Acute myeloid leukemia in the elderly (age 70 yr or older): long‐term survivors

Heiblig, Maël; Elhamri, Mohamed; Jeune, Caroline Le; Laude, Marie-Charlotte; Deloire, Alexandre; Wattel, Éric; Salles, Gilles; Thomas, Xavier

doi:10.1111/ejh.12811

Cited by 8 publications

(4 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analyses showed that patient age and risk category were significantly related to survival status. Previous studies have demonstrated that elderly patients have poorer AML outcomes, partly due to their poorer tolerance to chemotherapy treatment and their reluctance to accept intensive regimens [20, 21]. Our results also showed that the percentage of living patients was remarkably lower in the older group than in the younger group.…”

Section: Discussionsupporting

confidence: 63%

Selection of three miRNA signatures with prognostic value in non-M3 acute myeloid leukemia

Xue

Kang

et al. 2019

BMC Cancer

View full text Add to dashboard Cite

Background MiRNAs that are potential biomarkers for predicting prognosis for acute myeloid leukemia (AML) have been identified. However, comprehensive analyses investigating the association between miRNA expression profiles and AML survival remain relatively deficient. Method In the present study, we performed multivariate Cox’s analysis and principal component analysis (PCA) using data from The Cancer Genome Atlas (TCGA) to identify potential molecular signatures for predicting non-M3 AML prognosis. Result We found that patients who were still living were significantly younger at diagnosis than those who had died ( P = 0.001). In addition, there was a marked difference in living status among different risk category groups ( P = 0.022). A multivariate Cox model suggested that three miRNAs were potential biomarkers of non-M3 AML prognosis, including miR-181a-2, miR-25 and miR-362. Subsequently, PCA analyses were conducted to comprehensively represent the expression levels of these three miRNAs in each patient with a PCA value. According to the log-rank test, AML outcome for patients with lower PCA values was significantly different from those with higher PCA values ( P < 0.001). Further bioinformatic analysis revealed the biological functions of the selected miRNAs. Conclusion We conducted a comprehensive analysis of TCGA non-M3 AML data, identifying three miRNAs that are significantly correlated with AML survival. PCA values for the identified miRNAs are valuable for predicting AML prognosis. Electronic supplementary material The online version of this article (10.1186/s12885-019-5315-z) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionsupporting

confidence: 63%

Selection of three miRNA signatures with prognostic value in non-M3 acute myeloid leukemia

Xue

Kang

et al. 2019

BMC Cancer

View full text Add to dashboard Cite

show abstract

“…Higher incidence of negative prognostic factors connected with AML at an older age makes this disease difficult to cure 1,2 . Increasing risk of treatment‐related mortality is the reason why only less than half of the newly diagnosed patients aged 65 years or above are treated with a curative intent 2–4 . Despite the conventional induction chemotherapy consisting of combination of cytarabine with anthracycline antibiotic or with anthracenedione in its modification, the outcomes with remission rates 40%–50%, a median overall survival (OS) of less than 1 year and a 2‐year OS of less than 20% are much worse than in a younger patient population 1–6 .…”

Section: Introductionmentioning

confidence: 99%

How to select older patients with acute myeloid leukemia fit for intensive treatment?

Šustková

Semerád

Weinbergerová

et al. 2020

Hematological Oncology

View full text Add to dashboard Cite

Outcomes of the treatment of older patients with acute myeloid leukemia (AML) are unsatisfactory due to a higher incidence of negative patient‐ and disease‐related risk factors connected with aging. Prediction of poor tolerance to aggressive treatment and low response to standard intensive chemotherapy are the main root causes why the treatment decision is challenging. For a long time, negative prognostic factors for treatment outcomes, overall survival, and early death such as the age itself, low‐performance status, high‐comorbidity burden, adverse cytogenetics, and secondary AML have been known, and they are routinely taken into account during therapeutic balance. In consideration of the risk factors and specific laboratory results, prognostic models have been created. Despite the abovementioned facts, the survival of older patients with AML remains very poor, that holds true even for the intensive therapy. For that reason, there is an increased effort to find a better approach how to select patients who would benefit from intensive treatment without decreasing their quality of life through severe complications with risk of high treatment‐related mortality. Based on the results of clinical studies, the geriatric assessment could be the missing step which would help select older patients who are really fit for intensive treatment and who will benefit from it the most. This review focuses on the risk factors that should be taken under advisement when the decision about the treatment is made. With reference to the published information, we propose an algorithm how to identify fit, vulnerable, and frail patients.

