Contribution of measurable residual disease status to prediction accuracy of relapse and survival in adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation

Rodríguez-Arbolí, Eduardo; Othus, Megan; Orvain, Corentin; Zarling, Lucas C.; Sandmaier, Brenda M.; Milano, Filippo; Schoch, Gary; Davis, Chris; Deeg, H. Joachim; Appelbaum, Frederick R.; Storb, Rainer; Walter, Roland B.

doi:10.3324/haematol.2022.281631

Cited by 13 publications

(5 citation statements)

References 16 publications

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“…Although the retrospective nature does not allow to make direct comparisons between MAC and RIC populations due to baselines differences, MAC could not abrogate the adverse prognosis of MRD+ before HSCT, and the survival of MRD+ patients who received MAC was similar to RIC patients (both MRD− and MRD+). In line with our results, several studies demonstrate significant differences depending on the MRD status in patients receiving MAC, whereas this factor did not influence on OS and EFS on RIC patients ( 23 , 28 , 32 , 34 ). In the meta-analysis performed by Buckley et al., patients with MRD+ by different methods, including several studies using MFC, had significantly worse EFS an OS, and MAC was unable to attenuate the negative effects of a positive pretransplant MRD.…”

Section: Discussionsupporting

confidence: 92%

“…Several other published studies also reported that MRD+ had an impact on EFS due to an increased CIR ( 5 , 17 , 21 , 22 ). Furthermore, in many others, MRD+ also had an impact on OS ( 8 , 13 , 23 – 34 ). Although the incidence of relapse was higher in MRD+ patients, that did not have a statistically significant impact on OS in our cohort, maybe due to the shortest follow-up in the MRD− group.…”

Section: Discussionmentioning

confidence: 94%

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Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia

Núñez-Torrón Stock,

Jiménez Chillón,

Martín Moro

et al. 2024

Front. Oncol.

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BackgroundThe measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor. The interaction of pretransplant MRD and the conditioning intensity has not yet been clarified.ObjectiveThe aim of this study is to analyze the transplant outcomes of patients with AML who underwent HSCT in complete remission (CR), comparing patients with positive MRD (MRD+) and negative MRD (MRD−) before HSCT, and the interaction between conditioning intensity and pre-HSCT MRD.Study designWe retrospectively analyzed the transplant outcomes of 118 patients with AML who underwent HSCT in CR in a single institution, comparing patients with MRD+ and MRD− before HSCT using a cutoff of 0.1% on MFC, and the interaction between conditioning intensity and pre-HSCT MRD.ResultsPatients with MRD+ before HSCT had a significantly worse 2-year (2y) event-free survival (EFS) (56.5% vs. 32.0%, p = 0.018) than MRD− patients, due to a higher cumulative incidence of relapse (CIR) at 2 years (49.0% vs. 18.0%, p = 0.002), with no differences in transplant-related mortality (TRM) (2y-TRM, 19.0% and 25.0%, respectively, p = 0.588). In the analysis stratified by conditioning intensity, in patients who received MAC, those with MRD− before HSCT had better EFS (p = 0.009) and overall survival (OS) (p = 0.070) due to lower CIR (p = 0.004) than MRD+ patients. On the other hand, the survival was similar in reduced intensity conditioning (RIC) patients regardless of the MRD status.ConclusionsPatients with MRD+ before HSCT have worse outcomes than MRD− patients. In patients who received MAC, MRD− patients have better EFS and OS due to lower CIR than MRD+ patients, probably because they represent a more chemo-sensitive group. However, among RIC patients, results were similar regardless of the MRD status.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 94%

Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia

Núñez-Torrón Stock,

Jiménez Chillón,

Martín Moro

et al. 2024

Front. Oncol.

