allMT

Introduction

Acute lymphoblastic leukemia (ALL) studies across the globe have shown that delivering optimal maintenance therapy (MT) is crucial to achieve better treatment outcomes [1]. Delivering optimal MT includes prescribing maximum tolerated doses of 6-mercaptopurine (6MP) and methotraxate (MTX) based on patient’s blood counts (absolute neutrophil count (ANC), platelet count (PLT) and hemoglobin (HB)). In view of this, the allMT package was created to analyse and visualize the MT data (ANC/PLT/HB/6MP/MTX) for single patient or a given cohort at any center¹. The package was developed considering the ICiCLe-ALL-14 protocol [3] as default. It can be used to analyze data from centers with different MT protocols where in the user will need to alter the function defined ipnut argument/parameters.

Package

Using this package the user may:

Convert maintenance sheets (Tata Medical Center Kolkata, India format or user dependent) into a cleaner, single csv with longitudinal data for each patient.
Analyze MT [2]
- At an individual patient level
  - To track patient’s MT progression during or after therapy.
  - To track patient’s cycle-by-cycle MT progression during or after the therapy using summary measure (SM) weighted mean (6MP*MTX) vs weighted mean ANC parameters in a scatterplot.
  - Asses hematological toxicities - neutropenia, thrombocytopenia and anemia during MT.
  - Evaluate median time to first 6MP dose increase for the cohort.
  - Evaluate real time dosing decisions (stop, reduce or increase) by the physicians during MT based on MT dosing guidelines [2]
- At cohort level
  - SM plot to analyze MT for a given cohort defined by the user. SM is evaluated for each patient and plotted together to represent the entire cohort.
  - Compare SM for two or more cohort defined by the user to evaluate MT practice. Cohort comparisons can include clinical interventions, year-wise evolution, patients treated by two different set of physicians, or as user see it fit.
  - Asses hematological toxicities - neutropenia, thrombocytopenia and anemia during MT.
  - Plot depicting median time to first 6MP dose increase for the cohort.
  - Evaluate real time dosing decisions (stop, reduce or increase) by the physicians during MT based on MT dosing guidelines [2]

Installation

You can install the development version of allMT from GitHub with:

# install.packages("devtools")
devtools::install_github("tmungle/allMT")

Ethics approval statement for data

The anonymized clinical data set refers to patients treated on the ICiCLe-ALL-14 treatment protocol at the Tata Medical Center Kolkata (institutional review board approval EC/TMC/12/13 for the treatment protocol). Funding support for the ICiCLe-ALL-14 clinical study (Clinical Trials Registry-India reference CTRI/2015/12/006434) was provided by the National Cancer Grid (2016/001; 2016-) and the Indian Council of Medical Research (79/159/2015/NCD-III; 2017-19)

Contribution

By abiding to Contributor Code of Conduct, contribution to allMT in any form bug fixes/code modification/new code development is welcomed.

References

[1]

K. Schmiegelow, S. N. Nielsen, T. L. Frandsen, and J. Nersting, “Mercaptopurine/methotrexate maintenance therapy of childhood acute lymphoblastic leukemia: Clinical facts and fiction,” Journal of pediatric hematology/oncology, vol. 36, no. 7, p. 503, 2014.

[2]

T. D. Mungle, “Modelling clinical decision processes to optimise maintenance chemotherapy in children with acute lymphoblastic leukaemia,” PhD thesis, IIT Kharagpur, 2020.

[3]

N. Das et al., “Protocol for ICiCLe-ALL-14 (InPOG-ALL-15-01): A prospective, risk stratified, randomised, multicentre, open label, controlled therapeutic trial for newly diagnosed childhood acute lymphoblastic leukaemia in india,” Trials, vol. 23, no. 1, pp. 1–20, 2022.

The work was initiated as part of Tushar Mungle’s PhD work at IIT Kharagpur [2] and then continued at TTCRC, Tata Medical Center, Kolkata.↩︎