show abstract

“…Age is a fundamental risk factor, with median overall survival (OS) <6 months for elderly patients with AML receiving intensive therapy [1]. Several measurable and immeasurable factors, including poor performance status, adverse cytogenetics, genetic mutations, and complications, are responsible for poor prognosis [2][3][4][5].DNA methylation has been demonstrated to silence tumor suppressor transcription, contributing to the occurrence of hematopoietic disease [6]. Synthesized in the 1960s, the hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) play a role in reactivating the silenced genes and inducing the differentiation of leukemia cells [7,8].…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Combination Therapies of Hypomethylating Agents for Elderly Patients with Acute Myeloid Leukemia

Huang

Yun

Shen

2018

Acta Haematologica Polonica

View full text Add to dashboard Cite

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy, characterized by abnormal proliferation of progenitor cells. Age is a fundamental risk factor, with median overall survival (OS) <6 months for elderly patients with AML receiving intensive therapy [1]. Several measurable and immeasurable factors, including poor performance status, adverse cytogenetics, genetic mutations, and complications, are responsible for poor prognosis [2][3][4][5].DNA methylation has been demonstrated to silence tumor suppressor transcription, contributing to the occurrence of hematopoietic disease [6]. Synthesized in the 1960s, the hypomethylating agents (HMAs) azacitidine (AZA) and decitabine (DAC) play a role in reactivating the silenced genes and inducing the differentiation of leukemia cells [7,8]. Treatment with AZA or DAC in elderly patients with AML was investigated in clinical trials. Through the analysis in patients with low bone marrow blast count (20%-30%) receiving AZA 75 mg/m 2 or a conventional care regimen (CCR) [best supportive care (BSC), low-dose cytarabine, or intensive chemotherapy], an improved OS (24.5 versus 16 months) and similar morphologic complete remission (CR) (18% versus 16%) were confirmed in the AZA arm [9]. A survival advantage was also obtained from the AZA-AML-001 study, designed for elderly patients with AML with blasts of > 30% (10.4 versus 6.5 months) [10]. DAC given at 15 mg/m 2 /8 h for 3 consecutive days showed a relatively higher CR rate (15% versus 0%) but nondifferential OS (8 versus 6 months) when compared to BSC [11].Another dosage, which was defined as 20 mg/m 2 for 5 days, resulted in 17.8% CR, compared to 7.8% with BSC or low-dose cytarabine, and a modest 2-month improvement of the median OS (7.7 versus 5.5 months) [12]. In all mentioned studies, the CR rate ranged from 15% to 20% using either of the administration schedule. Therefore, appropriate combination therapies of HMAs have been initiated.In this review, we evaluated the safety and efficacy of combined regimens in the treatment of elderly patients with AML. Combined with chemotherapyIn a previous in vitro experiment, Neil et al. [13] suggested a synergistic effect of cytarabine (Ara-C) and AZA in L210 leukemic mice. This might be due to deoxycytidine kinase (dCK) inactivity related to Ara-C resistance. AZA was shown to induce dCK, phosphorylating Ara-C to its active compound Ara-CTP and restoring cell sensitivity toward Ara-C [14]. Standard induction chemotherapy in elderly patients with AML remains a "3+7" regimen characterized by the combination of intermediate-dose Ara-C administered for 7 days with an anthracycline for 3 days. Two randomized studies investigated AZA in conjunction with DA for treatment of elderly patients with AML in vivo.A pilot study aimed at elderly de novo AML patients with a leukocyte count of < 20,000/µl revealed a CR rate of 50% and median OS of 8.8 months [15]. However, large sample data from the AML-AZA trial failed to demonstrate favorable results, with nonsignificant shorter OS in ...

show abstract

Acute myeloid leukemia in the elderly (age 70 yr or older): long‐term survivors

Abstract: Improved results should come from a better selection of patients to a more 'personalized' therapeutic approach combined with better supportive care assessment.

Cited by 8 publications

References 47 publications

Selection of three miRNA signatures with prognostic value in non-M3 acute myeloid leukemia

Selection of three miRNA signatures with prognostic value in non-M3 acute myeloid leukemia

How to select older patients with acute myeloid leukemia fit for intensive treatment?

Combination Therapies of Hypomethylating Agents for Elderly Patients with Acute Myeloid Leukemia

Contact Info

Product

Resources

About