G-CSF预防发热性中性粒细胞减少症并维持给予计划的剂量

G-CSF FOR PROPHYLAXIS OF FEBRILE NEUTROPENIA AND MAINTENANCE OF SCHEDULED DOSE DELIVERY
G-CSF预防发热性中性粒细胞减少症并维持给予计划的剂量

* Filgrastim (category 1), tbo-filgrastim (category 1), or filgrastim-sndz (category 1) 山东省肿瘤医院呼吸肿瘤内科张品良
*非格司亭（1类）、梯瓦-非格司亭（1类）或非格司亭-山德士（1类）

▶ Daily dose of 5 mcg/kg (rounding to the nearest vial size by institution-defined weight limits) until post-nadir ANC recovery to normal or near-normal levels by laboratory standards.
▶5μg/kg 每日1次（四舍五入到根据体重确定的最接近的安瓿规格）直至中性粒细胞绝对值从最低点恢复至正常或基本正常的实验室标准。

▶ Start the next day or up to 3–4 days after completion of chemotherapy and treat through post-nadir recovery.
▶在化疗结束后的第2天或第3-4天开始治疗直至从最低点恢复。

* Pegfilgrastim (category 1)
*培非司亭（1类）

▶ One dose of 6 mg per cycle of treatment.
▶每个治疗周期1剂6 mg。

♢ The majority of trials administered pegfilgrastim the day after chemotherapy (category 1).
♢大多数试验在化疗后的第2天给予培非司亭（1类）。

♢ Beginning pegfilgrastim the day after chemotherapy is preferred. Although same-day administration of pegfilgrastim can be considered in certain circumstances, the results are mixed and better options now exist.
♢首选在化疗后的第2天开始培非司亭。虽然在某种情况下可以考虑当天给予培非司亭，但是结果形形色色，因此目前的做法是更好的选择。

♢ Administration of pegfilgrastim up to 3–4 days after chemotherapy is also reasonable based on trials with filgrastim.
♢基于非格司亭的试验，在化疗后3-4天给予培非司亭也是合理的。

▶ There is evidence to support use for chemotherapy regimens given every 3 weeks (category 1).
▶对于每3周1次的化疗方案有证据支持使用（1类）。

▶ There are phase II studies that demonstrate efficacy for chemotherapy regimens given every 2 weeks.
▶对于每两周1次的化疗方案，有些Ⅱ期研究证明有效。

▶ There are insufficient data to support use for weekly chemotherapy regimens; therefore, use of pegfilgrastim cannot be recommended.
▶对于每周1次的化疗方案，没有充分的数据支持使用；因此，不能推荐使用培非司亭。

* Prophylactic use of G-CSF in patients given concurrent chemotherapy and radiation is not recommended.
*在给予同时放化疗的患者中，不推荐预防性使用G-CSF。

* Subcutaneous route is preferred for all G-CSF listed above.
*上面列出的所有G-CSF，首选皮下注射。

* Prophylactic antibiotics are not routinely recommended for standard-dose chemotherapy. See NCCN Guidelines for Prevention and Treatment of Cancer-Related Infections.
*对于标准剂量化疗，不常规推荐预防性使用抗生素。见肿瘤相关感染的预防和治疗NCCN指南。

MYELOID GROWTH FACTORS FOR THERAPEUTIC USE
骨髓生长因子的治疗性应用

Possible Indications for the Initiation of Therapeutic MGF for Management of Febrile Neutropenia
启动治疗性骨髓生长因子合理的适应症是处理发热性中性粒细胞减少症

* Sepsis syndrome
*脓毒症综合征

* Age >65 years
*年龄> 65岁

* Absolute neutrophil count [ANC]<100/mcL
*中性粒细胞计数绝对值 [ANC] < 100/mcL

* Neutropenia expected to be more than 10 days in duration
*预期中性粒细胞减少症持续时间超过10天

* Pneumonia or other clinically documented infections
*肺炎或其他临床证明的感染

* Invasive fungal infection
*侵袭性真菌感染

* Hospitalization at the time of fever
*住院时发热

* Prior episode of febrile neutropenia
*既往发热性中性粒细胞减少症事件

MGF for Therapeutic Use and Maintenance of Scheduled Dose Delivery:
骨髓生长因子治疗性使用和维持给予计划的剂量：

* Filgrastim or filgrastim-sndz
*非格司亭或非格司亭-山德士

▶ Daily dose of 5 mcg/kg (rounding to the nearest vial size by institution-defined weight limits).
▶5μg/kg 每日1次（四舍五入到根据体重确定的最接近的安瓿规格）。

▶ Continue until post-nadir ANC recovery to normal or near-normal levels by laboratory standards.
▶持续到中性粒细胞绝对值从最低点恢复至正常或基本正常的实验室标准。

* Sargramostim
*沙格司亭

▶ Used in clinical trials at a dose of 250 mcg/m /d (rounding to the nearest vial size by institution-defined weight limits).
▶临床试验中使用的剂量是250μg/㎡/d（四舍五入到根据体重确定的最接近的安瓿规格）。

