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Clinical Responses of Glasdegibplus Low-Dose Ara-C, Azacitidine, and Decitabine Among Acute Myeloid Leukemia (AML) Patients Ineligible to Receive Intensive Chemotherapy: Comparative Effectiveness U...
http://www.bloodjournal.org/content/132/Suppl_1/2709

Nov 21st, 2018 - OBJECTIVES: Currently there is no standard treatment option for AML patients not fit for intensive chemotherapy. Further clinical challenges include poorer prognosis associated with advanced age. AML treatments among this population have not been directly compared in clinical trials. Furthermore, naïve comparisons of results across multiple trials are subject to bias related to not accounting f...

Clinical Outcomes in Pediatric Mixed Phenotype Acute Leukemia (MPAL) Differ Depending on Disease Classification Criteria; A Multi-Center Cohort Study
http://www.bloodjournal.org/content/132/Suppl_1/4080

Nov 21st, 2018 - INTRODUCTION: Mixed phenotype acute leukemia (MPAL) is a category of acute leukemia established in the World Health Organization (WHO) 2001 classification, significantly modified in WHO2008, and again refined in the most recent WHO2016 update. The current WHO2016 iteration conceptualizes MPAL as a stem cell disorder whereby most cases will manifest heterogeneity of lineage-specific antigen expr...

CLL Intraclonal Fractions Defined By Time Since Cell Birth/Division Promote a Leukemia-Supportive, Immune-Tolerant Microenvironment By Distinct Mechanisms
http://www.bloodjournal.org/content/132/Suppl_1/1836

Nov 21st, 2018 - Chronic lymphocytic leukemia (CLL) cells actively participate in the formation of the tumor microenvironment (TME). The interplay of CLL cells and leukemia-supporting cells such as Th2 cells and regulatory T cells (Tregs) promotes a leukemia-supportive, immune-tolerant TME. In these supportive/tolerogenic niches of lymph nodes (LN) and bone marrow (BM), CLL cells slowly proliferate, and the rat...

Clinical, Immunophenotypic and Genomic Findings of Acute Undifferentiated Leukemia and Comparison to AML with Minimal Differentiation: A Study from the Bone Marrow Pathology Group
http://www.bloodjournal.org/content/132/Suppl_1/1491

Nov 21st, 2018 - Introduction: Acute undifferentiated leukemia (AUL) is a rare type of acute leukemia that shows no evidence of differentiation along any lineage. Clinical, immunophenotypic and genetic data is limited: the largest study to date reported 16 AUL cases but did not use the current WHO classification and included limited genetic data on 5 cases (Ann Hematol 2013 92:747-758). Moreover, it is uncertai...

Combination of BCR-ABL1 Tyrosine Kinase Inhibitors with a Small Molecule LIM kinase1/2 Inhibitor in BCR-ABL1 Positive Acute Lymphoblastic Leukemia (ALL)
http://www.bloodjournal.org/content/132/Suppl_1/2705

Nov 21st, 2018 - Introduction: LIM kinases 1 and 2 (LIMK1/2) are downstream effectors at the crossroads of different signaling pathways implicated in the dynamics of the cytoskeleton via phosphorylation of cofilin family proteins, degradation of the matrix by phosphorylating MT1-MMP and control of the activity of Aurora kinase A. Recently, the oncogenic role of Rho kinases (ROCK) was identified to be constituti...

Coagulation and Fibrinolysis Imbalance Demonstrated By Novel Simultaneous Thrombin and Plasmin Generation Assay during L-Asparaginase Treatment Phase of Induction Therapy in Pediatric Acute Lymphob...
http://www.bloodjournal.org/content/132/Suppl_1/3972

Nov 21st, 2018 - Introduction: L-asparaginase (L-Asp) is one of the risk factor of thromboembolism during ALL chemotherapy. Although the pathogenesis has been still unclarified, L-Asp may have profound effects on hepatic synthesis of pro-, anti-coagulant and fibrinolytic factors. In addition, recent studies demonstrated that the age of over 10-years might be a risk factor for this L-Asp associated coagulopathy....

