NCCN骨髓生长因子临床实践指南2017.1版（2）
目录
●评估、风险评估和预防性应用(MGF-1)
●预防性给药的患者危险因素附加评估 (MGF-2)
●第二个化疗周期和后续化疗周期前的评估(MGF-3)
●骨髓生长因子在中性粒细胞减少性发热患者的治疗性用药 (MGF-4)
●存在发生中性粒细胞减少性发热中-高风险的疾病和化疗方案举例 (MGF-A)
●G-CSF在预防中性粒细胞减少性发热及维持计划剂量化疗中的运用 (MGF-B)
●骨髓生长因子的治疗性用药(MGF-C)
●骨髓生长因子在造血干细胞移植动员和移植后的应用(MGF-D)
●骨髓生长因子的毒性风险(MGF-E)
存在发生中性粒细胞减少性发热中-高风险的疾病和化疗方案举例
(MGF-A)
MGF-A(1/4)
存在发生中性粒细胞减少性发热高风险的疾病和化疗方案举例(>20%)a
●这份表并不全面；还有其它药物/方案存在发生中性粒细胞减少性发热的高风险。当这份举例的表格更新时，NCCN按癌症部位的治疗指南中方案的推荐会进行相应的考虑。
●化疗方案的类型只是风险评估中的一个组成部分。（见发生中性粒细胞减少性发热的患者危险因素，MGF-2）
●精确的风险包括：药物、剂量和治疗所处的情况（如初治患者还是先前接受过大量治疗的患者[heavily pretreated patients]）。（见MGF-1）。
急性淋巴细胞白血病(ALL)
●选择指南推荐的ALL治疗方案(见NCCN 急性淋巴细胞白血病指南)
膀胱癌
●剂量密集型MVAC b(甲氨蝶呤，长春花碱，多柔比星，顺铂) 1
乳腺癌
●剂量密集型AC-T b (多柔比星，环磷酰胺，紫杉醇) 2
●TAC (多西他赛，多柔比星，环磷酰胺) 3
●TC a,c (多西他赛，环磷酰胺) 4
●TCH a (多西他赛，卡铂，曲妥珠单抗) 5
霍奇金淋巴瘤
●升级版BEACOPP(博来霉素，依托泊苷，多柔比星，环磷酰胺，长春新碱，丙卡巴肼，泼尼松) 7
肾癌
●多柔比星/吉西他滨 8
非霍奇金淋巴瘤
●剂量调整的EPOCH a（依托泊苷，泼尼松，长春新碱，环磷酰胺，多柔比星）9
●ICE (异环磷酰胺，卡铂，依托泊苷) a,10,11
●剂量密集型CHOP-14 a,b (环磷酰胺，多柔比星，长春新碱，泼尼松) 12,13
●MINE a (美司钠 ，异环磷酰胺，米托蒽醌，依托泊苷) 14
●DHAP a (地塞米松，顺铂，阿糖胞苷) 15
●ESHAP a (依托泊苷，甲基强的松龙，顺铂，阿糖胞苷) 16
●HyperCVAD a (环磷酰胺，长春新碱，多柔比星，地塞米松) 17,18
黑色素瘤
● 达卡巴嗪为基础，联合IL-2、α干扰素（达卡巴嗪，顺铂，长春花碱，L-2， α干扰素）19
多发性骨髓瘤
●DT-PACE （地塞米松/沙利度胺/顺铂/多柔比星/环磷酰胺/依托泊苷）20 ± 硼替佐米（VTD-PACE）21
卵巢癌
●拓扑替康 a,22
●多西他赛23
软组织肉瘤
●MAID（美司钠，多柔比星，异环磷酰胺，达卡巴嗪）24
●多柔比星a,25
●异环磷酰胺/多柔比星26
小细胞肺癌
●拓扑替康27
睾丸癌
●VeIP（长春花碱，异环磷酰胺，顺铂）28
●VIP（依托泊苷，异环磷酰胺，顺铂）
●BEP（博来霉素，依托泊苷，顺铂）29,30
●TIP（紫杉醇，异环磷酰胺，顺铂）31
注解：
a.指南适用于联合或不联合单克隆抗体（如曲妥珠单抗、利妥昔单抗）的化疗方案。 加入单克隆抗体可能会增加中性粒细胞减少的风险。 利妥昔单抗是否联合化疗与中性粒细胞减少持续时间的延长有关。 有关在临床实践中什么时候推荐在上述方案联合单克隆抗体的详细信息，请参阅NCCN按癌症部位的治疗指南。
