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PH negative acute lymphoblastic leukemia in adolescents and young adults treated according a MRD adapted BFM ALL IC 2009 protocol: Argentine real-world data on 171 patients

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Abstract

Intensified pediatric chemotherapy regimens to treat adolescents and young adults (AYA) patients with Philadelphia negative acute lymphoblastic leukemia (ALL) have been associated with better outcomes. The local BFM 2009-based scheme complements the risk stratification assessing the measurable residual disease (MRD) along the induction phase with increasing levels of sensitivity. The present retrospective multicenter analysis included 171 AYA (15–40 years) patients treated accordingly between 2013 and 2019. Ninety-one percent obtained morphological complete remission, 67% a negative (<0.1%) MRD at day 33 (TP1), and 78% a negative (<0.01%) MRD at day 78 (TP2). The overall survival (OS) and the event-free survival (EFS) at 2 years were 62%±4.1 and 55%±4.1, respectively. The OS and EFS were significant better for prednisone responders, who achieved <10% BM blast at day 15, a negative MRD at TP1 or at TP2, and for low-risk patients. Age ≤30 years and WBC <30×109/L, particularly among B-phenotype, were also associated with longer OS. In the multivariable analyses, TP1 MRD positive (OS HR 2.8, 95% CI 1.4–5.7, p=0.004; EFS HR 3.0, 95% CI 1.6–5.7, p=0.001) and at TP2 (OS HR 2.6, 95% CI 1.3–5.3, p=0.012; EFS HR 2.6, 95% CI 1.3–5.1, p=0.006) were independently associated with earlier events. Age >30 years was also associated with a shorter survival (HR 3.1, 95% CI 1.3–7.5, p=0.014). Therefore, those 68 patients ≤30 years with TP1/TP2 negative MRD depicted a longer OS (2 years 85%±4.8). Based on our real-world data, the pediatric-based scheme is feasible in Argentina associated with better outcomes for younger AYA patients who achieved negative MRD at day 33 and 78.

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Acknowledgements

The authors thank the investigators of the Grupo Argentino de Leucemias Agudas (GALA) organized by the Sociedad Argentina de Hematología for the use of the AYA database, including other participating institutions such as Hospital Central de Mendoza, Sanatorio Sagrado Corazón, Sanatorio Anchorena, and Instituto de Oncohematología de la Patagonia Conciencia. Also, acknowledging the Grupo Argentino de Tratamiento de Leucemias Agudas (GATLA) for elaborating the therapeutic scheme adopted by the participant institutions.

Funding

This work was not specifically supported, but C.B.B. receives grants from the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT) (PICT 2017-0480 and 2019-1623) and by the Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) (PIP 2232).

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Author notes

  1. Equal authors’ contributions: María M Moirano and Carolina B Belli contributed equally to this work.

Authors and Affiliations

  1. FUNDALEU, Pte. José Evaristo Uriburu 1450, CABA, Buenos Aires, Argentina

    Luciana C Ferrari, María J Mela Osorio & Isolda I Fernández

  2. Hospital Universitario Austral, Pilar, Argentina

    María M Rivas

  3. Hospital de Alta Complejidad El Cruce, Florencio Varela, Argentina

    Alicia B Navickas & Lucía Agamennoni

  4. Hospital Italiano La Plata, La Plata, Argentina

    Hernán Dick & Jorge H Milone

  5. Hospital General de Agudos JM Ramos Mejía, Buenos Aires, Argentina

    Irene H Rey

  6. Hospital de Clínicas José de San Martín, Buenos Aires, Argentina

    Natalia E Carnelutto

  7. Centro de Educación Médica e Investigaciones Clínicas “Norberto Quirno” (CEMIC), Buenos Aires, Argentina

    Nicolás Cazap

  8. Hospital Privado Universitario de Córdoba, Córdoba, Argentina

    María B Castro

  9. Instituto Privado de Hematología y Hemoterapia, Paraná, Argentina

    Pedro Negri Aranguren

  10. Hospital General de Agudos C Durand, Buenos Aires, Argentina

    Laura A Fischman

  11. Instituto de Medicina Experimental (IMEX-CONICET)/ Academia Nacional de Medicina, Buenos Aires, Argentina

    Marco Lincango Yupanki & Carolina B Belli

  12. Hospital Interzonal General José San Martín, La Plata, Argentina

    María M Moirano

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  1. Luciana C Ferrari
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On behalf of the Grupo Argentino de Leucemias Agudas (GALA) and Grupo Argentino de Tratamiento de Leucemias Agudas (GATLA)

Contributions

L.C.F., M.M.R., M.M.M., and C.B.B. wrote the manuscript; L.C.F., M.L.Y., and C.B.B. analyzed the data. All authors discussed critically the published literature, revised, commented on previous versions, and approved the final manuscript.

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Correspondence to Luciana C Ferrari.

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Ferrari, L.C., Rivas, M.M., Navickas, A.B. et al. PH negative acute lymphoblastic leukemia in adolescents and young adults treated according a MRD adapted BFM ALL IC 2009 protocol: Argentine real-world data on 171 patients. Ann Hematol 102, 1087–1097 (2023). https://doi.org/10.1007/s00277-023-05151-3

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