Early assessment of minimal residual disease in AML by flow cytometry during aplasia identifies patients at increased risk of relapse

Köhnke, Thomas; Sauter, Daniela; Ringel, Katharina; Hoster, Eva; Laubender, RP; Hubmann, Max; Sk, Bohlander; Kakadia, PM; Schneider, Stephanie; Dufour, Annika; Sauerland, Maria-Cristina; Berdel, W. E.; Büchner, Thomas; Wörmann, Bernhard; Braess, Jan; Hiddemann, Wolfgang; Spiekermann, Karsten; Subklewe, Marion

doi:10.1038/leu.2014.186

Cited by 61 publications

(45 citation statements)

References 35 publications

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“…A positive minimal residual disease (MRD) status is considered a negative predictive factor and also as an established marker for relapse in ALL [4]. The same trend seems to emerge for AML [5,6]. Immunotherapy can be used to modify otherwise inevitable relapse in these scenarios.…”

Section: Acute Leukemiamentioning

confidence: 94%

Immunotherapy in adult acute leukemia

2017

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Section: Acute Leukemiamentioning

confidence: 94%

Immunotherapy in adult acute leukemia

2017

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“…Meanwhile, cytogenetic and molecular markers are regarded as the best predictors of survival in AML. Furthermore, early flow MRD during aplasia after the first chemotherapy can also predict RFS and might play an important role in the planning of postremission therapy for patients at a high risk [23]. Based on these results, patients would be selected for allogeneic stem cell transplantation.…”

Section: Discussionmentioning

confidence: 99%

The Time to Clearance of Peripheral Blood Blasts Predicts Complete Remission and Survival in Chinese Adults with Acute Myeloid Leukemia

Zhu²,

Zhang³

et al. 2016

Acta Haematol

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The value of clearance of peripheral blood blasts (PBB) as a predictor of outcomes in acute myeloid leukemia (AML) is controversial. To investigate the prognostic significance of the time to clearance of PBB after induction in Chinese patients with AML, a retrospective analysis of 146 patients with newly diagnosed AML at Shanghai Ruijin Hospital was performed. Patients were categorized into early blast clearance (EBC; ≤5 days) and delayed blast clearance (DBC; >5 days) groups based on a receiver operating characteristic analysis. Complete remission (CR) after induction chemotherapy was related to the time to clearance of PBB (p < 0.001). Relapse-free survival (RFS; p = 0.003) and overall survival (p < 0.001) were longer in the EBC group. Multivariate analysis demonstrated that the time to clearance of PBB and cytogenetic risk independently predicted CR and RFS. Early clearance of PBB after induction chemotherapy can be a significant predictor of survival outcomes in AML patients.

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“…23,28 Eleven additional patients had other types of NPM1 mutations, and no qPCR assay was available for these. Flow cytometric MRD assessment, based on detection of leukemia-associated immunophenotypes, was performed using FACSCalibur (BD Biosciences, San Jose, CA, USA; 60 patients) or NAVIOS (Beckman Coulter, Brea, CA, USA; 21 patients) instruments.…”

Section: Minimal Residual Disease Assessmentmentioning

confidence: 99%

Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia

Rothenberg‐Thurley

Amler²,

Goerlich³

et al. 2017

Leukemia

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Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance of these clones for AML relapse. Here, we characterized paired pre-treatment and remission samples from 126 AML patients for mutations in 68 leukemia-associated genes. Fifty patients (40%) retained ≥1 mutation during remission at a variant allele frequency of ≥2%. Mutation persistence was most frequent in DNMT3A (65% of patients with mutations at diagnosis), SRSF2 (64%), TET2 (55%), and ASXL1 (46%), and significantly associated with older age (p<.0001) and, in multivariate analyses adjusting for age, genetic risk, and allogeneic transplantation, with inferior relapse-free survival (hazard ratio, 2.34; p=.0039) and overall survival (hazard ratio, 2.14; p=.036). Patients with persisting mutations had a higher cumulative incidence of relapse before, but not after allogeneic stem cell transplantation. Our work underlines the relevance of mutation persistence during first remission as a novel risk factor in AML. Persistence of pre-leukemic clones may contribute to the inferior outcome of elderly AML patients. Allogeneic transplantation abrogated the increased relapse risk associated with persisting pre-leukemic clones, suggesting that mutation persistence may guide postremission treatment.

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Early assessment of minimal residual disease in AML by flow cytometry during aplasia identifies patients at increased risk of relapse

Cited by 61 publications

References 35 publications

Immunotherapy in adult acute leukemia

Immunotherapy in adult acute leukemia

The Time to Clearance of Peripheral Blood Blasts Predicts Complete Remission and Survival in Chinese Adults with Acute Myeloid Leukemia

Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia

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