Treatment of Relapse in Pediatric Patients with Acute Lymphoblastic Leukemia in Argentina: Results from a Clinical Trial and a Prospective Cohort
Article Sidebar
Main Article Content
Abstract
Introduction: since 2002, the Grupo Argentino para el Tratamiento de la Leucemia Aguda (GATLA)
has been implementing protocols from the Berlin-Frankfurt-Münster (BFM) group as the standard
treatment for relapses of acute lymphoblastic leukemia (ALL). In 2010, BFM developed the IntReALL 10
protocol, implemented in Argentina with the inherent limitations of the region.
Population and Methods: we treated a total of 180 patients under 18 years of age between 2010
and 2015 for high-risk relapsed acute lymphoblastic leukemia (ALL) in Argentina following a BFM
relapse protocol. This protocol openly compared standard treatment with an innovative (experimental)
therapeutic approach that included Clofarabine. Out of these, 171 patients were assessable, with 78
patients being centrally randomized in a clinical trial, and 93 were assigned to one of the arms based on
the treating group’s criteria (prospective cohort). The cohort where the treatment assignment had not
been randomized, was analyzed with adjustments for gender, age, and the presence or absence of Down
Syndrome, Philadelphia Chromosome, and T-cell immunophenotype.
Results: patients who received the experimental treatment had worse outcomes (double the five-year
mortality) compared to those who received the standard treatment. This difference reached statistical significance in the clinical trial (p=0.001) and the prospective cohort (p=0.0009).
Conclusions: our results support the continuation of the standard arm in BFM-type protocols for
relapsed ALL treatment and were consistent with the conclusions of the ALLIC-REC group.
Downloads
Article Details
Section
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
How to Cite
References
Stary J, Zimmermann M, Campbell M, et al. Intensive chemotherapy for childhood acute lymphoblastic leukemia: results of the randomized intercontinental trial ALL IC-BFM 2002. J Clin Oncol. 2014;32(3):174-184. https://doi.org/10.1200/JCO.2013.48.6522. DOI: https://doi.org/10.1200/JCO.2013.48.6522
Volejnikova J, Jarosova M, Pospisilova D, et al. Treatment and prognosis of childhood acute lymphoblastic leukemia on protocols ALL-BFM 90, 95 and ALL IC-BFM 2002: a retrospective single-center study from Olomouc, Czech Republic. Neoplasma. 2016;63(3):456-461. https://doi.org/10.4149/316_150910N482. DOI: https://doi.org/10.4149/316_150910N482
Makiya ML, Dibar E, Riccheri C, et al. Pattern of relapse of pediatric acute lymphoblastic leukemia (ALL), 25 years of experience of the Argentine Group of Acute Leukemia (GATLA) with BFM type protocols. Pediatr Blood Cancer. 2012;59(6):1027-1028. https://doi.org/10.1002/pbc.24295. DOI: https://doi.org/10.1002/pbc.24295
Steliarova-Foucher E, Colombet M, Ries LAG, et al. International incidence of childhood cancer, 2001-10: a population-based registry study. Lancet Oncol. 2017;18(6):719-731. https://doi.org/10.1016/S1470-2045(17)30186-9. Errata en: Lancet Oncol. 2017;18(6):e301. https://doi.org/10.1016/S1470-2045(17)30369-8. DOI: https://doi.org/10.1016/S1470-2045(17)30369-8
Pui CH, Mullighan CG, Evans WE, et al. Pediatric acute lymphoblastic leukemia: where are we going and how do we get there? Blood. 2012;120(6):1165-1174. https://doi.org/10.1182/blood-2012-05-378943. DOI: https://doi.org/10.1182/blood-2012-05-378943
Locatelli F, Schrappe M, Bernardo ME, et al. How I treat relapsed childhood acute lymphoblastic leukemia. Blood. 2012;120(14):2807-2816. https://doi.org/10.1182/blood-2012-02-265884. DOI: https://doi.org/10.1182/blood-2012-02-265884
Hossain MJ, Xie L, McCahan SM. Characterization of pediatric acute lymphoblastic leukemia survival patterns by age at diagnosis. J Cancer Epidemiol. 2014;2014:865979. https://doi.org/10.1155/2014/865979. DOI: https://doi.org/10.1155/2014/865979
von Stackelberg A, Völzke E, Kühl JS, et al. Outcome of children and adolescents with relapsed acute lymphoblastic leukaemia and non-response to salvage protocol therapy: a retrospective analysis of the ALL-REZ BFM Study Group. Eur J Cancer. 2011;47(1):90-97. https://doi.org/10.1016/j.ejca.2010.09.020. DOI: https://doi.org/10.1016/j.ejca.2010.09.020
von Stackelberg A, Locatelli F, Zugmaier G, et al. Phase I/phase II study of blinatumomab in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. J Clin Oncol. 2016;34(36):4381-4389. https://doi,org/10.1200/JCO.2016.67.3301. DOI: https://doi.org/10.1200/JCO.2016.67.3301
Makiya M. Tratamiento de la leucemia linfoblástica aguda pediátrica recaída.Hematología. 2013;17(No. Extraord.): 82-88.