b.一般来说，剂量密集型的化疗方案需要生长因子支持。
c.关于中性粒细胞减少性发热的风险是中度风险或高风险的报道因研究而异。
MGF-A(2/4)
存在发生中性粒细胞减少性发热中风险的疾病和化疗方案举例(10%-20%)a
●这份表并不全面；还有其它药物/方案存在发生中性粒细胞减少性发热的中度风险。当这份举例的表格更新时，NCCN按癌症部位的治疗指南中方案的推荐会进行相应的考虑。
●化疗方案的类型只是风险评估中的一个组成部分。（见发生中性粒细胞减少性发热的患者危险因素，MGF-2）
●精确的风险包括：药物、剂量和治疗所处的情况（如初治患者还是先前接受过大量治疗的患者[heavily pretreated patients]）。（见MGF-1）。
原发灶不明-腺癌
●吉西他滨/多西他赛32
乳腺癌
●多西他赛 a,33,34
●传统的CMF方案 (环磷酰胺，甲氨蝶呤，氟尿嘧啶) 35
●AC (多柔比星，环磷酰胺) + 序贯多西他赛 (仅紫杉醇部分) a,36
●FEC (氟尿嘧啶，表柔比星，环磷酰胺) + 序贯多西他赛a,37
●紫杉醇每21天1次a,38
宫颈癌
●顺铂/拓扑替康39,40,41
●紫杉醇/顺铂a,41
●拓扑替康42
●伊立替康43
结直肠癌
●FOLFOXa（氟尿嘧啶，甲酰四氢叶酸，奥沙利铂）44
食管癌和胃癌
●伊立替康/顺铂 a,45
●表柔比星/顺铂/5-氟尿嘧啶46
●表柔比星/顺铂/卡培他滨46
非霍奇金淋巴瘤
●GDP (吉西他滨，地塞米松，顺铂/卡铂) a,47
●CHOP a (环磷酰胺，多柔比星，长春新碱，泼尼松) 48,49 包括含聚乙二醇化脂质体多柔比星的方案50,51
非小细胞肺癌
●顺铂/紫杉醇52
●顺铂/长春瑞滨53
●顺铂/多西他赛52,54
●顺铂/依托泊苷55
●卡铂/紫杉醇a,d,56
●多西他赛54
卵巢癌
●卡铂/多西他赛57
胰腺癌
●FOLFIRINOXe
前列腺癌
●卡巴他赛f,58
小细胞肺癌
●依托泊苷/卡铂59
睾丸癌
●依托泊苷/顺铂60
子宫肉瘤
●多西他赛61
注解：
a.指南适用于联合或不联合单克隆抗体（如曲妥珠单抗、利妥昔单抗）的化疗方案。 加入单克隆抗体可能会增加中性粒细胞减少的风险。 利妥昔单抗是否联合化疗与中性粒细胞减少持续时间的延长有关。 有关在临床实践中什么时候推荐在上述方案联合单克隆抗体的详细信息，请参阅NCCN按癌症部位的治疗指南。
d.如果卡铂剂量是AUC> 6和/或患者是日本血统。
e.一项小型回顾性研究发现该方案用于新辅助治疗，患者发生中性粒细胞减少性发热的风险为17%；62一项随机研究发现该方案用于转移性疾病的患者（接受FOLFORINOX化疗的患者有42.5%使用G-CSF），发生中性粒细胞减少性发热的风险为5.4%。63但不推荐G-CSF用于一级预防，有高危临床特征的患者可考虑使用。
f.已公布的结果显示使用卡巴他赛的患者有8%的概率发生中性粒细胞减少性发热，但是有报道出现中性粒细胞减少相关性死亡。对于具有高危临床特征的患者应考虑使用G-CSF进行一级预防。
MGF-A(3/4,4/4)
化疗方案的参考文献
注意：每个方案列出的参考文献受临床试验中研究的具体人群、方法和中性粒细胞减少性发热的数据收集等因素限制。
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63.Conroy T, Desseigne F, Ychou M et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 2011;364:1817-1825.
