Bregni M, Siena S, Di Nicola M, Dodero A, Peccatori F, Ravagnani F, Danesini G, Laffranchi A, Bonadonna G, Gianni A M
Cristina Gandini Transplantation Unit, Department of Cancer Medicine, Istituto Nazionale, Tumori, Milano, Italy.
J Clin Oncol. 1996 Feb;14(2):628-35. doi: 10.1200/JCO.1996.14.2.628.
We compared hematologic and clinical effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) after treatment with high-dose cyclophosphamide (HD-CTX, 7 g/m2), given as the first phase of a high-dose sequential chemotherapy program that includes a myeloablative therapy with mobilized progenitor cell autografting.
Forty-nine consecutive patients with non-Hodgkin's lymphoma, Hodgkin's disease, or poor-prognosis breast cancer received GM-CSF (n = 27) or G-CSF (n = 22) after HD-CTX in two consecutive, nonrandomized studies. Cytokines were administered in continuous intravenous (i.v.) infusion for 14 to 15 days at a median dose of 5.5 and 10 micrograms/kg/d, respectively, starting 24 hours after HD-CTX.
Neutrophil recovery was faster with G-CSF administration (11.5 v 13.2 days; P = .01), whereas platelet counts recovered more rapidly with GM-CSF (13.7 v 16.6 days; P = .01). Prophylactic platelet transfusions were administered more frequently to patients treated with G-CSF than with GM-CSF (66% v 22% of the patients; P = .02). No clinically significant difference was observed between the two groups concerning days of absolute neutropenia or neutropenic fever. Both cytokines reduced the time to eligibility for subsequent chemotherapy administration compared with historical controls not given cytokine (14 to 16 v 20 days). Both cytokines increased circulation of hematopoietic progenitors. Most side effects were World Health Organization (WHO) median grade 1 to 2, were more frequent during GM-CSF than during G-CSF treatment, and were reversible by simple supportive measures and/or by dose reduction or suspension of the cytokine. Permanent suspension of cytokine administration was never required in either group.
GM-CSF or G-CSF administration after HD-CTX reduces hematologic toxicity of high-dose chemotherapy and induces circulation of large amounts of hematopoietic progenitors suitable for autografting in cancer patients.
在以大剂量序贯化疗方案的第一阶段给予大剂量环磷酰胺(HD-CTX,7 g/m²)治疗后,我们比较了粒细胞-巨噬细胞集落刺激因子(GM-CSF)和粒细胞集落刺激因子(G-CSF)的血液学及临床效果,该化疗方案包括采用动员的祖细胞自体移植进行清髓治疗。
在两项连续的非随机研究中,49例连续的非霍奇金淋巴瘤、霍奇金病或预后不良乳腺癌患者在HD-CTX后接受GM-CSF(n = 27)或G-CSF(n = 22)治疗。细胞因子在HD-CTX后24小时开始,以连续静脉输注方式给药14至15天,GM-CSF和G-CSF的中位剂量分别为5.5和10微克/千克/天。
给予G-CSF时中性粒细胞恢复更快(11.5天对13.2天;P = 0.01),而给予GM-CSF时血小板计数恢复更快(13.7天对16.6天;P = 0.01)。接受G-CSF治疗的患者比接受GM-CSF治疗的患者更频繁地接受预防性血小板输注(66%对22%的患者;P = 0.02)。两组在绝对中性粒细胞减少天数或中性粒细胞减少性发热天数方面未观察到临床显著差异。与未给予细胞因子的历史对照相比,两种细胞因子均缩短了后续化疗给药的合格时间(14至16天对20天)。两种细胞因子均增加了造血祖细胞的循环。大多数副作用为世界卫生组织(WHO)中位1至2级,GM-CSF治疗期间比G-CSF治疗期间更频繁,且通过简单的支持措施和/或通过降低剂量或暂停细胞因子给药可逆转。两组均从未需要永久停止细胞因子给药。
HD-CTX后给予GM-CSF或G-CSF可降低大剂量化疗的血液学毒性,并诱导大量适合癌症患者自体移植的造血祖细胞循环。