Decitabine in combination with low-dose cytarabine, aclarubicin and G-CSF tends to improve prognosis in elderly patients with high-risk AML

Hong, Ming; Zhu, Han; Sun, Qiang; Zhu, Yanxia; Miao, Yi; Yang, Hui; Qiu, Hai-Rong; Li, Jianyong; Shen, Qian

doi:10.18632/aging.102973

Cited by 22 publications

(24 citation statements)

References 40 publications

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“…months (19) . The fact that case1 is in continuous CR for 16 months and the latter two cases have the short remission time may be related to complex karyotype, and high VAF value (20) .Case4 and case 7 both have complex karyotype including -5/5q-and/or -7/7q-chromosomal deletions and TP53 mutation with VAF>20%.. More cases are needed for further study for VAF of TP53 and prognosis.…”

Section: Discussionmentioning

confidence: 99%

Venetoclax and Azacitidine Therapy in Elder Acute Myeloid Leukemia: A Retrospective Evaluation of Real-World Experience

Lan

et al. 2021

Preprint

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Background：To investigate the efficacy of venetoclax combined with azacytidine in the treatment of elderly patients with relapsed and refractory (R/R) acute myeloid leukemia（AML). Methods： The clinical data of 9 elderly AML patients over 65 years old, including 5 with R/R AML, using venetoclax and azacytidine were retrospectively analyzed. Results： Six males and 3 females with a median age of 71 years were included in this study, of which four patients had at least one relapse, and one patient did not get go into remission after 4 cycles of azacytidine monotherapy, deeming it refractory. Four patients had AML with myelodysplasia-related changes (AML-MRC). After 1 to 13 cycles of treatment using venetoclax and azacytidine, one of the 9 patients died early due to long duration of neutropenia and severe pulmonary infection caused by drugs. and six of the remaining 8 patients obtained complete response or complete response with incomplete hematologic recovery (CR/ CRi) , including five R/R patients. One patient did not respond to treatment after two cycles. For the side effects of the treatment, granulocytopenia occurred in all patients, and neutropenia occurred in 8 patients, lasting for an average of 10.5 (6-15) days and was most obvious in the second to third week of treatment. Three patients with TP53 gene mutation positive had following different outcomes. One relapsed patient achieved progression free remission (PFS) for 16 months up to date, and a second patient achieved complete remission but relapsed two months thereafter. Another patient had complete remission in myelology for 4months, but the variant allele fraction value (VAF) gradually increased, indicative that the disease was about to progress. Conclusion：Venetoclax combined with azacytidine regimen in elderly patients is an effective and well tolerated rescue scheme for R/R AML.The patients with TP53 mutation with lower VAF may be benifit from Venetoclax and azacytidine. Severe infection caused by neutropenia is an adverse reaction worthy of attention in the treatment process of the regimen.

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Section: Discussionmentioning

confidence: 99%

Venetoclax and Azacitidine Therapy in Elder Acute Myeloid Leukemia: A Retrospective Evaluation of Real-World Experience

Lan

et al. 2021

Preprint

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“…Genomic DNA (gDNA) was extracted from the bone marrow aspirates of each patient using an Autopure extractor (Qiagen, Hilden, Germany). Targeted gene sequencing (TGS) was tested on the Illumina Platforms (Kapa Biosystems, Wilmington, MA, USA) as previously described ( 9 ). A total of 42 genes were contained in the TGS panel, including ASXL1 , BCOR , BCORL1 , CALR , CBL , CEBPA , CSF3R , DNMT3A , ETV6 , EZH2 , FLT3 , GATA2 , IDH1 , IDH2 , JAK2 , KIT , KRAS , MLL , MPL , NF1 , NPM1 , NRAS , PDGFRA , PHF6 , PIGA , PPM1D , PTPN11 , RAD21, RUNX1 , SETBP1 , SF3B1 , SH2B3 , SMC1A , SMC3 , SRSF2 , STAG2 , STAT3 , TET2 , TP53 , U2AF1 , WT1 , and ZRSR2 .…”

Section: Methodsmentioning

confidence: 99%

The Prognostic Value of Sarcopenia in Acute Myeloid Leukemia Patients and the Development and Validation of a Novel Nomogram for Predicting Survival

