Impact of post-remission therapy in patients aged 65-70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria

Itzykson, Raphaël; Gardin, Claude; Pautas, Cécile; Thomas, Xavier; Turlure, Pascal; Raffoux, Emmanuel; Terré, Christine; Fenaux, Pierre; Castaigné, Sylvie; Dombret, Hervé; Boissel, Nicolas

doi:10.3324/haematol.2010.036921

Cited by 21 publications

(16 citation statements)

References 27 publications

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“…Cytogenetic abnormalities were categorized according to the ALFA cytogenetic classification [17]. t(8;21), inv (16), and t(16;16) are classified as favorable risk.…”

Section: Cytogenetic Analysismentioning

confidence: 99%

Neurofibromatosis‐1 gene deletions and mutations in de novo adult acute myeloid leukemia

et al. 2013

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On behalf of the French ALFA groupGermline heterozygous alterations of the tumor-suppressor gene neurofibromatosis-1 (NF1) lead to neurofibromatosis type 1, a genetic disorder characterized by a higher risk to develop juvenile myelomonocytic leukemia and/or acute myeloid leukemia (AML). More recently, somatic 17q11 deletions encompassing NF1 have been described in many adult myeloid malignancies. In this context, we aimed to define NF1 involvement in AML. We screened a total of 488 previously untreated de novo AML patients for the NF1 deletion using either array comparative genomic hybridization (aCGH) or real-time quantitative PCR/fluorescence in situ hybridization approaches. We also applied massively parallel sequencing for in depth mutation analysis of NF1 in 20 patients including five NF1-deleted patients. We defined a small~0.3 Mb minimal deleted region involving NF1 by aCGH and an overall frequency of NF1 deletion of 3.5% (17/485). NF1 deletion is significantly associated with unfavorable cytogenetics and with monosomal karyotype notably. We discovered six NF1 variants of unknown significance in 7/20 patients of which only one out of four disappeared in corresponding complete remission sample. In addition, only one out of five NF1-deleted patients has an acquired coding mutation in the remaining allele. In conclusion, direct NF1 inactivation is infrequent in de novo AML and may be a secondary event probably involved in leukemic progression. Am. J.

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“…Cytogenetic abnormalities were categorized according to the ALFA cytogenetic classification [17]. t(8;21), inv (16), and t(16;16) are classified as favorable risk.…”

Section: Cytogenetic Analysismentioning

confidence: 99%

Neurofibromatosis‐1 gene deletions and mutations in de novo adult acute myeloid leukemia

et al. 2013

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“…123 Intensified postremission chemotherapy in high-risk patients, especially older patients is without clear benefit. 164 Intensive chemotherapy followed by autologous HCT. One cycle of intensive chemotherapy followed by autologous HCT using peripheral blood CD34 1 cells offers condensed treatment.…”

Section: Intensive Postremission Therapymentioning

confidence: 99%

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

Döhner

Estey

Grimwade

et al. 2017

Blood

4,777

5,387

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The first edition of the European LeukemiaNet (ELN) recommendations for diagnosis and management of acute myeloid leukemia (AML) in adults, published in 2010, has found broad acceptance by physicians and investigators caring for patients with AML. Recent advances, for example, in the discovery of the genomic landscape of the disease, in the development of assays for genetic testing and for detecting minimal residual disease (MRD), as well as in the development of novel antileukemic agents, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. The recommendations include a revised version of the ELN genetic categories, a proposal for a response category based on MRD status, and criteria for progressive disease

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“…2 The difference did, however, seem more statistically significant (P=0.03) than clinically relevant (median survivals after complete remission of approximately 24 rather than 18 months). In neither study 1,2 was the intensity of post-remission therapy more relevant in patients who might be inherently more sensitive to anthracycline or cytarabine because they had "intermediate" rather than "unfavorable" prognosis cytogenetics; prognostically "favorable" cytogenetics are very uncommon in older patients. The ALFA investigators' data are consistent with the general consensus that post-remission therapy employing any permutation of anthracyline or cytarabine is unsatisfactory for the vast majority of patents age 60 years or more with AML in first complete remission.…”

Section: University Of Washington Medical Center and Fred Hutchinson mentioning

confidence: 97%

mentioning

confidence: 88%

“…1 In more detail, survival times were similar between patients treated with: (i) six courses of relatively "less intense" outpatient therapy, (ii) one course of inpatient therapy containing 45 mg/m 2 daunorubicin (or 9 mg/m 2 idarubicin) daily on days 1-4 + 200 mg/m 2 cytarabine daily on days 1-7 thus amounting, in total, to four times more anthracycline and 2.5 times more cytarabine than administered in the outpatient regimen, or (iii) two courses of inpatient therapy with a 4-to 6-fold increase in anthracycline and over 10-fold increase in cytarabine compared to the outpatient regimen. In contrast, a previous ALFA study found that patients aged 65 years or older who were randomly assigned to the outpatient regimen rather than to the one course inpatient regimen survived longer after achieving complete remission and also had a longer relapse-free survival.…”

Section: University Of Washington Medical Center and Fred Hutchinson mentioning

confidence: 99%

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Treatment of acute myeloid leukemia in the elderly

Estey¹

2011

Haematologica

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I n this issue of Haematologica, Itzykson et al. for the ALFA group show that the choice of post-remission therapy has seemingly little effect on duration of survival after complete remission in patients aged 65-70 years old with acute myeloid leukemia (AML).1 In more detail, survival times were similar between patients treated with: (i) six courses of relatively "less intense" outpatient therapy, (ii) one course of inpatient therapy containing 45 mg/m 2 daunorubicin (or 9 mg/m 2 idarubicin) daily on days 1-4 + 200 mg/m 2 cytarabine daily on days 1-7 thus amounting, in total, to four times more anthracycline and 2.5 times more cytarabine than administered in the outpatient regimen, or (iii) two courses of inpatient therapy with a 4-to 6-fold increase in anthracycline and over 10-fold increase in cytarabine compared to the outpatient regimen. In contrast, a previous ALFA study found that patients aged 65 years or older who were randomly assigned to the outpatient regimen rather than to the one course inpatient regimen survived longer after achieving complete remission and also had a longer relapse-free survival. 2 The difference did, however, seem more statistically significant (P=0.03) than clinically relevant (median survivals after complete remission of approximately 24 rather than 18 months). In neither study 1,2 was the intensity of post-remission therapy more relevant

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Impact of post-remission therapy in patients aged 65-70 years with de novo acute myeloid leukemia: a comparison of two concomitant randomized ALFA trials with overlapping age inclusion criteria

Cited by 21 publications

References 27 publications

Neurofibromatosis‐1 gene deletions and mutations in de novo adult acute myeloid leukemia

Neurofibromatosis‐1 gene deletions and mutations in de novo adult acute myeloid leukemia

Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel

Treatment of acute myeloid leukemia in the elderly

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