GIMEMA AML1310 trial of risk-adapted, MRD-directed therapy for young adults with newly diagnosed acute myeloid leukemia

被引：167

作者：

Venditti, Adriano ^{[1
,2
]}

Piciocchi, Alfonso ^{[3
]}

Candoni, Anna ^{[4
]}

Melillo, Lorella ^{[5
]}

Calafiore, Valeria ^{[6
]}

Cairoli, Roberto ^{[7
]}

De Fabritiis, Paolo ^{[8
]}

Storti, Gabriella ^{[9
]}

Salutari, Prassede ^{[10
]}

Lanza, Francesco ^{[11
]}

Martinelli, Giovanni ^{[12
,13
]}

Luppi, Mario ^{[14
]}

Mazza, Patrizio ^{[15
]}

Martelli, Maria Paola ^{[16
]}

Cuneo, Antonio ^{[17
]}

Albano, Francesco ^{[18
]}

Fabbiano, Francesco ^{[19
]}

Tafuri, Agostino ^{[20
]}

Chierichini, Anna ^{[21
]}

Tieghi, Alessia ^{[22
]}

Fracchiolla, Nicola Stefano ^{[23
]}

Capelli, Debora ^{[24
]}

Foa, Robin ^{[25
]}

Alati, Caterina ^{[26
]}

La Sala, Edoardo ^{[3
]}

Fazi, Paola ^{[3
]}

Vignetti, Marco ^{[3
]}

Maurillo, Luca ^{[2
]}

Buccisano, Francesco ^{[1
,2
]}

Del Principe, Maria Ilaria ^{[1
,2
]}

Irno-Consalvo, Maria ^{[1
]}

Ottone, Tiziana ^{[1
]}

Lavorgna, Serena ^{[1
]}

Voso, Maria Teresa ^{[1
,2
]}

Lo-Coco, Francesco ^{[1
,2
]}

Arcese, William ^{[1
,2
]}

Amadori, Sergio ^{[3
]}

机构：

[1] Univ Tor Vergata, Dept Biomed & Prevent, Hematol, Rome, Italy

[2] Fdn Policlin Tor Vergata, Viale Oxford 81, I-00133 Rome, Italy

[3] GIMEMA Fdn, Rome, Italy

[4] Azienda Sanit Univ Integrata Udine, Hematol, Udine, Italy

[5] Fdn IRCCS Casa Sollievo Sofferenza, UO Ematol, San Giovanni Rotondo, FG, Italy

[6] Osped Ferrarotto, Catania, Italy

[7] Osped Niguarda Ca Granda, Milan, Italy

[8] Osped S Eugenio, Rome, Italy

[9] Azienda Osped SG Moscati, Avellino, Italy

[10] Azienda USL Pescara, Pescara, Italy

[11] Osped S Maria delle Croci, Ravenna, Italy

[12] Ist Tumori Romagna, Meldola, Italy

[13] St Orsola Marcello Malpighi Hosp, Bologna, Italy

[14] Univ Modena & Reggio Emilia, Dipartimento Sci Med & Chirurg Maternoinfantili &, Ematol, Modena, Italy

[15] AO SS Annunziata POSG Moscati, Taranto, Italy

[16] Osped S Maria Misericordia, Perugia, Italy

[17] Azienda Osped Univ Arcispedale St Anna, Ferrara, Italy

[18] Univ Bari Aldo Moro, Dipartimento Emergenza & Trapianti Organi, Ematol, Bari, Italy

[19] Osped Riuniti Villa Sofia Cervello, Palermo, Italy

[20] Azienda Osped St Andrea, Rome, Italy

[21] San Giovanni Addolorata, Rome, Italy

[22] SC Ematol AUSL IRCCS Reggio Emilia, Meldola, Italy

[23] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Milan, Italy

[24] Osped Riuniti Umberto GM LANCISI, Ancona, Italy

[25] Univ Sapienza, Dipartimento Biotecnol Cellulari & Ematol, Ematol, Rome, Italy

[26] AO Bianchi Melacrino Morelli, Reggio Di Calabria, Italy

来源：

BLOOD | 2019年 / 132卷 / 12期

关键词：

MINIMAL RESIDUAL DISEASE; HEMATOPOIETIC-CELL TRANSPLANTATION; POSTREMISSION THERAPY; PROGNOSTIC RELEVANCE; STANDARD-RISK; STRATIFICATION; AML; RECOMMENDATIONS; CLASSIFICATION; MANAGEMENT;

D O I：

10.1182/blood.2018886960

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We designed a trial in which postremission therapy of young patients with de novo acute myeloid leukemia (AML) was decided combining cytogenetics/genetics and postconsolidation levels of minimal residual disease (MRD). After induction and consolidation, favorable-risk patients (FR) were to receive autologous stem cell transplant (AuSCT) and poor-risk patients (PR) allogeneic stem cell transplant (AlloSCT). Intermediate-risk patients (IR) were to receive AuSCT or AlloSCT depending on the postconsolidation levels of MRD. Three hundred sixty-one of 500 patients (72%) achieved a complete remission, 342/361 completed the consolidation phase and were treatment allocated: 165 (48%) to AlloSCT (122 PR, 43 IR MRD-positive) plus 23 rescued after salvage therapy, for a total of 188 candidates; 150 (44%) to AuSCT (115 FR, 35 IR MRD-negative) plus 27 IR patients (8%) with no leukemia-associated phenotype, for a total of 177 candidates. Overall, 110/177 (62%) and 130/188 (71%) AuSCT or AlloSCT candidates received it, respectively. Two-year overall (OS) and disease-free survival (DFS) of the whole series was 56% and 54%, respectively. Two-year OS and DFS were 74% and 61% in the FR category, 42% and 45% in the PR category, 79% and 61% in the IR MRD-negative category, and 70% and 67% in the IR MRD-positive category. In conclusion, AuSCT may still have a role in FR and IR MRD-negative categories. In the IRMRD-positive category, AlloSCT prolongs OS and DFS to equal those of the FR category. Using all the available sources of stem cells, AlloSCT was delivered to 71% of the candidates.

