A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia

Lauréne Fenwarth; Xavier Thomas; Stéphane de Botton; Nicolas Duployez; Jean Henri Bourhis; Auriane Lesieur; Gael Fortin; Paul Arthur Meslin; Ibrahim Yakoub-Agha; Pierre Sujobert; Pierre Yves Dumas; Christian Récher; Delphine Lebon; Céline Berthon; Mauricette Michallet; Arnaud Pigneux; Stéphanie Nguyen; Sylvain Chantepie; Norbert Vey; Emmanuel Raffoux; Karine Celli-Lebras; Claude Gardin; Juliette Lambert; Jean Valére Malfuson; Denis Caillot; Sébastien Maury; Benoit Ducourneau; Pascal Turlure; Emilie Lemasle; Cécile Pautas; Sylvie Chevret; Christine Terré; Nicolas Boissel; Gérard Socié; Hervé Dombret; Claude Preudhomme; Raphael Itzykson

doi:10.1182/blood.2020005524

A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia

Lauréne Fenwarth, Xavier Thomas, Stéphane de Botton, Nicolas Duployez, Jean Henri Bourhis, Auriane Lesieur, Gael Fortin, Paul Arthur Meslin, Ibrahim Yakoub-Agha, Pierre Sujobert, Pierre Yves Dumas, Christian Récher, Delphine Lebon, Céline Berthon, Mauricette Michallet, Arnaud Pigneux, Stéphanie Nguyen, Sylvain Chantepie, Norbert Vey, Emmanuel RaffouxKarine Celli-Lebras, Claude Gardin, Juliette Lambert, Jean Valére Malfuson, Denis Caillot, Sébastien Maury, Benoit Ducourneau, Pascal Turlure, Emilie Lemasle, Cécile Pautas, Sylvie Chevret, Christine Terré, Nicolas Boissel, Gérard Socié, Hervé Dombret, Claude Preudhomme, Raphael Itzykson

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31 Citations (Scopus)

Résumé

A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome predictions and tailor therapeutic decisions, including hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). We assessed the performance of the KB in guiding HSCT decisions in first complete remission (CR1) in 656 AML patients younger than 60 years from theALFA-0702 trial (NCT00932412).KB predictions of overall survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index, 68.9 vs 63.0).Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate, was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 minimal residual disease (MRD; interaction tests, P= .01 and P= .02, respectively). UsingKB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified, in a similar timedependent analysis, a significant interactionbetweenKBscore andHSCT, withHSCT inCR1being detrimental only in patients with a good prognosis based on KB simulations (KB score ≥40; interaction test, P = .01).We could finally integrate ELN 2017, NPM1 MRD, and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemotherapy-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates, whereas it significantly shortened OS in chemotherapy-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.

langue originale	Anglais
Pages (de - à)	524-532
Nombre de pages	9
journal	Blood
Volume	137
Numéro de publication	4
Les DOIs	https://doi.org/10.1182/blood.2020005524
état	Publié - 28 janv. 2021

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10.1182/blood.2020005524

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Fenwarth, L., Thomas, X., de Botton, S., Duployez, N., Bourhis, J. H., Lesieur, A., Fortin, G., Meslin, P. A., Yakoub-Agha, I., Sujobert, P., Dumas, P. Y., Récher, C., Lebon, D., Berthon, C., Michallet, M., Pigneux, A., Nguyen, S., Chantepie, S., Vey, N., ... Itzykson, R. (2021). A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia. Blood, 137(4), 524-532. https://doi.org/10.1182/blood.2020005524

@article{468eb76709f6472c8d9bdf380727a2a0,

title = "A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia",

abstract = "A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome predictions and tailor therapeutic decisions, including hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). We assessed the performance of the KB in guiding HSCT decisions in first complete remission (CR1) in 656 AML patients younger than 60 years from theALFA-0702 trial (NCT00932412).KB predictions of overall survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index, 68.9 vs 63.0).Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate, was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 minimal residual disease (MRD; interaction tests, P= .01 and P= .02, respectively). UsingKB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified, in a similar timedependent analysis, a significant interactionbetweenKBscore andHSCT, withHSCT inCR1being detrimental only in patients with a good prognosis based on KB simulations (KB score ≥40; interaction test, P = .01).We could finally integrate ELN 2017, NPM1 MRD, and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemotherapy-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates, whereas it significantly shortened OS in chemotherapy-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.",

author = "Laur{\'e}ne Fenwarth and Xavier Thomas and {de Botton}, St{\'e}phane and Nicolas Duployez and Bourhis, {Jean Henri} and Auriane Lesieur and Gael Fortin and Meslin, {Paul Arthur} and Ibrahim Yakoub-Agha and Pierre Sujobert and Dumas, {Pierre Yves} and Christian R{\'e}cher and Delphine Lebon and C{\'e}line Berthon and Mauricette Michallet and Arnaud Pigneux and St{\'e}phanie Nguyen and Sylvain Chantepie and Norbert Vey and Emmanuel Raffoux and Karine Celli-Lebras and Claude Gardin and Juliette Lambert and Malfuson, {Jean Val{\'e}re} and Denis Caillot and S{\'e}bastien Maury and Benoit Ducourneau and Pascal Turlure and Emilie Lemasle and C{\'e}cile Pautas and Sylvie Chevret and Christine Terr{\'e} and Nicolas Boissel and G{\'e}rard Soci{\'e} and Herv{\'e} Dombret and Claude Preudhomme and Raphael Itzykson",

