血液肿瘤儿童化疗后预防性使用重组人粒细胞/粒细胞-巨噬细胞集落刺激因子的疗效和安全性

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目的:探讨血液肿瘤患儿化疗后预防性使用重组人粒细胞/粒细胞巨噬细胞集落刺激因子(recombinant human granulocyte/granulocyte-macrophage colony-stimulating factor,rhG/GM-CSF)的疗效及不良反应。方法:比较血液肿瘤患儿接受强烈化疗后24~48 h预防性使用rhG/GMCSF后,中性粒细胞绝对值(absolute neutrophil count,ANC)恢复时间、感染发生率及不良反应。结果:2013年1月—2015年12月符合标准的预防性使用rhG/GM-CSF共248例次。ANC平均恢复时间为11.6 d(95%可信区间:11.1~12.0 d),单用rhG-CSF组为10.8 d(95%可信区间:10.1~11.4 d),单用rhGMCSF组为12.7 d(95%可信区间:11.9~13.4 d)。rhG-CSF组中性粒细胞水平恢复时间较rhGM-CSF组短(z=-4.649,P<0.01)。急性髓细胞白血病患者中性粒细胞水平的恢复时间较高危急性淋巴细胞白血病/淋巴母细胞型淋巴瘤和B细胞型非霍奇金淋巴瘤患者迟(z=4.819,P<0.01;z=5.595,P<0.01)。含大剂量阿糖胞苷方案组的中性粒细胞水平恢复时间较其他方案显著延长(z=5.417,P<0.01)。单用rhG-CSF组和单用rhGM-CSF组发热性中性粒细胞缺乏发生率分别为58.9%和57.8%,2组差异无统计学意义(P=0.87)。HR3方案治疗最易引起感染,发热性中性粒细胞缺乏发生率高达88.0%。感染相关死亡患者2例,其中单用rhGCSF组1例,为B细胞型非霍奇金淋巴瘤患者接受BB方案治疗后因脓毒血症而放弃治疗;另一例为单用rhGM-CSF,为高危急性淋巴细胞白血病患者接受HR3方案后发生耐药铜绿假单胞菌败血症而死亡。结论:血液肿瘤患儿化疗后预防性使用rhG/GM-CSF的安全性较好。今后,需要开展较大样本量的随机对照试验以证实预防性使用rhG/GM-CSF对降低化疗后感染发生率的价值。 Objective: To investigate the efficacy and adverse reactions of prophylactic use of recombinant human granulocyte / granulocyte-macrophage colony-stimulating factor (rhG / GM-CSF) in children with hemo-tumor after chemotherapy. Methods: The recovery time of absolute neutrophil count (ANC), the incidence of infection and adverse reactions were compared between 24 and 48 hours after the prophylaxis and treatment of rhG / GMCSF in children with hematological malignancies. Results: From January 2013 to December 2015, a total of 248 eligible anti-rhG / GM-CSF were given. The average recovery time for ANC was 11.6 days (95% confidence interval: 11.1-12.0 days), 10.8 days (95% confidence interval: 10.1- 11.4 days) for rhG-CSF alone and 12.7 days for rhGMCSF alone 95% confidence interval: 11.9 to 13.4 d). The recovery time of neutrophil in rhG-CSF group was shorter than that in rhGM-CSF group (z = -4.649, P <0.01). Acute myeloid leukemia patients with higher recovery time of neutrophils in patients with acute lymphoblastic leukemia / lymphoblastic lymphoma and B-cell non-Hodgkin’s lymphoma (z = 4.819, P <0.01; z = 5.595 , P <0.01). The neutrophil recovery time was significantly longer in the high-dose cytarabine-containing regimen than in the other regimens (z = 5.417, P <0.01). The incidence of febrile neutropenia in rhG-CSF alone and rhGM-CSF alone was 58.9% and 57.8%, respectively, with no significant difference between the two groups (P = 0.87). HR3 treatment most likely to cause infection, febrile neutropenia incidence as high as 88.0%. Infection-related death in 2 patients, including rhGCSF alone in 1 case, for the B-cell non-Hodgkin’s lymphoma patients after receiving BB treatment for sepsis and give up treatment; the other for rhGM-CSF alone, as Patients with high-risk acute lymphoblastic leukemia who died after receiving HR3 regimen developed resistant Pseudomonas aeruginosa sepsis. Conclusion: The safety of prophylactic rhG / GM-CSF in children with hematological malignancies after chemotherapy is better. In the future, larger randomized controlled trials will need to be conducted to demonstrate the value of prophylactic use of rhG / GM-CSF in reducing the incidence of post-chemotherapy infections.
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