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VERY EARLY REMISSION AND INCREASED APOPTOSIS WITH THE USE OF PENTOXIFYLLINE IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKEMIA
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  • Violeta Salceda Rivera,
  • Pablo Ortiz-Lazareno,
  • Alejandro Bravo-Cuellar,
  • Georgina Hernández-Flores,
  • Jesús Meza-Arroyo,
  • Monzerrat Pardo,
  • Ilse Delgado-Ruiz,
  • Hugo Romo-Rubio,
  • Feranando Sanchez-Zubieta,
  • Ramón Oscar Gonzalez-Ramella
Violeta Salceda Rivera
Universidad de Guadalajara Centro Universitario de Ciencias de la Salud
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Pablo Ortiz-Lazareno
Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS)
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Alejandro Bravo-Cuellar
Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS)
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Georgina Hernández-Flores
Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS)
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Jesús Meza-Arroyo
Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS)
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Monzerrat Pardo
Hospital Civil de Guadalajara
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Ilse Delgado-Ruiz
Hospital Civil de Guadalajara
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Hugo Romo-Rubio
Hospital Civil de Guadalajara
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Feranando Sanchez-Zubieta
Hospital Civil de Guadalajara
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Ramón Oscar Gonzalez-Ramella
Hospital Civil de Guadalajara
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Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood, and despite advances in cancer treatment, there are still cases of relapse and death secondary to resistance to chemotherapy or apoptosis. One of the mechanisms is the activation of the IKK/NF-κB signaling pathway that leads to the expression of genes that interfere with apoptosis. Pentoxifylline (PTX) can block phosphorylation of IκB, thus preventing the NF-κB activity, therefore the activation of anti-apoptotic genes. Procedure: Controlled versus placebo, randomized, double-blind clinical trial. Pediatric patients with ALL during induction therapy were assigned either to pentoxifylline or the placebo group. Bone marrow aspirates were performed on day-1, day-8, day-15, and day-22. We performed flow MRD, determination of apoptosis by annexin-V/propidium iodide test, and senescence by β-galactosidase activity. Results: PTX group had higher percentage of apoptotic cells on day-8 (41.3% vs 19.4%, p=0.029), and day-15 (35.0% vs 14.2%, p <0.01). No difference was observed in the senescence determinations. On day-8, the PTX group showed MRD of 0.25% vs 18.2% (p <0.01) in the placebo group; at day-15 the PTX group showed MRD of 0.09% vs 1.4% (p=0.02). Patients with MRD <0.01% at day-8 had 3-year OS of 81.6% vs 58.3% (p=0.03); at day-15 patients with MRD <0.01% at day-8 had 3-year OS of 77.9% vs 54.5% (p=0.03). Conclusion: PTX group showed a MRD <0.01% earlier, on day-8 and 15, and presented a higher percentage of apoptotic cells. In the entire cohort, patients with MRD <0.01% on day 8 or 15 showed better OS.