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Pentoxifylline during steroid window phase at induction to remission increases apoptosis in childhood with acute
O Gonzalez-Ramella1,2, P C Ortiz-Lazareno3, X Jiménez-López1,2
1Instituto de Investigación en Cáncer Infantil y de la Adolescencia, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.
Insights
Pentoxifylline (PTX) enhances prednisone-induced apoptosis in pediatric acute lymphoblastic leukemia (ALL) during the steroid window phase. This combination therapy shows promise for improving treatment outcomes in ALL patients.
Area of Science:
- Pediatric Oncology
- Hematology
- Pharmacology
Background:
- Pentoxifylline (PTX) is known to augment chemotherapy-induced apoptosis.
- The steroid window phase is a critical period in acute lymphoblastic leukemia (ALL) treatment.
Purpose of the Study:
- To assess the impact of adding PTX to prednisone (PRD) during the induction steroid window phase in pediatric ALL.
- To evaluate the effect of PTX on chemotherapy-induced apoptosis in ALL.
Main Methods:
- A randomized clinical trial involving 32 children with newly diagnosed ALL.
- Patients received either PRD alone or PRD with PTX during the 7-day pre-phase.
- Bone marrow aspiration and flow cytometry were used to measure apoptosis.
Main Results:
- Apoptosis levels were comparable at diagnosis across all groups.
- Significantly higher blast apoptosis was observed in the PTX group compared to the PRD group post-treatment (p < 0.001).
- No serious adverse events were linked to PTX administration.
Conclusions:
- PTX significantly potentiates PRD-induced blast apoptosis in pediatric ALL during the steroid window phase.
- The addition of PTX to the induction steroid window phase may enhance the efficacy of ALL treatment.
Purpose:
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.
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