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Prognostic impact of day 15 blast clearance in risk-adapted remission induction chemotherapy for younger patients with acute myeloid leukemia: long-term results of the multicenter prospective LAM-2001 trial by the GOELAMS study group.

ABSTRACT: Early response to chemotherapy has a major prognostic impact in acute myeloid leukemia patients treated with a double induction strategy. Less is known about patients treated with standard-dose cytarabine and anthracycline. We designed a risk-adapted remission induction regimen in which a second course of intermediate-dose cytarabine was delivered after standard "7+3" only if patients had 5% or more bone marrow blasts 15 days after chemotherapy initiation (d15-blasts). Of 823 included patients, 795 (96.6%) were evaluable. Five hundred and forty-five patients (68.6%) had less than 5% d15-blasts. Predictive factors for high d15-blasts were white blood cell count (P<0.0001) and cytogenetic risk (P<0.0001). Patients with fewer than 5% d15-blasts had a higher complete response rate (91.7% vs. 69.2%; P<0.0001) and a lower induction death rate (1.8% vs. 6.8%; P=0.001). Five-year event-free (48.4% vs. 25%; P<0.0001), relapse-free (52.7% vs. 36.9%; P=0.0016) and overall survival (55.3% vs. 36.5%; P<0.0001) were significantly higher in patients with d15-blasts lower than 5%. Multivariate analyses identified d15-blasts and cytogenetic risk as independent prognostic factors for the three end points. Failure to achieve early blast clearance remains a poor prognostic factor even after early salvage. By contrast, early responding patients have a favorable outcome without any additional induction course. (ClinicalTrials.gov identifier NCT01015196).

SUBMITTER: Bertoli S

PROVIDER: S-EPMC4007924 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Prognostic impact of day 15 blast clearance in risk-adapted remission induction chemotherapy for younger patients with acute myeloid leukemia: long-term results of the multicenter prospective LAM-2001 trial by the GOELAMS study group.

Bertoli Sarah S Bories Pierre P Béné Marie C MC Daliphard Sylvie S Lioure Bruno B Pigneux Arnaud A Vey Norbert N Delaunay Jacques J Leymarie Vincent V Luquet Isabelle I Blanchet Odile O Cornillet-Lefebvre Pascale P Hunault Mathilde M Bouscary Didier D Fegueux Nathalie N Guardiola Philippe P Dreyfus François F Harousseau Jean Luc JL Cahn Jean Yves JY Ifrah Norbert N Récher Christian C

Haematologica 20130823 1

Early response to chemotherapy has a major prognostic impact in acute myeloid leukemia patients treated with a double induction strategy. Less is known about patients treated with standard-dose cytarabine and anthracycline. We designed a risk-adapted remission induction regimen in which a second course of intermediate-dose cytarabine was delivered after standard "7+3" only if patients had 5% or more bone marrow blasts 15 days after chemotherapy initiation (d15-blasts). Of 823 included patients, ...[more]

PMID: 23975179

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Project description:Transcriptional changes were monitored in the wheat cultivar Renan 24 hours post i noculation with adapted and non-adapted Magnaporthe isolates using the Affymetrix wheat genome array GeneChip®. Wheat plants cv. Renan were grown in a peat and sand (1:1) mix at 23 C in a Sanyo Fitotron growth cabinet (Sanyo Gallenkamp PLC, Loughborough, U.K.) with a 16/8 h, light/dark cycle. Three Magnaporthe isolates were used in this expt, two wheat-adapted isolates (BR32, BR37) and one wheat non-adapted isolate (BR29). Magnaporthe isolates were grown for eleven days on Complete Media Agar at 25 C under a 16/8h, light/dark cycle. Conidia were harvested by flooding the plates with 5 mL of sterile inoculation solution [0.25% (w/v) gelatine and 0.01% (v/v) Tween 20] and scraping the conidia from the surface using a sterile glass rod. Conidia were filtered through sterile miracloth and the density adjusted to 1 x 10 5 conidia mL-1 with inoculation solution. Fourteen day old wheat seedlings mist inoculated with 4 mL of a Magnaporthe conidia suspension and plants were sealed in plastic propagators to maintain relative humidity c.100% and kept at 25 C in the dark for the first 24 hours post inoculation (hpi). Inoculation solution without Magnaporthe conidia was used as a mock-inoculation control. Leaf samples were collected 24 hpi for transcriptomics analysis from three independent biological experiments. Leaf tissue was ground under liquid nitrogen and total RNA extracted using a QIAquick RNeasy Plant Extraction Kit (Qiagen, Hilden, Germany), followed by TURBO DNaseTM (Ambion, Texas, U.S.A.) treatment. RNeasy Mini Spin column purification (Qiagen) was used to further purify RNA samples for array hybridisation. RNA quality checks, cRNA conversion and Affymetrix genome array hybridisation was carried out by the Nottingham Arabidopsis Stock Centre (NASC) array hybridisation service (http://affymetrix.arabidopsis.info/). ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor, Graham McGrann. The equivalent experiment is TA24 at PLEXdb.]

Dataset Information

Prognostic impact of day 15 blast clearance in risk-adapted remission induction chemotherapy for younger patients with acute myeloid leukemia: long-term results of the multicenter prospective LAM-2001 trial by the GOELAMS study group.

Publications

Prognostic impact of day 15 blast clearance in risk-adapted remission induction chemotherapy for younger patients with acute myeloid leukemia: long-term results of the multicenter prospective LAM-2001 trial by the GOELAMS study group.

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