Peripheral blood blast rate of clearance is an independent predictor of clinical response and outcomes in acute myeloid leukaemia

Holtzman, Noa G.; Chaer, Firas El; Ali, Omer; Patel, Ameet; Duong, Vu H.; Sausville, Edward A.; Singh, Zeba N.; Koka, Rima; Zou, Ying; Etemadi, Arash; Emadi, Ashkan

doi:10.1111/bjh.16261

Cited by 7 publications

(3 citation statements)

References 15 publications

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“…In our work we aimed to integrate MRD evaluation with PBC as an added, earlier, treatment‐related biomarker previously demonstrated to be a powerful predictor of response to chemotherapy by several studies, including ours 12‐18 . First, we confirmed the prognostic value of PBC in a cohort of selected patients who achieved CR after the first induction cycle.…”

Section: Discussionmentioning

confidence: 59%

“…In order to anticipate information about chemosensitivity, several studies evaluated the kinetics of blast disappearance from peripheral blood (PB) after a few days of induction chemotherapy 12‐18 . Despite using different methods, all reported a clear impact of the peripheral blast clearance (PBC) on the probability of response to induction chemotherapy and survival.…”

Section: Introductionmentioning

confidence: 99%

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Early peripheral blast cell clearance predicts minimal residual disease status and refines disease prognosis in acute myeloid leukemia

Mannelli¹,

Gianfaldoni²,

Bencini³

et al. 2020

American J Hematol

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Minimal residual disease (MRD) assessment in acute myeloid leukemia (AML) is increasingly used in risk stratification. However, several issues around this use are unresolved, including, among others, the most suitable time-point(s) for its application. Overall, late assessments appear more effective at distinguishing outcome but, in some studies, the early evaluations were already highly informative, anticipating the value of later ones. Our work integrated MRD with peripheral blast clearance (PBC), a treatment-related biomarker previously demonstrated to be a powerful predictor of response. From 2007 to 2014, we have studied 120 patients treated according to the NILG 02-06 trial and who achieved CR after induction. Patients in PBC-defined categories (separated by a 1.5-log threshold) showed significantly different probabilities of attaining MRD negativity, after either induction (MRD1) or consolidation (MRD2). Peripheral blast clearance combined with MRD1 largely anticipated MRD2-related information: when both biomarkers predicted chemosensitive disease (PBC high /MRD1 neg), the rate of MRD2-negativity was 90%, and DFS and OS estimates were 68% and 76% at 3 years, respectively. When both markers were unfavorable (PBC low /MRD1 pos), rates of MRD2 negativity, DFS, and OS were 20%, 34%, and 24%, respectively, at 3 years. In fact, MRD2 added prognostic value only in cases with discordant PBC/MRD1 data. Our data support a reasoned timing for MRD-based therapeutic decisions, modulated on individual chemosensitivity, an approach we have implemented in a forthcoming prospective multi-center trial by Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA). 1 | INTRODUCTION The term "minimal (measurable) residual disease" (MRD) refers to the presence of leukemic cells below the morphology-based threshold that defines complete remission (CR). The level of sensitivity for MRD detection is usually placed in a range between 10 −3 to 10 −5 , which is the capability to reveal one leukemic cell per 1000-100 000 normal cells. 1 The persistence of MRD predicts a poor outcome in acute myeloid leukemia (AML). 2-7 As a biomarker expressing the degree of actual response to chemotherapy, MRD catches the diversity of the Francesco Mannelli and Giacomo Gianfaldoni contributed equally to this work.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Early peripheral blast cell clearance predicts minimal residual disease status and refines disease prognosis in acute myeloid leukemia

Mannelli¹,

Gianfaldoni²,

Bencini³

et al. 2020

American J Hematol

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“…In addition, clinical studies have documented correlation between treatment failure and insufficient reduction of the PB blast cells at day 5 of therapy induction [6], or between complete remission and 90% of reduction in the circulating blast cells [7]. Likewise, other authors have reported that PB blast percentages at day 7 [8], determined by flow cytometry and morphologic analysis, might become a strong indicator of failure of the therapy induction [9]. However, the confidence interval of blast counting varies with the observer when assessing morphology alone [10].…”

Section: Introductionmentioning

confidence: 99%

Intra‐nucleus mosaic pattern (InMop) and whole‐cell Haralick combined‐descriptor for identifying and characterizing acute leukemia blasts on single cell peripheral blood images

et al. 2023

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Acute leukemia is usually diagnosed when a test of peripheral blood shows at least 20% of abnormal immature cells (blasts), a figure even lower in case of recurrent cytogenetic abnormalities. Blast identification is crucial for White Blood Cell (WBC) Counting, which depends on both identifying the cell type and characterizing the cellular morphology, processes susceptible of inter‐ and intraobserver variability. The present work introduces an image combined‐descriptor to detect blasts and determine their probable lineage. This strategy uses an Intra‐nucleus Mosaic pattern (InMop) descriptor that captures subtle nuclei differences within WBCs, and Haralick's statistics which quantify the local structure of both nucleus and cytoplasm. The InMop captures WBC inner‐nucleus structure by applying a multiscale Shearlet decomposition over a repetitive pattern (mosaic) of automatically‐segmented nuclei. As a complement, Haralick's statistics characterize the local structure of the whole cell from an intensity co‐occurrence matrix representation. Both InMoP and Haralick‐based descriptors are calculated using the b‐channel from Lab color‐space. The combined‐descriptor is assessed by differentiating blasts from non‐leukemic cells with support vector machine (SVM) classifiers and different transformation kernels, in two public and independent databases. The first database‐D1 (n=260) is composed of healthy and Acute Lymphoid Leukemia (ALL) single cell images, and second database‐D2 contains Acute Myeloid Leukemia (AML) blasts (n=3,294) and non‐blast (n=15,071) cell images. In a first experiment, blasts vs non‐blast differentiation is performed by training with a subset of D2 (n=6,588) and testing in D1 (n=260), obtaining a training AUC of 0.991±0.002 and AUC=0.782 for the independent validation. A second experiment automatically differentiates AML blasts (260 images from D2) from ALL blasts (260 images from D1), with an AUC of 0.93. In a third experiment, state‐of‐the‐art strategies, VGG16 and RESNEXT convolutional neural networks (CNN), separate blast from non‐blast cells in both databases. The VGG16 showed an AUC of 0.673 and the RESNEXT of 0.75. Reported metrics for all the experiments are area under the ROC curve (AUC), accuracy and F1‐score.This article is protected by copyright. All rights reserved.

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Multiplicity of Time Scales in Blood Cell Formation and Leukemia

Stiehl

2023

Mathematics Online First Collections

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Peripheral blood blast rate of clearance is an independent predictor of clinical response and outcomes in acute myeloid leukaemia

Cited by 7 publications

References 15 publications

Early peripheral blast cell clearance predicts minimal residual disease status and refines disease prognosis in acute myeloid leukemia

Early peripheral blast cell clearance predicts minimal residual disease status and refines disease prognosis in acute myeloid leukemia

Intra‐nucleus mosaic pattern (InMop) and whole‐cell Haralick combined‐descriptor for identifying and characterizing acute leukemia blasts on single cell peripheral blood images

Multiplicity of Time Scales in Blood Cell Formation and Leukemia

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