Silvestri F, Fanin R, Velisig M, Barillari G, Virgolini L, Zaja F, Russo D, Baccarani M
Division of Hematology, University Hospital, Udine, Italy.
Tumori. 1994 Dec 31;80(6):453-8. doi: 10.1177/030089169408000609.
The aim of the study was to evaluate the role and potential benefit of granulocyte colony-stimulating factor (G-CSF, Filgrastim), administered following cytotoxic chemotherapy with the ABVD regimen in Hodgkin's disease, in maintaining cycle schedule and dose intensity and in decreasing neutropenia and number of infections.
Twenty-two patients affected by high-risk Hodgkin's disease (14 localized and 8 diffuse), aged 15 to 69 years (median, 34), were given ABVD chemotherapy for a total of 6 courses (for the purpose of this study, each single course of chemotherapy was considered as two 15-day periods). No patient was given G-CSF after the first cycle. After each cycle, G-CSF was administered only for: 1)absolute neutrophil count < 1 x 10(9)/L between cycles; 2) delay in cycle schedule due to an absolute neutrophil count < 1 x 10(9)/L on the planned day of treatment; or 3) fever or a documented infection, regardless the absolute neutrophil count. Once administered, G-CSF was maintained in the subsequent cycles.
Seventeen of 22 patients (77%) required the administration of G-CSF (5 micrograms/kg b.w.; a median of 5 doses/cycle); most of them (13/17) before the 5th dose of chemotherapy. The main reason for introducing G-CSF into therapy was neutropenia during the interval between courses (n = 4) or on the planned day of treatment (n = 11). Comparing 112 courses where G-CSF was not administered with 124 where it was, in the latter group we observed: 1) a significantly lower (P = 0.0002) incidence of cycle delays (0 vs 13), with a median delay of 7 days (5 to 11). The main reason for cycle delay was neutropenia (n = 13); 2) a greater dose intensity delivered to the patients while on G-CSF (100% vs 95.2 +/- 8.8%; P = 0.0001); 3) an absolute neutrophil count significantly higher at day 8 (P < 0.0001) and day 15 (P < 0.0001); 4) a significantly lower (P = 0.0003) incidence of neutropenia (2 vs. 17). No difference in the incidence of infections was observed between the two groups of cycles (P = 0.5889), but the duration and severity of the same were greater during chemotherapy without G-CSF, requiring antibiotic therapy and causing cycle delay.
In conclusion, our data suggest the use of Filgrastim in Hodgkin's disease also during conventional-dose chemotherapy with ABVD. It is not required from the first dose of therapy, but as soon as neutropenia appears between cycles or on the planned day of treatment. Then, its use allows maintenance of the chemotherapy schedule and dose intensity. It also decreases frequency, duration and severity of neutropenia and its sequelae.
本研究旨在评估粒细胞集落刺激因子（G-CSF，非格司亭）在霍奇金淋巴瘤患者接受ABVD方案细胞毒性化疗后，对维持化疗周期安排和剂量强度、减少中性粒细胞减少及感染次数的作用和潜在益处。
22例高危霍奇金淋巴瘤患者（14例局限性和8例弥漫性），年龄15至69岁（中位数34岁），接受ABVD化疗共6个疗程（本研究中，每个化疗单疗程视为两个15天周期）。第1周期后未给予任何患者G-CSF。每个周期后，仅在以下情况给予G-CSF：1）周期之间绝对中性粒细胞计数<1×10⁹/L；2）计划治疗日因绝对中性粒细胞计数<1×10⁹/L导致周期延迟；或3）发热或有记录的感染，无论绝对中性粒细胞计数如何。一旦给予，后续周期持续使用G-CSF。
22例患者中有17例（77%）需要使用G-CSF（5微克/千克体重；中位数为5剂/周期）；其中大多数（13/17）在第5剂化疗前使用。引入G-CSF治疗的主要原因是疗程间隔期（n = 4）或计划治疗日（n = 11）出现中性粒细胞减少。将未使用G-CSF的112个疗程与使用G-CSF的124个疗程进行比较，在后一组中我们观察到：1）周期延迟发生率显著降低（P = 0.0002）（0%对13%），中位延迟7天（5至11天）。周期延迟的主要原因是中性粒细胞减少（n = 13）；2）使用G-CSF时给予患者的剂量强度更高（100%对95.2±8.8%；P = 0.0001）；3）第8天（P < 0.0001）和第15天（P < 0.0001）绝对中性粒细胞计数显著更高；4）中性粒细胞减少发生率显著降低（P = 0.0003）（2%对17%）。两组周期感染发生率无差异（P = 0.5889），但在未使用G-CSF的化疗期间感染持续时间和严重程度更大，需要抗生素治疗并导致周期延迟。
总之,我们的数据表明，在霍奇金淋巴瘤患者接受ABVD常规剂量化疗期间也可使用非格司亭。治疗首剂无需使用，而是一旦在周期之间或计划治疗日出现中性粒细胞减少即开始使用。然后，其使用可维持化疗方案和剂量强度。它还可降低中性粒细胞减少及其后遗症的发生频率、持续时间和严重程度。
