Patient-reported outcomes in early phase trials for patients with myelodysplastic syndromes.

Patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) experience a wide range of symptoms due both to their underlying disease and the effects of treatment. Designing early phase trials to explore effective therapies in these patients should not only examine anti-tumor activity, but also consider the effects of treatments on how patients feel and function. Assessing symptomatic toxicities associated with new therapies in early phase trials from the patient perspective is best measured using patient-reported outcomes (PROs) and offers valuable insight and complementary information to the traditional adverse event reporting in cancer clinical trials.

Allogeneic hematopoietic cell transplantation in elderly patients with myelodysplastic syndromes: Considerations and challenges.

Myelodysplastic syndromes/neoplasms (MDS) and related diseases are highly heterogeneous myeloid stem cell cancers that predominantly affect the elderly. The only curative treatment is allogeneic hematopoietic cell transplantation (HCT). Given the prevalence of age-related comorbidities, HCT in patients aged 65 years or older requires a highly personalized approach.

Breaking Boundaries: Immunotherapy for Myeloid Malignancies.

Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment options available to patients. Immunotherapy in myeloid malignancies, however, faces numerous challenges due to the dynamic nature of the disease, immune dysregulation, and the development of immune evasion mechanisms.

Infections and antimicrobial prophylaxis in patients with myelodysplastic syndromes.

Infectious complications are an important cause of morbidity and mortality in patients with myelodysplastic syndromes (MDS). Preventing infections could significantly improve both survival and quality of life. Unfortunately, both infections and antimicrobial prophylaxis in patients with MDS are incompletely assessed due to the heterogeneity of disorders included in each publication, changing definitions over time, and lack of standardized prophylaxis practices.

CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific expansion and toxicity.

Chimeric antigen receptor (CAR) T cells directed against CD19 (CAR19) are a revolutionary treatment for B-cell lymphomas (BCLs). CAR19 cell expansion is necessary for CAR19 function but is also associated with toxicity. To define the impact of CAR19 expansion on patient outcomes, we prospectively followed a cohort of 236 patients treated with CAR19 (brexucabtagene autoleucel or axicabtagene ciloleucel) for mantle cell lymphoma (MCL), follicular lymphoma, and large BCL (LBCL) over the course of 5 years and obtained CAR19 expansion data using peripheral blood immunophenotyping for 188 of these patients.

How I reduce and treat posttransplant relapse of MDS.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative option for patients with high-risk myelodysplastic syndromes (MDS). Advances in conditioning regimens and supportive measures have reduced treatment-related mortality and increased the role of transplantation, leading to more patients undergoing HSCT. However, posttransplant relapse of MDS remains a leading cause of morbidity and mortality for this procedure, necessitating expert management and ongoing results analysis.

Collection of peripheral blood mononucleated cells for chronic graft-versus-host disease immunology research: safety and effectiveness of leukapheresis in 132 patients.

Background: Chronic graft-versus-host disease (GVHD) is a major cause of late morbidity and non-relapse mortality in recipients of allogeneic hematopoietic cell transplantation (HCT). Its biology, however, remains poorly understood, making the studies of its biology and immunomodulatory therapies a difficult task. Such research is often hampered by lymphopenia which is common in these patients and precludes studies of critical cellular subsets across the spectrum of severity of disease.

Outcomes of Cancer Patients with COVID-19 in a Hospital System in the Chicago Metropolitan Area.

Patients with a history of malignancy have been shown to be at an increased risk of COVID-19-related morbidity and mortality. Poorer clinical outcomes in that patient population are likely due to the underlying systemic illness, comorbidities, and the cytotoxic and immunosuppressive anti-tumor treatments they are subjected to. We identified 416 cancer patients with SARS-CoV-2 infection being managed for their malignancy at Northwestern Medicine in Chicago, Illinois, between March and July of 2020.

T time: Emerging and new therapies for peripheral T-cell lymphoma.

Peripheral T-cell Lymphomas (PTCL) are a heterogenous group of aggressive non-Hodgkin lymphomas that are far less sensitive to chemotherapy than their B-cell counterparts. Despite their poor prognosis, they are treated similarly to most aggressive B-cell lymphomas, heavily relying on CHOP or CHOP-like combination chemotherapy irrespective of their different subtypes or biology. The last decade has seen the emergence of many targeted therapies that include histone deacetylase inhibitors, hypomethylating agents, monoclonal antibodies and PIK3 inhibitors, among others.

