MA或MOED方案联合造血生长因子动员自体外周血干细胞效果观察

目的：探讨米托蒽醌(MIT)为主的MA或MOED化疗方案联合造血生长因子对自体外周血干细胞(APBSC)的动员效果。方法：12例患者用MA联合造血生长因子动员方案(Ⅰ组)，8例患者用MOED联合造血生长因子动员方案(Ⅱ组)，两组均在白细胞(WBC)降至最低点开始回升时。皮下注射G-CSF或G-CSF+GM-CSF至采集结束。wBC恢复至＞2.5×109／L，CD34)+细胞比例＞1.0％时，用血细胞分离机连续2天采集APBSC。当累计采集的单个核细胞(MNC)达到4×108／kg以上时停止采集。以文献报道的环磷酰胺联合造血生长因子动员方案为对照(Ⅲ组)。结果：Ⅰ组动员方案在两次采集的CD34)+细胞数量优于Ⅱ组动员方案。Ⅰ组和Ⅱ组两种动员方案在第1次采集的CD34)+细胞数、采集次数、骨髓抑制强度方面优于Ⅱ组动员方案，但是第2次采集CD34)+细胞较少。20例患者连续采集APBSC 2次，共采集到MNC(4.36±2.08)×108／kg，CD34)+细胞(9.87±7.30)×106／kg，CFU-GM(2.86±2.10)×104／kg。18例接受自体外周血干细胞移植(APBSCT)者造血功能均获得满意重建。结论：以MIT为主的化疗联合造血生长因子是一种安全、高效的APBSC动员方法。     

自体外周血造血干细胞的动员和采集及冷冻保存研究

目的 评价自体外周血造血干细胞的动员和采集及冷冻保存效果。方法 20例病人采用大剂量化疗加刺激因子动员自体外周血干细胞(APBSC)后用CS—3000血细胞分离机和程控降温仪进行了65次APBSC采集和冷冻保存。结果 经化疗 rhG-CSF动员后采集的PBSC总数、CD34~ 细胞总数和CFU—GM总数不同病人相差较大,分别为MNC5.56±2.00×10~8/kg,CD34~ 23.25±41.90×10~6/kg,CFU—GM 21.68±15.39×10~4/kg。化疗后平均15.1天,用rhG—CSF7.9天CD34~ 细胞达峰值。经冷冻保存的干细胞回输后均使病人造血重建,采集与回输的PBSC数与造血重建时间相关。结论 本研究APBSC动员和采集及冷冻保存的效果肯定,APBSCT后全部病人造血重建,移植成功。     

中剂量环磷酰胺为主的联合化疗加同一剂量G-CSF动员恶性血液病患者自体外周血干细胞

目的:观察中剂量环磷酰胺(CTX)为主的联合化疗加G蛳CSF对恶性血液病患者自体外周血造血干细胞(APBSC)的动员效果。方法:31例患者接受中剂量CTX 2.2 g/m2(1.8 g/m2~3.0 g/m2)联合VP16(600 mg ~ 800 mg)或Ara蛳C(1.0 g/m2 ~ 2.0 g/m2)化疗,WBC降至最低值后开始皮下注射G蛳CSF 300 μg/d直至采集结束。WBC≥(3.0~5.0)×109/L时开始采集,当单个核细胞(MNC)累计≥3.8×108/kg或CD+34细胞≥2.0×106/kg时停止采集。结果:采集次数为(2.9±1.0)次,G蛳CSF持续应用时间为(7.4±2.0)d,采集到的MNC细胞数为(5.53±2.54)×108/kg,CD+34细胞数为(9.46±7.24)×106/kg,CFU蛳GM(46.02±70.58)×104/kg。全部移植患者造血功能均获满意重建。结论:中剂量CTX为主的联合化疗加同一剂量G蛳CSF对血液病患者的APBSC动员是安全、有效的。     

