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A Bayesian joint model for multivariate longitudinal and time-to-event data with application to ALL maintenance

Damitri Kundu1, Partha Sarkar2, Manash Pratim Gogoi3

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|March 8, 2023
PubMed
Summary

This study on childhood Acute Lymphocytic Leukemia (ALL) found that neutrophil and platelet counts, not white blood cell counts, predict relapse. Lower 6MP and higher MTx doses reduced relapse probability in ALL patients.

Keywords:
Acute lymphocytic leukemia (ALL)MCMCjoint modellongitudinal outcomesposterior predictive distribution

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Area of Science:

  • Pediatric Oncology
  • Biostatistics
  • Translational Cancer Research

Background:

  • Acute Lymphocytic Leukemia (ALL) is the most common childhood cancer.
  • Standard treatments involve drugs like 6-mercaptopurine (6MP) and methotrexate (MTx).
  • Identifying biomarkers for relapse prediction and treatment effectiveness is crucial.

Purpose of the Study:

  • To identify longitudinal biomarkers associated with time-to-relapse in pediatric ALL patients.
  • To assess the effectiveness of 6MP and MTx treatments in relation to relapse.
  • To develop and validate a statistical model for analyzing longitudinal biomarkers and time-to-relapse.

Main Methods:

  • A Bayesian joint model was developed, integrating a linear mixed model for longitudinal biomarkers (white blood cell, neutrophil, platelet counts) and a semi-parametric proportional hazards model for time-to-relapse.
  • The model analyzed data from 236 pediatric ALL patients treated at TTCRC, Kolkata.
  • The model's ability to assess covariate effects and impute missing data was evaluated.

Main Results:

  • Neutrophil and platelet counts were significantly associated with time-to-relapse in ALL patients.
  • White blood cell count showed no significant association with time-to-relapse.
  • Lower 6MP doses and higher MTx doses were linked to a reduced probability of relapse.
  • Patients classified as "high-risk" at presentation exhibited the lowest relapse probability.

Conclusions:

  • The developed Bayesian joint model effectively identifies biomarkers predicting relapse in pediatric ALL.
  • Neutrophil and platelet counts are critical prognostic indicators for ALL relapse.
  • Treatment strategies involving adjusted 6MP and MTx dosages may influence relapse rates, with potential implications for high-risk groups.