Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute lymphoblastic leukemia.
OBJECTIVE
Pentoxifylline (PTX) has been shown to increase chemotherapy-induced apoptosis. A clinical trial was developed to evaluate the effect of the addition of PTX to the induction steroid window phase in children with acute lymphoblastic leukemia (ALL).


METHODS
Thirty-two children were enrolled on this study. Children with a new diagnosis of ALL were randomly assigned to receive prednisone (PRD) 40 mg/m(2)/day only during the 7-day treatment pre-phase (PRD group, 11 patients) or to receive PRD with PTX (10 mg/kg/day) (PTX group, 11 patients); the control group included children with normal bone marrow (10 patients). Bone marrow aspiration (BMA) was performed at diagnosis (day -7) in all groups, and at day 0 (end of PRD window) for patients with ALL (PRD and PTX groups). Apoptosis was evaluated by flow cytometry (FC) using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) stains. Statistical analysis was performed using the Mann-Whitney U test.


RESULTS
Apoptotic index at day -7 was similar in all groups. However, at day 0 post-treatment, apoptosis was significantly higher in the PTX group than in the PRD group (p < 0.001). There were no serious adverse effects associated with PTX.


CONCLUSIONS
PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase.
Instituto de Investigación en Cáncer Infantil y de la Adolescencia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.|Department of Pediatric Hematology and Oncology, Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Guadalajara, Jalisco, Mexico.
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Gonzalez-Ramella
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
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Ortiz-Lazareno
Instituto de Investigación en Cáncer Infantil y de la Adolescencia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.|Department of Pediatric Hematology and Oncology, Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Guadalajara, Jalisco, Mexico.
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Jiménez-López
Instituto de Investigación en Cáncer Infantil y de la Adolescencia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.|Department of Pediatric Hematology and Oncology, Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Guadalajara, Jalisco, Mexico.
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Gallegos-Castorena
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
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Hernández-Flores
Instituto de Investigación en Cáncer Infantil y de la Adolescencia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.|Department of Pediatric Hematology and Oncology, Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Guadalajara, Jalisco, Mexico.
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Medina-Barajas
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
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Meza-Arroyo
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.
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Jave-Suárez
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico.|Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, Jalisco, Mexico.
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Lerma-Díaz
Instituto de Investigación en Cáncer Infantil y de la Adolescencia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.|Department of Pediatric Hematology and Oncology, Hospital Civil de Guadalajara Dr. Juan I. Menchaca, Guadalajara, Jalisco, Mexico.
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Sánchez-Zubieta
División de Inmunología, Centro de Investigación Biomédica de Occidente (CIBO), Instituto Mexicano del Seguro Social (IMSS), Sierra Mojada 800, Col. Independencia, 44340, Guadalajara, Jalisco, Mexico. abravocster@gmail.com.|Centro Universitario de los Altos, Universidad de Guadalajara, Tepatitlán de Morelos, Jalisco, Mexico. abravocster@gmail.com.
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Bravo-Cuellar
D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D016166:Free Radical Scavengers / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D010431:Pentoxifylline / Q000627:therapeutic use*; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D011241:Prednisone / Q000627:therapeutic use*; D011379:Prognosis; D012074:Remission Induction
D000893:Anti-Inflammatory Agents; D016166:Free Radical Scavengers; D010431:Pentoxifylline; D011241:Prednisone
Acute lymphoblastic leukemia; Apoptosis; Pentoxifylline