A phase I study of MLN4924 and belinostat in relapsed/refractory acute myeloid leukemia or myelodysplastic syndrome.

Purpose: Relapsed and/or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome continue to have a poor prognosis with limited treatment options despite advancements in rational combination and targeted therapies. Belinostat (an HDAC inhibitor) and Pevonedistat (a NEDD8 inhibitor) have each been independently studied in hematologic malignancies and have tolerable safety profiles with limited single-agent activity. Preclinical studies in AML cell lines and primary AML cells show the combination to be highly synergistic, particularly in high-risk phenotypes such as p53 mutant and FLT-3-ITD positive cells.

Universal posttransplant cyclophosphamide after allogeneic transplant, a retrospective single institution study.

Background: The excellent results of posttransplant cyclophosphamide in decreasing graft-versus-host disease (GVHD) after haploidentical (HI) allogeneic transplant have challenged current donor selection algorithms.

Patients And Methods: We compared outcomes after matched sibling (MSD) versus alternative donor transplant using identical graft-versus-host disease (GVHD) prophylaxis including posttransplant cyclophosphamide (PTCy. Endpoints included engraftment, time outside of the hospital in the first 100 days after transplant, overall survival (OS), non-relapse mortality (NRM) and percentage of patients disease-free and off immunosuppression (DFOI) at one year and at the last follow-up.

Improving patient understanding and outcomes in myelodysplastic syndromes - An animated patient guide to MDS with visual formats of learning.

Objectives: Patient education resources that address barriers to health literacy to improve understanding and outcomes in myelodysplastic syndromes (MDS) are limited. The aim of this study was to evaluate the impact and outcomes benefits of cancer educational modules (which includes the 'You and MDS' website and YouTube hosted resources) related to MDS education, awareness, understanding and health outcomes.

Methods: This was a retrospective study of learner feedback, metrics, and utilization data from July 2018 to August 2021.

The Impact of Prior Salvage Treatment With Immune Checkpoint Inhibitors on Hodgkin Lymphoma Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Single-Center Experience.

Introduction: The objective of the study was to assess the impact of the previous use of immune-checkpoint inhibitors (ICIs) on the clinical course of Hodgkin Lymphoma (HL) patients undergoing autologous hematopoietic stem cell transplantation (ASCT).

Methods: A single-center, retrospective chart review of adult HL patients who received ASCT from January 1, 2014, to December 31, 2019, was conducted. Primary endpoints included the length of stay (LOS) and the composite outcome of late-onset noninfectious fever (LONIF) or late-onset hypotension (LOH) requiring intravenous fluid (IVF) resuscitation.

Incorporation of posttransplant cyclophosphamide as part of standard immunoprophylaxis for all allogeneic transplants: a retrospective, single institution study.

The addition of posttransplant cyclophosphamide (PTCy) to standard graft-versus-host disease (GVHD) prophylaxis following haploidentical blood stem transplants has resulted in relatively low rates of GVHD. As GVHD remains a major cause of morbidity and mortality in patients receiving transplants from matched donors, we began to use PTCy in all blood stem cell transplants in 2016 and compared our recent experience with PTCy after matched sibling and unrelated donor transplants (N = 49) to the earlier 2-year period (N = 41) when PTCy was not used. Endpoints included graft-versus-host, relapse-free-survival (GRFS), overall survival, non-relapse mortality, and percentage of patients disease-free and off immunosuppression (DFOI) at 1 year and at the last follow-up.

Lactobacillus rhamnosus GG probiotic enteric regimen does not appreciably alter the gut microbiome or provide protection against GVHD after allogeneic hematopoietic stem cell transplantation.

Graft-versus-host disease (GVHD) is a major adverse effect associated with allogeneic stem cell transplant. Previous studies in mice indicated that administration of the probiotic Lactobacillus rhamnosus GG can reduce the incidence of GVHD after hematopoietic stem cell transplant. Here we report results from the first randomized probiotic enteric regimen trial in which allogenic hematopoietic stem cell patients were supplemented with Lactobacillus rhamnosus GG.

Molecular Mutations and Their Cooccurrences in Cytogenetically Normal Acute Myeloid Leukemia.

Adult acute myeloid leukemia (AML) clinically is a disparate disease that requires intensive treatments ranging from chemotherapy alone to allogeneic hematopoietic cell transplantation (allo-HCT). Historically, cytogenetic analysis has been a useful prognostic tool to classify patients into favorable, intermediate, and unfavorable prognostic risk groups. However, the intermediate-risk group, consisting predominantly of cytogenetically normal AML (CN-AML), itself exhibits diverse clinical outcomes and requires further characterization to allow for more optimal treatment decision-making.

PDCD2 functions in cancer cell proliferation and predicts relapsed leukemia.

PDCD2 is an evolutionarily conserved eukaryotic protein with unknown function. The Drosophlia PDCD2 ortholog Zfrp8 has an essential function in fly hematopoiesis. Zfrp8 mutants exhibit marked lymph gland hyperplasia that results from increased proliferation of partially differentiated hemocytes, suggesting Zfrp8 may participate in cell growth.