环磷酰胺或足叶乙甙联合粒细胞集落刺激因子动员自体外周血造血干细胞的对照研究

背景与目的:通过动员采集获得高质量的自体外周血造血干细胞(autologousperipheralbloodstemcell,APBSC)是造血干细胞移植成功的关键,环磷酰胺(cyclophosphamide,CTX)联合重组人粒细胞集落刺激因子(recombinedhumangranulocytecolony-stimulatingfactor,rhG-CSF)是APBSC经典的动员方案,足叶乙甙(etoposide,VP-16)联合rhG-CSF是近年来应用的另一个动员方案。本研究的目的是比较上述两种动员方案对恶性淋巴瘤和生殖细胞肿瘤患者APBSC的动员效果。方法:共有52例恶性实体瘤患者,其中CTX方案组26例,剂量为CTX3.5g/m2加rhG-CSF5μg·kg-1·d-1;VP-16方案组26例,VP-16的剂量随机采用1000mg/m2或1500mg/m2加rhG-CSF5μg·kg-1·d-1。两组均在白细胞(whitebloodcell,WBC)降至最低点时开始皮下注射rhG-CSF,直至采集结束前一天。当CTX组WBC恢复到2.5×109/L、VP-16组WBC恢复到5.0×109/L以上时开始连日采集APBSC,当累计采集的单个核细胞(mononuclearcell,MNC)≥5×108/kg或CD34+细胞≥2×106/kg时停止采集。患者经预处理后回输采集到的APBSC。比较两组动员采集过程中的血液学指标变化、采集细胞数量、造血重建时间、不良反应等。结果:CTX组患者化疗后外周血中WBC和血小板(platelet,PLT)降至最低值的时间明显早于VP-     

环磷酰胺联合G-CSF动员外周血造血干细胞的实验和临床观察

目的评价环磷酰胺(CTX)联合G-CSF(粒细胞集落刺激因子)对自体外周血造血干细胞(PBSC)的动员效果和毒性反应.方法CTX 3.5～4g/m2第1、2天静滴,WBC降至最低点时开始注射G-CSF 4.5(3.5～5)μg/kg@天,至PBSC采集结束.当WBC恢复至(1.9～3.0)×109/L以上,以及MNC(单个核细胞)≥20%～30%和外周血CD34+≥1%时采集APBSC,当累计采集MNC≥2.0×108/kg和CD34+细胞≥2.0×106/kg时停止采集.结果23例患者经CTX+G-CSF动员后第9(7～10)天WBC最低,为0.65(0.25～0.9)×109/L,G-CSF给药开始时间为动员后第10(8～11)天,持续6.5(5～11)天,第13(11～20)天开始采集PBSC,持续2天,采集得MNC 2.5(1.3～8.9)×108/kg,CFU-GM 6.8(2.8～11.6)×105/kg,CD34+细胞4.9(2.5～8.9)×106/kg,1例患者出现心包炎,无其他严重毒性反应;21例接受自体外周血干细胞移植支持下超大剂量化疗均获得满意造血重建.结论CTX联合G-CSF是高效和安全的PBSC动员方案,值得临床广泛应用.     

大剂量多西他塞联合粒细胞集落刺激因子用于恶性实体瘤外周血造血干/祖细胞动员

目的观察大剂量多西他塞联合粒细胞集落刺激因子(G-CSF)在恶性实体瘤患者动员采集自体外周血造血干/祖细胞的有效性和安全性。方法30例恶性实体瘤患者入组,第一天采用多西他塞120mg/m2经静脉持续滴注3小时,在白细胞1.0×109/L左右时每天给予G-CSF5μg/kg,分早晚两次皮下注射,直至采集结束。结果在给予多西他塞后平均第(6.47±1.01)天白细胞降至1.0×109/L,皮下注射G-CSF平均(3.50±1.01)天即多西他塞动员后平均第(9.97±1.03)天开始外周血造血干/组细胞单采,每人每天采集一次,采集两天,共获CD34+细胞中位数3.49×106/kg(1.71×106～16.69×106/kg),其中CD34+细胞>2.0×106/kg的患者25例。不同采集时间获CD34+细胞数差异无统计学意义(P=0.651)。6例发生关节轻度疼痛,3例轻度腹泻,1例口腔粘膜炎。结论多西他塞120mg/m2联合G-CSF5μg/kg是恶性实体瘤患者动员采集自体干/祖细胞的有效安全方案。     