G-CSF在预防中性粒细胞减少性发热及维持计划剂量化疗中的运用 (MGF-B)
●非格司亭(1类推荐)，tbo-非格司亭a (1类推荐)，或非格司亭-sndz b(1类推荐)
►每日剂量5mcg/kg（根据研究所确定的体重限量选择最接近的包装瓶剂量），直至经过低点后ANC恢复到实验室标准的正常或接近正常值。
►化疗结束后次日或3-4日开始应用，用至低点过后恢复。c
●聚乙二醇非格司亭 (1类推荐)
►每个疗程单次使用6mg。
◊基于临床试验的数据，应在化疗结束后次日给予聚乙二醇非格司亭 (1类推荐)。
◊对于无法回到医疗机构进行次日给药的患者，存在替代方案。d
◊基于非格司亭的临床试验，化疗后3-4日给予聚乙二醇非格司亭也是合理的。
►已有证据支持在每三周一次的化疗中应用 (1类推荐)。
► II期研究显示在每两周一次的化疗中聚乙二醇非格司亭有效。
►目前尚无足够的证据支持聚乙二醇非格司亭在每周给药的细胞毒性化疗方案中应用；因此，在这种情况下的应用不推荐。
●同步放化疗的患者不推荐预防性应用G-CSFs。
●皮下注射为上述所列所有G-CSF的首选给药途径。
●有关预防性抗感染（例如：病毒、真菌、细菌）的信息参见NCCN癌症相关感染的预防与治疗。
注解：
a.Tbo-非格司亭被FDA以原研生物药品批准，而非作为非格司亭的仿制药。所有这些G-CSF，适应症是用于缩短与临床中性粒细胞减少性发热发生率显著相关的非骨髓恶性肿瘤患者接受骨髓抑制治疗后的严重中性粒细胞下降持续时间。
b.非格司亭-sndz是第一个获FDA审批的生物仿制品。更多详细的信息见讨论部分。
c.研究表明，较短的G-CSF给药持续时间可能不那么有效。(Weycker D, Li X, Tzivelekis S, et al. Burden of chemotherapy-induced febrile neutropenia hospitalizations in US clinical practice, by use and patterns of prophylaxis with colony-stimulating factor. Support Care Cancer 2017;25:439-447.)
d.有一个获得FDA审批的给药装置已经实现了聚乙二醇非格司亭在化疗当天设置、第二天全剂量给药（大约在设置后27小时）。(Yang BB, Morrow PK, Wu X, et al. Comparison of pharmacokinetics and safety of pegfilgrastim administered by two delivery methods: on-body injector and manual injection with a prefilled syringe. Cancer Chemother Pharmacol 2015;75:1199-1206.)
骨髓生长因子的治疗性用药(MGF-C)
引发MGF治疗性给药用于中性粒细胞减少性发热的可能适应症 a,b
●败血症综合征
●年龄> 65岁
●绝对中性粒细胞计数[ANC] <100 / mcL
●中性粒细胞减少的持续时间预计在10天以上
●肺炎或其他临床证实的感染
●侵入性真菌感染
●发热时正在住院
●先前发生过中性粒细胞减少性发热
MGF用于治疗的给药剂量：c
●非格司亭或非格司亭-sndz d
►每日剂量5mcg/kg（根据研究所确定的体重限量选择最接近的包装瓶剂量）。
►继续给药直至经过低点后ANC恢复到实验室标准的正常或接近正常值。
●沙莫司亭（为重粗细胞集落刺激因子）
►在临床试验中使用的剂量为250 mcg/m2/d 根据研究所确定的体重限量选择最接近的包装瓶剂量）。
►继续给药直至经过低点后ANC恢复到实验室标准的正常或接近正常值。
注解：
a.使用或不使用MGF治疗中性粒细胞减少性发热的决定是有争议的。 有关详细信息，请参阅讨论。
b.Smith TJ, Khatcheressian J, Lyman G, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J Clin Oncol 2006;24:3187-3205.
