Myeloid Toxicity of Cancer Treatment

Kurtin, Sandra

doi:10.6004/jadpro.2012.3.4.2

Cited by 26 publications

(12 citation statements)

References 49 publications

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“…Younger patients maintained stricter behavioral practices during active cancer therapy, possibly re ecting a greater proportion of patients with haematological diseases, a population often treated with bone marrow transplants and highly myelosuppressive regimens. These patients have deeper and longer durations of neutropenia, associated with protocols with higher myelotoxic potential 11 , possibly accounting for the strict daily practices adopted by this patient population.…”

Section: Discussionmentioning

confidence: 99%

Real-world behavioral practices of cancer patients: time to shift from health related-QoL to real-life-QoL

Shachar,

Peleg-Hasson,

Vorobiof

et al. 2023

Preprint

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Background Health-related quality of life (HR-QoL) is an assessments tool commonly used as an endpoint in clinical trials. While it evaluates the presence of various symptoms, it does not measure patients’ ability to maintain normal daily activities during cancer therapy. We designed a real-life quality of life (RL-QoL) tool, validated among a cohort of actively treated cancer patients at a single cancer center prior to the COVID-19 pandemic. Using this tool we discovered that most patients reported compromised daily activities. In this study we aimed to examine RL-QoL in an international cohort of patients. Methods A locally validated questionnaire was distributed internationally using the Belong.life digital health platform. We examined real-world patient reported practices, provided by patients voluntarily and anonymously. The survey consisted of demographic, clinical, behavioral parameters and sources guiding and supporting patient practices. Independent clinical and demographic variables were analyzed, and a multivariate logistic regression was performed identifying factors predicting restrictive behavior. Results The study comprised 1,395 patient reported outcomes. Most respondents were from the United Stated (1142, 78.43%), 225 (15.45%) from Israel, and a minority (89, 6.11%) from other countries. The majority of participants (1,005, 72.88%) reported at least one adopted limitation in daily activities, and 305 (21.86%) maintained more than half of these constraints. Daily life restrictions included avoiding sun exposure (779, 57.83%), international travel (417, 33.33%), indoor public places (431, 33.13%), hair dyeing (271, 22.72%), domestic tourism (284, 21.93%), contact with friends and family (231, 17.69%), children and grandchildren (202, 16.33%), outdoor public spaces (190, 14.62%), and contact with pets (135, 10.41%). Multiple sources were implicated by patients guiding their behavior, including health-care professionals (951, 65.95%), non-medical authorities including the internet, patient forums, partners, friends, and family (171, 11.86%), and both non-medical authorities and the health-care team (320, 22.19%). There was no association between country of origin (p=0.118), and education level (p=0.3591) across patients who maintained strict (≥50% of the limitations) and less strict restrictions (<50% of the limitations). A significant association was noted between younger age (p=0.0014), female sex (p=0.0141) and primary cancer site (p<0.0001), and the adoption of strict restrictions. Conclusion The majority of patients globally reported compromised daily activities, which are likely attributed to misconceptions about therapy and disease. These findings call for the assessment of an overlooked measure, RL-QoL, as an additional endpoint of clinical trials, aiming to achieve the ultimate benefit for our patients, a measure of a full and meaningful life.

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Section: Discussionmentioning

confidence: 99%

Real-world behavioral practices of cancer patients: time to shift from health related-QoL to real-life-QoL

Shachar,

Peleg-Hasson,

Vorobiof

et al. 2023

Preprint

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“…Bone marrow toxicity, i.e. hemato-or myelotoxicity, are often the dose-limiting side effects of chemotherapy [54]. However, so far surprisingly little attention has been paid to the development of systems to reliably predict such toxicities in vitro.…”

