Ponatinib vs Imatinib in Frontline Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia: A Randomized Clinical Trial.

Importance: In newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), disease progression due to acquired resistance to first- or second-generation BCR::ABL1 tyrosine kinase inhibitors is common. Ponatinib inhibits BCR::ABL1 and all single-mutation variants, including T315I.

Objective: To compare frontline ponatinib vs imatinib in adults with newly diagnosed Ph+ ALL.

Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: final results.

Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway. This phase 2 study evaluated dosing, efficacy, and safety of add-on PI3Kδ inhibitor parsaclisib for patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib.

Combining cell-free RNA with cell-free DNA in liquid biopsy for hematologic and solid tumors.

Current use of liquid biopsy is based on cell-free DNA (cfDNA) and the evaluation of mutations or methylation pattern. However, expressed RNA can capture mutations, changes in expression levels due to methylation, and provide information on cell of origin, growth, and proliferation status. We developed an approach to isolate cell-free total nucleic acid (cfDNA) and used targeted next generation sequencing to sequence cell-free RNA (cfRNA) and cfDNA as new approach in liquid biopsy.

Differential Diagnosis of Hematologic and Solid Tumors Using Targeted Transcriptome and Artificial Intelligence.

Diagnosis and classification of tumors is increasingly dependent on biomarkers. RNA expression profiling using next-generation sequencing provides reliable and reproducible information on the biology of cancer. This study investigated targeted transcriptome and artificial intelligence for differential diagnosis of hematologic and solid tumors.

Venetoclax Plus Gilteritinib for -Mutated Relapsed/Refractory Acute Myeloid Leukemia.

Purpose: The FMS-related tyrosine kinase 3 (FLT3) inhibitor gilteritinib is standard therapy for relapsed/refractory -mutated () acute myeloid leukemia (AML) but seldom reduces burden or induces sustained efficacy. Gilteritinib combines synergistically with the BCL-2 inhibitor venetoclax in preclinical models of AML.

Methods: This phase Ib open-label, dose-escalation/dose-expansion study (ClinicalTrials.

Measurable Residual Disease in High-Risk Acute Myeloid Leukemia.

Mounting evidence suggests measurable residual disease (MRD) assessments are prognostic in acute myeloid leukemia (AML). High-risk AML encompasses a subset of AML with poor response to therapy and prognosis, with features such as therapy-related AML, an antecedent hematologic disorder, extramedullary disease (in adults), and selected mutations and cytogenetic abnormalities. Historically, few patients with high-risk AML achieved deep and durable remission with conventional chemotherapy; however, newer agents might be more effective in achieving MRD-negative remission.

Isatuximab monotherapy in patients with refractory T-acute lymphoblastic leukemia or T-lymphoblastic lymphoma: Phase 2 study.

The poor prognosis of acute T-cell lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in older adults and patients with relapsed/refractory illness is an unmet clinical need, as there is no defined standard of care and there are few treatment options. Abnormally elevated CD38 expression in T-ALL and T-LBL is associated with tumor expansion and disease development, making CD38 a potential target for anti-T-ALL and T-LBL treatment. Isatuximab is a monoclonal antibody that binds to a specific epitope on CD38.

Ponatinib dose-ranging study in chronic-phase chronic myeloid leukemia: a randomized, open-label phase 2 clinical trial.

In PACE (Ponatinib Ph+ ALL and CML Evaluation), a phase 2 trial of ponatinib that included patients with chronic-phase chronic myeloid leukemia (CP-CML) resistant to multiple prior tyrosine kinase inhibitors (TKIs), ponatinib showed deep and durable responses, but arterial occlusive events (AOEs) emerged as notable adverse events. Post hoc analyses indicated that AOEs are dose dependent. We assessed the benefit/risk ratio across 3 ponatinib starting doses in the first prospective study to evaluate a novel, response-based, dose-reduction strategy for TKI treatment.

Ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed AML: a phase 1 study.

Ivosidenib (AG-120) and enasidenib (AG-221) are targeted oral inhibitors of the mutant isocitrate dehydrogenase (mIDH) 1 and 2 enzymes, respectively. Given their effectiveness as single agents in mIDH1/2 relapsed or refractory acute myeloid leukemia (AML), this phase 1 study evaluated the safety and efficacy of ivosidenib or enasidenib combined with intensive chemotherapy in patients with newly diagnosed mIDH1/2 AML. Ivosidenib 500 mg once daily and enasidenib 100 mg once daily were well tolerated in this setting, with safety profiles generally consistent with those of induction and consolidation chemotherapy alone.

Venetoclax and hypomethylating agents (HMAs) induce high response rates in MDS, including patients after HMA therapy failure.

Treatment-naive and relapsed/refractory MDS patients receiving venetoclax and HMAs have an ORR of 59% with 63% of responders proceeding to transplant. Allogeneic stem cell transplantation after treatment with venetoclax in combination with HMA is associated with prolonged survival.

Oral cedazuridine/decitabine for MDS and CMML: a phase 2 pharmacokinetic/pharmacodynamic randomized crossover study.