note = "Publisher Copyright: {\textcopyright} 2021 by The American Society of Hematology.",

year = "2021",

month = jan,

day = "28",

doi = "10.1182/blood.2020005524",

language = "English",

volume = "137",

pages = "524--532",

journal = "Blood",

issn = "0006-4971",

number = "4",

}

Fenwarth, L, Thomas, X, de Botton, S, Duployez, N, Bourhis, JH, Lesieur, A, Fortin, G, Meslin, PA, Yakoub-Agha, I, Sujobert, P, Dumas, PY, Récher, C, Lebon, D, Berthon, C, Michallet, M, Pigneux, A, Nguyen, S, Chantepie, S, Vey, N, Raffoux, E, Celli-Lebras, K, Gardin, C, Lambert, J, Malfuson, JV, Caillot, D, Maury, S, Ducourneau, B, Turlure, P, Lemasle, E, Pautas, C, Chevret, S, Terré, C, Boissel, N, Socié, G, Dombret, H, Preudhomme, C & Itzykson, R 2021, 'A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia', Blood, VOL. 137, Numéro 4, p. 524-532. https://doi.org/10.1182/blood.2020005524

TY - JOUR

T1 - A personalized approach to guide allogeneic stem cell transplantation in younger adults with acute myeloid leukemia

AU - Fenwarth, Lauréne

AU - Thomas, Xavier

AU - de Botton, Stéphane

AU - Duployez, Nicolas

AU - Bourhis, Jean Henri

AU - Lesieur, Auriane

AU - Fortin, Gael

AU - Meslin, Paul Arthur

AU - Yakoub-Agha, Ibrahim

AU - Sujobert, Pierre

AU - Dumas, Pierre Yves

AU - Récher, Christian

AU - Lebon, Delphine

AU - Berthon, Céline

AU - Michallet, Mauricette

AU - Pigneux, Arnaud

AU - Nguyen, Stéphanie

AU - Chantepie, Sylvain

AU - Vey, Norbert

AU - Raffoux, Emmanuel

AU - Celli-Lebras, Karine

AU - Gardin, Claude

AU - Lambert, Juliette

AU - Malfuson, Jean Valére

AU - Caillot, Denis

AU - Maury, Sébastien

AU - Ducourneau, Benoit

AU - Turlure, Pascal

AU - Lemasle, Emilie

AU - Pautas, Cécile

AU - Chevret, Sylvie

AU - Terré, Christine

AU - Boissel, Nicolas

AU - Socié, Gérard

AU - Dombret, Hervé

AU - Preudhomme, Claude

AU - Itzykson, Raphael

PY - 2021/1/28

Y1 - 2021/1/28

N2 - A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome predictions and tailor therapeutic decisions, including hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). We assessed the performance of the KB in guiding HSCT decisions in first complete remission (CR1) in 656 AML patients younger than 60 years from theALFA-0702 trial (NCT00932412).KB predictions of overall survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index, 68.9 vs 63.0).Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate, was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 minimal residual disease (MRD; interaction tests, P= .01 and P= .02, respectively). UsingKB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified, in a similar timedependent analysis, a significant interactionbetweenKBscore andHSCT, withHSCT inCR1being detrimental only in patients with a good prognosis based on KB simulations (KB score ≥40; interaction test, P = .01).We could finally integrate ELN 2017, NPM1 MRD, and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemotherapy-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates, whereas it significantly shortened OS in chemotherapy-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.

AB - A multistage model instructed by a large dataset (knowledge bank [KB] algorithm) has recently been developed to improve outcome predictions and tailor therapeutic decisions, including hematopoietic stem cell transplantation (HSCT) in acute myeloid leukemia (AML). We assessed the performance of the KB in guiding HSCT decisions in first complete remission (CR1) in 656 AML patients younger than 60 years from theALFA-0702 trial (NCT00932412).KB predictions of overall survival (OS) were superior to those of European LeukemiaNet (ELN) 2017 risk stratification (C-index, 68.9 vs 63.0).Among patients reaching CR1, HSCT in CR1, as a time-dependent covariate, was detrimental in those with favorable ELN 2017 risk and those with negative NPM1 minimal residual disease (MRD; interaction tests, P= .01 and P= .02, respectively). UsingKB simulations of survival at 5 years in a scenario without HSCT in CR1 (KB score), we identified, in a similar timedependent analysis, a significant interactionbetweenKBscore andHSCT, withHSCT inCR1being detrimental only in patients with a good prognosis based on KB simulations (KB score ≥40; interaction test, P = .01).We could finally integrate ELN 2017, NPM1 MRD, and KB scores to sort 545 CR1 patients into 278 (51.0%) HSCT candidates and 267 (49.0%) chemotherapy-only candidates. In both time-dependent and 6-month landmark analyses, HSCT significantly improved OS in HSCT candidates, whereas it significantly shortened OS in chemotherapy-only candidates. Integrating KB predictions with ELN 2017 and MRD may thus represent a promising approach to optimize HSCT timing in younger AML patients.

UR - http://www.scopus.com/inward/record.url?scp=85099907941&partnerID=8YFLogxK

U2 - 10.1182/blood.2020005524

DO - 10.1182/blood.2020005524

M3 - Article

C2 - 32871585

AN - SCOPUS:85099907941

SN - 0006-4971

VL - 137

SP - 524

EP - 532

JO - Blood

JF - Blood

IS - 4

ER -