Geriatric assessment and survival among older adults receiving postremission therapy for acute myeloid leukemia.
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ABSTRACT:
SUBMITTER: Saad M
PROVIDER: S-EPMC7735162 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The incidence of acute myeloid leukemia (AML) increases with age, but the outcomes for older adults with AML are poor due to underlying tumor biology, poor tolerance to aggressive treatment, and the physiologic changes of aging. Because of the underlying heterogeneity in health status, treatment decisions are difficult in this population. A geriatric assessment (GA) refers to the use of various validated tools to assess domains that are important in older adults including physical function, cognition, comorbidities, polypharmacy, social support, and nutritional status. In older patients with cancer, a GA can guide treatment decision-making, predict treatment toxicity, and guide supportive care interventions. Compared to solids tumors, there is a relative lack of studies evaluating the use of a GA in older patients with AML. In this review, we will discuss the principles, common domains, feasibility, and benefits of GA, with a focus on older patients with AML that includes practical applications for clinical management.
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Project description:Acute myeloid leukemia (AML) presents therapeutic challenges in older adults because of high-risk leukemia biology conferring chemoresistance, and poor functional status resulting in increased therapy-related toxicities. Recent FDA approval of 8 new drugs for AML has increased therapeutic armamentarium and also provides effective low-intensity treatment options. Rational therapy selection strategies that consider individual's risk of therapy-related toxicities and probability of disease control can maximize benefits of available treatments. Studies have demonstrated that fitness level, measured by geriatric assessment can predict therapy-related toxicities, whereas cytogenetic and mutation results correlate with the probability of responses to standard chemotherapy. We are approaching an era when we move from "one size fits all" approach to personalized therapy selection based on geriatric assessment, genetic and molecular profiling.
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Project description:ObjectivesTo investigate changes in inflammatory biomarkers during induction therapy for older adults with acute myeloid leukemia (AML) and their associations with geriatric assessment (GA) measures and outcomes.MethodsThis was a single institution ancillary study to a prospective observational study (N = 20 consecutive adults aged ≥60 with newly diagnosed AML who received induction chemotherapy). Biomarkers (Interleukin-6 [IL-6], IL-6 soluble receptor [IL-6 sR], tumor necrosis factor alpha [TNFα], TNFα soluble receptor 1 [TNFα sR1], interleukin-3 [IL-3], C-reactive protein [CRP]) were collected at start of induction, weekly for three weeks, and post-induction and were compared over time using paired t-tests. GA was administered at baseline and post-induction, and correlated with biomarker levels using Spearman correlations. Survival was estimated using Kaplan-Meier and compared by categorized biomarker level using Wilcoxon tests.ResultsBiomarker levels were stable during induction, except for CRP and IL-6 sR. Declines in objectively measured physical function [Short Physical Performance Battery (SPPB); r = 0.71, p < 0.01] and increases in self-reported limitation in instrumental activities of daily living (r = 0.81, p < 0.01) were correlated with increased TNFα sR1. Declines in SPPB were correlated with increased CRP (r = -0.73, p < 0.01). Improvement in depression was correlated with increased IL-6 sR (r = -0.59 p = 0.02). Survival was shorter in those with baseline TNFα or CRP levels above the median (6.1 vs. 40.2 months and 5.5 vs. 27.6 months respectively, p = 0.04 for both).ConclusionAmong older adults with AML, the relationships between TNFα sR1, CRP, and IL-6 sR with change in physical and emotional health during treatment warrants further investigation.
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Project description:Acute myeloid leukemia (AML) most commonly affects patients older than 60 years. Outcomes of treatment of older AML patients have been poor. The advent of reduced-intensity conditioning (RIC) regimens made allogeneic hematopoietic cell transplantation (HCT) an available treatment option with curative intent for older AML patients. Because older patients are often excluded from clinical trials, little is known about the stratification of their risks before allogeneic HCT. While recent studies of RIC and allogeneic HCT have shown little impact of age on outcomes, other variables such as the recipient health status and the AML disease status and chromosomal aberrations have proven to be of prognostic significance. Here, the authors review recent studies of allogeneic HCT for older patients with AML with detailed evaluation of risk factors for relapse as well as non-relapse mortality. The authors have integrated the currently available information on transplant risks into a five-category risk-benefit system that could aid in the decision-making in this patient population.