c.Tbo-非格司亭和聚乙二醇非格司亭仅用于预防性用药。 有关详细信息，请参阅讨论部分。
d.非格司亭-sndz是第一个获FDA审批的生物仿制品。更多详细的信息见讨论部分。
骨髓生长因子在造血干细胞移植动员和移植后的应用(MGF-D)
自体造血干细胞移植的动员
●生长因子单药：1-3
►非格司亭或非格司亭-sndza或tbo-非格司亭
◊剂量：10-32mcg/kg/d，皮下注射，每日1次或两次，第4或第5日开始采集直至白细胞分离术。
●联合化疗后用非格司亭或非格司亭-sndza或tbo-非格司亭，以期达到粒细胞恢复时动员的目标。4-6
►大约在化疗结束后24h开始使用非格司亭或非格司亭-sndza或tbo-非格司亭。
●同步使用非格司亭或非格司亭-sndza +沙莫司亭（2B类推荐）
►非格司亭或非格司亭-sndza 7.5 mcg/kg每天早上应用，沙莫司亭7.5 mcg/kg每个晚上应用，第5天开始白细胞分离术。7
●非格司亭或非格司亭-sndza或tbo-非格司亭+普乐沙福（选择性用于非霍奇金淋巴瘤或多发性骨髓患者）8-10
►普乐沙福的适应征：
◊先前接受过大量治疗的患者[heavily pretreated patients]11或先前接受过>10周期的细胞毒药物化疗或以前动员失败过的患者，或接受过6疗程以上的来那度胺、或氟达拉滨，或盆腔放疗而存在动员不足的危险因素。
◊当外周血CD34+细胞计数未达最佳标准时作为“及时治疗”或“解救”。12-14
►剂量
◊非格司亭或非格司亭-sndza或tbo-非格司亭的剂量：10mcg/kg/d×4天，在第4天晚上，第5天（隔天上午）采集前的11小时开始皮下注射普乐沙福。
◊普乐沙福剂量：对体重＞83kg的患者，0.24mg/kg/d；对体重≤83kg的患者，20mg（固定剂量）或0.24mg/kg/d，最多给药4次（如果肌酐清除率>50ml/min，最大剂量40mg/d）。
异基因移植供者的动员
●异基因干细胞供者：15-18
►非格司亭(首选)或非格司亭-sndza （2B类推荐）或tbo-非格司亭（2B类推荐）
◊剂量：10mcg/kg/d，皮下注射，第4或第5日开始采集。19-21
►普乐沙福（2B类推荐）用于正常供者尚在研究之中。22,23
●粒细胞输注的异基因供者：
►非格司亭(首选)或非格司亭-sndza （2B类推荐）或tbo-非格司亭（2B类推荐）
◊剂量:5mcg/kg/d，皮下注射，采集前8-24h口服地塞米松10mg
支持治疗的选择
●非格司亭b,25或非格司亭-sndza或tbo-非格司亭
►自体造血干细胞移植或脐血移植后
►5mcg/kg/d，移植后+5天开始，直到ANC恢复（例如：> 1.5×109 /L × 2 天）。c
●沙莫司亭26-28
►自体造血干细胞移植或移植后推迟的造血干细胞移植
►250mcg/m2/d，直到ANC > 1.5×109 /L × 3 天。
●聚乙二醇非格司亭29
►自体造血干细胞移植后
注解：
a.非格司亭-sndz是第一个获FDA审批的生物仿制品。更多详细的信息见讨论部分。
b.非格司亭加快粒细胞恢复而不影响生存，详见讨论。
c.有关其它的剂量信息，请参阅包装说明书：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=97cc73cc-b5b7-458a-a933-77b00523e193. (Accessed March 14, 2016.)
参考文献：
1.Kroger N, Zeller W, Fehse N, et al. Mobilizing peripheral blood stem cells with high-dose G-CSF alone is as effective as with Dexa-BEAM plus G-CSF in lymphoma patients. Br J Haematol
1998;102:1101–1106.
2.Elayan MM, Horowitz JG, Magraner JM, et al. Tbo-filgrastim versus filgrastim during mobilization and neutrophil engraftment for autologous stem cell transplantation. Biol Blood Marrow Transplant 2015;21:1921-1925.
3.Trifilio S, Zhou Z, Galvin J, et al. Filgrastim versus tbo-filgrastim to reduce the duration of neutropenia after autologous hematopoietic stem cell transplantation: TBO, or not TBO, that is the question. Clin Transplant 2015;29:1128-1132.
4.Haynes A, Hunter A, McQuaker G, et al. Engraftment characteristics of peripheral-blood stem-cells mobilized with cyclophosphamide and the delayed addition of G-CSF. Bone Marrow Transplant 1995;16:359-363.
5.Matasar MJ, Czuczman MS, Rodriguez MA, et al. Ofatumumab in combination with ICE or DHAP chemotherapy in relapsed or refractory intermediate grade B-cell lymphoma. Blood 2013;122:499-50.