A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome.

Background: Ezatiostat is a glutathione analog prodrug glutathione S-transferase P1-1 (GSTP1-1) inhibitor. This study evaluated 2 extended dose schedules of oral ezatiostat in 89 heavily pretreated patients with low to intermediate-1 risk myelodysplastic syndrome (MDS).

Methods: Patients were randomized by 1 stratification factor-baseline cytopenia (anemia only vs anemia with additional cytopenias)-to 1 of 2 extended dosing schedules.

Differentiation-associated miR-22 represses Max expression and inhibits cell cycle progression.

Differentiation agents such as 12-O-tetradecanoylphorbol-13-acetate (TPA) engage cell signaling pathways that activate downstream transcriptional programs necessary for cell differentiation. Recent evidence has indicated microRNAs (miRNAs) are an integral part of these transcriptional programs, which target key proteins and impact cell growth thereby facilitating changes required for differentiation. To further investigate the role of miRNAs in cell growth and differentiation, we focused on miR-22, a miRNA induced by TPA in the HL-60 leukemia cell line model of monocytic differentiation.

miR-320 targets transferrin receptor 1 (CD71) and inhibits cell proliferation.

Objective: MicroRNAs (miRNAs) have been implicated in complex vertebrate developmental systems, such as hematopoiesis, and may play an integral role in the development of human cancers. Based on these observations, we investigated the contribution of miRNAs to acute myelogenous leukemia cell lineage-specific differentiation.

Materials And Methods: To facilitate the identification of miRNAs and their targets relevant to leukemic cell differentiation, changes miRNA expression were analyzed in the human leukemia cell line HL-60, which historically has been utilized to study lineage-specific changes in response to the differentiation agent 12-O-tetradecanoylphorbol-13-acetate (TPA).

Nuclear factor-kappaB modulation in patients undergoing induction chemotherapy for acute myelogenous leukemia.

Purpose: Nuclear factor-kappaB (NF-kappaB) is constitutively expressed in many acute myelogenous leukemia (AML) cells and AML stem cells. Ex vivo treatment of AML cells with inhibitors of NF-kappaB results in diminished AML cell survival and enhances the cytotoxic effects of chemotherapeutic agents. The purpose of this study was to determine if standard anti-inflammatory agents modulate AML cell nuclear NF-kappaB when administered in conjunction with induction chemotherapy.

A pilot study of allogeneic cellular therapy for patients with advanced hematologic malignancies.

Allogeneic hematopoietic stem cell transplantation provides curative therapy for some patients with advanced hematologic malignancies. Disease response after allogeneic transplant is, at least in part, mediated by donor immune cells. In this report we describe a cellular therapy using haploidentical peripheral blood stem cells administered after very low dose total body irradiation (TBI) (100cGy).

Sequential topoisomerase targeting and analysis of mechanisms of resistance to topotecan in patients with acute myelogenous leukemia.

Resistance to topoisomerase I (TOP1)-targeting drugs such as topotecan often involves upregulation of topoisomerase II (TOP2), with accompanying increased sensitivity to TOP2-targeting drugs such as etoposide. This trial was designed to investigate sequential topoisomerase targeting in the treatment of patients with high-risk acute myelogenous leukemia. An initial cohort of patients received topotecan and cytosine arabinoside daily for 5 days.

A phase I clinical trial of 12- O-tetradecanoylphorbol-13-acetate for patients with relapsed/refractory malignancies.

Phorbol esters activate protein kinase C and modulate a variety of downstream cell signaling pathways. 12-O-tetradecanoylphorbol-13-acetate (TPA) is a phorbol ester that induces differentiation or apoptosis in a variety of cell lines at low concentrations. A phase I dose escalation trial of TPA was undertaken for patients with relapsed or refractory malignancies.

12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dual-specificity phosphatase expression and AML cell survival.

12-O-Tetradecanoylphorbol-13-acetate (TPA) is being developed as a therapeutic agent by virtue of its being a potent modulator of signal transduction in pre-clinical models of AML [Strair RK, Schaar D, Goodell L, Aisner J, Chin KV, Eid J, et al. Administration of a phorbol ester to patients with hematological malignancies: preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate. Clin Cancer Res 2002;8:2512-8].

Antineoplastic effects of partially HLA-matched irradiated blood mononuclear cells in patients with renal cell carcinoma.

Purpose: Vaccines, cytokines, and other biologic-based therapies are being developed as antineoplastic agents. Many of these agents are designed to induce an autologous immune response directed against the malignancy. In contrast, hematopoietic stem-cell transplantation is being developed as a form of allogeneic immunotherapy.

Administration of a phorbol ester to patients with hematological malignancies: preliminary results from a phase I clinical trial of 12-O-tetradecanoylphorbol-13-acetate.

Purpose: Phorbol esters are capable of inducing a broad range of cellular effects,including the maturation/differentiation of hematopoietic cell lines (E. Huberman and M. F.