An oncolytic vaccinia virus expressing CXCL11 combined with PD-L1 blockade significantly reduces tumor burden and improves survival in murine cancer models.

Preexisting therapy-resistant leukemia stem cell populations underlie the cellular origin of relapse in acute myeloid leukemia.

Myeloproliferative neoplasm cells recruit Gli1 positive mesenchymal stromal cells to transdifferentiate into fibrosis-causing myofibroblasts, a process that can be inhibited by a Gli inhibitor.

iPSC lines derived from MDS and AML patient samples can map clonal evolution, disease progression and regression, and identify disease stage-specific medication effects.

Measurable residual disease (MRD) has emerged as a primary marker of risk severity and prognosis in acute myeloid leukemia (AML). There is, however, ongoing debate about MRD-based surveillance and treatment. A literature review was performed using the PubMed database with the keywords MRD or residual disease in recently published journals. Identified articles describe the prognostic value of pre-transplant MRD and suggest optimal timing and techniques to quantify MRD. Several studies address the implications of MRD on treatment selection and hematopoietic stem cell transplant, including patient candidacy, conditioning regimen, and transplant type. More prospective, randomized studies are needed to guide the application of MRD in the treatment of AML, particularly in transplant.

Introduction: Acute myeloid leukemia (AML) remains a disease with high mortality, especially for older patients and those with relapsed/refractory (R/R) disease. With recent advances in molecular testing, targeting particular leukemogenic mutations such as those occurring in isocitrate dehydrogenase (IDH) became possible. Enasidenib is a new small-molecule inhibitor of mutant isocitrate dehydrogenase-2 (IDH2). Aim: The objective of this article is to review the evidence for the use of enasidenib in R/R AML, as well as to outline future directions of enasidenib therapy. Evidence Review: Enasidenib was approved in August 2017, after a successful Phase I/II trial showing an overall response rate (ORR) of 40.3% in R/R disease, with 19.3% of patients achieving complete remission (CR). Enrollees in the trial were mostly older adults. The most prominent toxicities were hyperbilirubinemia and IDH-differentiation syndrome (IDH-DS), though the drug was generally well tolerated and the maximum tolerated dose was not reached. A Phase III trial is currently ongoing. Conclusion: Enasidenib provides a new therapeutic option for patients with R/R AML. Further studies are ongoing to ascertain its role in combination with other agents and newly diagnosed disease.

TP53 is a key tumor suppressor gene that plays an important role in regulating apoptosis, senescence, and DNA damage repair in response to cellular stress. Although somewhat rare, TP53-mutated AML has been identified as an important molecular subgroup with a prognosis that is arguably the worst of any. Survival beyond one year is rare after induction chemotherapy with or without consolidative allogeneic stem cell transplant. Although response rates have been improved with hypomethylating agents, outcomes remain particularly poor due to short response duration. Improvements in our understanding of AML genetics and biology have led to a surge in novel treatment options, though the clinical applicability of these agents in TP53-mutated disease remains largely unknown. This review will focus on the epidemiology, molecular characteristics, and clinical significance of TP53 mutations in AML as well as emerging treatment options that are currently being studied.

The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid haemopathies characterized by defective differentiation of haematopoietic cells and expansion of the abnormal clone. This leads to bone marrow failure with the resulting peripheral blood cytopenias and evolution to or toward acute myeloid leukaemia that characterize MDS clinically. The clinical heterogeneity of MDS has led several groups to analyze patient and clinical characteristics to develop prognostic scoring systems yielding estimates of overall and leukaemia-free survival to guide clinical decision-making. These models have evolved over time as our understanding of the pathogenesis, natural history, and treatment of MDS has improved. Rapid advances in flow cytometric analysis, adjuncts to standard metaphase cytogenetics, and gene mutation analysis are revolutionizing our understanding of MDS pathogenesis and prognosis. Despite the existence of multiple well-validated prognostic scoring systems, further refinements of current models with these new sources of prognostic data are needed and are described herein.

Chronic lymphocytic leukemia (CLL) is a chronic, progressive lymphoproliferative disorder characterized by a monoclonal population of functionally incompetent lymphocytes. Renal involvement is rare and poorly described. A 57-year-old male with no prior medical history was diagnosed with CLL and followed with a watch and wait approach. He was referred to our institution several months later due to concern for Richter's transformation to diffuse large B-cell lymphoma. A positron emission tomography/computed tomography scan showed no evidence of diffuse large B-cell lymphoma; however, the patient was noted to have hypoalbuminemia, nephrotic range proteinuria, an acute left renal vein thrombus, and a right pulmonary embolus. A nephrotic syndrome workup including autoimmunity and infection was unremarkable, and a kidney biopsy was deferred due to concern for renal compromise in the setting of a renal vein thrombus. The patient was treated with 6 cycles of reduced-dose fludarabine, cyclophosphamide, and rituximab for a presumed CLL-associated nephrotic syndrome and anticoagulation for his venous thromboemboli. At 6-month follow-up, the patient achieved complete remission of his CLL with normalization of all cell lines and resolution of his nephrotic range proteinuria. Repeat computed tomography scans showed no evidence of recurrent venous thromboemboli. This case demonstrates a potential role of empiric chemotherapy in cases of CLL-associated nephrotic syndrome given its potentially life-threatening sequelae and response to treatment.