Saber Wael, Zhang Mei-Jie, Steinert Patricia, Chen Min, Horowitz Mary M
Center for International Blood and Marrow Transplant Research, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, Wisconsin.
Center for International Blood and Marrow Transplant Research, Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
Biol Blood Marrow Transplant. 2016 Aug;22(8):1460-1466. doi: 10.1016/j.bbmt.2016.04.008. Epub 2016 May 7.
Clinical trials evaluating palifermin have enrolled few pediatric patients, precluding safety analyses in large groups of children. We compared hematopoietic cell transplantation (HCT) outcomes among pediatric patients who did or did not receive palifermin as a preventive treatment for oral mucositis. Pediatric patients and controls, matched for HCT and donor type, disease, disease status, and age, were selected from the Center for International Blood and Marrow Transplant Research database and a 1:3 matched cohort analysis was performed. Stratified Cox proportional hazards models were built and propensity score adjustments were used to compare overall and disease-free survival outcomes between palifermin-treated and untreated patients. Three controls were identified for 90% of palifermin recipients. The remaining cases were matched with 2 (8%) controls or 1 (2%) control, for a total of 210 palifermin-treated patients matched with 606 controls. Median follow-up was 31 months in cases and 36 months in controls. Fifty-seven percent of patients underwent allogeneic HCT, mostly for acute leukemia, and 43% underwent autologous HCT, mostly for solid tumors. In univariate analyses, 2-year survival and disease-free survival rates after allogeneic HCT (58% versus 66%, P = .109; 49% versus 60%, P = .06) and after autologous HCT (73% versus 77%, P = .474; 60% versus 64%, P = .637) were similar between palifermin-treated patients and matched controls. In multivariate analysis, palifermin treatment did not significantly increase the risk of mortality (relative risk [RR], 1.20; 95% confidence interval [CI], .87 to 1.66) or of relapse (RR, 1.12; 95% CI, .78 to 1.62) compared with matched controls. No significant differences in rates of acute or chronic graft-versus-host disease (GVHD) were observed between palifermin-treated patients and matched controls. Among pediatric patients undergoing HCT, overall survival, disease-free survival, neutrophil recovery, and GVHD rates were similar between palifermin-treated patients and matched controls.
评估帕利夫明的临床试验纳入的儿科患者较少，无法对大量儿童进行安全性分析。我们比较了接受或未接受帕利夫明作为口腔黏膜炎预防性治疗的儿科患者的造血细胞移植（HCT）结果。从国际血液和骨髓移植研究中心数据库中选取了在HCT、供体类型、疾病、疾病状态和年龄方面相匹配的儿科患者及对照，并进行了1:3匹配队列分析。构建了分层Cox比例风险模型，并使用倾向评分调整来比较接受帕利夫明治疗和未治疗患者的总生存和无病生存结果。为90%的帕利夫明接受者确定了3名对照。其余病例与2名（8%）对照或1名（2%）对照匹配，共有210名接受帕利夫明治疗的患者与606名对照匹配。病例组的中位随访时间为31个月，对照组为36个月。57%的患者接受了异基因HCT，主要用于治疗急性白血病，43%的患者接受了自体HCT，主要用于治疗实体瘤。在单因素分析中，接受帕利夫明治疗的患者与匹配对照在异基因HCT后2年生存率和无病生存率（58%对66%，P = 0.109；49%对60%，P = 0.06）以及自体HCT后（73%对77%，P = 0.474；60%对64%，P = 0.637）相似。在多因素分析中，与匹配对照相比，帕利夫明治疗并未显著增加死亡风险（相对风险[RR]，1.20；95%置信区间[CI]，0.87至1.66）或复发风险（RR，1.12；95%CI，0.78至1.62）。在接受帕利夫明治疗的患者与匹配对照之间，未观察到急性或慢性移植物抗宿主病（GVHD）发生率的显著差异。在接受HCT的儿科患者中，接受帕利夫明治疗的患者与匹配对照在总生存、无病生存、中性粒细胞恢复和GVHD发生率方面相似。
