Cytarabine dose in the consolidation treatment of AML: a systematic review and meta-analysis

Magina, Kinkini N.; Pregartner, Gudrun; Zebisch, Armin; Wölfler, Albert; Neumeister, Peter; Greinix, Hildegard; Berghold, Andrea; Sill, Heinz

doi:10.1182/blood-2017-04-777722

Cited by 55 publications

(49 citation statements)

References 17 publications

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“…Previous reports showed the assessment of intermediate-dose cytarabine monotherapy vs. intermediate-dose cytarabine combination treatment of standard dose chemotherapies did not present a significant difference with respect to RFS and OS. 24 Thus, no matter which standard dose chemotherapies were used, all patients can be considered as to be received with consolidation treatments equally. The only difference is the induction chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis

Huang¹,

Hu²,

Lu³

et al. 2019

CMAR

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Background: According to the recent National Comprehensive Cancer Network (NCCN) guidelines, the risk level in acute myeloid leukemia (AML) patients with FLT3-ITD and NPM1 double mutation (AML FLT3-ITD+/NPM1+) depends on the allelic ratio of FLT3-ITD. But despite a low or high allelic ratio of FLT3-ITD, AML FLT3-ITD+/NPM1+ patients belong to the favorable or intermediate risk, for whom allogeneic stem cell transplantation is not obligated. However, some latest studies pointing out that NPM1 and FLT3-ITD double mutation patients showed an inferior prognosis, which have raised concern about the risk categorization and more effective treatment of AML FLT3-ITD+/NPM1+ patients. Methods: A total of 76 patients were selected for coexisting FLT3 and NPM1 mutations with normal cytogenetics. The prognostic risk factors were analyzed, and treatment strategies including allogeneic stem cell transplantati1on and chemotherapy were compared. Results: In 76 AML FLT3-ITD+/NPM1+ patients, 36.8% of patients had hyperleukocytosis (HL) and DNMT3A R882 mutation was the most common concomitant gene (23.7%). For 53 patients in the complete remission (CR), 22 had received allogeneic hematopoietic stem cell transplantation (allo-HSCT) on first complete remission (CR1). Patients in transplantation group had better overall survival (OS) and disease-free survival (DFS) than chemotherapy only (P=0.002 and 0.001, respectively). In multivariable Cox model analyses, HL and DNMT3A R882 mutation were independent adverse prognostic factors (all P<0.05) for AML FLT3-ITD+/NPM1+ patients. Nevertheless, allo-HSCT was an independent good factor of OS and DFS (P=0.001 and 0.000; HR =0.173 and 0.138; 95% CI were 0.062-0.483 and 0.049-0.389). And allo-HSCT could moderately improve the poor prognosis of AML FLT3-ITD+/NPM1+/DNMT3A R882+. Conclusion: Although, AML FLT3-ITD+/NPM1+ patients are categorized as favorable or intermediate risk levels according to recent NCCN and ELN guidelines, these patients should receive allo-HSCT in CR1 for a longer survival. AML FLT3-ITD+/NPM1+ patients with DNMT3A R882 mutation had a very poor prognosis, and allo-HSCT could moderately improve their survival.

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Section: Discussionmentioning

confidence: 99%

Acute myeloid leukemia patient with FLT3-ITD and NPM1 double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis

Huang¹,

Hu²,

Lu³

et al. 2019

CMAR

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“…Two meta-analyses have examined published data on HDAC vs. IDAC for AML consolidation therapy [ 77 , 78 ]. Interpretation was difficult for both meta-analyses as trial design and cytarabine doses varied considerably between the included studies over a period of 25 years.…”

Section: Bridging Strategiesmentioning

confidence: 99%

Bridging Strategies to Allogeneic Transplant for Older AML Patients

Hecker

Miller

Götze

et al. 2018

Cancers

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Treatment options for older patients with intermediate or high-risk acute myeloid leukemia (AML) remain unsatisfactory. Allogeneic stem cell transplantation, the treatment of choice for the majority of younger AML patients, has been hampered in elderly patients by higher treatment related mortality, comorbidities and lack of a suitable donor. With the higher availability of suitable donors as well as of reduced intensity conditioning regimens, novel low intensity treatments prior to transplantation and optimized supportive care, the number of older AML patients being successfully transplanted is steadily increasing. Against this background, we review current treatment strategies for older AML patients planned for allogeneic stem cell transplantation based on clinical trial data, discussing differences between approaches with advantages and pitfalls of each. We summarize pre-treatment considerations that need to be taken into account in this highly heterogeneous older population. Finally, we offer an outlook on areas of ongoing clinical research, including novel immunotherapeutic approaches that may improve access to curative therapies for a larger number of older AML patients.

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“…In AML, parameters influencing treatment decisions as well as outcome include both patient-specific characteristics and leukemia-specific aberrations. Among the former, patient´s age and comorbidities are important variables; among the latter, the type of leukemia, white blood cell count, and genetic aberrations significantly influence response to induction therapy, type of consolidation treatment, and survival [21][22][23]. An AML risk classification scheme based on cytogenetic abnormalities was proposed as early as in 1998 [24].…”

Section: Introductionmentioning

confidence: 99%

Functional Classification of TP53 Mutations in Acute Myeloid Leukemia

Dutta

Pregartner

Rücker

et al. 2020

Cancers

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Mutations of the TP53 gene occur in a subset of patients with acute myeloid leukemia (AML) and confer an exceedingly adverse prognosis. However, whether different types of TP53 mutations exert a uniformly poor outcome has not been investigated yet. Here, we addressed this issue by analyzing data of 1537 patients intensively treated within protocols of the German-Austrian AML study group. We classified TP53 mutations depending on their impact on protein structure and according to the evolutionary action (EAp53) score and the relative fitness score (RFS). In 98/1537 (6.4%) patients, 108 TP53 mutations were detected. While the discrimination depending on the protein structure and the EAp53 score did not show a survival difference, patients with low-risk and high-risk AML-specific RFS showed a different overall survival (OS; median, 12.9 versus 5.5 months, p = 0.017) and event-free survival (EFS; median, 7.3 versus 5.2 months, p = 0.054). In multivariable analyses adjusting for age, gender, white blood cell count, cytogenetic risk, type of AML, and TP53 variant allele frequency, these differences were statistically significant for both OS (HR, 2.14; 95% CI, 1.15–4.0; p = 0.017) and EFS (HR, 1.97; 95% CI, 1.06–3.69; p = 0.033). We conclude that the AML-specific RFS is of prognostic value in patients with TP53-mutated AML and a useful tool for therapeutic decision-making.

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Cytarabine dose in the consolidation treatment of AML: a systematic review and meta-analysis

Cited by 55 publications

References 17 publications

<p>Acute myeloid leukemia patient with <em>FLT3-ITD</em> and <em>NPM1</em> double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis </p>

<p>Acute myeloid leukemia patient with <em>FLT3-ITD</em> and <em>NPM1</em> double mutation should undergo allogeneic hematopoietic stem cell transplantation in CR1 for better prognosis </p>

Bridging Strategies to Allogeneic Transplant for Older AML Patients

Functional Classification of TP53 Mutations in Acute Myeloid Leukemia

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