▶ Continue until post-nadir ANC recovery to normal or near-normal levels by laboratory standards.
▶持续到中性粒细胞绝对值从最低点恢复至正常或基本正常的实验室标准。

MYELOID GROWTH FACTORS IN MOBILIZATION AND POST HEMATOPOIETIC CELL TRANSPLANT
骨髓生长因子用于动员和造血干细胞移植后

Mobilization of Hematopoietic Progenitor Cells in Autologous Setting
自体造血祖细胞的动员

* Single-agent growth factor:
*生长因子单药：

▶ Filgrastim or filgrastim-sndz or tbo-filgrastim
▶非格司亭或非格司亭-山德士或梯瓦-非格司亭

♢ Dose: 10–32 mcg/kg/d by subcutaneous injection, in daily or twice-daily dosing. Begin apheresis on day 4 or 5 and continue until leukapheresis.
♢剂量：10-32μg/kg/d皮下注射，每日1次或每日2次。在第4或第5天开始单采直至白细胞采集结束

* Combination chemotherapy followed by filgrastim/filgrastim-sndz /tbo-filgrastim with the goal of mobilization during count recovery.
*联合化疗然后在中性粒细胞计数恢复期间用非格司亭/非格司亭-山德士/梯瓦-非格司亭达到动员的目的。

▶ Filgrastim/filgrastim-sndz /tbo-filgrastim is started about 24 hours after completion of chemotherapy.
▶大约在化疗结束后24小时开始非格司亭/非格司亭-山德士/梯瓦-非格司亭。

* Concurrent filgrastim/filgrastim-sndz + sargramostim (category 2B)
*同时非格司亭/非格司亭-山德士+沙格司亭（2B类）

▶ Filgrastim/filgrastim-sndz 7.5 mcg/kg each morning, sargramostim 7.5 mcg/kg each evening, and leukapheresis beginning on day 5.
▶每天早晨非格司亭/非格司亭-山德士7.5μg/kg、每天晚上沙格司亭7.5μg/kg，在第5天时开始分离白细胞。

* Filgrastim/filgrastim-sndz /tbo-filgrastim + plerixafor (for selected patients with non-Hodgkin's lymphoma or multiple myeloma)
*非格司亭/非格司亭-山德士/梯瓦-非格司亭+普乐沙福（用于选择的非霍奇金淋巴瘤或多发性骨髓瘤患者）

▶ Plerixafor is indicated for:
▶普乐沙福适用于：

♢ Patients who were heavily pre-treated or had prior treatment with >10 cycles of cytotoxic chemotherapy, or those who have failed prior collection attempts or exhibit risk factors for being poor mobilizers due to more than 6 cycles of lenalidomide or fludarabine, or radiation to the pelvis.
♢既往强烈治疗过或既往细胞毒药物化疗治疗>10周期或既往采集失败或由于超过6周期的来那度胺或氟达拉滨或骨盆放射有动员不良危险因素的患者。

♢ As “just in time” or “rescue” in the case of suboptimal peripheral CD34+ count.
♢在外周CD34+计数未达最佳标准的情况下作为“非常及时”或“救援”。

▶ Dosing:
▶给药剂量：

♢ Filgrastim/filgrastim -sndz /tbo- filgrastim dose: 10 mcg/kg/d x 4 days. On the evening of day 4, start plerixafor by subcutaneous injection 11 hours prior to day 5 collection (the next morning).
♢非格司亭/非格司亭-山德士/梯瓦-非格司亭剂量：10μg/kg/d×4天。在第4天晚上，第5天采集（次日上午）前的11小时开始普乐沙福皮下注射。

♢ Plerixafor dose: 0.24 mg/kg/d for patients weighing >83 kg; 20 mg (fixed dose), or 0.24 mg/kg/d for patients weighing ≤83 kg, maximum 4 doses (if creatinine clearance >50 mL/min, maximum dose 40 mg/d)
♢普乐沙福剂量：对于体重> 83kg的患者0.24mg/kg/d；20mg（固定剂量），或对于体重≤83kg的患者0.24mg/kg/d，最多4剂（如果肌酐清除率＞50ml/min，最大剂量40mg/d）。

Mobilization of Allogeneic Donors
同种异体捐献者的动员

* Allogeneic hematopoietic cell donors:
*同种异体造血细胞捐献者:

▶ Filgrastim (preferred) or filgrastim-sndz (category 2B) or tbo-filgrastim (category 2B)
▶非格司亭（首选）或非格司亭-山德士（2B类）或梯瓦-非格司亭（2B类）

♢ Dose: 10 mcg/kg/d by subcutaneous injection, start collection on day 4 or 5.
♢剂量：10μg/kg/d皮下注射，在第4或第5天开始采集。

▶ Plerixafor (category 2B): Use in normal donors is under study.
▶普乐沙福（2B类）：用于在研究中的正常供体。

* For granulocyte transfusion:
*粒细胞输注：

▶ Filgrastim or filgrastim-sndz (category 2B) or tbo-filgrastim (category 2B)
▶非格司亭或非格司亭-山德士（2B类）或梯瓦-非格司亭（2B类）