引用

页码：935 / 945

页数：11

共 41 条

[1]

Acute Myeloid Leukemia, NCCN CLIN PRACTICE G

[2] Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia: Time to Move Toward a Minimal Residual Disease-Based Definition of Complete Remission? [J].

Araki, Daisuke ;

Wood, Brent L. ;

Othus, Megan ;

Radich, Jerald P. ;

Halpern, Anna B. ;

Zhou, Yi ;

Mielcarek, Marco ;

Estey, Elihu H. ;

Appelbaum, Frederick R. ;

Walter, Roland B. .

JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (04) :329-+

[3] Pre-transplant persistence of minimal residual disease does not contraindicate allogeneic stem cell transplantation for adult patients with acute myeloid leukemia [J].

Buccisano, F. ;

Maurillo, L. ;

Piciocchi, A. ;

Del Principe, M. I. ;

Picardi, A. ;

Cerretti, R. ;

Cudillo, L. ;

De Angelis, G. ;

Sarlo, C. ;

Cefalo, M. ;

Ditto, C. ;

Di Veroli, A. ;

Mariotti, B. ;

Nasso, D. ;

De Bellis, E. ;

Del Poeta, G. ;

Voso, M. T. ;

Sconocchia, G. ;

Lo Coco, F. ;

Arcese, W. ;

Amadori, S. ;

Venditti, A. .

BONE MARROW TRANSPLANTATION, 2017, 52 (03) :473-475

[4] Cytogenetic and molecular diagnostic characterization combined to postconsolidation minimal residual disease assessment by flow cytometry improves risk stratification in adult acute myeloid leukemia [J].

Buccisano, Francesco ;

Maurillo, Luca ;

Spagnoli, Alessandra ;

Del Principe, Maria Ilaria ;

Fraboni, Daniela ;

Panetta, Paola ;

Ottone, Tiziana ;

Consalvo, Maria Irno ;

Lavorgna, Serena ;

Bulian, Pietro ;

Ammatuna, Emanuele ;

Angelini, Daniela F. ;

Diamantini, Adamo ;

Campagna, Selenia ;

Ottaviani, Licia ;

Sarlo, Chiara ;

Gattei, Valter ;

Del Poeta, Giovanni ;

Arcese, William ;

Amadori, Sergio ;

Lo Coco, Francesco ;

Venditti, Adriano .

BLOOD, 2010, 116 (13) :2295-2303

[5] Minimal residual disease prior to allogeneic hematopoietic cell transplantation in acute myeloid leukemia: a meta-analysis [J].

Buckley, Sarah A. ;

Wood, Brent L. ;

Othus, Megan ;

Hourigan, Christopher S. ;

Ustun, Celalettin ;

Linden, Michael A. ;

DeFor, Todd E. ;

Malagola, Michele ;

Anthias, Chloe ;

Valkova, Veronika ;

Kanakry, Christopher G. ;

Gruhn, Bernd ;

Buccisano, Francesco ;

Devine, Beth ;

Walter, Roland B. .

HAEMATOLOGICA, 2017, 102 (05) :865-873

[6] Genomics of Acute Myeloid Leukemia Diagnosis and Pathways [J].

Bullinger, Lars ;

Doehner, Konstanze ;

Doehner, Hartmut .

JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (09) :934-946

[7] Attempts to Optimize Induction and Consolidation Treatment in Acute Myeloid Leukemia: Results of the MRC AML12 Trial [J].

Burnett, Alan K. ;

Hills, Robert K. ;

Milligan, Donald W. ;

Goldstone, Anthony H. ;

Prentice, Archibald G. ;

McMullin, Mary-Frances ;

Duncombe, Andrew ;

Gibson, Brenda ;

Wheatley, Keith .

JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (04) :586-595

[8]

Cohen P, 2005, J CLIN ONCOL, V23, p576S

[9] The European LeukemiaNet AML Working Party consensus statement on allogeneic HSCT for patients with AML in remission: an integrated-risk adapted approach [J].

Cornelissen, Jan J. ;

Gratwohl, Alois ;

Schlenk, Richard F. ;

Sierra, Jorge ;

Bornhaeuser, Martin ;

Juliusson, Gunnar ;

Racil, Zdenek ;

Rowe, Jacob M. ;

Russell, Nigel ;

Mohty, Mohamad ;

Lowenberg, Bob ;

Socie, Gerard ;

Niederwieser, Dietger ;

Ossenkoppele, Gert J. .

NATURE REVIEWS CLINICAL ONCOLOGY, 2012, 9 (10) :579-590

[10] Haploidentical, unmanipulated, G-CSF-primed bone marrow transplantation for patients with high-risk hematologic malignancies [J].

Di Bartolomeo, Paolo ;

Santarone, Stella ;

De Angelis, Gottardo ;

Picardi, Alessandra ;

Cudillo, Laura ;

Cerretti, Raffaella ;

Adorno, Gaspare ;

Angelini, Stefano ;

Andreani, Marco ;

De Felice, Lidia ;

Rapanotti, Maria Cristina ;

Sarmati, Loredana ;

Bavaro, Pasqua ;

Papalinetti, Gabriele ;

Di Nicola, Marta ;

Papola, Franco ;

Montanari, Mauro ;

Nagler, Arnon ;

Arcese, William .

BLOOD, 2013, 121 (05) :849-857

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