6.Barlogie B, Anaissie E, van Rhee F, et al. Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3. Br J Haematol 2007;138:176-185.
7.Lonial S, Akhtari M, Kaufman J, et al. Mobilization of hematopoietic progenitors from normal donors using the combination of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor results in fewer plasmacytoid dendritic cells in the graft and enhanced donor T cell engraftment with Th1 polarization: results from a randomized clinical trial. Biol Blood Marrow Transplant. 2013;19:460-467.
8.Becker PS. Optimizing stem cell mobilization: lessons learned. J Natl Compr Canc Netw 2014;12:1443-1449.
9.DiPersio JF, Micallef IN, Stiff PJ, et al. Phase III prospective randomized double-blind placebo-controlled trial of plerixafor plus granulocyte colony-stimulating factor compared with placebo plus granulocyte colony-stimulating factor for autologous stem-cell mobilization and transplantation for patients with non-Hodgkin's lymphoma. J Clin Oncol 2009;27:4767-4773.
10.DiPersio JF, Stadtmauer EA, Nademanee A, et al. Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009;113:5720-5726.
11.Stiff P, Micallef I, McCarthy P, et al. Treatment with plerixafor in non-Hodgkin's lymphoma and multiple myeloma patients to increase the number of peripheral blood stem cells when given a mobilizing regimen of G-CSF: Implications for the heavily pretreated patient. Biol Blood Marrow Transplant 2009;15:249–256.
12.Dugan MJ, Maziarz RT, Bensinger WI, et al. Safety and preliminary efficacy of plerixafor (Mozobil) in combination with chemotherapy and G-CSF: an open label, multicenter, exploratory trial in patients with multiple myeloma and non-Hodgkin's lymphoma undergoing stem cell mobilization. Bone Marrow Transplant 2010;45:39-47.
13.Gopal AK, Karami M, Mayor J, et al. The effectSive use of plerixafor as a real-time rescue strategy for patients poorly mobilizing autologous CD34(+) cells. J Clin Apher 2012;27:81-87.
14.Milone G, Tripepi G, Martino M, et al. Early measurement of CD34+ cells in peripheral blood after cyclophosphamide and granulocyte colony-stimulating factor treatment predicts later CD34+ mobilisation failure and is a possible criterion for guiding "on demand" use of plerixafor. Blood Transfus 2013;11:94-101.
15.Antelo ML, Zabalza A, Sanchez Anton MP, et al. Mobilization of hematopoietic progenitor cells from allogeneic healthy donors using a new biosimilar G-CSF. J Clin Apher 2015.
16.Schmitt M, Xu X, Hilgendorf I, et al. Mobilization of PBSC for allogeneic transplantation by the use of the G-CSF biosimilar XM02 in healthy donors. Bone Marrow Transplant 2013;48:922-925.
17.Sivgin S, Karakus E, Keklik M, et al. Evaluation of the efficacy and safety of original filgrastim (Neupogen(R)), biosimilar filgrastim (Leucostim(R)) and Lenograstim (Granocyte(R)) in CD34(+) peripheral hematopoietic stem cell mobilization procedures for allogeneic hematopoietic stem cell transplant donors. Transfus Apher Sci 2016;54:410-415.
18.Danylesko I, Sareli R, Bloom-Varda N, et al. Biosimilar Filgrastim (Tevagrastim, XM02) for Allogeneic Hematopoietic Stem Cell Mobilization and Transplantation in Patients with Acute Myelogenous Leukemia/Myelodysplastic Syndromes. Biol Blood Marrow Transplant 2016;22:277-283.
19.Bensinger WI, Weaver CH, Appelbaum FR, et al. Transplantation of allogeneic peripheral blood stem cells mobilized by recombinant human granulocyte colony-stimulating factor. Blood 1995;85:1655-1658.
20.Cavallaro AM, Lilleby K, Majolino I, et al. Three to six year follow-up of normal donors who received recombinant human granulocyte colony-stimulating factor. Bone Marrow Transplant 2000;25:85-89.
21.Rinaldi C, Savignano C, Pasca S, et al. Efficacy and safety of peripheral blood stem cell mobilization and collection: a single-center experience in 190 allogeneic donors. Transfusion 2012;52:2387-2394.
22.Gattillo S, Marktel S, Rizzo L, et al. Plerixafor on demand in ten healthy family donors as a rescue strategy to achieve an adequate graft for stem cell transplantation. Transfusion 2015;55:1993-2000.