Henze G, v Stackelberg A, Eckert C. ALL-REZ BFM--the consecutive trials for children with relapsed acute lymphoblastic leukemia. Klin Padiatr. 2013;225 Suppl 1:S73-8. https://doi.org/10.1055/s-0033-1337967. DOI: https://doi.org/10.1055/s-0033-1337967
Austin PC, Stuart EA. Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies. Stat Med. 2015;34(28):3661-3679. https://doi.org/10.1002/sim.6607. DOI: https://doi.org/10.1002/sim.6607
VanderWeele TJ, Ding P. Sensitivity analysis in observational research: introducing the e-value. Ann Intern Med. 2017;167(4):268-274. https://doi.org/10.7326/M16-2607. DOI: https://doi.org/10.7326/M16-2607
Ng MH, Lau KM, Hawkins BR, et al. HLA-B67 may be a male-specific HLA marker of susceptibility to relapsed childhood ALL in Hong Kong Chinese and HLA-A33 or HLA-B17 signifies a higher presentation leukocytosis: a retrospective analysis on 53 transplant candidates (1989-2003). Ann Hematol. 2006;85(8):535-341. https://doi.org/10.1007/s00277-006-0118-0. DOI: https://doi.org/10.1007/s00277-006-0118-0
Meeske KA, Ji L, Freyer DR, et al. Comparative toxicity by sex among children treated for acute lymphoblastic leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2015;62(12):2140-2149. https://doi.org/10.1002/pbc.25628. DOI: https://doi.org/10.1002/pbc.25628
Oskarsson T, Söderhäll S, Arvidson J, et al. Treatment-related mortality in relapsed childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2018;65(4):e26909. https://doi.org/10.1002/pbc.26909. DOI: https://doi.org/10.1002/pbc.26909
Shah N, Al-Ahmari A, Al-Yamani A, et al. Outcome and toxicity of chemotherapy for acute lymphoblastic leukemia in children with Down syndrome. Pediatr Blood Cancer. 2009;52(1):14-19. https://doi.org/10.1002/pbc.21737. DOI: https://doi.org/10.1002/pbc.21737
Salzer WL, Burke MJ, Devidas M, et al. Toxicity associated with intensive postinduction therapy incorporating clofarabine in the very high-risk stratum of patients with newly diagnosed high-risk B-lymphoblastic leukemia: a report from the Children's Oncology Errata en: Cancer. 2021;127(21):4106-4107. https://doi.org/10.1002/cncr.33597. DOI: https://doi.org/10.1002/cncr.33597
Final report summary - INTREALL (International study for treatment of childhood relapsed ALL 2010 with standard therapy, systematic integration of new agents, and establishment of standardized diagnostic and research) [Internet]. Berlín: IntReALL Consortium; 2018 mayo 2 [citado 2023 feb 27]. Disponible en: https://cordis.europa.eu/project/id/278514/reporting.