Azacitidine in the treatment of older patients affected by acute myeloid leukemia: A report by the Rete Ematologica Pugliese (REP)

Delia, Mario; Carluccio, Paola; Buquicchio, Caterina; Vergine, Carolina; Greco, Gianpiero; Amurri, B; Melpignano, Angela; Melillo, Lorella; Cascavilla, Nicola; Giacosa, Attilio; Capalbo, Silvana; Tarantini, Giuseppe; Mazza, Patrizio; Pavone, Vincenzo; Renzo, Nicola Di; Specchia, Giorgina

doi:10.1016/j.leukres.2015.08.005

Cited by 5 publications

(6 citation statements)

References 32 publications

(39 reference statements)

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“…29,56,[60][61][62][63][64][65][66][67][68][69][70][71][72] High-quality evidence showed that the risk of death was 1.72 times higher when patients with worse performance status (ECOG score of 21) were compared with those with better performance status (ECOG score of ,2) (HR [95% confidence interval], 1.72 [1.47-2.01]). 60,64,[73][74][75][76][77][78][79][80][81][82][83]123 There was also high-quality evidence showing that the risk of death was 1.59 times higher when patients with more comorbidities (HCT-CI score of 31) were compared with those with fewer comorbidities (HCT-CI score of ,3) (HR [95% confidence interval], 1.59 [1.28-1.98]). 54,84 Studies in which researchers assessed these associations using other methods for measuring the variables suggested similar increases in the risk of death.…”

Section: Prognosis In Older Adults With Amlmentioning

confidence: 99%

American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

et al. 2020

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Background: Older adults with acute myeloid leukemia (AML) represent a vulnerable population in whom disease-based and clinical risk factors, patient goals, prognosis, and practitioner- and patient-perceived treatment risks and benefits influence treatment recommendations. Objective: These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about management of AML in older adults. Methods: ASH formed a multidisciplinary guideline panel that included specialists in myeloid leukemia, geriatric oncology, patient-reported outcomes and decision-making, frailty, epidemiology, and methodology, as well as patients. The McMaster Grading of Recommendations Assessment, Development and Evaluation (GRADE) Centre supported the guideline-development process, including performing systematic evidence reviews (up to 24 May 2019). The panel prioritized clinical questions and outcomes according to their importance to patients, as judged by the panel. The panel used the GRADE approach, including GRADE’s Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. Results: The panel agreed on 6 critical questions in managing older adults with AML, mirroring real-time practitioner-patient conversations: the decision to pursue antileukemic treatment vs best supportive management, the intensity of therapy, the role and duration of postremission therapy, combination vs monotherapy for induction and beyond, duration of less-intensive therapy, and the role of transfusion support for patients no longer receiving antileukemic therapy. Conclusions: Treatment is recommended over best supportive management. More-intensive therapy is recommended over less-intensive therapy when deemed tolerable. However, these recommendations are guided by the principle that throughout a patient’s disease course, optimal care involves ongoing discussions between clinicians and patients, continuously addressing goals of care and the relative risk-benefit balance of treatment.

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Section: Prognosis In Older Adults With Amlmentioning

confidence: 99%

American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

et al. 2020

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“…De la Fuente reported that age greater than 80 years, ECOG status 2, adverse cytogenetic markers, bone marrow blasts greater than 30.0%, and high levels of pretreatment white blood cells were predictive of lower OS in the study population. 12 In a second noncomparative study by Delia et al, 13 median OS was 23 months in patients whose disease responded to azacitidine treatment versus 6 months in patients whose disease did not respond to therapy. Garcia-Manero et al 14 found that the 1-year OS among patients receiving azacitidine plus pracinostat was 60%; median OS was not reached in the overall population nor in the subpopulations of interest (patients with highrisk cytogenetics, AML as a result of myelodysplastic syndromes, or patients who had received prior anticancer therapy).…”

Section: Outcomes Associated With Azacitidine Treatment In Aml Patienmentioning

confidence: 98%

“…CR rates of 46% and 42% were reported. 13,14 Safety. Three studies assessed the safety of azacitidine for AML patients aged 60 years or older.…”

Section: Response Ratesmentioning

confidence: 99%

“…The AEs that were most often associated with azacitidine were febrile neutropenia (28.0%), thrombocytopenia (23.7%), and pneumonia (19.1%). In a retrospective study assessing the effectiveness of azacitidine, 13 commonly reported AEs (of any grade) included febrile neutropenia (21.0%) and infection (13.0%). In the same study, myelosuppression (31.0%) was the highest reported grade 3/4 AE, while grade 3/4 neutropenia, thrombocytopenia, and pancytopenia each occurred in less than 10.0% of patients.…”

