.2‐39). NPM1 was detected in 11/40 patients by conventional immunohistochemical technique on BM biopsy, 11/39 patients by BMA technique, and 9/29 by BM clot technique. The BMA technique had Sensitivity of 100%, Specificity of 78.6%, positive predictive value of 64.7%, negative predictive value of 100%, and diagnostic accuracy of 84.6%. The BM clot technique had sensitivity of 77.8%, specificity of 90.0%, and positive predictive value of 77.8%, negative predictive of 90.0%, and diagnostic accuracy 86.2%.Summary/Conclusion:The BMA technique had good sensitivity and so could be used as a cheap screening method even in patients with profound thrombocytopenia. BM clot technique had good specificity. Both BMA and BM clot techniques could be a reasonable cheap option if combined together in cases in which BM biopsy could not be done.image
PB1772 TUMOR‐FORMING PLASMACYTOID DENDRITIC CELLS IN ACUTE MYELOMONOCYTIC/MONOCYTIC LEUKEMIA
Authors: Zhu L. , Wang P. , Zhang W. , Li Q. , Deng X. , Liu S. , Liu Y. , Kong P. , Rao J. , Zhang X. 
Published: June 2019

Background:lasmacytoid dendritic cells (PDCs) act as a link between innate and adaptive immunity, PDCs infiltration has been reported in infectious diseases, autoimmune diseases and neoplasms. Our previous work reported PDCs infiltration could occur in AML patients, but the clinical significance of PDC in AML was rarely investigated, based on DC induction from hematopoietic stem cells, myeloid progenitors and monocytes, we presume acute myelomonocytic/monocytic leukemia cases share PDCs phenotypes originally.Aims:To clarify the conception andevaluated the expression of PDCs in bone marrow.Methods:80 acute myelomonocytic leukemia(AML‐M4) and 83 acute monocytic leukemia (AML‐M5) patients was included in this study for the examination of PDCs expression.Results:62 cases were positive for PDCs, which were closely associated with cycles of chemotherapy before achieved CR, patients’ WBC count, Hb concentration, platelet count and bone marrow blasts, and the patients with PDC infiltration had a shorter survival time, meanwhile, allo‐HSCT could abrogated the side effects of PDCs on AML patients.Summary/Conclusion:PDC infiltration has a possible role in risk stratification for patients AML‐M4/M5, and our work emphasizes the significance of heterogeneity of AML‐M4/M5.
PB1781 THE OUTCOME OF PREGNANCY‐ASSOCIATED HEMATOLOGICAL CANCERS IN TAIWAN
Authors: Li S.‐S. , Hsu Y.‐T. , Yen C.‐C. , Wu P.‐Y. , Chen Y.‐W. , Li C.‐Y. , Chen T.‐Y. 
Published: June 2019

Background:Pregnancy‐associated cancers, usually defined as cancers diagnosed during pregnancy or one year after delivery, is a diagnostic and therapeutic challenge to doctors. Hematological malignancies are among the most common types of cancer in women of child‐bearing age. However, the impact of pregnancy on the maternal and neonatal outcome is largely unknown.Aims:To investigate the impact of pregnancy on the outcome of patients with pregnancy‐associated hematological malignancies.Methods:We identified patients with pregnancy‐associated cancers by intersecting the Taiwan Cancer Registry with the Birth Certificate Application. Patients were grouped into pregnant (diagnosed during pregnancy) and lactating (diagnosed within one year after delivery) group. Female patients of child‐bearing age (16‐49 years) who were not pregnant at the diagnosis of cancer were used as a control.Results:From the year 2001 to 2015, cancer was diagnosed during pregnancy and one year after delivery in 512 and 2151 patients, respectively. Lymphoma and leukemia are the 5th and 6th most common subtype of pregnancy‐associated cancer. Survival is not significantly different between pregnant, lactating, and non‐pregnant leukemia patients (p = 0.49). A higher proportion of aggressive B‐cell lymphomas is observed in lymphomas diagnosed during pregnancy (73.6%), as compared with the lactating (38.6%) and non‐pregnant (39.5%) group (p < 0.01). The proportion of advanced stage lymphoma in the pregnant or lactating group was not different from that in the non‐pregnant group (Odds ratio [OR] 0.87 & 0.98, p = 0.85 & 0.97, respectively). Compared with the non‐pregnant group, the survival in pregnancy group was not significantly different (Hazard ratio [HR] 1.41, p = 0.40), while the survival in the lactating group is markedly better (HR 0.19, p < 0.01). After controlled with age, stage, year of diagnosis, and histology, lactating status remained an independent prognostic marker (HR 0.12, p = 0.03).Summary/Conclusion:Lymphoma diagnosed within one year after delivery carries a good prognosis. Further study is needed to investigate the effect of lactation‐associated hormones in lymphoma.image