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Introduction: Acute myeloid leukemia (AML) is associated with poor outcomes and is generally incurable. Therefore, understanding preferences of older adults with AML is critical. We sought to assess whether best-worst scaling (BWS) can be used to capture attributes considered by older adults with AML when making initial treatment decisions and longitudinally, as well as assess changes in health-related quality of life (HRQoL) and decisional regret over time., Materials and Methods: In a longitudinal study for adults ≥60 years with newly diagnosed AML, we collected: (1) attributes of treatment most important to patients using BWS, (2) HRQoL using EQ-5D-5L, (3) decisional regret using the Decisional Regret Scale, and (4) treatment worthiness using the "Was it worth it?" questionnaire. Data was collected at baseline and over six months. A hierarchical Bayes model was used to allocate percentages out of 100%. Due to small sample size, hypothesis testing was performed at α = 0.10 (2-tailed). We analyzed how these measures differed by treatment choice (intensive vs. lower intensity treatment)., Results: Mean age of patients was 76 years (n = 15). At baseline, the most important attributes of treatment to patients were response to treatment (i.e., chance that the cancer will respond to treatment; 20.9%). Compared to those who received lower intensity treatment (n = 7) or best supportive care (n = 2), those who received intensive treatment (n = 6) generally ranked "alive one year or more after treatment" (p = 0.03) with higher importance and ranked "daily activities" (p = 0.01) and "location of treatment" (p = 0.01) with less importance. Overall, HRQoL scores were high. Decisional regret was mild overall and lower for patients who chose intensive treatment (p = 0.06)., Discussion: We demonstrated that BWS can be used to assess the importance of various treatment attributes considered by older adults with AML when making initial treatment decisions and longitudinally throughout treatment. Attributes of treatment important to older patients with AML differed between treatment groups and changed over time. Interventions are needed to re-assess patient priorities throughout treatment to ensure care aligns with patient preferences., Competing Interests: Declaration of Competing Interest Dr. Loh has served as a consultant to Pfizer and Seattle Genetics and has received honoraria from Pfizer. All other authors have no relevant competing interests to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: Recent data have shown improved outcomes in selected older adults with acute myeloid leukemia (AML) following allogeneic hematopoietic stem cell transplantation (HSCT). Nonetheless, practice patterns for referring and performing HSCT vary. We aimed to evaluate referral, utilization, and reasons for not referring/proceeding to HSCT in older adults with AML., Materials and Methods: This is a single center retrospective analysis of patients aged ≥60 years diagnosed with AML evaluating rates of HSCT referral and utilization. Fisher's exact test was used to compare rates of referral and utilization across age groups and years of diagnosis., Results: Median age of the 97 patients was 70 years (range 61-95); 30% (29/97) were referred for HSCT and of these, 69% (20/29) received HSCT. Common documented reasons (can be multiple) for not referring were performance status (n = 21), advanced age (n = 16), patient refusal (n = 15), refractory disease (n = 14), and prohibitive comorbidity (n = 6). Among patients who were referred but did not receive HSCT (n = 9/29), documented reasons for not proceeding with HSCT were refractory disease (n = 5), advanced age (n = 2), and prohibitive comorbidity (n = 2). HSCT referral and utilization rates significantly decreased with age (p < 0.01) but were generally stable over time from 2014 to 2017 (p = 0.40 for referral and p = 0.56 for utilization)., Discussion: Despite improvements in supportive care and HSCT techniques, HSCT referral and utilization rates remained low among older adults with AML but stable over time., Competing Interests: Conflicts of Interest Dr. Loh has received honoraria from Pfizer, and has served as a consultant to Pfizer and Seattle Genetics. All other authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Older patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) have worse survival rates compared to younger patients, and experience more intense inpatient healthcare at the end of life (EOL) compared to patients with solid tumors. Advance care planning (ACP) has been shown to limit aggressive and burdensome care at EOL for patients with AML and MDS. The purpose of this study was to better understand ACP from the perspective of clinicians, older patients with AML and MDS, and their caregivers., Materials and Methods: We conducted semi-structured interviews with 45 study participants. Interviews were audio-recorded and transcribed. Open coding and focused content analysis were used to organize data and develop and contextualize categories and subcategories., Results: Guided by our specific aims, we developed four themes: (1) The language of ACP and medical order for life-sustaining treatment (MOLST) does not resonate with patients, (2) There is no uniform consensus on when ACP is currently happening, (3) Oncology clinician-perceived barriers to ACP (e.g., patient discomfort, patient lack of knowledge, and lack of time), and (4) Patients felt that they are balancing fear and hope when navigating their AML or MDS diagnosis., Discussion: The results of this study can be used to develop interventions to promote serious illness conversations for patients with AML and MDS and their caregivers to ensure that patient care aligns with patient values., Competing Interests: Declaration