Section: Response Ratesmentioning

confidence: 99%

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Effectiveness and Safety of Therapeutic Regimens for Elderly Patients With Acute Myeloid Leukemia: A Systematic Literature Review

Bell

Galaznik

Huelin

et al. 2018

Clinical Lymphoma Myeloma and Leukemia

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Acute myeloid leukemia (AML) is the second most common leukemia among adults. Although the median age at diagnosis is 67 years, with approximately one third of patients aged 75 years or older, limited treatment options exist for the elderly, who have 5-year survival rates of only 5%. A systematic review was conducted to examine effectiveness and safety outcomes of treatment regimens in elderly (≥60 years old) patients with AML. Published literature on the topic was scant, and the review included only 22 articles examining outcomes. Twelve studies examined treatment-specific outcomes; most of these examined azacitidine or intensive chemotherapy (IC). An international randomized controlled trial found that azacitidine significantly improved overall survival relative to conventional regimens including IC and low-dose cytarabine in patients aged > 65 years. Similar results in favor of azacitidine were demonstrated in 2 other studies. IC was generally associated with longer survival versus lower-intensity therapy or best supportive care. Findings suggest that azacitidine is a viable option for elderly AML patients who are ineligible for IC, and emerging agents used in combination with azacitidine could have a major impact in this difficult-to-treat population.

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“…Nowadays, there are a wide variety of assays commonly applied for the evaluation of genome-wide DNA methylation, but none of them is currently performed in clinical practice; in fact, the response to hypomethylating therapy is currently based only on clinical parameters [16, 17].…”

Section: Introductionmentioning

confidence: 99%

Droplet digital PCR for the quantification of Alu methylation status in hematological malignancies

et al. 2018

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BackgroundAlu repeats, belonging to the Short Interspersed Repetitive Elements (SINEs) class, contain about 25% of CpG sites in the human genome. Alu sequences lie in gene-rich regions, so their methylation is an important transcriptional regulation mechanism. Aberrant Alu methylation has been associated with tumor aggressiveness, and also previously discussed in hematological malignancies, by applying different approaches. Moreover, today different techniques designed to measure global DNA methylation are focused on the methylation level of specific repeat elements.In this work we propose a new method of investigating Alu differential methylation, based on droplet digital PCR (ddPCR) technology.MethodsForty-six patients with hematological neoplasms were included in the study: 30 patients affected by chronic lymphocytic leukemia, 7 patients with myelodysplastic syndromes at intermediate/high risk, according with the International Prognostic Scoring System, and 9 patients with myelomonocytic leukemia. Ten healthy donors were included as controls. Acute promyelocytic leukemia-derived NB4 cell line, either untreated or treated with decitabine (DEC) hypomethylating agent, was also analyzed.DNA samples were investigated for Alu methylation level by digestion of genomic DNA with isoschizomers with differential sensitivity to DNA methylation, followed by ddPCR.ResultsUsing ddPCR, a significant decrease of the global Alu methylation level in DNA extracted from NB4 cells treated with DEC, as compared to untreated cells, was observed. Moreover, comparing the global Alu methylation levels at diagnosis and after azacytidine (AZA) treatment in MDS patients, a statistically significant decrease of Alu sequences methylation after therapy as compared to diagnosis was evident. We also observed a significant decrease of the Alu methylation level in CLL patients compared to HD, and, finally, for CMML patients, a decrease of Alu sequences methylation was observed in patients harboring the SRSF2 hotspot gene mutation c.284C>D.ConclusionsIn our work, we propose a method to investigate Alu differential methylation based on ddPCR technology. This assay introduces ddPCR as a more sensitive and immediate technique for Alu methylation analysis. To date, this is the first application of ddPCR to study DNA repetitive elements. This approach may be useful to profile patients affected by hematologic malignancies for diagnostic/prognostic purpose.Electronic supplementary materialThe online version of this article (10.1186/s13000-018-0777-x) contains supplementary material, which is available to authorized users.

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Azacitidine in the treatment of older patients affected by acute myeloid leukemia: A report by the Rete Ematologica Pugliese (REP)

Cited by 5 publications

References 32 publications

American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults

Effectiveness and Safety of Therapeutic Regimens for Elderly Patients With Acute Myeloid Leukemia: A Systematic Literature Review

Droplet digital PCR for the quantification of Alu methylation status in hematological malignancies

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