♢ Single dose: 5 mcg/kg subcutaneously with dexamethasone 10 mg PO 8–24 hours prior to collection.
♢单次量：在采集前8–24小时5μg/kg皮下注射加地塞米松10mg口服。

Supportive Care Options
支持治疗选择

* Filgrastim or filgrastim-sndz or tbo-filgrastim
*非格司亭或非格司亭-山德士或梯瓦-非格司亭

▶ Post autologous hematopoietic cell or cord blood transplant
▶自体造血细胞或脐血移植后

▶ 5 mcg/kg/d. Begin day +5 post transplant until recovery of ANC (eg, >1.5 x 10^9 /L x 2 d).
▶5μg/kg/d。移植后第+5天开始直至中性粒细胞绝对值计数恢复（如＞1.5×10×109/L×2d）。

* Sargramostim
*沙格司亭

▶ Post autologous hematopoietic cell transplant or delayed hematopoietic engraftment after transplant 250 mcg/m2/d until ANC >1.5 x 10^9 /L x 3 d.
▶自体造血细胞移植后或移植后造血植入延迟250μg/㎡/d直至中性粒细胞绝对值计数>1.5x109/L x 3d。

* Pegfilgrastim
*培非司亭

▶ Post autologous hematopoietic cell transplant
▶自体造血细胞移植后

TOXICITY RISKS WITH MYELOID GROWTH FACTORS
骨髓生长因子的毒性风险

Filgrastim and derivative products including pegfilgrastim
非格司亭和衍生产品包括培非司亭

* Warnings
*警告

▶ Allergic reactions
▶过敏反应

♢ Skin: rash, urticaria, facial edema
♢皮肤：皮疹、荨麻疹、面神经水肿

♢ Respiratory: wheezing, dyspnea
♢呼吸：哮鸣、呼吸困难

♢ Cardiovascular: hypotension, tachycardia, anaphylaxis
♢心血管：低血压、心动过速、过敏反应

▶ Bleomycin-containing regimens: pulmonary toxicity
▶含博莱霉素方案：肺毒性

▶ Splenic rupture
▶脾破裂

▶ Acute respiratory distress syndrome
▶急性呼吸窘迫综合征

▶ Alveolar hemorrhage and hemoptysis
▶肺泡出血和咯血

▶ Sickle cell crises (only in patients with sickle cell disease)
▶镰刀细胞危象（仅在镰刀细胞病患者中）

▶ MDS and AML
▶骨髓增生异常综合征和急性髓性白血病

* Precautions
* 预防

▶ Cutaneous vasculitis
▶皮肤血管炎

▶ Immunogenicity
▶免疫原性

* Adverse reactions
*不良反应

▶ Bone pain
▶骨痛

Sargramostim
沙格司亭

* Warnings
*警告

▶ Fluid retention: edema, capillary leak syndrome, pleural and/or pericardial effusion
▶限制液体水肿、毛细血管渗漏综合征、胸膜和/或心包积液

▶ Respiratory symptoms: Sequestration of granulocytes in pulmonary circulation, dyspnea
▶呼吸道症状：肺循环粒细胞扣留、呼吸困难

▶ Cardiovascular symptoms: Occasional transient supraventricular arrhythmia. Use with caution in patients with preexisting cardiac disease.
▶心血管症状：偶尔一过性室上性心律失常。既往存在心脏病的患者慎用。

▶ Renal and hepatic dysfunction: Elevation of serum creatinine or bilirubin and hepatic enzymes. Monitor patients who display renal or hepatic dysfunction prior to initiation of treatment.
▶肾和肝功能异常：血肌酐或胆红素及肝酶升高。在开始治疗前监测肾或肝功能异常的患者。

* Adverse events occurring in >10% of patients receiving sargramostim in controlled clinical trials and reported in a higher frequency than placebo ▶ AML - fever, skin reactions, metabolic disturbances, nausea, vomiting, weight loss, edema, anorexia
*在对照临床试验中接受沙格司亭的患者不良事件发生率>10%，高于安慰剂▶急性髓性白血病—发热、皮肤反应、代谢障碍、恶心、呕吐、体重减轻、水肿、厌食

▶ Autologous hematopoietic cell transplant or peripheral blood progenitor cell transplant - asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
▶自体造血细胞移植或外周血祖细胞移植—乏力、不适、腹泻、皮疹、周围性水肿、尿路异常

▶ Allogeneic hematopoietic cell transplant or peripheral blood progenitor cell transplant - abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high blood urea nitrogen (BUN), and high cholesterol
▶ 异体造血细胞移植或外周血祖细胞移植—腹痛、寒战、胸痛、腹泻、恶心、呕吐、呕血、吞咽困难、吞咽困难、胃肠出血、瘙痒、骨痛、关节痛、眼出血、高血压、心动过速、胆红素血症、高血糖、肌酐升高、低镁血症、水肿、咽炎、鼻衄、呼吸困难、失眠、焦虑、血尿素氮（BUN）高以及高胆固醇