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Measurable residual disease, conditioning regimen intensity, and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: A registry analysis of 2292 patients by the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation.
Am J Hematol. 2018 09; 93(9):1142-1152.AJ

Abstract

Patients with acute myeloid leukemia (AML) in morphological first complete remission (CR1) pre-allogeneic hematopoietic cell transplantation (HCT) may have measurable residual disease (MRD) by molecular and immunophenotyping criteria. We assessed interactions of MRD status with HCT conditioning regimen intensity in patients aged <50 years (y) or ≥50y. This was a retrospective study by the European Society for Blood and Marrow Transplantation registry. Patients were >18y with AML CR1 MRD NEG/POS and recipients of HCT in 2000-2015. Conditioning regimens were myeloablative (MAC), reduced intensity (RIC) or non-myeloablative (NMA). Outcomes included leukemia free survival (LFS), overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM), chronic graft-vs-host (cGVHD), and GVHD-free and relapse-free survival (GRFS). The 2292 eligible patients were categorized into four paired groups: <50y MRD POS MAC (N = 240) vs RIC/NMA (N = 58); <50y MRD NEG MAC (N = 665) vs RIC/NMA (N = 195); ≥50y MRD POS MAC (N = 126) vs RIC/NMA (N = 230), and ≥50y MRD NEG MAC (N = 223) vs RIC/NMA (N = 555). In multivariate analysis RIC/NMA was only inferior to MAC for patients in the <50y MRD POS group, with worse RI (HR 1.71) and LFS (HR 1.554). Patients <50Y MRD NEG had less cGVHD after RIC/NMA HCT (HR 0.714). GRFS was not significantly affected by conditioning intensity in any group. Patients aged <50y with AML CR1 MRD POS status should preferentially be offered MAC allo-HCT. Prospective studies are needed to address whether patients with AML CR1 MRD NEG may be spared the toxicity of MAC regimens. New approaches are needed for ≥50y AML CR1 MRD POS.

Authors+Show Affiliations

Department of Haematology, Leeds Teaching Hospitals Trust, University of Leeds, Leeds, United Kingdom.EBMT Paris Study Office/CEREST-TC, Paris, France.CHU de Lille, LIRIC, INSERM U995, Université de Lille, Lille, France.Comprehensive Cancer Center, Stem Cell Transplantation Unit, Helsinki University Hospital, Helsinki, Finland.Service d'Hématologie Greffe, Hôpital Saint-Louis, Assistance Publique Hôpitaux de Paris, Paris, France.Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden.Service d'Hématologie, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France.Hematology Department, CHRU Besancon, INSERM UMR1098, Universite de Franche-Comte, Besancon, France.Department of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.Department of Haematology, Institute Gustave Roussy, Paris, France.Department of Haematology, Centre Hospital, Universitaire Grenoble Alpes, Grenoble, France.Acute Leukemia Working Party, European Society for Blood and Marrow Transplantation Paris Study Office/European Center for Biostatistical and Epidemiological Evaluation in Hematopoietic Cell Therapy (CEREST-TC), Paris, France.Hopital Saint-Antoine, Université Pierre and Marie Curie, Institut National de la Santé et de la Recherche Médicale Unite Mixte de Recherche U938, Paris, France.Division of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29981272