Inhibitory effects of Tomivosertib in acute myeloid leukemia.

The MAPK-interacting kinases 1 and 2 (MNK1/2) have generated increasing interest as therapeutic targets for acute myeloid leukemia (AML). We evaluated the therapeutic potential of the highly-selective MNK1/2 inhibitor Tomivosertib on AML cells. Tomivosertib was highly effective at blocking eIF4E phosphorylation on serine 209 in AML cells.

Hematological manifestations of COVID-19.

The emergence of the Coronavirus Disease -19 (COVID-19) pandemic, has had a tremendous global impact, resulting in substantial morbidity and mortality worldwide and especially in the United States, where nearly one third of the cases are located. Although involvement of the lower respiratory track accounts for most of the morbidity and mortality seen, the virus involves several organ systems and the syndrome exhibits clinical diversity with a wide range of symptoms and manifestations. The involvement of elements of the hematopoietic system is prominent in severe cases and associated with poor outcomes and mortality.

Unique morphologic and genetic characteristics of acute myeloid leukemia with chromothripsis: a clinicopathologic study from a single institution.

Chromothripsis is a unique type of genomic instability and is recognized in various cancers. In myeloid neoplasms (MNs), chromothripsis was linked to poor prognosis and specific genetic alterations (complex karyotype, 5q deletions, and loss of TP53). However, the clinicopathologic features of MNs with chromothripsis have not been thoroughly characterized.

Inhibitory effects of SEL201 in acute myeloid leukemia.

MAPK interacting kinase (MNK), a downstream effector of mitogen-activated protein kinase (MAPK) pathways, activates eukaryotic translation initiation factor 4E (eIF4E) and plays a key role in the mRNA translation of mitogenic and antiapoptotic genes in acute myeloid leukemia (AML) cells. We examined the antileukemic properties of a novel MNK inhibitor, SEL201. Our studies provide evidence that SEL201 suppresses eIF4E phosphorylation on Ser209 in AML cell lines and in primary patient-derived AML cells.

An integrative approach reveals genetic complexity and epigenetic perturbation in acute promyelocytic leukemia: a single institution experience.

Acute promyelocytic leukemia (APL) is a distinct type of acute myeloid leukemia that is defined by the presence of the translocations that mostly involve the RARA gene. The most frequent translocation is the t(15;17), which fuses the RARA gene with the PML gene. Previous studies have shown that other cooperative mutations are required for the development of APL after the initiating event of the t(15;17).

How Precision Medicine Is Changing Acute Myeloid Leukemia Therapy.

Pretreatment somatic mutations influence acute myeloid leukemia (AML) pathogenesis and responses to chemotherapy. Integration of cytogenetic abnormalities and molecular mutations, co-occurring and in isolation, have resulted in a more refined prognostic assessment. In addition, research performed over the last few years has led to the development of novel therapies and new drug approvals in patients with both newly diagnosed and relapsed/refractory (R/R) AML.

Next-Generation Sequencing in Myeloproliferative Neoplasms: Is This Indicated in All Patients?

Purpose Of Review: To discuss the impact that next-generation sequencing has had on myeloproliferative neoplasm prognosis and treatment response.

Recent Findings: Extended genetic testing has led to a more comprehensive understanding of the mutational landscape in the myeloproliferative neoplasms. More refined prognostic models that predict disease course have therefore been developed.

Novel Therapies and Approaches to Relapsed/Refractory HL Beyond Chemotherapy.

Although Hodgkin lymphoma (HL) is highly curable with first-line therapy, relapses occur in approximately 10⁻20% of patients with early stage disease and 30⁻40% of patients with advanced stage disease. The standard approach for relapsed or refractory disease is salvage therapy, followed by consolidation with high dose therapy and autologous stem cell transplant (ASCT). Patients who achieve a complete response to salvage therapy prior to ASCT have better outcomes, thus recent studies have focused on incorporating newer agents in this setting.