of Competing Interest Dr. Loh has served as a consultant to Pfizer and Seattle Genetics and has received honoraria from Pfizer., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: The onset of symptoms and the diagnosis of acute myeloid leukemia (AML) often occur suddenly and may lead to a range of emotional responses. Understanding patients' experiences and emotional states allows clinicians to tailor care to patients' needs. Previous studies have largely focused on patients' experiences at diagnosis and after remission has been achieved among those who received intensive chemotherapy. In this study, we evaluated experiences of older patients with AML who had received or were receiving treatments of varying intensity, in both outpatient and inpatient settings, and who were at different stages in their treatment course at the time of our interviews., Materials and Methods: We conducted a single center qualitative study which aimed to understand factors influencing older patients' treatment decision-making and the findings were previously reported. This analysis specifically explored older patients' experiences at various stages after AML diagnosis. We purposively sampled patients based on treatment intensity and stage of treatment (undergoing induction treatment, post-remission treatment, or post-allogeneic hematopoietic stem cell transplant). We recruited fifteen patients aged ≥60 years with AML. The sample size was determined based on reaching data saturation for the primary study aim. For this analysis, data saturation was reached by the fourteenth manuscript. In-depth semi-structured interviews that had been recorded and transcribed were re-analyzed using inductive thematic analysis to explore patients' experiences. Coding was performed using Atlas.ti. We identified themes with the aim of capturing the most commonly shared experiences., Results: Mean age of the fifteen patients was 72.1 years; all had received one or more treatments including intensive induction therapy (10/15), lower-intensity treatment (7/15), and/or hematopoietic stem cell transplant (3/15). Patients experienced strong negative emotional responses, including shock, that were barriers to processing information and meaningful communication. Patients also shared their perspectives on communication with healthcare professionals (including thoughts on adequacy of information provided) and coping strategies., Discussion: Understanding older patients' experiences, including emotional responses and barriers to communication and decision making, at AML diagnosis and throughout the illness trajectory allows clinicians to address patients' supportive care needs during this difficult period., Competing Interests: Declaration of Competing Interest Dr. Loh has served as a consultant to Pfizer and Seattle Genetics, and has received honoraria from Pfizer. All other authors have no relevant conflicts of interest to report., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: We have shown the Exercise for Cancer Patients (EXCAP ©® ) exercise program improved physical function and symptoms and reduced inflammatory markers in patients with cancer. However, adherence to exercise was lower in older adults compared to their younger counterparts. We then leveraged a mobile app to deliver EXCAP ©® and adapted the intervention [Geriatric-Oncology (GO)-EXCAP] for older patients with myeloid neoplasms. In this pilot randomized trial, the primary goal is to determine effect sizes. We propose to assess the preliminary efficacy of GO-EXCAP compared to a behavioral placebo control on physical function, patient-reported outcomes (fatigue, mood, and quality of life), and inflammatory markers in 100 patients aged ≥60 years with myeloid neoplasms receiving outpatient chemotherapy., Methods: GO-EXCAP consists of the EXCAP ©® exercise prescription (daily home-based progressive aerobic walking and resistance exercises with rated perceived exercise of 5-8), EXCAP ©® kit (i.e., activity tracker, resistance bands, print manual, bag), a mobile app, and an in-person or virtual session with the exercise physiologist to deliver exercise prescription. The intervention will last for three cycles of chemotherapy (approximately 12 weeks). The primary outcome measure will be physical function (Short Physical Performance Battery). Secondary outcome measures include fatigue (Brief Fatigue Inventory), mood (Center for Epidemiologic Studies Depression Scale), and quality of life (Functional Assessment of Cancer Therapy-Leukemia). Exploratory outcome measures include inflammatory markers., Discussion: Older adults with myeloid neoplasms receiving outpatient chemotherapy serve as an ideal model for studying an individually tailored mobile health exercise intervention in vulnerable older patients receiving cancer treatments to prevent physical function decline and improve symptoms., Competing Interests: Declaration of Competing Interest Dr. Loh has served as a consultant to Pfizer and Seattle Genetics, and has received honoraria from Pfizer. All other authors have no relevant conflicts of interest to report., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Older patients with myeloid neoplasms (MN) receiving outpatient chemotherapy are at risk of experiencing treatment-related toxicities such as functional decline. A mobile health (mHealth) exercise intervention may ameliorate these toxicities. This qualitative study aimed to inform the design of a mHealth exercise intervention for this population., Methods: This was a qualitative study of thirteen patients aged ≥60 years receiving hypomethylating agents for MN. EXCAP©® is a home-based walking and progressive resistance exercise program. We combined EXCAP©® with a mobile app; the combination (GO-EXCAP Mobile App) has not been previously tested. A brief verbal description about