Objective: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in prophylaxis neutropenia after chemotherapy in patients with lymphoma. Methods: This was a multicenter, single arm, open, phase Ⅳ clinical trial. Included 410 patients with lymphoma received multiple cycles of chemotherapy and PEG-rhG-CSF was administrated as prophylactic. The primary endpoint was the incidence of Ⅲ/Ⅳ grade neutropenia and febrile neutropenia (FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application during the whole period of chemotherapy was observed. Results: ①Among the 410 patients, 8 cases (1.95%) were contrary to the selected criteria, 35 cases (8.54%) lost, 19 cases (4.63%) experienced adverse events, 12 cases (2.93%) were eligible for the termination criteria, 15 cases (3.66%) develpoed disease progression or recurrence, thus the rest 321 cases (78.29%) were into the Per Protocol Set. ②During the first to fourth treatment cycles, the incidences of grade Ⅳ neutropenia after prophylactic use of PEG-rhG-CSF were 19.14% (49/256) , 12.5% (32/256) , 12.18% (24/197) , 13.61% (20/147) , respectively. The incidences of FN were 3.52% (9/256) , 0.39% (1/256) , 2.54% (5/197) , 2.04% (3/147) , respectively. After secondary prophylactic use of PEG-rhG-CSF, the incidences of Ⅳ grade neutropenia decreased from 61.54% (40/65) in the screening cycle to 16.92% (11/65) , 18.46% (12/65) and 20.75% (11/53) in 1-3 cycles, respectively. The incidences of FN decreased from 16.92% (11/65) in the screening cycle to 1.54% (1/65) , 4.62% (3/65) , 3.77% (2/53) in 1-3 cycles, respectively. ③The proportion of patients who received antibiotic therapy during the whole period of chemotherapy was 34.39% (141/410) . ④The incidence of adverse events associated with PEG-rhG-CSF was 4.63% (19/410) . The most common adverse events were bone pain[3.90% (16/410) ], fatigue (0.49%) and fever (0.24%) . Conclusion: During the chemotherapy in patients with lymphoma, the prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade Ⅲ/Ⅳ neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve its cure rate.
目的： 评价聚乙二醇化重组人粒细胞刺激因子（PEG-rhG-CSF）预防淋巴瘤患者化疗后发生中性粒细胞减少症的有效性和安全性。 方法： 本研究为多中心、开放、单臂、Ⅳ期临床试验。纳入410例淋巴瘤患者接受多周期化疗并预防性使用PEG-rhG-CSF。主要观察患者各化疗周期Ⅲ/Ⅳ度中性粒细胞减少症和发热性中性粒细胞减少（FN）的发生率，同时观察患者整个化疗期间抗生素的使用率。 结果： ①410例患者中，违背入选标准8例（1.95%），失访35例（8.54%），发生不良事件19例（4.63%），出现符合终止研究标准者12例（2.93%），疾病进展或复发15例（3.66%），故最终321例（78.29%）进入符合方案集。②在第1~4个治疗周期，初级预防给予PEG-rhG-CSF后，Ⅳ度中性粒细胞减少症的发生率分别为19.14%（49/256）、12.50%（32/256）、12.18%（24/197）、13.61%（20/147），FN的发生率分别为3.52%（9/256）、0.39%（1/256）、2.54%（5/197）、2.04%（3/147）；次级预防给药后，Ⅳ度中性粒细胞减少症的发生率从61.54%（40/65）降至16.92%（11/65）、18.46%（12/65）、20.75%（11/53），FN的发生率从16.92%（11/65）降至1.54%（1/65）、4.62%（3/65）、3.77%（2/53）。③整个化疗期间接受抗生素治疗的受试者比例为34.39%（141/410）。④与PEG-rhG-CSF相关的不良事件发生率为4.63%（19/410），最常见的不良反应为骨痛[3.90%（16/410）]、乏力（0.49%）和发热（0.24%）。 结论： 在淋巴瘤患者化疗过程中，预防性使用PEG-rhG-CSF能够有效降低化疗过程中Ⅲ/Ⅳ度中性粒细胞减少症和FN的发生率，确保淋巴瘤患者接受标准剂量化疗，提高治愈率。.
Keywords: Granulocyte colony-stimulating factor; Lymphoma; Neutropenia; Polyethylene glycols; Protective agent.