Related Experiment Video
Updated: Sep 4, 2025
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Efficacy and tolerability of a modified pediatric-inspired intensive regimen for acute lymphoblastic leukemia in
Anand Ashwin Patel1, Joseph Heng1, Emily Dworkin2
1Department of Medicine Section of Hematology-Oncology University of Chicago Chicago Illinois USA.
Insights
A modified pediatric regimen (RD-10403) showed promising safety and efficacy in older adults with acute lymphoblastic leukemia (ALL), achieving a 77% remission rate and 55% overall survival at 3 years.
Area of Science:
- Hematology
- Oncology
- Clinical Trials
Background:
- Acute lymphoblastic leukemia (ALL) predominantly affects pediatric and young adult populations, but 20% of diagnoses occur in patients aged 55 and older.
- Intensive pediatric regimens improve outcomes in younger patients but pose toxicity challenges in older adults, particularly those with higher BMI.
- Asparaginase and corticosteroids, key components of pediatric ALL regimens, are associated with increased toxicity in elderly patients and those with comorbidities.
Purpose of the Study:
- To evaluate the safety and efficacy of a dose-modified pediatric regimen (RD-10403) in older adults (≥50 years) and younger adults with comorbidities.
- To assess the complete remission rate, event-free survival (EFS), and overall survival (OS) of the modified regimen.
Main Methods:
- A dose-modified Cancer and Leukemia Group B 10403 regimen (RD-10403) with reduced doses of pegylated asparaginase and corticosteroids was administered.
- The study included 30 patients with Philadelphia-chromosome negative ALL who were ≥50 years old or younger adults with significant metabolic or hepatic comorbidities.
- Safety endpoints included toxicity rates and induction-related mortality.
Main Results:
- The complete remission rate on day 28 was 77%.
- Three-year event-free survival (EFS) was 54%, and estimated 3-year overall survival (OS) was 55%.
- Grade 3+ toxicity occurred in 40% of patients during induction, with a 3% induction-related mortality rate.
Conclusions:
- The dose-modified RD-10403 regimen demonstrates acceptable safety and efficacy in older adults and younger adults with comorbidities with Philadelphia-chromosome negative ALL.
- Further prospective evaluation of RD-10403 is warranted to confirm its efficacy and safety profile.
- This regimen may serve as a foundation for future chemoimmunotherapy combination studies in this patient population.
Abstract:
Although acute lymphoblastic leukemia (ALL) is most common in pediatric and adolescent and young adult (AYA) patients, 20% of cases are diagnosed in patients ≥ 55 years old. Use of intensive pediatric regimens in AYA populations has demonstrated excellent tolerability and significant improvements in event-free survival (EFS) and overall survival (OS). The backbone of pediatric regimens includes asparaginase and corticosteroids, both of which are associated with more toxicity in older patients and those with body mass index (BMI) ≥ 30 kg/m which leads to poor tolerance of these regimens. We tested the safety and efficacy of a dose-modified The Cancer and Leukemia Group B 10403 regimen using reduced doses of pegylated (PEG)-asparaginase (ASP) and corticosteroids (RD-10403) in 30 patients with Philadelphia-chromosome negative ALL who were ≥50-year-old and younger adults with significant metabolic or hepatic co-morbidities. The complete remission rate on day 28 was 77%, 3-year EFS was 54%, and estimated 3-year OS was 55%. Grade 3+ toxicity was noted in 40% of patients during induction, and induction-related mortality was 3%. Additional prospective evaluation of RD-10403 is merited to determine efficacy and safety of this regimen and to serve as a framework for chemoimmunotherapy combination therapy.
More Related Videos
06:08Assessment of Chimeric Antigen Receptor T Cell-Associated Toxicities Using an Acute Lymphoblastic Leukemia Patient-Derived Xenograft Mouse Model
Published on: February 10, 2023
07:38Intracellular Phosphoflow Cytometry of Acute Myeloid Leukemia Patient-Derived Xenotransplants
Published on: June 6, 2025
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
01:21Factors Affecting Drug Response: Overview