Non-anthracycline based remission induction therapy for newly diagnosed patients with acute myeloid leukemia aged 60 or older

Bashey, Asad; Liu, Lin; Ihasz, Anita; Medina, Bridget; Corringham, Sue; Keese, Katherine; Carrier, Ewa; Castro, Januario E.; Holman, Peter; Lane, Thomas A.; Hassidim, Kamran; Ball, Edward D.

doi:10.1016/j.leukres.2005.09.002

Cited by 13 publications

(6 citation statements)

References 8 publications

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“…Therefore, it is conceivable that the dismal prognosis of post-MDS AML is related to concomitant unfavourable cytogenetics, rather than to previous MDS history. The combination of F plus ARA-C offers the possibility of deliver high dose chemotherapy, with less toxicity as compared to conventional regimens high-dose ARA-C based [29][30][31][32][33]. In a study on elderly AML patients, in which conventional FLAG was compared to intermediate dose ARA-C plus G-CSF, a high CR rate with acceptable extrahaematologic toxicity was reported after FLAG, even though in absence of significant survival advantage [34].…”

Section: Discussionmentioning

confidence: 99%

Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome

Ferrara

Palmieri

Izzo

et al. 2010

Hematological Oncology

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Acute myeloid leukaemia (AML) secondary to myelodysplastic syndrome (MDS) is characterized by poor prognosis, namely in older patients. The combination of fludarabine (F) with cytarabine (ARA-C) ± G-CSF was proven as effective in patients with poor risk AML. The efficacy and toxicity of a regimen including F + ARA-C as sequential continuous infusion (CI-FLA) in 64 untreated patients aged >60 years, in which AML arose after a previous MDS, was investigated. Median age was 67 years (61-81). In patients achieving CR, an additional course, followed by G-CSF to mobilize CD34+ cells and subsequent autologous stem cell transplantation (ASCT) were programmed. Overall, 43 patients (67%) achieved complete remission (CR). There were 10 induction deaths (16%), while 11 patients (17%) were refractory to induction treatment. Thirty-four patients (79% of remitters) were eligible for the consolidation and 30 were monitorized for the mobilization of CD34+ cells, collection being successful in 20 of them (67%). Median number of CD34+ cells/kg collected was 6.8 × 10E6. Thirteen patients (20% of the whole population) received ASCT. Median disease free survival (DFS) and overall survival (OS) were 10 and 9 months, respectively. Survival at 5 years is projected to 15%. The only parameter significantly related to either DFS duration or OS duration was unfavourable cytogenetics, which did significantly influence also CR achievement. CI-FLA is effective in elderly patients with AML secondary to previously diagnosed MDS. Best results are achievable in the subgroup of patients with diploid karyotype.

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Section: Discussionmentioning

confidence: 99%

Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome

Ferrara

Palmieri

Izzo

et al. 2010

Hematological Oncology

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“…95 Several anthracyclinefree intensive induction regimens have shown similar efficacy in comparison with "713" regimen, although only a minority was tested in randomized trials. [96][97][98][99][100] These options are listed in Table 6.…”

Section: Non-anthracycline Induction and Treatment Strategiesmentioning

confidence: 99%

Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper

et al. 2020

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The incidence of acute myeloid leukemia (AML) increases with age. Intensive induction chemotherapy containing cytarabine and an anthracycline has been part of the upfront and salvage treatment of AML for decades. Anthracyclines are associated with a significant risk of cardiotoxicity (especially anthracycline-related left ventricular dysfunction [ARLVD]). In the older adult population, the higher prevalence of cardiac comorbidities and risk factors may further increase the risk of ARLVD. In this article of the Young International Society of Geriatric Oncology group, we review the prevalence of ARLVD in patients with AML and factors predisposing to ARLVD, focusing on older adults when possible. In addition, we review the assessment of cardiac function and management of ARLVD during and after treatment. It is worth noting that only a minority of clinical trials focus on alternative treatment strategies in patients with mildly declined left ventricular ejection fraction or at a high risk for ARLVD. The limited evidence for preventive strategies to ameliorate ARLVD and alternative strategies to anthracycline use in the setting of cardiac comorbidities are discussed. Based on extrapolation of findings from younger adults and nonrandomized trials, we recommend a comprehensive baseline evaluation of cardiac function by imaging, cardiac risk factors, and symptoms to risk stratify for ARLVD. Anthracyclines remain an appropriate choice for induction although careful risk-stratification based on cardiac disease, risk factors, and predicted chemotherapy-response are warranted. In case of declined left ventricular ejection fraction, alternative strategies should be considered.

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“…A salvage regimen in common use is ‘FLAG’, which combines fludarabine, cytarabine (ara‐C) and granulocyte colony‐stimulating factor (G‐CSF) priming (Estey et al , 1994; Visani et al , 1994; Estey et al , 1999; Jackson et al , 2001; Carella et al , 2001; Ferrara et al , 2002; Ossenkoppele et al , 2004; Bashey et al , 2006). Clofarabine is structurally related to fludarabine.…”

Section: Introductionmentioning

confidence: 99%

Clofarabine with high dose cytarabine and granulocyte colony‐stimulating factor (G‐CSF) priming for relapsed and refractory acute myeloid leukaemia

et al. 2011

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SUMMARY This phase I/II study was conducted to determine the maximum tolerated dose, toxicity, and efficacy of clofarabine in combination with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming (GCLAC), in the treatment of patients with relapsed or refractory acute myeloid leukaemia (AML). Dose escalation of clofarabine occurred without dose-limiting toxicity, so most patients were treated at the maximum dose, 25 mg/m2/day with cytarabine 2 g/m2/day, each for 5 days, and G-CSF 5 μg/kg, beginning the day before chemotherapy and continuing daily until neutrophil recovery. The complete remission (CR) rate among the 46 evaluable patients was 46% (95% confidence interval [CI] 31–61%) and the CR + CR but with a platelet count <100 x 109/l rate was 61% (95% CI 45–75%). Multivariate analysis showed that responses to GCLAC were independent of age, cytogenetic risk category, and number of prior salvage regimens. GCLAC is highly active in relapsed and refractory AML and warrants prospective comparison to other regimens, as well as study in untreated patients.

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Non-anthracycline based remission induction therapy for newly diagnosed patients with acute myeloid leukemia aged 60 or older

Cited by 13 publications

References 8 publications

Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome

Continuous sequential infusion of fludarabine and cytarabine for elderly patients with acute myeloid leukaemia secondary to a previously diagnosed myelodysplastic syndrome

Anthracycline-related cardiotoxicity in older patients with acute myeloid leukemia: a Young SIOG review paper

Clofarabine with high dose cytarabine and granulocyte colony‐stimulating factor (G‐CSF) priming for relapsed and refractory acute myeloid leukaemia

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