et al. 2022

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BackgroundAcute myeloid leukemia (AML) occurs frequently in the elderly, of whom the prognosis is dismal. Sarcopenia is a progressive and generalized skeletal muscle disorder associated with an increased possibility of adverse outcomes. This study aims to explore the prognostic value of sarcopenia in AML patients and develop a novel prognostic model.MethodsA total of 227 AML patients were enrolled. Body composition was assessed by bioelectrical impedance analysis before treatment. Sarcopenia was diagnosed by low muscle quantity. Cox proportional hazard regression model were applied to verify prognostic variables for overall survival (OS) and disease-free survival (DFS). A novel prognostic model of nomogram was developed and validated by ‘R’.ResultsForty-one (18.1%) patients were defined as sarcopenia. The median age of the sarcopenic group was significantly greater than the non-sarcopenic group (median 70 vs. 64 years, P = 0.001). Sarcopenic patients showed significantly less height (P = 0.002), weight (P <0.001), Body Mass Index (P <0.001), Fat Mass (P = 0.017), Fat-free Mass (P <0.001), Appendicular Skeletal Muscle Mass (P <0.001), Skeletal Muscle Index (P <0.001), Fat-free Mass Index (P <0.001), and hemoglobin level (P = 0.025) than the non-sarcopenic ones. Patients in the sarcopenic group also showed a statistically shorter OS and DFS (median OS: 13.7 vs. 55.6 months, P = 0.003; median DFS: 12.5 months vs. not reached, P = 0.026). ELN high risk [Hazard Ratio (HR): 1.904, 95% Confidence Interval (CI): 1.018–3.562, P = 0.044), sarcopenia (HR: 1.887, 95% CI: 1.071–3.324, P = 0.028), and reduced-intensity regimens (HR: 3.765, 95% CI: 1.092–12.980, P = 0.036) were independent predictors for OS in multivariate analysis. A nomogram for predicting OS was constructed using the above three factors. The c index, calibration plots and decision curve analyses (DCA) showed better discrimination, calibration, and net benefits of the nomogram than the ELN model.ConclusionSarcopenia was common and had an inferior prognosis in AML and needs more attention in clinical practice.

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“…HMAs combined with CAG regimen [LDAC, aclarubicin and granulocyte colony-stimulating factor (G-CSF)] tends to improve the prognosis of older patients with high-risk AML [15] . In patients with R/R AML, it was observed that increased dosage of the conventional CAG regimen was more effective as salvage therapy [16] .…”

Section: Introductionmentioning

confidence: 99%

Single-center retrospective clinical evaluation of venetoclax combined with HMAs and half-dose CAG in the treatment of unfit or refractory/relapsed AML

Chen

Zhao

Li³

et al. 2022

Preprint

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Purpose The prognosis of unfit or relapsed/refractory (R/R) AML patients remains poor. Venetoclax has been proved to have anti-leukemia stem cell activity. However, there is little published information on the efficacy and safety of VEN combined with both demethylated drugs and half-dose chemotherapy in the treatment of unfit or R/R AML patients.Methods In this study, we retrospectively analyzed the clinical characteristics, treatment details, safety profile and clinical outcomes of unfit or R/R AML patients who were treated with VEN+ HMAs+ half-dose CAG.Results A total of 21 AML patients were involved in the study, 11 patients (52.4%) were in the unfit group, while 10 patients (47.6%) were in R/R group. FLT3 (6/21, 28.6%) was the most common gene aberration. Patients in the R/R group were found more likely to carry KIT (5/ 10, 50%) when compared to the unfit group (0/11, 0%) (P = 0.012). The median duration of CR+ CRi was 11.5 months (95% CI 8.9 to 14.1). Twelve patients achieved CR (57.1%), two CRi (9.5%), and three PR (14.3%), for an ORR 80.9% (17/21) and cCR 66.7% (14/21). CR was observed in 100% (5/5) AML patients with TP53, 80% (4/5) AML patients with IDH, 75% (3/4) AML patients with NPM1, 50% (3/6) AML patients with FLT3, 40% (2/5) AML patients with KIT, 40% (2/5) AML patients with DNMT3A, and 20% (1/5) AML patients with RUNX1. The most common AEs during VEN+ HMAs+ half-dose CAG therapy were persistent cytopenia, infection and gastrointestinal symptoms (decreased appetite, nausea, vomiting and diarrhea).Conclusion The results of this investigation show that VEN+ HMAs+ half-dose CAG demonstrated promising efficacy (even high-risk cytogenetics) and a tolerable safety profile in unfit or R/R AML patients.

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Decitabine in combination with low-dose cytarabine, aclarubicin and G-CSF tends to improve prognosis in elderly patients with high-risk AML

Cited by 22 publications

References 40 publications

Venetoclax and Azacitidine Therapy in Elder Acute Myeloid Leukemia: A Retrospective Evaluation of Real-World Experience

Venetoclax and Azacitidine Therapy in Elder Acute Myeloid Leukemia: A Retrospective Evaluation of Real-World Experience

The Prognostic Value of Sarcopenia in Acute Myeloid Leukemia Patients and the Development and Validation of a Novel Nomogram for Predicting Survival

Single-center retrospective clinical evaluation of venetoclax combined with HMAs and half-dose CAG in the treatment of unfit or refractory/relapsed AML

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