化疗联合单一剂量rhG-CSF用于自体外周血造血干细胞移植的临床研究

背景与目的:总结广东省干细胞多中心研究协作组自1999年6月至2001年12月间55例自体外周血造血干细胞移植治疗造血系统恶性疾病的资料,对化疗联合单一剂量rhG-CSF用于自体外周血造血干细胞移植前动员及移植后造血重建的效果进行研究和评价。方法:全部病例(急性髓细胞性白血病28例,急性淋巴细胞性白血病9例,非霍奇金淋巴瘤14例,其他4例)采用化疗+重组粒系集落刺激因子(rhG-CSF,格拉诺赛特)联合动员方案,其中白血病患者主要采用EA方案,恶性淋巴瘤患者主要采用以CTX为主的方案。rhG-CSF用量为250μg/d,WBC升至>4×109/L后,连续1～2天采集PBSC。移植后+3天开始使用rhG-CSF250μg/d,并观察造血重建情况。结果:动员所需的时间即自化疗开始至采集的平均时间为(18.08±3.63)天,rhG-CSF平均应用剂量为4.15μg·(kg·d)-1,应用时间平均7.12天。55例患者平均采集1.38次,采集到的MNC细胞数为(4.09±1.69)×109/kg,CD34+细胞平均值为8.5×106/kg,CFU-GM平均为(6.1±5.8)×105/kg。WBC恢复至>1.0×109/L及中性粒细胞绝对值>0.5×109/L的中位天数分别为10天和10.5天,全部移植患者均获满意的造血重建。结论:我们采用的EA和以CTX为主的化疗联合单一剂量rhG-CSF,是一种安全有效的动员自体外周血造血干细胞的方法,单一剂量rh     

改良CVP联合rhG-CSF动员方案外周血干细胞移植治疗血液肿瘤及实体瘤41例

目的:研究改良CVP联合rhG-CSF方案对血液肿瘤和实体瘤41例患者自体外周血干细胞移植(APBSCT)动员及造血重建效果.方法:2001年3月至2006年3月采用改良CVP联合rhG-CSF动员方案,完成APBSCT 41例(血液肿瘤32例,实体瘤9例),平均年龄39.6岁(18岁～67岁).WBC升至4.0×109/L左右采集单个核细胞(MNC)并计数MNC和CD34 细胞数;预处理结束48h～72h回输MNC.结果:动员期间患者WBC均降至1.0×109/L以下,PLT 40×109以下.34例1次采集成功,7例(双次移植5例)作第2次采集.采集MNC数 0.9×108/kg～8.3×108/kg(2.8±2.0 ×108/kg),CD34 细胞1.1×106/kg～9.4×106/kg(3.2±2.6×106/kg).预处理后所有病例均达到骨髓抑制,WBC恢复到1.0×109/L时间为 8～ 16d(平均 11.3d);38例PLT恢复到50×109/L时间为 13～ 22d(平均 16.8d),3例PLT恢复延迟,最长 35d.随访15～65个月,持续完全缓解19例(46.3%),部分缓解或好转13例(31.7%),总有效率78.0%,无效9例(22.0%),无1例发生移植相关死亡(其中5例带瘤生存,17例死亡).结论:改良CVP联合rhG-CSF动员方案行APBSCT是一种安全有效的动员自体外周血造血干细胞的方法,临床疗效满意.     

外周血造血干细胞的动员、采集和移植后造血重建

目的对13例健康供者及患者外周血造血干细胞的动员和采集效果进行分析。方法健康供者用rhG-CSF动员;患者采用强化疗加rhG-CSF或和rhGM-CSF动员,COBESpectro血细胞分离机全自动造血干细胞程序采集单个核细胞。结果13例移植中8例一次采集成功,1例(即首例)采集4次,余者采集2次。采集后的MNC6×108/kg～12×108/kg,CD3+4细胞3×106/kg～34×106/kg。移植后全部患者造血均获重建,异基因外周血造血干细胞移植一个月后DNA指纹图均提示植活。结论rhG-CSF可作为健康供者的安全有效动员剂,强化疗加rhG-CSF或/和rhGM-CSF是白血病、淋巴瘤自体外周血造血干细胞移植的有效动员方法之一。     

