Post-Transplantation Day +100 Minimal Residual Disease Detection Rather Than Mixed Chimerism Predicts Relapses after Allogeneic Stem Cell Transplantation for Intermediate-Risk Acute Myelogenous Leukemia Patients Undergoing Transplantation in Complete Remission

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@article{c33ab2b387574b38ab3f6d7f97120391,
title = "Post-Transplantation Day +100 Minimal Residual Disease Detection Rather Than Mixed Chimerism Predicts Relapses after Allogeneic Stem Cell Transplantation for Intermediate-Risk Acute Myelogenous Leukemia Patients Undergoing Transplantation in Complete Remission",
abstract = "Chimerism and minimal residual disease (MRD) are suggested to be prognostic for post-transplantation relapse in patients with acute myelogenous leukemia (AML). Nevertheless, the predictive value of both approaches in homogeneous populations remains underinvestigated. Here we suggest that MRD may have greater predictive value for relapse than mixed chimerism (MC) in intermediate-risk AML patients. Seventy-nine patients with intermediate-risk AML (40 males; median age, 57 years [range, 19 to 77 years]) were included. MRD detection on day +100 was performed in bone marrow via multiparameter flow cytometry (MFC) and quantitative real-time PCR (qPCR) for patients with an NPM1 mutation. Chimerism analysis was performed in peripheral blood. MC was defined as the persistence of <99.9% of donor alleles. The area under the receiver operating characteristic curve was highest for qPCR-MRD (.93), followed by MFC-MRD (.80) and MC (.65). The highest rate of relapse at 3 years was observed in day +100 qPCR-MRD-positive patients (100%), followed by MFC-MRD-positive patients (55%; P < .001). No patients with MC and without detectable MRD experienced relapse. The median 3-year overall survival (OS) and leukemia-free survival (LFS) for patients with MC without detectable MRD were both 86% (range, 61% to 96%), significantly higher than the values in day +100 MFC-MRD-positive patients (OS, 61% [range, 36% to 84%]; LFS: 30% [range, 11% to 59%]) and with day +100 qPCR-MRD-positive patients (OS: 17% [range, 3% to 56%], P = .001; LFS: 0%, P < .001). In patients with intermediate-risk AML, the qPCR-MRD on day +100 was highly predictive for relapse and long-term survival after allogeneic stem cell transplantation, followed closely by MFC-MRD. In contrast, chimerism status had limited predictive potential. Thus, molecular and flow cytometry MRD monitoring rather than MC in the first several months post-transplantation can identify patients at increased risk of relapse who may benefit from early post-transplantation preemptive intervention.",
author = "Evgeny Klyuchnikov and Anita Badbaran and Radwan Massoud and Ulrike Fritzsche-Friedland and Petra Freiberger and Francis Ayuk and Christine Wolschke and Ulrike Bacher and Nicolaus Kr{\"o}ger",
note = "Copyright {\textcopyright} 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.",
year = "2022",
month = jul,
doi = "10.1016/j.jtct.2022.04.009",
language = "English",
volume = "28",
pages = "374.e1--374.e9",
journal = "TRANSPL CELL THER",
issn = "2666-6375",
publisher = "Elsevier BV",
number = "7",

}

RIS

TY - JOUR

T1 - Post-Transplantation Day +100 Minimal Residual Disease Detection Rather Than Mixed Chimerism Predicts Relapses after Allogeneic Stem Cell Transplantation for Intermediate-Risk Acute Myelogenous Leukemia Patients Undergoing Transplantation in Complete Remission

