A Multivariable Mixed-Effects Framework for Predicting Disease Progression in Acute Myeloid Leukemia Using Peripheral Hematology, FLT3 Expression, and Patient Compliance
- 1University of Alborz, Department of Paramedical Sciences, Karaj, Iran
Abstract
BackgroundThe clinical course of acute leukemias and related hematologic neoplasms is defined by aggressive clonal proliferation, severe hematopoietic disruption, and recurrent molecular alterations. Although serial bone marrow biopsies, multiparameter flow cytometry, and next-generation sequencing remain standard surveillance modalities, procedural invasiveness, high costs, and operational turnaround times limit their frequency. Minimally invasive, scalable biomarkers--integrating routine hematologic indices, targeted gene expression, circulating oncoprotein levels, and patient compliance metrics--may provide an accessible framework for dynamic monitoring.
MethodsIn this longitudinal cohort study of 66 patients across 272 serial encounters (discrete follow-up intervals: days 0, 14, 41, 71, and 78), we assessed the prognostic value of peripheral complete blood counts (white blood cell count [WBC], hemoglobin [Hb]), molecular indicators (FLT3, NPM1, and DNMT3A transcript levels; targeted soluble FLT3 quantification), and medication adherence. The primary clinical endpoint was longitudinal progression to critical deterioration or disease-related mortality. Generalized linear mixed-effects models (GLMM) with patient-specific random intercepts were constructed to account for intra-subject repeated measures. Predictors were standardized per 1-SD increment. Model performance was assessed via the Akaike Information Criterion (AIC) and the Concordance index (C-index).
ResultsLeukocyte expansion correlated inversely with hemoglobin concentration (r = -0.877, p < 0.001), reflecting bone marrow infiltration and secondary erythroid suppression. Multivariable mixed-effects modeling confirmed that elevated WBC count (adjusted odds ratio [aOR] = 1.52 per 1-SD increase; 95% CI: 1.24-1.86; p < 0.001) and reduced medication adherence (aOR = 0.58; 95% CI: 0.44-0.76; p < 0.001) independently predicted adverse clinical transition. Integrating targeted molecular markers (FLT3 expression and soluble protein levels) with routine hematologic indices and adherence demonstrated superior calibration and discrimination over single-domain models ({Delta}AIC [≥] 116; Harrells C-index = 0.81).
ConclusionsReadily accessible peripheral hematologic indices, targeted molecular quantification, and medication adherence provide complementary prognostic information regarding disease activity. Integrating these low-burden parameters into clinical workflows offers an efficient, scalable paradigm for early risk stratification in hematologic malignancies.
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BibTeX
@misc{dumar2026multivariable,
title = {{A Multivariable Mixed-Effects Framework for Predicting Disease Progression in Acute Myeloid Leukemia Using Peripheral Hematology, FLT3 Expression, and Patient Compliance}},
author = {M. M. Amiri Dumar and M. Aghajani},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.04.26364699},
url = {https://www.medrxiv.org/content/10.64898/2026.10.04.26364699v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A Multivariable Mixed-Effects Framework for Predicting Disease Progression in Acute Myeloid Leukemia Using Peripheral Hematology, FLT3 Expression, and Patient Compliance
AU - M. M. Amiri Dumar
AU - M. Aghajani
PY - 2026
DA - 2026/10/04
PB - medRxiv
DO - 10.64898/2026.10.04.26364699
UR - https://www.medrxiv.org/content/10.64898/2026.10.04.26364699v1
AB - BackgroundThe clinical course of acute leukemias and related hematologic neoplasms is defined by aggressive clonal proliferation, severe hematopoietic disruption, and recurrent molecular alterations. Although serial bone marrow biopsies, multiparameter flow cytometry, and next-generation sequencing remain standard surveillance modalities, procedural invasiveness, high costs, and operational turnaround times limit their frequency. Minimally invasive, scalable biomarkers--integrating routine hematologic indices, targeted gene expression, circulating oncoprotein levels, and patient compliance metrics--may provide an accessible framework for dynamic monitoring. MethodsIn this longitudinal cohort study of 66 patients across 272 serial encounters (discrete follow-up intervals: days 0, 14, 41, 71, and 78), we assessed the prognostic value of peripheral complete blood counts (white blood cell count [WBC], hemoglobin [Hb]), molecular indicators (FLT3, NPM1, and DNMT3A transcript levels; targeted soluble FLT3 quantification), and medication adherence. The primary clinical endpoint was longitudinal progression to critical deterioration or disease-related mortality. Generalized linear mixed-effects models (GLMM) with patient-specific random intercepts were constructed to account for intra-subject repeated measures. Predictors were standardized per 1-SD increment. Model performance was assessed via the Akaike Information Criterion (AIC) and the Concordance index (C-index). ResultsLeukocyte expansion correlated inversely with hemoglobin concentration (r = -0.877, p < 0.001), reflecting bone marrow infiltration and secondary erythroid suppression. Multivariable mixed-effects modeling confirmed that elevated WBC count (adjusted odds ratio [aOR] = 1.52 per 1-SD increase; 95% CI: 1.24-1.86; p < 0.001) and reduced medication adherence (aOR = 0.58; 95% CI: 0.44-0.76; p < 0.001) independently predicted adverse clinical transition. Integrating targeted molecular markers (FLT3 expression and soluble protein levels) with routine hematologic indices and adherence demonstrated superior calibration and discrimination over single-domain models ({Delta}AIC [≥] 116; Harrells C-index = 0.81). ConclusionsReadily accessible peripheral hematologic indices, targeted molecular quantification, and medication adherence provide complementary prognostic information regarding disease activity. Integrating these low-burden parameters into clinical workflows offers an efficient, scalable paradigm for early risk stratification in hematologic malignancies.
ER -