Citation

Gilleece, Maria H., et al. "Measurable Residual Disease, Conditioning Regimen Intensity, and Age Predict Outcome of Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First Remission: a Registry Analysis of 2292 Patients By the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation." American Journal of Hematology, vol. 93, no. 9, 2018, pp. 1142-1152.
Gilleece MH, Labopin M, Yakoub-Agha I, et al. Measurable residual disease, conditioning regimen intensity, and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: A registry analysis of 2292 patients by the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation. Am J Hematol. 2018;93(9):1142-1152.
Gilleece, M. H., Labopin, M., Yakoub-Agha, I., Volin, L., Socié, G., Ljungman, P., Huynh, A., Deconinck, E., Wu, D., Bourhis, J. H., Cahn, J. Y., Polge, E., Mohty, M., Savani, B. N., & Nagler, A. (2018). Measurable residual disease, conditioning regimen intensity, and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: A registry analysis of 2292 patients by the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation. American Journal of Hematology, 93(9), 1142-1152. https://doi.org/10.1002/ajh.25211
Gilleece MH, et al. Measurable Residual Disease, Conditioning Regimen Intensity, and Age Predict Outcome of Allogeneic Hematopoietic Cell Transplantation for Acute Myeloid Leukemia in First Remission: a Registry Analysis of 2292 Patients By the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation. Am J Hematol. 2018;93(9):1142-1152. PubMed PMID: 29981272.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Measurable residual disease, conditioning regimen intensity, and age predict outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukemia in first remission: A registry analysis of 2292 patients by the Acute Leukemia Working Party European Society of Blood and Marrow Transplantation. AU - Gilleece,Maria H, AU - Labopin,Myriam, AU - Yakoub-Agha,Ibrahim, AU - Volin,Liisa, AU - Socié,Gerard, AU - Ljungman,Per, AU - Huynh,Anne, AU - Deconinck,Eric, AU - Wu,Depei, AU - Bourhis,Jean Henri, AU - Cahn,Jean Yves, AU - Polge,Emmanuelle, AU - Mohty,Mohamad, AU - Savani,Bipin N, AU - Nagler,Arnon, Y1 - 2018/08/15/ PY - 2018/04/21/received PY - 2018/06/13/revised PY - 2018/06/18/accepted PY - 2018/7/8/pubmed PY - 2019/7/10/medline PY - 2018/7/8/entrez SP - 1142 EP - 1152 JF - American journal of hematology JO - Am J Hematol VL - 93 IS - 9 N2 - Patients with acute myeloid leukemia (AML) in morphological first complete remission (CR1) pre-allogeneic hematopoietic cell transplantation (HCT) may have measurable residual disease (MRD) by molecular and immunophenotyping criteria. We assessed interactions of MRD status with HCT conditioning regimen intensity in patients aged <50 years (y) or ≥50y. This was a retrospective study by the European Society for Blood and Marrow Transplantation registry. Patients were >18y with AML CR1 MRD NEG/POS and recipients of HCT in 2000-2015. Conditioning regimens were myeloablative (MAC), reduced intensity (RIC) or non-myeloablative (NMA). Outcomes included leukemia free survival (LFS), overall survival (OS), relapse incidence (RI), non-relapse mortality (NRM), chronic graft-vs-host (cGVHD), and GVHD-free and relapse-free survival (GRFS). The 2292 eligible patients were categorized into four paired groups: <50y MRD POS MAC (N = 240) vs RIC/NMA (N = 58); <50y MRD NEG MAC (N = 665) vs RIC/NMA (N = 195); ≥50y MRD POS MAC (N = 126) vs RIC/NMA (N = 230), and ≥50y MRD NEG MAC (N = 223) vs RIC/NMA (N = 555). In multivariate analysis RIC/NMA was only inferior to MAC for patients in the <50y MRD POS group, with worse RI (HR 1.71) and LFS (HR 1.554). Patients <50Y MRD NEG had less cGVHD after RIC/NMA HCT (HR 0.714). GRFS was not significantly affected by conditioning intensity in any group. Patients aged <50y with AML CR1 MRD POS status should preferentially be offered MAC allo-HCT. Prospective studies are needed to address whether patients with AML CR1 MRD NEG may be spared the toxicity of MAC regimens. New approaches are needed for ≥50y AML CR1 MRD POS. SN - 1096-8652 UR - https://www.unboundmedicine.com/medline/citation/29981272/Measurable_residual_disease_conditioning_regimen_intensity_and_age_predict_outcome_of_allogeneic_hematopoietic_cell_transplantation_for_acute_myeloid_leukemia_in_first_remission:_A_registry_analysis_of_2292_patients_by_the_Acute_Leukemia_Working_Party_European_Society_of_Blood_and_Marrow_Transplantation_ L2 - https://doi.org/10.1002/ajh.25211 DB - PRIME DP - Unbound Medicine ER -