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Project description:We summarize recent advances for acute myeloid leukemia (AML) in older patients, with a focus on immunotherapeutics. Although the recently updated US SEER data still show that the majority of older AML patients do not receive any therapy, this reality is slowly changing. Advances in our understanding of the biology of AML and in the field of immunology are facilitating the development of alternative therapeutic options for patients, affording more and novel opportunities for potentially curative treatment.Data from multiple cooperative groups show that older patients benefit from the incorporation of gemtuzumab ozogamicin, an anti-CD33 mAb toxin, into induction regimens. The first prospective study for reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation in older AML patients was reported at the American Society of Hematology Annual Meeting, 2012; the approach was feasible and improved disease-free survival over conventional chemotherapy. Proof-of-concept trials targeting specific antigens such as WT1 or novel unique leukemia-associated antigens are currently underway, as well as other trials using chimeric antigen receptor T cells or (natural killer/effector cells in nontransplantation settings.Wider application of immunotherapies such as allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning have altered the landscape and offer potential for cure of an increasing number of older AML patients.
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Project description:Anthracyclines constitute the backbone of intensive adult acute myeloid leukemia (AML) therapy. Cardiotoxicity is one of its most serious adverse effects, and its incidence increases with cumulative dose. Dexrazoxane is a cardioprotective agent used in conjunction with anthracycline therapy. There is limited data of its usage in adult AML patients. We report the outcomes of six older adults at high risk of anthracycline-induced cardiotoxicity who received dexrazoxane during induction/re-induction therapy. Five had preserved left-ventricular function while two proceeded onto stem-cell transplantation. Additional investigation of dexrazoxane in adult leukemia therapy is warranted, particularly in older patients at highest risk for cardiovascular mortality.
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Project description:The patient´s survival estimate is important for clinical decision-making, especially in frail patients with multimorbidities. We aimed to develop a multidimensional geriatric prognosis index (GPI) for 3- and 5-year mortality in community-dwelling elderly and to validate the GPI in a separate hospital-based population. The GPI was constructed using data for 988 participants in the Korean Longitudinal Study on Health and Aging (KLoSHA) and cross-validated with 1109 patients who underwent a geriatric assessment at the Seoul National University Bundang Hospital (SNUBH). The GPI, with a total possible score of 8, included age, gender, activities of daily living, instrumental activities of daily living, comorbidities, mood, cognitive function, and nutritional status. During the 5-year observation period, 179 KLoSHA participants (18.1%) and 340 SNUBH patients (30.7%) died. The c-indices for 3- and 5-year mortality were 0.78 and 0.80, respectively, in the KLoSHA group and 0.73 and 0.80, respectively, in the SNUBH group. Positive linear trends were observed for GPI scores and both 3- and 5-year mortality in both groups. In conclusions, using common components of a geriatric assessment, the GPI can stratify the risk of 3- and 5-year mortality in Korean elderly people both in the community and hospital.
