Reducing chemotherapy dose intensity by 25% and adding rituximab improves survival in pediatric mature B-cell
Venkatraman Radhakrishnan1, Venkatakrishnan Kritthivasan1, Balaji Thiruvengadam Kothandan1
1Department of Medical and Pediatric Oncology, Cancer Institute (WIA), Adyar, Chennai, Tamil Nadu, India.
Insights
Reducing chemotherapy intensity by 25% and adding rituximab significantly improved outcomes for pediatric B-cell non-Hodgkin lymphoma (NHL) in low- and middle-income countries. This approach led to high complete metabolic response rates and excellent survival, addressing historical challenges in these regions.
Area of Science:
- Pediatric Oncology
- Hematology
- Clinical Research
Background:
- Pediatric B-cell non-Hodgkin lymphoma (NHL) outcomes are historically poor in low- and middle-income countries (LMICs).
- High treatment-related mortality and relapse rates contribute to inferior outcomes in these regions.
- Previous treatment protocols require optimization for LMIC settings.
Purpose of the Study:
- To evaluate the impact of a modified Lymphome Malin de Burkitt (LMB) protocol on pediatric B-NHL outcomes.
- To assess the efficacy of reducing chemotherapy dose intensity by 25% combined with rituximab.
- To improve survival rates and reduce treatment-related mortality in pediatric B-NHL patients in LMICs.
Main Methods:
- Enrollment of pediatric patients (<18 years) with LMB group B and C disease (Sept 2017-Oct 2022).
- Administration of the LMB-89 protocol with a 25% chemotherapy dose reduction and addition of rituximab.
- Response assessment via PET/CT at interim (4 cycles) and end of treatment.
Main Results:
- High response rates: 88% complete metabolic response (CMR) interim, 92% CMR at end of treatment.
- Excellent survival: 4-year event-free survival of 88% and overall survival of 92%.
- Low mortality: Two deaths, one from progression, one from sepsis, in 25 patients.
Conclusions:
- A 25% reduction in chemotherapy dose intensity plus rituximab significantly improves outcomes in pediatric B-NHL.
- This modified approach offers a promising strategy for managing pediatric B-NHL in LMICs.
- The findings suggest a viable alternative to standard, higher-intensity chemotherapy regimens in resource-limited settings.
Background And Objectives:
Pediatric B-cell non-Hodgkin lymphomas (NHL) in low- and middle-income countries (LMICs) have historically had inferior outcomes due to higher treatment-related mortality (TRM) and relapses. To address this issue, we evaluated the impact of reducing chemotherapy dose intensity by 25% and adding rituximab on outcomes in pediatric B-NHL.
Patients And Methods:
Patients, less than 18 years of age with group B and C disease as per the Lymphome Malin de Burkitt (LMB) risk stratification were enrolled between September 2017 and October 2022. The LMB-89 protocol, with a 25% reduction in all chemotherapy doses and the addition of rituximab, was administered. The response was assessed using positron emission tomography with computed tomography (PET/CT) after four cycles of chemotherapy (interim) and at the end of treatment.
Results:
The study included 25 patients with a median age of 6.9 years, among whom 20 (80%) were males. Twenty patients had group B and five had group C disease. Complete metabolic response (CMR) was achieved by 22/25 (88%) patients, and three (12%) achieved partial metabolic response (PMR) in the interim PET/CT. At the end of treatment, 22/24 (92%) patients achieved CMR, one had PMR, and one had progressive disease. The median follow-up was 45 months (range: 3-71 months). The 4-year event-free survival and overall survival were 88% and 92%, respectively. There were two deaths, one due to disease progression and the other due to sepsis.
Conclusion:
Our study demonstrates a significant improvement in outcomes in pediatric B-NHL compared to previous reports from LMICs, achieved through a 25% reduction in chemotherapy dose intensity and the addition of rituximab.
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