AU - Klyuchnikov, Evgeny

AU - Badbaran, Anita

AU - Massoud, Radwan

AU - Fritzsche-Friedland, Ulrike

AU - Freiberger, Petra

AU - Ayuk, Francis

AU - Wolschke, Christine

AU - Bacher, Ulrike

AU - Kröger, Nicolaus

N1 - Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

PY - 2022/7

Y1 - 2022/7

N2 - Chimerism and minimal residual disease (MRD) are suggested to be prognostic for post-transplantation relapse in patients with acute myelogenous leukemia (AML). Nevertheless, the predictive value of both approaches in homogeneous populations remains underinvestigated. Here we suggest that MRD may have greater predictive value for relapse than mixed chimerism (MC) in intermediate-risk AML patients. Seventy-nine patients with intermediate-risk AML (40 males; median age, 57 years [range, 19 to 77 years]) were included. MRD detection on day +100 was performed in bone marrow via multiparameter flow cytometry (MFC) and quantitative real-time PCR (qPCR) for patients with an NPM1 mutation. Chimerism analysis was performed in peripheral blood. MC was defined as the persistence of <99.9% of donor alleles. The area under the receiver operating characteristic curve was highest for qPCR-MRD (.93), followed by MFC-MRD (.80) and MC (.65). The highest rate of relapse at 3 years was observed in day +100 qPCR-MRD-positive patients (100%), followed by MFC-MRD-positive patients (55%; P < .001). No patients with MC and without detectable MRD experienced relapse. The median 3-year overall survival (OS) and leukemia-free survival (LFS) for patients with MC without detectable MRD were both 86% (range, 61% to 96%), significantly higher than the values in day +100 MFC-MRD-positive patients (OS, 61% [range, 36% to 84%]; LFS: 30% [range, 11% to 59%]) and with day +100 qPCR-MRD-positive patients (OS: 17% [range, 3% to 56%], P = .001; LFS: 0%, P < .001). In patients with intermediate-risk AML, the qPCR-MRD on day +100 was highly predictive for relapse and long-term survival after allogeneic stem cell transplantation, followed closely by MFC-MRD. In contrast, chimerism status had limited predictive potential. Thus, molecular and flow cytometry MRD monitoring rather than MC in the first several months post-transplantation can identify patients at increased risk of relapse who may benefit from early post-transplantation preemptive intervention.

AB - Chimerism and minimal residual disease (MRD) are suggested to be prognostic for post-transplantation relapse in patients with acute myelogenous leukemia (AML). Nevertheless, the predictive value of both approaches in homogeneous populations remains underinvestigated. Here we suggest that MRD may have greater predictive value for relapse than mixed chimerism (MC) in intermediate-risk AML patients. Seventy-nine patients with intermediate-risk AML (40 males; median age, 57 years [range, 19 to 77 years]) were included. MRD detection on day +100 was performed in bone marrow via multiparameter flow cytometry (MFC) and quantitative real-time PCR (qPCR) for patients with an NPM1 mutation. Chimerism analysis was performed in peripheral blood. MC was defined as the persistence of <99.9% of donor alleles. The area under the receiver operating characteristic curve was highest for qPCR-MRD (.93), followed by MFC-MRD (.80) and MC (.65). The highest rate of relapse at 3 years was observed in day +100 qPCR-MRD-positive patients (100%), followed by MFC-MRD-positive patients (55%; P < .001). No patients with MC and without detectable MRD experienced relapse. The median 3-year overall survival (OS) and leukemia-free survival (LFS) for patients with MC without detectable MRD were both 86% (range, 61% to 96%), significantly higher than the values in day +100 MFC-MRD-positive patients (OS, 61% [range, 36% to 84%]; LFS: 30% [range, 11% to 59%]) and with day +100 qPCR-MRD-positive patients (OS: 17% [range, 3% to 56%], P = .001; LFS: 0%, P < .001). In patients with intermediate-risk AML, the qPCR-MRD on day +100 was highly predictive for relapse and long-term survival after allogeneic stem cell transplantation, followed closely by MFC-MRD. In contrast, chimerism status had limited predictive potential. Thus, molecular and flow cytometry MRD monitoring rather than MC in the first several months post-transplantation can identify patients at increased risk of relapse who may benefit from early post-transplantation preemptive intervention.

U2 - 10.1016/j.jtct.2022.04.009

DO - 10.1016/j.jtct.2022.04.009

M3 - SCORING: Journal article

C2 - 35429661

VL - 28

SP - 374.e1-374.e9

JO - TRANSPL CELL THER

JF - TRANSPL CELL THER

SN - 2666-6375

IS - 7

ER -