Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia

Claudia Núñez-Torrón Stock; Carlos Jiménez Chillón; Fernando Martín Moro; Juan Marquet Palomanes; Miguel Piris Villaespesa; Ernesto Roldán Santiago; Eulalia Rodríguez Martín; Anabelle Chinea Rodríguez; Valentín García Gutiérrez; Gemma Moreno Jiménez; Javier López Jiménez; Pilar Herrera Puente

doi:10.3389/fonc.2024.1394648

Survival after allogeneic transplantation according to pretransplant minimal residual disease and conditioning intensity in patients with acute myeloid leukemia

Front Oncol. 2024 May 2:14:1394648. doi: 10.3389/fonc.2024.1394648. eCollection 2024.

Authors

Claudia Núñez-Torrón Stock^{1

2

3}, Carlos Jiménez Chillón⁴, Fernando Martín Moro⁵, Juan Marquet Palomanes⁵, Miguel Piris Villaespesa⁵, Ernesto Roldán Santiago⁶, Eulalia Rodríguez Martín⁶, Anabelle Chinea Rodríguez⁵, Valentín García Gutiérrez^{2

5}, Gemma Moreno Jiménez⁵, Javier López Jiménez^{2

5}, Pilar Herrera Puente^{2

5}

Affiliations

¹ Departamento de Hematología y Hemoterapia, Hospital Universitario Infanta Sofía, Madrid, Spain.
² Medicine and Medical Specialties Department, Universidad Alcalá de Henares, Madrid, Spain.
³ Medicine Department, Universidad Europea de Madrid, Madrid, Spain.
⁴ Departamento de Hematología y Hemoterapia, Hospital Universitario Gregorio Marañón, Madrid, Spain.
⁵ Departamento de Hematología y Hemoterapia, Hospital Universitario Ramón y Cajal, Madrid, Spain.
⁶ Departamento de Inmunología, Hospital Universitario Ramón y Cajal, Madrid, Spain.

Abstract

Background: The measurement of minimal residual disease (MRD) by multiparametric flow cytometry (MFC) before hematopoietic stem cell transplantation (HSCT) in patients with acute myeloid leukemia (AML) is a powerful prognostic factor. The interaction of pretransplant MRD and the conditioning intensity has not yet been clarified.

Objective: The aim of this study is to analyze the transplant outcomes of patients with AML who underwent HSCT in complete remission (CR), comparing patients with positive MRD (MRD+) and negative MRD (MRD-) before HSCT, and the interaction between conditioning intensity and pre-HSCT MRD.

Study design: We retrospectively analyzed the transplant outcomes of 118 patients with AML who underwent HSCT in CR in a single institution, comparing patients with MRD+ and MRD- before HSCT using a cutoff of 0.1% on MFC, and the interaction between conditioning intensity and pre-HSCT MRD.

Results: Patients with MRD+ before HSCT had a significantly worse 2-year (2y) event-free survival (EFS) (56.5% vs. 32.0%, p = 0.018) than MRD- patients, due to a higher cumulative incidence of relapse (CIR) at 2 years (49.0% vs. 18.0%, p = 0.002), with no differences in transplant-related mortality (TRM) (2y-TRM, 19.0% and 25.0%, respectively, p = 0.588). In the analysis stratified by conditioning intensity, in patients who received MAC, those with MRD- before HSCT had better EFS (p = 0.009) and overall survival (OS) (p = 0.070) due to lower CIR (p = 0.004) than MRD+ patients. On the other hand, the survival was similar in reduced intensity conditioning (RIC) patients regardless of the MRD status.

Conclusions: Patients with MRD+ before HSCT have worse outcomes than MRD- patients. In patients who received MAC, MRD- patients have better EFS and OS due to lower CIR than MRD+ patients, probably because they represent a more chemo-sensitive group. However, among RIC patients, results were similar regardless of the MRD status.

Keywords: acute myeloid leukemia; allogeneic transplantation; conditioning intensity; minimal residual disease; monosomal karyotype.

Copyright © 2024 Núñez-Torrón Stock, Jiménez Chillón, Martín Moro, Marquet Palomanes, Piris Villaespesa, Roldán Santiago, Rodríguez Martín, Chinea Rodríguez, García Gutiérrez, Moreno Jiménez, López Jiménez and Herrera Puente.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. We received a grant for help with the preparation of the manuscript (financed by Jazz Pharmaceuticals as part of the “Publibecas” grant program of the GETH). The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.