Combined Ibrutinib and Venetoclax in Patients with Treatment-Naïve High-Risk Chronic Lymphocytic Leukemia (CLL)
http://www.bloodjournal.org/content/132/Suppl_1/696

Nov 21st, 2018 - Background: Ibrutinib (IBR), a BTK inhibitor, and venetoclax (VEN), a BCL-2 inhibitor are approved for patients (pts) with CLL. The rationale for combining IBR and VEN includes: 1) preclinical models showing synergism with the combination, 2) non-overlapping toxicity profiles; 3) non-overlapping mechanisms of action; 4) complementary activity in treating disease compartments. We report results ...

Combinatorial Genetics Uncovers Novel Targets for the Treatment of Npm1/Cohesin Mutated AML
http://www.bloodjournal.org/content/132/Suppl_1/2598

Nov 21st, 2018 - Current precision medicine approaches typically target a single genetic mutation. However, adult acute myeloid leukemia (AML) is difficult to treat due to its genetic complexity. Approximately 30 somatic mutations have been found to be recurrent, with an average of 5-15 mutations present per patient (Cancer Genome Atlas 2013). Therefore, combinatorial genetic approaches have the power to uncove...

Combined Targeting of BET Family Proteins and BCL2 Is Synergistic in Acute Myeloid Leukemia Cells Overexpressing S100A8 and S100A9
http://www.bloodjournal.org/content/132/Suppl_1/2634

Nov 21st, 2018 - Background The 5-year survival rate for acute myeloid leukemia (AML) remains poor with most patients succumbing to relapse or refractory disease. Recently, the BCL2 specific inhibitor venetoclax has shown promising anti-leukemia activity in high-risk AML patients. Most patients, however, ultimately develop resistance to monotherapy and novel combination treatments with venetoclax are needed for...

Comparative Analysis between RQ-PCR, Digital-Droplet-PCR and Next-Generation-Sequencing (NGS) of Immunoglobulin/T-Cell Receptor Gene Rearrangements to Monitor Minimal Residual Disease in Adult Acut...
http://www.bloodjournal.org/content/132/Suppl_1/2828

Nov 21st, 2018 - Background. Minimal residual disease (MRD) is the strongest prognostic factor in both children and adults with acute lymphoblastic leukemia (ALL). Currently, it is most widely monitored by molecular methods based on real-time-quantitative-PCR (RQ-PCR). Digital-droplet-PCR (ddPCR) and next-generation-sequencing (NGS) represent advanced tools that have the potential to overcome some limitations o...

Comparative Effectiveness of Combination Glasdegib+ Low-Dose Cytarabine (GLAS+LDAC) Vs Combination Venetoclax + Low-Dose Cytarabine (VEN+LDAC) Among Older Acute Myeloid Leukemia (AML) Patients Inel...
http://www.bloodjournal.org/content/132/Suppl_1/1429

Nov 21st, 2018 - BACKGROUND: Older AML patients are often NIC and face poorer prognoses. Among less intensive AML treatments, GLAS+LDAC showed improved efficacy vs LDAC alone in a Phase II randomized controlled trial (RCT). Recently, a phase I/II single arm study of VEN+LDAC showed longer overall survival (OS) in naive comparison to GLAS+LDAC. However, naïve comparisons across trials do not account for within-t...

Comparison of Efficacy and Toxicity of CD19-Specific Chimeric Antigen Receptor T-Cells Alone or in Combination with Ibrutinib for Relapsed and/or Refractory CLL
http://www.bloodjournal.org/content/132/Suppl_1/299

Nov 21st, 2018 - Background We reported durable responses to CD19-specific chimeric antigen receptor-modified T-cell therapy (JCAR014) in relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) patients (pts) after prior failure of ibrutinib (Turtle, JCO 2017; NCT01865617). In those pts, ibrutinib was not administered during CAR-T cell immunotherapy. Continuation of ibrutinib through leukapheresis, lymphod...

Comparison of Salvage Chemotherapy Regimens in Relapsed/Refractory Acute Myeloid Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/2708

Nov 21st, 2018 - Background Induction therapy for acute myeloid leukemia (AML) with a cytarabine-anthracycline regimen (7+3) is well-established; however, there is no standard salvage therapy for patients with relapsed/refractory AML (RR-AML). There is a paucity of data regarding outcomes with salvage regimens in RR-AML that include cladribine, cytarabine, and filgrastim with mitoxantrone (CLAG-M) or without mi...

