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A Phase II Study of Dasatinib and Dexamethasone As Primary Therapy Followed By Transplantation for Adults with Newly Diagnosed Ph/BCR-ABL1-Positive Acute Lymphoblastic Leukemia (Ph+ ALL): Final Res...
http://www.bloodjournal.org/content/132/Suppl_1/309

Nov 21st, 2018 - Dasatinib with corticosteroid yields high complete remission (CR) rates in Ph+ ALL with minimal induction death. Optimal post-remission therapy is not known. We report a prospective study evaluating dasatinib/dexamethasone induction then consolidation with reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT), autologous HCT (autoHCT), or chemotherapy alon...

A Phase II Trial of Nivolumab Combined with Ibrutinib for Patients with Richter Transformation
http://www.bloodjournal.org/content/132/Suppl_1/296

Nov 21st, 2018 - Background: Outcomes of patients (pts) with Richter transformation (RT) remain dismal with a median survival of less than 1 year with chemoimmunotherapy (CIT). Dysfunction of T cells, NK cells and other immune subsets is common in pts with CLL. Checkpoint blockade is an emerging treatment approach for pts with RT (Ding et al. Blood 2017; Younes et al. ASH 2017). Methods: We designed an investig...

A Refined Regimen for Maximally Eliminating Early Life-Threatening Complications for Patients with High-Risk Acute Promyelocytic Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/3994

Nov 21st, 2018 - Life-threatening complications, such as severe bleeding and/or differentiation syndrome at admission and/or along with induction treatment, among high-risk patients with acute promyelocytic leukemia (APL) are a worldwide puzzle towards the cure of the disease. Taking the rationale that high WBC count, at least in part, may cause cytokine storm related symptoms, we designed this refined regimen ...

ABL Tyrosine Kinase Inhibitors (TKIs) Are Associated with Increased Rho-Associated Kinase (ROCK) Activity That May Contribute to Vascular Toxicity in Patients with Chronic Myeloid Leukemia (CML)
http://www.bloodjournal.org/content/132/Suppl_1/1739

Nov 21st, 2018 - Introduction The use of 2nd or 3rd generation ABL TKIs in patients with CML is associated with vascular toxicity, including peripheral arterial occlusive disease and cardiovascular and cerebrovascular events. However, Imatinib, a 1st generation TKI, has not been shown to increase risk of cardiovascular events (Douxfils J et al. JAMA Oncol 2016;2:625). Therefore, there is a need to identify risk...

Acalabrutinib in Treatment-Naive (TN) Chronic Lymphocytic Leukemia (CLL): Updated Results from the Phase 1/2 ACE-CL-001 Study
http://www.bloodjournal.org/content/132/Suppl_1/692

Nov 21st, 2018 - Background: Bruton tyrosine kinase (BTK) is a critical component of B-cell receptor signaling pathway and a validated therapeutic target for CLL. Acalabrutinib is a highly selective, potent, covalent BTK inhibitor with minimal off-target activity that has been shown to have an overall response rate (ORR) of 95% (85% partial response [PR]; 10% PR with lymphocytosis [PRL]) after a median follow-u...

Activated CLL B Cells Variably Modulate microRNA-155 Levels in Naïve CD4+ T Cells, and the Direction and Magnitude of microRNA-155 Change Correlates with Th17 Levels and Clinical Course
http://www.bloodjournal.org/content/132/Suppl_1/4402

Nov 21st, 2018 - T-helper 17 (Th17) cells constitute a subset of T cells that characteristically secrete IL-17. In addition to their normal adaptive immune functions, Th17 cells also play roles in supporting dysfunctional immune responses found in autoimmunity and cancer. Several studies suggest that Th17 cells play a protective role in chronic lymphocytic leukemia (CLL). For example, CLL patients exhibit varie...

Activation of NF-Kappa B-p62-NRF2 Signaling Supports the Survival of CLL Cells That Express High Levels of ROR1
http://www.bloodjournal.org/content/132/Suppl_1/3122

Nov 21st, 2018 - Recent studies have linked the autophagy adaptor p62/SQSTM1 to tumorigenesis via NRF2 signaling. Increased accumulation p62 is associated with disease progression in many cancers, however its expression in CLL has yet to be investigated. Importantly, p62, encoded by the SQSTM1 gene, mRNA expression and protein accumulation is regulated by nuclear factor-kappa B (NF-κB), a key transcription fact...