the intervention was provided to the participants but they did not perform it. Participants were interviewed and inductive thematic analysis was used to analyze the data., Results: Mean age was 71.6 (SD 8.5). Three themes were identified: 1) Perceptions of the intervention feasibility, 2) Ways to leverage the app to deliver the exercise intervention, and 3) Personalized exercise goals. Walking and resistance exercises were perceived to be feasible. Patients were comfortable initiating the intervention in cycle 2 of chemotherapy, with exercise increments occurring from week 2-4 of the cycle. Ways to leverage the app to deliver EXCAP©® include 1) Video feature for exercise demonstration and interactions, and 2) Exercise data and symptom surveys to be communicated to the exercise physiologist and primary oncology team. Preservation of existing function and activity was an important goal to participants., Conclusions: Our findings provide insights about the preferences of older adults with MN for a mHealth exercise intervention., Competing Interests: Declaration of Competing Interest Dr. Loh serves as a consultant to Pfizer and Seattle Genetics. Dr. Mohile received research funding from Carevive for other projects. All other authors have no relevant conflicts of interest to report., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Most cancers evolve over time as patients initially responsive to therapy acquire resistance to the same drugs at relapse. Cancer stem cells have been postulated to represent a therapy-refractory reservoir for relapse, but formal proof of this model is lacking. We prospectively characterized leukemia stem cell populations (LSCs) from a well-defined cohort of patients with acute myelogenous leukemia (AML) at diagnosis and relapse to assess the effect of the disease course on these critical populations. Leukemic samples were collected from patients with newly diagnosed AML before therapy and after relapse, and LSC frequency was assessed by limiting dilution analyses. LSC populations were identified using fluorescent-labeled cell sorting and transplantation into immunodeficient NOD/SCID/interleukin 2 receptor γ chain null mice. The surface antigen expression profiles of pretherapy and postrelapse LSCs were determined for published LSC markers. We demonstrate a 9- to 90-fold increase in LSC frequency between diagnosis and relapse. LSC activity at relapse was identified in populations of leukemic blasts that did not demonstrate this activity before treatment and relapse. In addition, we describe genetic instability and exceptional phenotypic changes that accompany the evolution of these new LSC populations. This study is the first to characterize the evolution of LSCs in vivo after chemotherapy, identifying a dramatic change in the physiology of primitive AML cells when the disease progresses. Taken together, these findings provide a new frame of reference by which to evaluate candidate AML therapies in which both disease control and the induction of more advanced forms of disease should be considered., (© 2016 by The American Society of Hematology.)

High BAALC expression levels are associated with poor outcome in cytogenetically normal acute myeloid leukemia (CN-AML) patients. Recently, miR-3151 was discovered in intron 1 of BAALC. To evaluate the prognostic significance of miR-3151 expression levels and to gain insight into the biologic and prognostic interplay between miR-3151 and its host, miR-3151 and BAALC expression were measured in pretreatment blood of 179 CN-AML patients. Gene-expression profiling and miRNA-expression profiling were performed using microarrays. High miR-3151 expression was associated with shorter disease-free and overall survival, whereas high BAALC expression predicted failure of complete remission and shorter overall survival. Patients exhibiting high expression of both miR-3151 and BAALC had worse outcome than patients expressing low levels of either gene or both genes. In gene-expression profiling, high miR-3151 expressers showed down-regulation of genes involved in transcriptional regulation, posttranslational modification, and cancer pathways. Two genes, FBXL20 and USP40, were validated as direct miR-3151 targets. The results of the present study show that high expression of miR-3151 is an independent prognosticator for poor outcome in CN-AML and affects different outcome end points than its host gene, BAALC. The combination of both markers identified a patient subset with the poorest outcome. This interplay between an intronic miR and its host may have important biologic implications.

Background: Given the significant activity and tolerability of gemcitabine in patients with relapsed Hodgkin's lymphoma (HL), the critical role that nuclear factor kappa B (NF-kappaB) appears to play in the pathogenesis of this tumor, the ability of bortezomib to inhibit NF-kappaB activity, and laboratory studies suggesting synergistic antitumor effects of gemcitabine and bortezomib, we hypothesized that this combination would be efficacious in patients with relapsed or refractory HL., Patients and Methods: A total of 18 patients participated. Patients received 3-week cycles of bortezomib 1 mg/m(2) on days 1, 4, 8, and 11 plus gemcitabine 800 mg/m(2) on days 1 and 8., Results: The overall response rate for all patients was 22% (95% confidence interval 3% to 42%). Three patients developed grade III transaminase elevation: one was removed from the study and two had doses of gemcitabine held. Almost all patients exhibited inhibition of proteasome activity with treatment., Conclusions: The combination of gemcitabine and bortezomib is a less active and more toxic regimen in relapsed HL than other currently available treatments. It poses a risk of severe liver toxicity and should be pursued with caution in other types of cancer.