Introduction

Acute Lymphoblastic Leukemia (ALL)

ALL treatment is broadly divided into 2 phases - Intensive Phase and Maintenance Phase. The intensive phase of treatment is further divided into 4 sub-phases – induction, consolidation, interim maintenance and delayed intensification [1].

Maintenance therapy (MT), the longest phase of ALL treatment consists of ~2 years (96 weeks or 8 cycles - 12 weeks per cycle) [1]. Patients are advised to visit hospital every alternate week (every two weeks) for consultation and on a weekly basis in case of toxicities (neutropenia, thrombocytopenia or any other). Overall, a patient should ideally have a minimum of 48 visits during MT. During each visit, patient’s blood report is examined for the following parameters - absolute neutrophil count (ANC), platelet count (PLT) and hemoglobin (HB) to adjust (or dose titrations) the drugs: 6-mercaptopurine (6MP) and Methotrexate (MTX) that are prescribed on weekly basis.

Package

ALL studies, across the globe, have shown that delivering optimal MT is crucial to achieve better treatment outcomes [2]. Delivering optimal MT is ensured by prescribing maximum tolerated 6MP and MTX doses that are adjusted patient’s hospital visit. In view of this, the package was created to analyse and visualize the ALL MT data (ANC/PLT/HB/6MP/MTX)¹. The use of package would assist physicians to evaluate MT for a given patient or a cohort at any center. Although, the package was developed considering the ICiCLe-ALL-14 protocol [1] as default, it can be used to analyze data from centers with different MT protocols. In case of different protocol, the user will need to alter the defined parameters specific to protocol as function arguments.

Using this package the user may:

1. Convert maintenance sheets (Tata Medical Center Kolkata, India format or user dependent) into a cleaner, single csv with longitudinal data for each patient.

2. Analyze MT

   • At an individual patient level

     • To track patient’s MT progression during or after therapy [3].

     • 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.

   • 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 [3].

     • Compare SM for two different cohort defined by the user to evaluate MT practice. Cohort comparisons can include clinical interventions, year-wise practice evolution, patients treated by two different set of physicians, or as user see it fit [3].

3. Evaluate real time dosing decisions (stop, reduce or increase) by the physicians during MT based on MT dosing guidelines for the individual patient or cohort [3].

4. Evaluate hematological toxicities - neutropenia, thrombocytopenia and anemia during MT for the individual patient or cohort.

5. Evaluate/plot median time to first 6MP dose increase for the individual patient or cohort [3].

# library(allMT)

Data

1. The data recording sheet used by TMC can be downloaded/copied as

   # Uncomment below line before running the snippet
   # library(allMT)
   pat_data <- system.file("extdata/tmc_data/", "UPN_916.xls", package = "allMT")
   dest_path <- getwd() # user may choose a different destination 
   file.copy(pat_data, dest_path)
   #> [1] TRUE

2. To use functions of the package, the data needs to be in a specific format as described in below example. Sample data² for 3 individual patient is available as UPN_914, UPN_915, and UPN_916 as rda with the library for viewing. Additionally, UPN_914, UPN_915, UPN_916, UPN_917 and UPN_918 are present under the folder “/extdata/processed_data/” as csv format to run any examples.

   Data can be checked or saved as

   # Below code should work for any user independent of OS
   # pat_data <- system.file("extdata/processed_data/", "UPN_916.csv", package = "allMT")
   # pat_df <- utils::read.csv(pat_data, header = TRUE, sep = ",")
   # # head(pat_df)

Functions