Acute Myeloid Leukemia Expands Osteoprogenitor Rich Niche in the Bone Marrow but Resorbs Mature Bone Causing Osteopenia/Osteoporosis in Animal Models
http://www.bloodjournal.org/content/132/Suppl_1/86

Nov 21st, 2018 - Acute myeloid leukemia (AML) is one of the most aggressive hematological malignancy that originates in the bone marrow (BM). Despite advances in the molecular characterization of AML, factors regulating its progression are still not known. Among several BM niches that support AML growth in the BM, the osteogenic niche has gained attention in recent years owing to its potential role in leukemoge...

Adherence to Tyrosine Kinase Inhibitor Affects Overall Survival in Adult Korean Chronic Myeloid Leukemia Patients; Based on the National Health Information Database
http://www.bloodjournal.org/content/132/Suppl_1/1745

Nov 21st, 2018 - Objectives We evaluated clinical characteristics including adherence and its effects on overall survival (OS) in Korean patients diagnosed with chronic myeloid leukemia (CML) using National Health Information Database "NHID". Methods This study included patients 15 and older who were diagnosed with Philadelphia chromosome positive CML (ICD code C921) from 2005 to 2013 and prescribed with tyrosi...

Adoptive T-Cell Therapy for Acute Lymphoblastic Leukemia Targeting Multiple Tumor Associated Antigens
http://www.bloodjournal.org/content/132/Suppl_1/2693

Nov 21st, 2018 - Background: Leukemic relapse remains the major cause of treatment failure in hematopoietic stem cell transplant (HSCT) recipients. While the infusion of donor lymphocytes to prevent and treat relapse has been clinically implemented this strategy does not provide durable remissions and carries the risk of life-threatening graft-versus-host disease (GVHD). More recently the adoptive transfer of T...

ALKBH5 Functions As an Oncogene in Acute Myeloid Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/3910

Nov 21st, 2018 - N6-methyladenosine (m6A), the most abundant internal modification in eukaryotic messenger RNAs (mRNAs) has been shown to play important roles in diverse cellular and pathological processes (Deng X, et al. Cell Res. 2018;28:507-517). ALKBH5, recently identified as a m6A demethylase, was reported to promote tumorigenesis and proliferation in glioblastoma stem-like cells (GSCs) (Zhang, S. et al. C...

Allogeneic CAR-T Cell Therapy for Treatment of Relapse after Allo-HSCT in Patients with Refractory CML Lymphoid Blast Crisis: Significance of HLA Matched Donor/Patient Pair in the Safety/Efficacy o...
http://www.bloodjournal.org/content/132/Suppl_1/4275

Nov 21st, 2018 - Introduction: CD19-specific CAR-T cells have shown promise in the treatment of relapsed or refractory Ph+ ALL. It remains to be established whether allogeneic CAR-T cells have clinical activity in patients with relapsed CML lymphoid blast crisis with a history of allo-HSCT. Here we report our experience in two cases of allogeneic CAR-T cell therapy for treatment of relapse after allo-HSCT in pa...

AML with Mutations in IDH1 and DNMT3A Exhibits a Distinct Epigenetic Signature with Poorer Overall Survival
http://www.bloodjournal.org/content/132/Suppl_1/1471

Nov 21st, 2018 - Acute Myeloid Leukemia (AML) is a biologically diverse disease with subtypes that can be identified through integrated cytogenetic, mutational, and epigenetic characterization. Mutations in epigenetic regulators such as IDH1, IDH2, and DNMT3A are among the most common gene mutations found in AML (Cancer Genome Atlas Research et al. 2013; Papaemmanuil et al. 2016). Targeted inhibitors of IDH1 an...

