Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges.

Importance Patients with acute myeloid leukemia (AML) receiving intensive chemotherapy experience substantial decline in their quality of life (QOL) and mood during their hospitalization for induction chemotherapy and often receive aggressive care at the end of life (EOL). However, the role of specialty palliative care for improving the QOL and care for this population is currently unknown. Objective To assess the effect of integrated palliative and oncology care (IPC) on patient-reported and EOL outcomes in patients with AML. Design, Setting, and Participants We conducted a multisite randomized clinical trial of IPC (n = 86) vs usual care (UC) (n = 74) for patients with AML undergoing intensive chemotherapy. Data were collected from January 2017 through July 2019 at 4 tertiary care academic hospitals in the United States. Interventions Patients assigned to IPC were seen by palliative care clinicians at least twice per week during their initial and subsequent hospitalizations. Main Outcomes and Measures Patients completed the 44-item Functional Assessment of Cancer Therapy–Leukemia scale (score range, 0-176) to assess QOL; the 14-item Hospital Anxiety and Depression Scale (HADS), with subscales assessing symptoms of anxiety and depression (score range, 0-21); and the PTSD Checklist–Civilian version to assess posttraumatic stress disorder (PTSD) symptoms (score range, 17-85) at baseline and weeks 2, 4, 12, and 24. The primary end point was QOL at week 2. We used analysis of covariance adjusting and mixed linear effect models to evaluate patient-reported outcomes. We used Fisher exact test to compare patient-reported discussion of EOL care preferences and receipt of chemotherapy in the last 30 days of life. Results Of 235 eligible patients, 160 (68.1%) were enrolled; of the 160 participants, the median (range) age was 64.4 (19.7-80.1) years, and 64 (40.0%) were women. Compared with those receiving UC, IPC participants reported better QOL (adjusted mean score, 107.59 vs 116.45;P = .04), and lower depression (adjusted mean score, 7.20 vs 5.68;P = .02), anxiety (adjusted mean score, 5.94 vs 4.53;P = .02), and PTSD symptoms (adjusted mean score, 31.69 vs 27.79;P = .01) at week 2. Intervention effects were sustained to week 24 for QOL (β, 2.35; 95% CI, 0.02-4.68;P = .048), depression (β, −0.42; 95% CI, −0.82 to −0.02;P = .04), anxiety (β, −0.38; 95% CI, −0.75 to −0.01;P = .04), and PTSD symptoms (β, −1.43; 95% CI, −2.34 to −0.54;P = .002). Among patients who died, those receiving IPC were more likely than those receiving UC to report discussing EOL care preferences (21 of 28 [75.0%] vs 12 of 30 [40.0%];P = .01) and less likely to receive chemotherapy near EOL (15 of 43 [34.9%] vs 27 of 41 [65.9%];P = .01). Conclusions and Relevance In this randomized clinical trial of patients with AML, IPC led to substantial improvements in QOL, psychological distress, and EOL care. Palliative care should be considered a new standard of care for patients with AML. Trial Registration ClinicalTrials.gov Identifier:NCT02975869

/pdf/effectiveness-of-integrated-palliative-and-oncology-care-for-3lq6u00od3.pdf

Effectiveness of Integrated Palliative and Oncology Care for Patients With Acute Myeloid Leukemia: A Randomized Clinical Trial.

Acute myeloid leukemia (AML) is a costly disease, and its impact is greater in developing countries (DC). We will review the current concept of what are DC, compare the differences in the epidemiology and economic burden of this disease between developed and DC, and finally, analyze the barriers and possible solutions that DC should implement to achieve better results. DC is a frequently misunderstood name. The way we use to measure human development is changing, and multidimension metrics better define what are DC. With this in mind, we show the differences in the AML epidemiology and the impact of economic burden in DC. We analyze the barriers to access therapy from a clinician point of view, to show that most DC shared similar challenges but with a diverse healthcare structure. Finally, we provide several possible solutions for a more integrated and timely treatment that allows better results not only in terms of survival but with a better quality of life. The economic burden of AML treatment in DC is high, and the results are poor. It is crucial to face this challenge and propose new treatment approaches to achieve better results.

/pdf/access-to-therapy-for-acute-myeloid-leukemia-in-the-2emwigmocx.pdf

Access to Therapy for Acute Myeloid Leukemia in the Developing World: Barriers and Solutions.

Abnormal expression of microRNA (miR)-21 has been reported in various types of cancers. However, the role and mechanism of miR-21 remain to be elucidated in acute myeloid leukemia (AML). In the present study, it was observed that miR-21 was upregulated and Kruppel-like factor 5 (KLF5) was downregulated in AML cells compared with normal bone marrow cells. Dual luciferase reporter assays revealed that KLF5 was a direct target of miR-21. Indeed, miR-21 overexpression resulted in a downregulation of KLF5 expression, while miR-21 inhibition had the opposite effect in AML cells. In addition, miR-21 overexpression promoted the proliferation of AML cells in vitro. Notably, using a mouse xenograft model, miR-21 overexpression was demonstrated to result in enhanced tumor growth and suppressed KLF5 expression in the xenograft tumors in vivo. In conclusion, the present results indicated that miR-21 promoted proliferation through directly regulating KLF5 expression in AML cells. miR-21 may thus serve as an oncogene in AML, providing a potential target for AML therapy.

/pdf/microrna-21-promotes-proliferation-in-acute-myeloid-leukemia-3efwt202yz.pdf

MicroRNA-21 promotes proliferation in acute myeloid leukemia by targeting Krüppel-like factor 5.

Acute myeloid leukemia (AML) is a very heterogeneous group of disorders with large differences in the percentage of immature blasts that presently are classified according to the specific mutations that trigger malignant proliferation among thousands of mutations reported thus far. It is an aggressive disease for which few targeted therapies are available and still has a high recurrence rate and low overall survival. The main reason for AML relapse is believed to be due to leukemic stem cells (LSCs) that have unlimited self-renewal capacity and long residence in a quiescent state, which promote greater resistance to traditional therapies for this cancer. AML LSCs have low oxidative stress levels, which appear to be caused by a combination of low mitochondrial activity and high activity of ROS-removing pathways. In this sense, oxidative stress has been thought to be an important new potential target for the treatment of AML patients, targeting the eradication of AML LSCs. The aim of this review is to discuss some drugs that induce oxidative stress to direct new goals for future research focusing on redox imbalance as an effective strategy to eliminate AML LSCs. 

Emerging drugs targeting cellular redox homeostasis to eliminate acute myeloid leukemia stem cells.

Systematic reviews of economic burden and health-related quality of life in patients with acute myeloid leukemia

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Systematic reviews of economic burden and health-related quality of life in patients with acute myeloid leukemia