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“…Consistent with the performance characteristics of the assay and our approach in previous analyses, any level of MRD was considered MRD + . 12 , 13 , 14 , 15 …”

Section: Methodsmentioning

confidence: 99%

Phase 1/2 study of sorafenib added to cladribine, high-dose cytarabine, G-CSF, and mitoxantrone in untreated AML

et al. 2023

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The multikinase inhibitor sorafenib improves event-free survival (EFS) when used with 7+3 in younger adults with newly diagnosed acute myeloid leukemia (AML) irrespective of FLT3 mutation status. Here, we evaluated adding sorafenib to CLAG-M (cladribine, high-dose cytarabine, G-CSF, mitoxantrone) in a phase 1/2 trial of 81 adults age ≤60 years with newly diagnosed AML or high-grade myeloid neoplasm. Forty-six patients were treated in phase 1 with escalating doses of sorafenib and mitoxantrone. No maximum tolerated dose was reached, and a regimen including mitoxantrone at 18 mg/m2/day and sorafenib 400 mg twice daily was declared the recommended phase 2 dose (RP2D). Among 41 patients treated at the RP2D, a measurable residual disease-negative complete remission (MRDneg CR) rate of 83% (95% confidence interval [CI]: 68-93%) was obtained. Four-week mortality was 2% (95% CI: 0-13%). One-year overall survival (OS) and EFS were 80% (95% CI: 69-94%) and 76% (95% CI 64-90%), without significant difference in MRDneg CR rates, OS, or EFS between patients with or without FLT3-mutated disease. Comparing outcomes with CLAG-M/sorafenib to a matched cohort of 76 patients treated with CLAG-M alone, multivariable adjusted survival estimates were improved for the 41 patients receiving CLAG-M/sorafenib at RP2D (OS: hazard ratio [HR]=0.24 [95% CI: 0.07-0.82], P=0.023; EFS: HR=0.16 [95% CI: 0.05-0.53], P=0.003). Statistically significant benefit was limited to patients with intermediate-risk disease (in univariate analysis, P=0.01 for OS and P=0.02 for EFS). These data suggest CLAG-M/sorafenib is safe and improves OS and EFS relative to CLAG-M alone, with benefit primarily for patients with intermediate-risk disease. The trial is registered on clinicialtrials.gov as NCT02728050.

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“…Arbolí et al [19] developed a neural network method for disease status classification of patients. The model outperformed SVM (Support Vector Machine), random forest, and decision tree models, successfully learning the high-dimensional EHR (Electronic Health Record) data structure of phenotype hierarchy.…”

Section: B Medical Document Classification Modelsmentioning

confidence: 99%

Empowering Medical Data Analysis: An Advanced Deep Fusion Model for Sorting Medicine Document

Bo,

Shanshan,

Qing

et al. 2024

IEEE Access

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To enhance the accuracy of medical document classification, we propose an advanced deep fusion model for sorting medicine document. Specifically, we enhance text representation using the bidirectional encoder representation from transformers (BERT). BERT is a bidirectional model that considers context information in input sequences. This capability is particularly valuable for medical document, as medical information often requires understanding in a global context, such as diagnoses, medical history, and treatment plans. Furthermore, BERT can learn the semantics of words and phrases, comprehending the different meanings of the same word in distinct contexts, which is crucial for representing medical document. For example, In the context of cardiology, stroke often refers to a cerebrovascular accident, which is a condition where blood flow to the brain is disrupted, leading to neurological impairment. This type of stroke is related to the brain and is a significant concern in the field of cardiology due to its impact on the circulatory system. In dermatology, stroke might be used to refer to a type of skin condition, such as stroking the skin. However, this context is less common and not related to the cerebrovascular meaning. Subsequently, we employ both Convolutional Neural Network (ConvNet) and Bidirectional Long Short Term Memory (Bi-LSTM) to extract local features and global long-term dependencies, respectively. Their outputs are then fused to extract useful document features at multiple levels, effectively capturing the documental structure. The proposed deep fusion model leverages the complementary strengths of these components, enhancing the model's generalization ability and mitigating the risk of over-fitting. Ultimately, by comparing our approach with state-of-the-art methods in medical document classification, we demonstrate the effectiveness of the proposed methodology.

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Contribution of measurable residual disease status to prediction accuracy of relapse and survival in adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation

Abstract: Not available.

Cited by 13 publications

References 16 publications

Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia

Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia

Phase 1/2 study of sorafenib added to cladribine, high-dose cytarabine, G-CSF, and mitoxantrone in untreated AML

Empowering Medical Data Analysis: An Advanced Deep Fusion Model for Sorting Medicine Document

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