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Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2020.tde-12072019-090313
Document
Author
Full name
Gerson Hiroshi Yoshinari Júnior
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2019
Supervisor
Committee
Rego, Eduardo Magalhães (President)
Colli, Leandro Machado
Traina, Fabíola
Yang, Hyun Mo
Title in Portuguese
Um modelo de equações diferenciais ordinárias aplicado à leucemia promielocítica aguda
Keywords in Portuguese
Ecologia
Equações Diferenciais Ordinárias
Leucemia Promielocítica Aguda
Modelo Matemático
Abstract in Portuguese
A Leucemia Promielocítica Aguda (LPA) é uma condição incomum, potencialmente letal, no qual o tratamento baseado em análise de risco de recaída levou a melhores resultados terapêuticos. Devido à raridade e sobrevida global relativamente alta, ensaios clínicos prospectivos para investigar protocolos alternativos de tratamento são desafiadores. Modelos matemáticos podem oferecer informações úteis neste cenário, otimizando tempo e custos de estudo, aumento as chances de resultados positivos. Foram coletados dados clínicos e laboratoriais dos primeiros 30 dias de tratamento de todos os 39 pacientes diagnosticados com LPA tratados no Hospital das Clínicas de Ribeirão Preto (HCRP) sob o protocolo de tratamento do International Consortium on Acute Leukemia (ICAL). Foi proposto um modelo matemático baseado em Equações Diferenciais Ordinárias (EDOs) que representa a dinâmica dos leucócitos no sangue periférico e os efeitos do protocolo ICAL de tratamento na dinâmica da doença. Observou-se que a coorte do HCRP apresenta características demográficas e desfechos clínicos comparáveis aos publicados em estudos prévios em LPA. Com 41,8 meses de seguimento mediano, sobrevida livre de recaída e sobrevida global em dois anos foram ambos de 78,7%. Para um conjunto adequado de dados laboratoriais, as soluções oferecidas pelo modelo ajustam-se adequadamente. Informações derivadas do modelo podem auxiliar na prática clínica e no desenho de ensaios clínicos, sugerindo protocolos de tratamento e determinando riscos de recaída.
Title in English
A mathematical model on acute promyelocytic leukemia based on ordinary differential equations
Keywords in English
Acute Promyelocytic Leukemia
Ecology
Mathematical Model
Ordinary Differential Equations
Abstract in English
Acute Promyelocytic Leukemia (APL) is a rare condition, potentially lethal, in which risk-based therapy led to better outcomes. Due to its rarity and relatively high overall survival rate, prospective randomized trials to investigate alternative treatment schedules are challenging. Mathematical models may provide useful information in this matter. We collected clinical data from 39 patients treated for APL under the International Consortium on Acute Leukemia (ICAL) protocol and laboratory data during induction. We propose a mathematical model based on Ordinary Differential Equations (ODEs) that represents the dynamics of leucocytes in peripheral blood and the effect of ICAL treatment on the disease's dynamics. We observed that our cohort presents demographic characteristics and clinical outcomes similar to previous clinical trials on APL. With 41.8 months of follow-up, relapse-free survival and overall survival at two years were both 78.7%. For an adequate set of clinical data, the model solutions show good fit. Pieces of information derived from the model may assist in clinical practice and design of clinical trials, suggesting alternative chemotherapy protocols and determining the risk of relapse.
 
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Publishing Date
2020-01-14
 
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