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Project description:Relapse is a major problem in acute myeloid leukemia (AML) and adversely affects survival. In this phase 2 study, we investigated the effect of vaccination with dendritic cells (DCs) electroporated with Wilms' tumor 1 (WT1) messenger RNA (mRNA) as postremission treatment in 30 patients with AML at very high risk of relapse. There was a demonstrable antileukemic response in 13 patients. Nine patients achieved molecular remission as demonstrated by normalization of WT1 transcript levels, 5 of which were sustained after a median follow-up of 109.4 months. Disease stabilization was achieved in 4 other patients. Five-year overall survival (OS) was higher in responders than in nonresponders (53.8% vs 25.0%; P = .01). In patients receiving DCs in first complete remission (CR1), there was a vaccine-induced relapse reduction rate of 25%, and 5-year relapse-free survival was higher in responders than in nonresponders (50% vs 7.7%; P < .0001). In patients age ?65 and >65 years who received DCs in CR1, 5-year OS was 69.2% and 30.8% respectively, as compared with 51.7% and 18% in the Swedish Acute Leukemia Registry. Long-term clinical response was correlated with increased circulating frequencies of polyepitope WT1-specific CD8+ T cells. Long-term OS was correlated with interferon-?+ and tumor necrosis factor-?+ WT1-specific responses in delayed-type hypersensitivity-infiltrating CD8+ T lymphocytes. In conclusion, vaccination of patients with AML with WT1 mRNA-electroporated DCs can be an effective strategy to prevent or delay relapse after standard chemotherapy, translating into improved OS rates, which are correlated with the induction of WT1-specific CD8+ T-cell response. This trial was registered at www.clinicaltrials.gov as #NCT00965224.
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Project description:BACKGROUND/OBJECTIVES:The incidence of myeloma in older adults is increasing, yet little is known about geriatric impairments in these patients. We aimed to examine the prevalence of geriatric impairments in older adults with myeloma and the association between geriatric assessment and autologous stem cell transplant eligibility. DESIGN:Prospective cohort study. SETTING:Two academic medical centers. PARTICIPANTS:A total of 40 adults 65 years and older with newly diagnosed myeloma were enrolled. MEASUREMENT:Participants completed a primarily self-administered geriatric assessment, including measures of functional status, comorbidities, polypharmacy, psychosocial status, social support, quality of life, cognition, and physical performance. Outcomes were autologous stem cell transplant eligibility and receipt. RESULTS:Forty patients enrolled; their mean age was 71 years. Geriatric impairments were common: 62% reported dependence in one or more instrumental activities of daily living (IADL), 76.9% had polypharmacy (four or more medications), and 47.5% had one or more comorbidities. Median time on the Timed Up and Go was 13.3 ± 4.9 seconds. Those considered candidates for autologous stem cell transplant (N = 26) were younger, with fewer comorbidities, better performance status, and faster performance on the Timed Up and Go test. Factors independently associated with receiving autologous stem cell transplant (N = 21) included age and IADL dependence. CONCLUSION:Impairments in geriatric domains are common in this population, even among those considered to have a good performance status. Geriatric assessment domains are associated with both transplant eligibility and receipt. J Am Geriatr Soc 67:987-991, 2019.
| S-EPMC7006442 | biostudies-literature
Project description:BackgroundControversy exists regarding the optimal chemotherapy regimen for older adults with acute myeloid leukemia (AML).Patients and methodsWe analyzed data from the US National Cancer Data Base of 25,621 patients aged 60 to 79 years, with a diagnosis of AML from 2004 to 2014, who had received single-agent versus multiagent chemotherapy. A Cox proportional hazard model was used for overall survival (OS) analysis for the entire study cohort and separately for patients who had received single-agent (n = 6743) versus multiagent (n = 6743) chemotherapy, matched for age, Charlson comorbidity index, and AML subtype.ResultsThe use of multiagent chemotherapy was high overall (70%) but declined with factors, such as increasing age, Charlson comorbidity index, AML subtype other than good risk, academic center, lower rate of high school graduation, and more recent year of diagnosis. Patients treated with multiagent chemotherapy had greater 1-year OS (43% vs. 28%), especially for patients aged 60 to 69 years and those with good-risk AML or Charlson comorbidity index of 0 to 1. OS (hazard ratio, 1.32; 95% confidence interval, 1.28-1.36) remained more favorable for the multiagent chemotherapy group on multivariable analysis. This was confirmed in a matched cohort analysis.ConclusionsTo the best of our knowledge, this is the largest real-world study that has demonstrated an association between factors such as age, comorbidity, and AML subtype and the use of multiagent chemotherapy. The use of multiagent chemotherapy was associated with improved OS, especially for patients aged <70 years, those with good-risk AML, and those with a low Charlson comorbidity index.
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