Gonzalez-Ramella O, Ortiz-Lazareno P C, Jiménez-López X, Gallegos-Castorena S, Hernández-Flores G, Medina-Barajas F, Meza-Arroyo J, Jave-Suárez L F, Lerma-Díaz J M, Sánchez-Zubieta F, Bravo-Cuellar A
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.
Clin Transl Oncol. 2016 Apr;18(4):369-74. doi: 10.1007/s12094-015-1376-x. Epub 2015 Sep 2.
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).
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.
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.
PTX potentiates blast apoptosis induced by PRD in children with ALL during steroid window phase.
已证实己酮可可碱（PTX）可增加化疗诱导的细胞凋亡。开展了一项临床试验，以评估在急性淋巴细胞白血病（ALL）患儿的诱导类固醇窗口期添加PTX的效果。
32名儿童参与了本研究。新诊断为ALL的儿童被随机分配，仅在7天的治疗前期接受泼尼松（PRD）40mg/m²/天（PRD组，11例患者），或接受PRD联合PTX（10mg/kg/天）（PTX组，11例患者）；对照组包括骨髓正常的儿童（10例患者）。所有组在诊断时（第-7天）进行骨髓穿刺（BMA），ALL患者（PRD组和PTX组）在第0天（PRD窗口期结束时）进行骨髓穿刺。使用膜联蛋白V-异硫氰酸荧光素（FITC）/碘化丙啶（PI）染色通过流式细胞术（FC）评估细胞凋亡。使用曼-惠特尼U检验进行统计分析。
所有组在第-7天的凋亡指数相似。然而，在治疗后第0天，PTX组的细胞凋亡明显高于PRD组（p<0.001）。未发现与PTX相关的严重不良反应。
在类固醇窗口期，PTX可增强PRD诱导的ALL患儿原始细胞凋亡。