23.Schriber J, Fauble V, Sproat LO, Briggs A. Plerixafor 'just in time' for stem cell mobilization in a normal donor. Bone Marrow Transplant 2011;46:1026-1027.
24.Stroncek DF, Matthews CL, Follmann D, et al. Kinetics of G-CSF-induced granulocyte mobilization in healthy subjects: effects of route of administration and addition of dexamethasone. Transfusion 2002;42:597-602.
25.Trivedi M, Martinez S, Corringham S, et al. Review and revision of clinical practice of using G-CSF after autologous and allogeneic hematopoietic stem cell transplantation at UCSD. J Oncol Pharm Pract 2011;17:85-90.
26.Nemunaitis J, Rabinowe SN, Singer JW, et al. Recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for lymphoid malignancy: Pooled results of a randomized, double-blind, placebo controlled trial. N Engl J Med 1991;324:1773-1778.
27.Nemunaitis J, Singer JW, Buckner CD, et al. Use of recombinant human granulocyte-macrophage colony-stimulating factor in graft failure after bone marrow transplantation. Blood 1990;76:245-253.
28.Ippoliti C, Przepiorka D, Giralt S, et al. Low-dose non-glycosylated rhGM-CSF is effective for the treatment of delayed hematopoietic recovery after autologous marrow or peripheral blood stem cell transplantation. Bone Marrow Transplant 1993;11:55-59.
29.Castagna L, Bramanti S, Levis A, et al. Pegfilgrastim versus filgrastim after high-dose chemotherapy and autologous peripheral blood stem cell support. Ann Oncol 2010;21:1482-1485.
骨髓生长因子的毒性风险(MGF-E)
非格司亭及其衍生产品包括聚乙二醇化非格司亭a,b,c
●警示
►过敏反应
◊皮肤：皮疹，红斑，颜面水肿
◊呼吸道：哮喘，呼吸困难
◊心血管：低血压，心动过速、过敏性反应
►含博莱霉素的方案：肺毒性d
►脾脏破裂d
►急性呼吸窘迫综合症
►肺泡出血和咳血
►镰状细胞病危象：仅在镰状细胞病患者
►MDS及AMLe
●谨慎
►皮肤血管炎
►免疫原性
●不良反应
►骨痛
沙莫司亭a,c
●警示
►体液储留：水肿，毛细血管渗漏综合症，胸腔和/或心包积液
►呼吸道症状：粒细胞滞留于肺循环，呼吸困难
►心血管症状：偶尔可致短暂的阵发性室上性心律失常，在既往有心脏疾病的患者中应用需要小心。
►肾脏和肝脏功能不全：血清肌酐或胆红素和肝酶升高。对于用药前存在肾脏和肝脏功能不全的患者需要监测。
●在临床对照试验中接受沙格司亭治疗的患者出现的发生率大于10%不良事件和报告的高于安慰剂组的不良反应
►AML-发热，皮肤反应，代谢失衡，恶心，呕吐，体重下降，水肿，厌食
►用于自体造血细胞移植或外周血干细胞移植时的不良反应：乏力，萎靡不振，腹泻，皮疹，外周水肿，泌尿系统疾病
►用于异基因造血细胞移植或外周血干细胞移植时的不良反应：腹痛，寒战，胸痛，腹泻，恶心，呕吐，吞咽困难，胃肠道出血，皮肤瘙痒，骨痛，关节痛，高血压，眼出血，高血压，心动过速，高胆色素血症，高血糖，肌酐升高，低镁血症，水肿，咽炎，鼻衄，失眠，焦虑，血尿素氮升高，高胆固醇血症。
注解
a.完整的处方信息参见各产品说明书。
b.并非上述所列的毒性反应在每次使用均会出现，但非格司亭和聚乙二醇非格司亭预计有类似毒性。
c. 毒性数据基于说明书及参加临床研究的不同患者人群。非格司亭及其衍生物的毒性数据来源于非骨髓恶性肿瘤的研究，沙格司亭的毒性数据主要基于白血病患者及移植患者研究，且所列毒性主要发生于静脉给药途径，皮下给药时可能会有所不同。
d.详细信息见讨论部分。
e.Lyman等报道G-CSF相关AML/MDS发生的绝对及相对风险分别为0.41%和1.92%，总体死亡率升高。详见讨论及参考文献。
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