Section: Discussionmentioning

confidence: 99%

A parallelized, perfused 3D triculture model of leukemia for in vitro drug testing of chemotherapeutics

et al. 2022

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Leukemia patients undergo chemotherapy to combat the leukemic cells (LCs) in the bone marrow. During therapy not only the LCs, but also the blood-producing hematopoietic stem and progenitor cells (HSPCs) may be destroyed. Chemotherapeutics targeting only the LCs are urgently needed to overcome this problem and minimize life-threatening side-effects. Predictive in vitro drug testing systems allowing simultaneous comparison of various experimental settings would enhance the efficiency of drug development. Here, we present a 3D human leukemic bone marrow model perfused using a magnetic, parallelized culture system to ensure media exchange. Chemotherapeutic treatment of the acute myeloid leukemia cell line KG-1a in 3D magnetic hydrogels seeded with mesenchymal stem/stromal cells (MSCs) revealed a greater resistance of KG-1a compared to 2D culture. In 3D tricultures with HSPCs, MSCs and KG-1a, imitating leukemic bone marrow, HSPC proliferation decreased while KG-1a cells remained unaffected post treatment. Non-invasive metabolic profiling enabled continuous monitoring of the system. Our results highlight the importance of using biomimetic 3D platforms with proper media exchange and co-cultures for creating in vivo-like conditions to enable in vitro drug testing. This system is a step towards drug testing in biomimetic, parallelized in vitro approaches, facilitating the discovery of new anti-leukemic drugs.

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“…Neutropenia of grade 3 or 4 ( table 1 ) at two consecutive study visits up to day 14 or thrombocytopenia of grade 3 or 4 ( table 1 ) at two consecutive study visits up to day 14 accompanied by neutropenia or thrombocytopenia of grade 2, 3 or 4 at both study visits and accompanied by an IPF below 2.5% at one or two of the consecutive study visits ( figure 2 ). 31 …”

Section: Methods and Analysismentioning

confidence: 99%

Epirubicin for the Treatment of Sepsis and Septic Shock (EPOS-1): study protocol for a randomised, placebo-controlled phase IIa dose-escalation trial

Thomas-Rüddel,

Bauer,

Moita

et al. 2024

BMJ Open

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IntroductionSepsis remains the major cause of death among hospitalised patients in intensive care. While targeting sepsis-causing pathogens with source control or antimicrobials has had a dramatic impact on morbidity and mortality of sepsis patients, this strategy remains insufficient for about one-third of the affected individuals who succumb. Pharmacological targeting of mechanisms that reduce sepsis-defining organ dysfunction may be beneficial. When given at low doses, the anthracycline epirubicin promotes tissue damage control and lessens the severity of sepsis independently of the host–pathogen load by conferring disease tolerance to infection. Since epirubicin at higher doses can be myelotoxic, a first dose–response trial is necessary to assess the potential harm of this drug in this new indication.Methods and analysisEpirubicin for the Treatment of Sepsis and Septic Shock-1 is a randomised, double-blind, placebo-controlled phase 2 dose-escalation phase IIa clinical trial to assess the safety of epirubicin as an adjunctive in patients with sepsis. The primary endpoint is the 14-day myelotoxicity. Secondary and explorative outcomes include 30-day and 90-day mortality, organ dysfunction, pharmacokinetic/pharmacodynamic (PK/PD) and cytokine release. Patients will be randomised in three consecutive phases. For each study phase, patients are randomised to one of the two study arms (epirubicin or placebo) in a 4:1 ratio. Approximately 45 patients will be recruited. Patients in the epirubicin group will receive a single dose of epirubicin (3.75, 7.5 or 15 mg/m2depending on the study phase. After each study phase, a data and safety monitoring board will recommend continuation or premature stopping of the trial. The primary analyses for each dose level will report the proportion of myelotoxicity together with a 95% CI. A potential dose-toxicity association will be analysed using a logistic regression model with dose as a covariate. All further analyses will be descriptive.Ethics and disseminationThe protocol is approved by the German Federal Institute for Drugs and Medical Devices. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT05033808.

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Myeloid Toxicity of Cancer Treatment

Cited by 26 publications

References 49 publications

Real-world behavioral practices of cancer patients: time to shift from health related-QoL to real-life-QoL

Real-world behavioral practices of cancer patients: time to shift from health related-QoL to real-life-QoL

A parallelized, perfused 3D triculture model of leukemia for in vitro drug testing of chemotherapeutics

Epirubicin for the Treatment of Sepsis and Septic Shock (EPOS-1): study protocol for a randomised, placebo-controlled phase IIa dose-escalation trial

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