Treatment Outcomes in Children with Relapsed Acute Lymphoblastic Leukemia Using ALL-REZ BFM 2002 Protocol: Data from a Single-Center Trial
Abstract
Background
Despite considerable therapy success in newly diagnosed pediatric acute lymphoblastic leukemia (ALL), treatment of relapses remains challenging and requires a personalized approach. In the Russian Federation, the treatment of relapsed ALL is based on ALL-REZ BFM 2002, the protocol suggesting a risk-adapted strategy with assessing eligibility for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in high-risk patients. Global and national experience with implementation of this program demonstrated a therapeutic plateau, which indicates the need for modernizing the standard chemotherapy regimens and introducing novel targeted and immunological approaches.
Aim
To assess the long-term outcomes of treating children with the first ALL relapse using ALL-REZ BFM 2002 at a single medical center. MATERIALS &
Methods
This study enrolled 73 patients with the confirmed diagnosis of the first ALL relapse who received a complete course of therapy according to ALL-REZ BFM 2002 at the Hematologic Malignancy Units No. 1 and No. 2 at the Research Institute of Pediatric Oncology and Hematology, N.N. Blokhin National Medical Cancer Research Center, from 2018 to 2024. The median age was 9.3 years (range 3–17 years), most of them were boys (71 %). The data analysis was conducted as of February 1, 2026.
Results
The analysis of the total cohort showed the 5-year overall survival of 54.6 % and event-free survival of 48.7 % (in the S1 and S2 risk subgroups 100 % and 52.2 %, respectively). Allo-HSCT improved the 5-year disease-free survival (DFS) up to 72.5 %. The administration of targeted immunotherapy with blinatumomab or inotuzumab ozogamicin as bridge therapy prior to allo-HSCT in minimal residual disease (MRD)-positive patients resulted in further improvement of this rate up to 83.6 %.
Conclusion
The risk-adapted ALL-REZ BFM 2002 protocol shows efficacy in patients with the first ALL relapse. Introducing blinatumomab/inotuzumab ozogamicin to achieve MRD-negative remissions prior to allo-HSCT improves DFS rates in patients with B-lineage ALL. Treatment outcomes in T-ALL patients remains poor due to high resistance to chemotherapy.