Spatial Regulation of Thrombopoiesis in the Bone Marrow
http://www.bloodjournal.org/content/132/Suppl_1/SCI-23

Nov 21st, 2018 - Blood platelets play key roles in hemostasis and thrombosis and are the second most abundant cell type in the circulation. Due to their short life span of only a few days, anuclear platelets are continuously replenished and thus provide a classic system to study hematopoiesis. In mammals, platelets are produced by megakaryocytes (MKs) that are predominantly residing in the bone marrow (BM). MKs...

Complex 3q26/EVI1 Rearrangements Genocopy Inv(3)/t(3;3) Acute Myeloid Leukemias By Enhancer Hijacking, EVI1 Overexpression, Absent MDS1-EVI1 and Low GATA2 Expression
http://www.bloodjournal.org/content/132/Suppl_1/2766

Nov 21st, 2018 - Introduction Acute myeloid leukemia (AML) with inv(3)(q21q26) or t(3;3)(q21;q26) overexpress EVI1 and have a very poor prognosis. EVI1 is part of the MECOM (MDS1-EVI1-Combination) locus from which MDS1-EVI1 and EVI1 can be transcribed from two different promoters. Although EVI1 is expressed at high levels, MDS1-EVI1 is absent or expressed at very low levels in inv(3)/t(3;3)-AMLs. Aberrant EVI1 ...

Comprehensive Genomic Analysis of IDH Inhibitor-Treated AML Samples Delineates Molecular Mechanisms of Differentiation and Heterogeneous Patterns of Acquired Resistance
http://www.bloodjournal.org/content/132/Suppl_1/441

Nov 21st, 2018 - Allosteric inhibitors of mutant IDH1 or IDH2 induce differentiation of IDH-mutant AML myeloblasts, which in some patients (pts) can lead to a life-threatening differentiation syndrome (DS). The in vivo mechanism of how IDH inhibitors induce differentiation and occasionally DS is not fully understood. Furthermore, responders to the inhibitors often lose the differentiation effect, after median o...

Comprehensive Analysis of 343 Genes Using Targeted Sequencing Panel By Next-Generation Sequencer in 77 Pediatric AML Patients with Normal and Complex Karyotypes: Jccg Study, JPLSG AML-05
http://www.bloodjournal.org/content/132/Suppl_1/1530

Nov 21st, 2018 - Introduction Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous disease caused by various genetic alterations. Some prognosis-associated chromosomal aberrations and gene mutations such as t(8;21), inv(16), monosomy 7, and FLT3-ITD have been adopted for risk stratification. Although treatment outcomes have improved via stratification therapy, relapse and mortality are sti...

Lymphopenia As an Early Predictor of Immune Related Adverse Events
http://www.bloodjournal.org/content/132/Suppl_1/4958

Nov 21st, 2018 - Introduction Immune checkpoint inhibitors (ICI) are a novel class of medications which offer a potential curative option for many cancer patients who previously had a more dismal prognosis. Programmed cell death protein 1 (PD-1) is a molecule that modulates cellular immunity to limit autoimmunity, but can also be co-opted by cancers and infections to create immune tolerance. Nivolumab and pembr...

Comprehensive Single-Cell RNA-Sequencing Mapping of Primary Acute Myeloid Leukemias and Profiling of NPM1-Mutated Cells
http://www.bloodjournal.org/content/132/Suppl_1/995

Nov 21st, 2018 - Introduction: Acute myeloid leukemia (AML) evolution is a multistep process in which cells evolve from hematopoietic stem and progenitor cells (HSPCs) that acquire genetic anomalies, such as chromosomal rearrangements and mutations, which define distinct subgroups. Mutations in Nucleophosmin 1 (NPM1), which occur in ~30% patients, are the most frequent subgroup-defining mutations in AML and app...

2nd cycle Remission Achievement with 7+3 Is Associated with Shorter Survival in Adults with Newly Diagnosed Acute Myeloid Leukemia: Analysis of Recent SWOG Trials
http://www.bloodjournal.org/content/132/Suppl_1/3978

Nov 21st, 2018 - Background: Intensive chemotherapy will induce a complete morphologic remission (CR) in many adults with acute myeloid leukemia (AML). Whether it matters that a remission is obtained early, i.e. with the first cycle of chemotherapy, has remained controversial. Data from historic and contemporary trials with double induction chemotherapies showed patients who achieved a CR with the first inducti...