Treatment of Elderly Patients With Acute Myeloid Leukemia

Thomas, Xavier; Jeune, Caroline Le

doi:10.1007/s11864-017-0445-5

Cited by 20 publications

(16 citation statements)

References 110 publications

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“…Accordingly, a longstanding concept in the treatment of AML is to induce committed maturation of these cancerous cells, promoting clearance of the malignant clones and allowing normal progenitors to repopulate the marrow. Such an approach could yield therapies that are less toxic than the current standard of care of chemotherapy and hematopoietic stem cell transplantation, which is often unsuitable for elderly patients and those with significant comorbidities ( Döhner et al., 2010 ; Juliusson 2011 ; Thomas and le Jeune, 2017 ). However, while this strategy has proven effective in AML subtypes with specific driver mutations, most notably acute promyelocytic leukemia with PML-RARA fusion and AML with IDH1/IDH2 mutation, attempts to extend this approach to treatment of AML more generally have proven unsuccessful to date.…”

Section: Introductionmentioning

confidence: 99%

Combined epigenetic and metabolic treatments overcome differentiation blockade in acute myeloid leukemia

et al. 2021

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Section: Introductionmentioning

confidence: 99%

Combined epigenetic and metabolic treatments overcome differentiation blockade in acute myeloid leukemia

et al. 2021

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“…1,11 Minimally myelosuppressive regimens have been used in adults with relapsed AML or in those with de novo AML who were too frail to receive standard induction therapy. [32][33][34][35] A combination of low-dose cytarabine with low-dose aclarubicin administered concurrently with G-CSF was first used in Japan. 36 A variation of this regimen that substitutes omacetaxine mepesuccinate for aclarubicin has been used extensively in China 37,38 and with different anthracyclines in other regions.…”

Section: Discussionmentioning

confidence: 99%

Minimally myelosuppressive regimen for remission induction in pediatric AML: long-term results of an observational study

Chen

Gao

et al. 2021

Blood Advances

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Treatment refusal and death as a result of toxicity account for most treatment failures among children with acute myeloid leukemia (AML) in resource-constrained settings. We recently reported the results of treating children with AML with a combination of low-dose cytarabine and mitoxantrone or omacetaxine mepesuccinate with concurrent granulocyte colony-stimulating factor (G-CSF) (low-dose chemotherapy [LDC]) for remission induction followed by standard postremission strategies. We have now expanded the initial cohort and have provided long-term follow-up. Eighty-three patients with AML were treated with the LDC regimen. During the study period, another 100 children with AML received a standard-dose chemotherapy (SDC) regimen. Complete remission was attained in 88.8% and 86.4% of patients after induction in the LDC and SDC groups, respectively (P = .436). Twenty-two patients in the LDC group received SDC for the second induction course. Significantly more high-risk AML patients were treated with the SDC regimen (P = .035). There were no significant differences between the LDC and SDC groups in 5-year event-free survival (61.4% ± 8.7% vs 65.2% ± 7.4%, respectively; P = .462), overall survival (72.7% ± 6.9% vs 72.5% ± 6.2%, respectively; P = .933), and incidence of relapse (20.5% ± 4.5% vs 17.6% ± 3.9%, respectively; P = .484). Clearance of mutations based on the average variant allele frequency at complete remission in the LDC and SDC groups was 1.9% vs 0.6% (P < .001) after induction I and 0.17% vs 0.078% (P = .052) after induction II. In conclusion, our study corroborated the high remission rate reported for children with AML who received at least 1 course of LDC. The results, although preliminary, also suggest that long-term survival of these children is comparable to that of children who receive SDC regimens.

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“…For these patients, we suggest trying a combination of targeted therapy such as an FLT3 inhibitor. There have been studies showing that the addition of sorafenib to chemotherapy improved OS and DFS in older AML patients with FLT3-ITD mutations [55], and when combined with hypomethylating drugs, sorafenib showed promising results [56].…”

Section: Discussionmentioning

confidence: 99%

Genetic features and efficacy of decitabine-based chemotherapy in elderly patients with acute myeloid leukemia

Wang

Guan

et al. 2021

Hematology

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Objectives: The outcome of elderly acute myeloid leukemia (AML) patients is poor, which was traditionally attributed to patient-and leukemia-related factors. However, studies about the genetic features of these elderly patients have not been integrated and the genetic mechanism of their poor outcome is less known. Methods: Here, we used next generation sequencing (NGS) to identify the genetic features of elderly AML patients and confirmed the efficacy of chemotherapy based on molecular aberrations. Mutations in 111 genes relevant to hematological malignancy was analysed by virtue of NGS and the genetic differences were compared between elderly (n=52) and young (n=161) AML patients. Furthermore, the outcome of decitabine-based chemotherapy was identified in elderly patients. Results: Frequencies of adverse genetic alterations, such as RUNX1 and secondary-type mutations (ASXL1, STAG2 and spliceosome), were much higher in elderly patients, while the frequency of WT1 mutations was much lower. Moreover, epigenetic mutations such as DNMT3A, TET2, ASXL1 and IDH2, were also more common in elderly patients. Furthermore, there were 39 elderly patients receiving the decitabine-based chemotherapy, and the results showed that the overall response rate (ORR) and complete remission rate (CR) were 76.9% and 71.8%, respectively. The median overall survival (OS) for those older patients was 12 months, and the 2-year OS probability was 20.5%. Discussion: Our study provides deep understanding into the molecular mechanisms of the poor outcome of elderly AML patients. Conclusion: Epigenetic mutations play an important role, and decitabine-based regimen can be used as alternative first-line chemotherapy for elderly patients.

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Treatment of Elderly Patients With Acute Myeloid Leukemia

Cited by 20 publications

References 110 publications

Combined epigenetic and metabolic treatments overcome differentiation blockade in acute myeloid leukemia

Combined epigenetic and metabolic treatments overcome differentiation blockade in acute myeloid leukemia

Minimally myelosuppressive regimen for remission induction in pediatric AML: long-term results of an observational study

Genetic features and efficacy of decitabine-based chemotherapy in elderly patients with acute myeloid leukemia

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