AMV564, a Bivalent Bispecific (2×2) CD33/CD3 T-Cell Engager, Is Active and Improves Survival in a Mouse Model of Acute Myeloid Leukemia
http://www.bloodjournal.org/content/132/Suppl_1/2727

Nov 21st, 2018 - Background: AMV564 is a novel bivalent, bispecific (2x2) CD33/CD3 targeted immunotherapy that binds both CD33 and the invariant CD3ε on T-cell receptors with strong avidity, thus creating an immune synapse between CD33-expressing cells and T cells, initiating T-cell directed lysis of CD33 expressing cells, and inducing expansion, differentiation and proliferation of T cells. AMV564 is being eva...

Anti-CD20 Monoclonal Antibodies Hijack the B-Cell Receptor Signaling Cascade Thereby Activating the NOTCH1 Signaling Pathway
http://www.bloodjournal.org/content/132/Suppl_1/588

Nov 21st, 2018 - NOTCH1 is a cell surface receptor, regulation of which depends on the integrity and subsequent cleavage of its inhibitory domain. Subtle mechanical forces transmitted after ligand-binding [Wang et al., 2013] or removal of Ca2+-ions [Rand et al., 2000] make the site accessible for cleavage, resulting in release of the transcription factor NICD1. Mutations in NOTCH1 that prolong NICD1 activity ha...

Anti-Human CD117 CAR T-Cells Efficiently Eliminate Hematopoietic Stem and CD117-Positive AML Cells
http://www.bloodjournal.org/content/132/Suppl_1/4063

Nov 21st, 2018 - Introduction: Acute Myeloid Leukemia (AML) is a clonal disease of the hematopoietic system that originates from immature hematopoietic stem and progenitor cells (HSPC). Because some AML-initiating cells are comparatively resistant to conventional cytotoxic agents, disease relapses are common with current treatment approaches. As an alternative, immunological eradication of leukemic cells by ado...

Argx-110 Targeting CD70, in Combination with Azacitidine, Shows Favorable Safety Profile and Promising Anti-Leukemia Activity in Newly Diagnosed AML Patients in an Ongoing Phase 1/2 Clinical Trial
http://www.bloodjournal.org/content/132/Suppl_1/2680

Nov 21st, 2018 - Outcomes in elderly patients with acute myeloid leukemia (AML) are still adverse, as the majority does not qualify for intensive therapy or allogenic stem cell transplantation (ASCT). DNA hypomethylating agents (HMAs) induce remissions and prolong survival in a fraction of these patients. However, overall prognosis remains dismal and all patients progress due to therapy-resistant leukemia stem ...

AraC-Daunorubicin-Etoposide (ADE) Response Prediction in Pediatric AML Patients Using a Computational Biology Modeling (CBM) Based Precision Medicine Workflow
http://www.bloodjournal.org/content/132/Suppl_1/4034

Nov 21st, 2018 - Background: Pediatric AML (pAML) treatment outcomes can vary due to genomic heterogeneity. Thus, selecting the right drugs for a given patient is challenging. There is a need for a priori means of predicting treatment responses based on tumor "omics". Computational biology modeling (CBM) is a precision medicine approach by which biological pathways of tumorigenesis are mapped using mathematical...

Assessment of the Genomic Landscape of Intermediate Risk Acute Myeloid Leukemia As Defined By 2010 ELN Risk Classification
http://www.bloodjournal.org/content/132/Suppl_1/994

Nov 21st, 2018 - Background: In 2010 an international expert working group (European LeukemiaNet, ELN) has published recommendations for the diagnosis and management of acute myeloid leukemia (AML) including a risk stratification by cyto- and molecular genetics, subdividing AML into four risk groups. Emerging data on molecular markers in AML has led to an update of stratification criteria by ELN in 2017 includi...

Aurora Kinase a/MDM2-Mediated SETD2 Loss of Function in Chronic Myeloid Leukemia Patients in Blast Crisis Induces Genetic Instability and Can be Therapeutically Targeted
http://www.bloodjournal.org/content/132/Suppl_1/1726

Nov 21st, 2018 - The SETD2 protein is a histone methyltransferase that specifically catalyzes the trimethylation of Lysine 36 on histone H3 (H3K36me3). SETD2/H3K36me3 are implicated in transcript elongation and splicing, DNA repair, chromosome segregation. SETD2 gene deletions and/or mutations (mostly frameshift or nonsense) have been reported in solid tumors (clear cell renal cell carcinoma, bladder cancer, lu...