Treating relapsed B cell-precursor ALL in children with a setting-adapted mitoxantrone-based intensive chemotherapy...

Area of Science:

• Pediatric Oncology
• Hematology
• Clinical Trial Adaptation

Background:

• Relapsed acute lymphoblastic leukemia (ALL) in low- and middle-income countries (LMICs) presents significant challenges due to high treatment toxicity and limited resources.
• Existing treatment protocols often lead to prohibitive toxicities and are not always feasible in resource-constrained environments.

Purpose of the Study:

• To evaluate the efficacy and tolerability of a locally adapted mitoxantrone-based chemotherapy protocol for non-high-risk relapsed B-ALL (rALL) in LMICs.
• To assess the feasibility of modifying established protocols to suit local healthcare capacities and patient needs.

Main Methods:

• A retrospective and prospective analysis of 82 patients with standard and intermediate-risk rALL treated on the TMH rALL-18 protocol (November 2018 - January 2021).
• The protocol involved a 7-block multi-agent chemotherapy regimen including mitoxantrone, followed by local irradiation and maintenance, with serial modifications based on clinical experience.
• Toxicity monitoring, supportive care management, and minimal residual disease (MRD) assessment were integral parts of the treatment.

Main Results:

• The study treated 82 patients (3 SR rALL, 79 IR rALL). Grade 3/4 toxicities were observed in 321 instances, with 43% occurring during induction.
• Despite outpatient induction, 82.9% of patients required supportive care admissions. Sepsis, including multidrug-resistant organisms, led to 12 deaths during reinduction.
• Post-reinduction MRD negativity was achieved in 80.6% of evaluable patients. The estimated 2-year event-free survival was 58%, and overall survival was 60.3%.

Conclusions:

• A locally adapted mitoxantrone-based protocol can achieve acceptable survival rates for non-high-risk rALL in LMICs, despite significant toxicities and resource limitations.
• Protocol modifications, such as cytarabine dose reduction after observing remission deaths, were implemented to improve tolerability.
• Strengthening supportive care and adapting protocols to balance efficacy and tolerability are crucial strategies for managing rALL in LMICs until targeted therapies become widely accessible.