This phase 2 study was designed to compare systemic decitabine exposure, demethylation activity, and safety in the first 2 cycles with cedazuridine 100 mg/decitabine 35 mg vs standard decitabine 20 mg/m2 IV. Adults with International Prognostic Scoring System intermediate-1/2- or high-risk myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML) were randomized 1:1 to receive oral cedazuridine/decitabine or IV decitabine in cycle 1, followed by crossover to the other treatment in cycle 2. All patients received oral cedazuridine/decitabine in subsequent cycles.

Loncastuximab tesirine, an anti-CD19 antibody-drug conjugate, in relapsed/refractory B-cell acute lymphoblastic leukemia.

Relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) remains a therapeutic challenge. Loncastuximab tesirine is an antibody-drug conjugate against CD19, an antigen expressed in many B-cell malignancies. This open-label, single-arm, dose-escalation, dose-expansion study assessed the safety, tolerability, pharmacokinetics (PKs), immunogenicity, and preliminary clinical activity of loncastuximab tesirine in adults with R/R B-ALL.

Evaluation of direct oral anticoagulants for the treatment of venous thromboembolism in the oncology population.

Direct oral anticoagulants (DOACs) have become an attractive option for the treatment of venous thromboembolism (VTE) in cancer patients. However, their use is currently not recommended as first-line treatment by national guidelines due to limited data in this patient population. The objective of this study was to evaluate the practice and safety patterns of DOACs when used for VTE treatment in the oncology population.

Phase Ib Study of Glasdegib, a Hedgehog Pathway Inhibitor, in Combination with Standard Chemotherapy in Patients with AML or High-Risk MDS.

This open-label, multicenter, dose-finding, phase Ib study (NCT01546038) evaluated the safety, pharmacokinetics, pharmacodynamics, and clinical activity of the novel Hedgehog pathway Smoothened inhibitor glasdegib (PF-04449913) in patients ( = 52) with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Glasdegib 100 or 200 mg was administered orally, once daily in 28-day cycles, in combination with low-dose cytarabine (arm A) or decitabine (arm B) to newly diagnosed patients considered not suitable for standard induction chemotherapy, and in combination with cytarabine/daunorubicin (arm C) to fit patients. The study followed a standard 3+3 dose-escalation design.

Safety, efficacy, and clinical utility of asparaginase in the treatment of adult patients with acute lymphoblastic leukemia.

Adults with acute lymphoblastic leukemia (ALL) are known to have inferior outcomes compared to the pediatric population. Although the reasons for this are likely manyfold, the agents utilized and the increased intensity of pediatric treatments compared to adult treatments are likely significant contributing factors. Asparaginase, an enzyme that converts asparagine to aspartic acid, forms the backbone of almost all pediatric regimens and works by depleting extracellular asparagine, which ALL cells are unable to synthesize.

The CIRAS study: a case control study to define the clinical, immunologic, and radiographic features of aromatase inhibitor-induced musculoskeletal symptoms.

Aromatase inhibitors (AIs) are widely prescribed for post-menopausal hormone receptor-positive breast cancer; however, musculoskeletal symptoms limit their tolerability. The purpose of this study was to determine whether joint pain in women receiving AIs is associated with inflammatory arthritis as measured by the disease activity score-28 (DAS-28), and to evaluate association with tenosynovitis on ultrasound. A total of 48 postmenopausal women with stage I-III breast cancer and hand pain were recruited from the Lombardi Comprehensive Cancer Center.

The RNA Modification Database, RNAMDB: 2011 update.

Since its inception in 1994, The RNA Modification Database (RNAMDB, http://rna-mdb.cas.albany.

Thermal conductivity and particle agglomeration in alumina nanofluids: experiment and theory.

In recent years many experimentalists have reported an anomalously enhanced thermal conductivity in liquid suspensions of nanoparticles. Despite the importance of this effect for heat transfer applications, no agreement has emerged about the mechanism of this phenomenon, or even about the experimentally observed magnitude of the enhancement. To address these issues, this paper presents a combined experimental and theoretical study of heat conduction and particle agglomeration in nanofluids.

Post-transcriptional modifications in the small subunit ribosomal RNA from Thermotoga maritima, including presence of a novel modified cytidine.

Post-transcriptional modifications of RNA are nearly ubiquitous in the principal RNAs involved in translation. However, in the case of rRNA the functional roles of modification are far less established than for tRNA, and are subject to less knowledge in terms of specific nucleoside identities and their sequence locations. Post-transcriptional modifications have been studied in the SSU rRNA from Thermotoga maritima (optimal growth 80 degrees C), one of the most deeply branched organisms in the Eubacterial phylogenetic tree.

A novel method for sequence placement of modified nucleotides in mixtures of transfer RNA.

Sequence placement of post-transcriptionally modified nucleosides in tRNA can be experimentally difficult, particularly in cases involving new or unexpected modifications or sequence sites. We describe a mass spectrometry-based approach to this problem, involving the following steps: crude isolations of one or several tRNAs by HPLC from an unfractionated tRNA mixture; digestion to oligonucleotide mixtures by RNase T1; analysis by combined HPLC/electrospray ionization-MS for recognition of modifications; and direct gas-phase sequencing of selected targets in the mixture by LC/MS/MS. Isoacceptor identity can be established in favorable cases when tRNA gene sequences are available.