REDUCTION IN EARLY TREATMENT-RELATED MORTALITY IN THE NATIONAL BRAZILIAN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA PROTOCOL (GBTLI-LLA 2021)
10 affiliations
- 1Grupo de Apoio ao Adolescente e à Criança com Câncer (GRAAC), São Paulo, SP, Brazil
- 2Beneficência Portuguesa, São Paulo, SP, Brazil
- 3Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Recife, PE, Brazil
- 4Hospital Infantil Albert Sabin, Fortaleza, CE, Brazil
- 5Hospital Pequeno Príncipe, Curitiba, PR, Brazil
- 6Hospital Araújo Jorge, Goiânia, GO, Brazil
- 7Hospital Oncológico Infantil Otavio Lobo, Belém, PA, Brazil
- 8Hospital Nossa Senhora da Glória, Vitória, ES, Brazil
- 9Hospital Beneficência Portuguesa, São Paulo, SP, Brazil
- 10St Jude Children's Hospital, United States
Abstract
Background: The treatment of pediatric acute lymphoblastic leukemia (ALL) is highly successful worldwide; however, treatment-related mortality remains unacceptably high in many low- and middle-income countries. Children treated on the previous Brazilian national ALL protocol (GBTLI), which used a Berlin-Frankfurt-Münster (BFM)-based backbone, experienced approximately 6% induction mortality. The primary objective of the GBTLI-2021 protocol was to reduce treatment-related mortality while maintaining excellent leukemia control. Methods: The GBTLI-2021 protocol is based on the St. Jude Total XV backbone, following its successful implementation in Recife, Brazil (ReLLA). Eligible patients were 1–21 years of age, and enrollment began on January 1, 2023. Initial risk stratification incorporated age, presenting white blood cell count, extramedullary disease, cytogenetic/molecular abnormalities, and ploidy. Risk assignment was refined using MRD measured on days 19 and 49. This protocol introduced several modifications designed to reduce induction toxicity, including administration of only two doses of daunorubicin during B-lineage ALL induction with postponement of the second dose in patients with profound neutropenia, risk-adapted use of pegaspargase, and continuous national case discussions and education involving participating centers. Patients were reviewed twice weekly through a centralized multidisciplinary discussion involving all participating institutions. Results: A total of 1497 children with ALL were enrolled from 41 centers across Brazil through May 31, 2026. B-lineage ALL accounted for 85% of cases, T-ALL for 13%, and Philadelphia chromosome-positive (Ph+) ALL for 2%. Induction mortality decreased from 6.2% with the previous GBTLI protocol to 3% with GBTLI-2021(p < 0,001). Mortality during complete remission also declined from 3.6% to 2.0%. The greatest improvement was observed in B-lineage ALL, where mortality decreased from 8.7% to 2.7%, whereas reductions were more modest in T-ALL (8.0% to 7.0%) and Ph+ ALL (11.0% to 8.0%). Importantly, the complete remission rate remained unchanged at 98%, indicating that reduced treatment intensity during induction did not compromise antileukemic efficacy. Conclusion: The implementation of the GBTLI-2021 protocol across a nationwide collaborative network reduced induction mortality by nearly one-half while maintaining a 98% remission rate. These findings suggest that judicious reduction of induction intensity, together with continuous education, centralized case discussions, and protocol adherence, can substantially improve outcomes in resource-constrained settings without compromising leukemia control.
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BibTeX
@article{seber2026reduction,
title = {{REDUCTION IN EARLY TREATMENT-RELATED MORTALITY IN THE NATIONAL BRAZILIAN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA PROTOCOL (GBTLI-LLA 2021)}},
author = {Adriana SEBER and Maria Lucia De Martino LEE and Mecneide Mendes LINS and Maria do Céu Diniz BORBOREMA and Viviany VIANA and Alejandra Adriana Cardoso DE CASTRO and Vanusa Maria ROSA and Alayde Vieira WANDERLEY and Glaucia Perini Zouain FIGUEIREDO and Fabricio Tera ROMAGNOL and Ana Virginia LOPES and Maria Julia Gonçalves DE MELO and Raul RIBEIRO},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.108425},
url = {https://doi.org/10.1016/j.htct.2026.108425},
note = {CC BY},
}
RIS
TY - JOUR
TI - REDUCTION IN EARLY TREATMENT-RELATED MORTALITY IN THE NATIONAL BRAZILIAN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA PROTOCOL (GBTLI-LLA 2021)
AU - Adriana SEBER
AU - Maria Lucia De Martino LEE
AU - Mecneide Mendes LINS
AU - Maria do Céu Diniz BORBOREMA
AU - Viviany VIANA
AU - Alejandra Adriana Cardoso DE CASTRO
AU - Vanusa Maria ROSA
AU - Alayde Vieira WANDERLEY
AU - Glaucia Perini Zouain FIGUEIREDO
AU - Fabricio Tera ROMAGNOL
AU - Ana Virginia LOPES
AU - Maria Julia Gonçalves DE MELO
AU - Raul RIBEIRO
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.108425
UR - https://doi.org/10.1016/j.htct.2026.108425
AB - Background: The treatment of pediatric acute lymphoblastic leukemia (ALL) is highly successful worldwide; however, treatment-related mortality remains unacceptably high in many low- and middle-income countries. Children treated on the previous Brazilian national ALL protocol (GBTLI), which used a Berlin-Frankfurt-Münster (BFM)-based backbone, experienced approximately 6% induction mortality. The primary objective of the GBTLI-2021 protocol was to reduce treatment-related mortality while maintaining excellent leukemia control. Methods: The GBTLI-2021 protocol is based on the St. Jude Total XV backbone, following its successful implementation in Recife, Brazil (ReLLA). Eligible patients were 1–21 years of age, and enrollment began on January 1, 2023. Initial risk stratification incorporated age, presenting white blood cell count, extramedullary disease, cytogenetic/molecular abnormalities, and ploidy. Risk assignment was refined using MRD measured on days 19 and 49. This protocol introduced several modifications designed to reduce induction toxicity, including administration of only two doses of daunorubicin during B-lineage ALL induction with postponement of the second dose in patients with profound neutropenia, risk-adapted use of pegaspargase, and continuous national case discussions and education involving participating centers. Patients were reviewed twice weekly through a centralized multidisciplinary discussion involving all participating institutions. Results: A total of 1497 children with ALL were enrolled from 41 centers across Brazil through May 31, 2026. B-lineage ALL accounted for 85% of cases, T-ALL for 13%, and Philadelphia chromosome-positive (Ph+) ALL for 2%. Induction mortality decreased from 6.2% with the previous GBTLI protocol to 3% with GBTLI-2021(p < 0,001). Mortality during complete remission also declined from 3.6% to 2.0%. The greatest improvement was observed in B-lineage ALL, where mortality decreased from 8.7% to 2.7%, whereas reductions were more modest in T-ALL (8.0% to 7.0%) and Ph+ ALL (11.0% to 8.0%). Importantly, the complete remission rate remained unchanged at 98%, indicating that reduced treatment intensity during induction did not compromise antileukemic efficacy. Conclusion: The implementation of the GBTLI-2021 protocol across a nationwide collaborative network reduced induction mortality by nearly one-half while maintaining a 98% remission rate. These findings suggest that judicious reduction of induction intensity, together with continuous education, centralized case discussions, and protocol adherence, can substantially improve outcomes in resource-constrained settings without compromising leukemia control.
SN - 2531-1379
SN - 2531-1387
ER -