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Measurable residual disease study through three different methods can anticipate relapse and guide pre-emptive therapy in childhood acute myeloid leukemia

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Abstract

Purpose

Although outcomes of children with acute myeloid leukemia (AML) have improved over the last decades, around one-third of patients relapse. Measurable (or minimal) residual disease (MRD) monitoring may guide therapy adjustments or pre-emptive treatments before overt hematological relapse.

Methods

In this study, we review 297 bone marrow samples from 20 real-life pediatric AML patients using three MRD monitoring methods: multiparametric flow cytometry (MFC), fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR).

Results

Patients showed a 3-year overall survival of 73% and a 3-year event-free survival of 68%. Global relapse rate was of 25%. All relapses were preceded by the reappearance of MRD detection by: (1) MFC (p = 0.001), (2) PCR and/or FISH in patients with an identifiable chromosomal translocation (p = 0.03) and/or (3) one log increase of Wilms tumor gene 1 (WT1) expression in two consecutive samples (p = 0.02). The median times from MRD detection to relapse were 26, 111, and 140 days for MFC, specific PCR and FISH, and a one log increment of WT1, respectively.

Conclusions

MFC, FISH and PCR are complementary methods that can anticipate relapse of childhood AML by weeks to several months. However, in our series, pre-emptive therapies were not able to prevent disease progression. Therefore, more sensitive MRD monitoring methods that further anticipate relapse and more effective pre-emptive therapies are needed.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

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Acknowledgements

We would like to acknowledge the hematologists involved in the bone marrow transplantation of patients Drs. José María Moraleda, Andrés Sánchez-Salinas, Joaquín Gómez-Espuch and Jorge Montserrat Coll, nurses and other healthcare members from the pediatric hematology and oncology department, laboratory technicians María Carmen Martínez Solano and María Dolores García Arnao, and especially to all patients and families.

Funding

The researcher M.V.M.S. was funded by Asociación Pablo Ugarte (APU).

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Authors and Affiliations

  1. Pediatric Oncohematology Department, Clinic University Hospital Virgen de la Arrixaca and Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120, Murcia, Spain

    Eduardo Ramos Elbal, José Luis Fuster, Ana María Galera, Mar Bermúdez Cortés, María Esther Llinares, Irene Jiménez & Mercedes Plaza

  2. Immunology Service, Clinic University Hospital Virgen de la Arrixaca and Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120, Murcia, Spain

    José Antonio Campillo, Helios Martínez Banaclocha, José Antonio Galián, María Victoria Martínez Sánchez, Manuel Muro & Alfredo Minguela

  3. Haematology Service, Clinic University Hospital Virgen de la Arrixaca and Biomedical Research Institute of Murcia Pascual Parrilla (IMIB), 30120, Murcia, Spain

    Miguel Blanquer Blanquer

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  1. Eduardo Ramos Elbal
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Correspondence to Alfredo Minguela.

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The study was performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Ramos Elbal, E., Fuster, J.L., Campillo, J. et al. Measurable residual disease study through three different methods can anticipate relapse and guide pre-emptive therapy in childhood acute myeloid leukemia. Clin Transl Oncol 25, 1446–1454 (2023). https://doi.org/10.1007/s12094-022-03042-z

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