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CLINICAL TRIAL article

Front. Oncol.
Sec. Pediatric Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1401262
This article is part of the Research Topic Immunological Therapies in Pediatric Cancers: A Latin American Perspective View all articles

Very Early Remission and Increased Apoptosis with the Use of Pentoxifylline in Children with Acute Lymphoblastic Leukemia

Provisionally accepted
Violeta Salceda Rivera Violeta Salceda Rivera 1Pablo C. Ortiz-Lazareno Pablo C. Ortiz-Lazareno 2Georgina Hernandez Georgina Hernandez 2Jorge Vazquez Urrutia Jorge Vazquez Urrutia 2Jesus Meza Arroyo Jesus Meza Arroyo 2Monzerrat Pardo Zepeda Monzerrat Pardo Zepeda 1Hugo Romo Rubio Hugo Romo Rubio 1Cesar Barba Barba Cesar Barba Barba 1Fernando Sanchez Zubieta Fernando Sanchez Zubieta 3Oscar Gonzalez Ramella Oscar Gonzalez Ramella 3*Alejandro Bravo-Cuellar Alejandro Bravo-Cuellar 4*
  • 1 Civil Hospital of Guadalajara, Guadalajara, Mexico
  • 2 Centro de Investigación Biomédica de Occidente (CIBO), Guadalajara, Jalisco, Mexico
  • 3 Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
  • 4 Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlan, Jalisco, Mexico

The final, formatted version of the article will be published soon.

    Despite the improvement in survival in acute lymphoblastic leukemia (ALL), there are still cases with evasion of chemotherapy-induced apoptosis. The IKK/NF-κB signaling pathway contributes to antiapoptotic gene expression. Pentoxifylline (PTX) inhibits IκB phosphorylation, blocking NF-κB and antiapoptotic activity. We conducted a randomized, double-blind clinical trial on pediatric ALL patients undergoing induction therapy, assigning them to PTX or placebo group. Bone marrow aspirates were obtained on days 1, 8, 15, and 22. Apoptosis was assessed using Annexin-V/propidium iodide. Results indicated that the PTX group exhibited higher apoptosis on day-8 (41.3% vs. 19.4%, p =0.029) and day-15 (35.0% vs. 14.2%, p <0.01). On day-8, the PTX group displayed an MRD of 0.25% vs. 18.2% (p <0.01) in placebo group; on day-15, the PTX group demonstrated an MRD of 0.09% vs. 1.4% (p =0.02). Patients achieving an MRD <0.01% on day-8 demonstrated a 3-year Overall Survival (OS) of 81.6% vs. 58.3% (p =0.03); on day-15, patients with MRD <0.01% had a 3-year OS of 77.9% vs. 54.5% (p =0.03). The PTX group achieved an MRD of <0.01% earlier on days-8 and 15, along with a higher apoptosis rate, indicating a more favorable therapeutic response. In the entire cohort, patients achieving MRD <0.01% on day-8 or 15 displayed superior OS. In conclusion, our study demonstrates that PTX enhances apoptosis and reduces MRD in pediatric acute lymphoblastic leukemia patients.

    Keywords: MRD1, ALL2, clinical trials3, apoptosis4, Pentoxifylline5, early remission6, childhood7, treatment response8

    Received: 15 Mar 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Salceda Rivera, Ortiz-Lazareno, Hernandez, Vazquez Urrutia, Meza Arroyo, Pardo Zepeda, Romo Rubio, Barba Barba, Sanchez Zubieta, Gonzalez Ramella and Bravo-Cuellar. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Oscar Gonzalez Ramella, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Mexico
    Alejandro Bravo-Cuellar, Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlan, Jalisco, Mexico

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.