长春瑞滨联合G-CSF动员实体瘤自体外周血造血干细胞的疗效评估

目的:观察长春瑞滨(Vinorelbine,NVB)联合粒细胞集落刺激因子(granulocyte colony stimulating factor,G-CSF)对化疗敏感性实体瘤患者自体外周血造血干细胞(autologous peripheral blood stem cells,APBSC)的动员效果并对其毒性反应进行评估。方法:选取对NVB敏感性实体瘤病例,按75mg/m2的总剂量静脉注射,按不同时间间隔分次给予,待白细胞降至最低点时开始给予rhG-CSF5μg/(kg.d)皮下注射,白细胞倍增当日及次日采集APBSC。检测分离CD34 细胞数量,观察动员期间不良反应。用采集的APBSC回输预处理后实体瘤患者,评估骨髓造血恢复情况。结果:入选的3例患者均进行2次APBSC采集,采集液中单个核细胞(MNC)和CD34 细胞数均达到造血重建阈值,可以支持2~3个周期的大剂量化疗。整个动员过程中未出现严重毒副反应。3例患者在接受APBSC支持下的大剂量化疗后,造血功能在短期内均获得满意重建。结论:NVB联合G-CSF可作为化疗敏感性实体瘤患者APBSC动员的一种方法,具有良好的临床应用前景。     

Granulocyte function in myeloblastic leukaemia.

A study of granulocyte function in myeloblastic leukaemia is reported. Function was assessed by the ability of peripheral blood granulocytes to ingest and kill Candida albicans in bitro. Depressed cidal activity was observed in 11 patients with smouldering leukaemia and in 19 patients with acute myeloid leukaemia. Cidal activity was lowest in the untreated acute disease; this improved during cytoreduction therapy and was maintained when remission occurred. Leukaemic plasma depressed the function of control granulocytes; the possible role of a plasma "factor" is discussed.     

Granulocyte growth factors: Achieving a consensus

A consensus meeting held under the auspices of the EuropeanSchool of Oncology concluded that the use of granulocyte growthfactors is definitely indicated, or acceptable given existingevidence, in the following circumstances: to alleviate congenitalneutropenia; in the mobilisation of peripheral blood progenitorcells for autotransfusion; to encourage engraftment followingbone marrow transplantation and in cases of failed engraftment;to support continuationof ganciclovir anti-CMV therapy in certainpatients with AIDS, where the switch to foscarnet is contraindicatedor where toxicity to foscarnetdevelops. It was also agreed that there is an overwhelming need for carefullycontrolled clinical trials in a wide range of indications inwhich growth factor use may improve outcome. In the majorityof tumours, the possible benefit of dose optimisation and intensification,and therefore the role of growth factors in support of suchmeasures has still to be defined. Extramedullary toxicitiesmay in these instances become dose limiting. growth factors, neturopenia, peripheral blood, progenitor cells, bone marrow transplantation, AIDS     

The Potential Benefit of Granulocyte Transfusion Therapy

The future of granulocyte transfusions depends in large part upon our ability to overcome technical problems, particularly related to dose. Certainly the attempts at technical improvements have made an impact on granulocyte availability and donor pools large enough to support twice daily transfusions should also improve the efficacy of a series of transfusions. The majority of bacterial infections in neutropenic patients do not necessitate granulocyte transfusions due to the rapid empiric use of modern broad-spectrum antibiotics. However, a proportion still do, and selection of appropriate candidates for granulocyte transfusions may improve the outcome. The use in fungal infections remains experimental, but as has been said by others in addition to myself, should be studied. Issues of histocompatibility remain complex. Patients rendered severely immunocompromised may have less of an alloimmunization response to transfusion products, but alloimmunization continues to be a complication of granulocyte transfusions. Patients undergoing bone marrow transplant have the advantage of access to an HLA-matched marrow and granulocyte donor. The techniques of granulocyte transfusion therapy must continue to be improved and utilized in part because our microbial foes continue to change and to resist our antibiotic improvements. As George Bernard Shaw said: "There is at bottom only one genuinely scientific treatment for all diseases and that is to stimulate the phagocytes. Drugs are a delusion".     

Granulocyte colony-stimulating factors: finding the right indication

PURPOSE OF REVIEW: Neutropenic complications including febrile neutropenia represent major dose-limiting toxicities of cancer chemotherapy. Recommendations for the use of recombinant myeloid growth factors to reduce the risk of neutropenic complications and sustain dose intensity continue to evolve. RECENT FINDINGS: Several randomized controlled trials and meta-analyses have confirmed that the myeloid growth factors reduce the risk of neutropenic complications and may facilitate delivered dose intensity in patients receiving cancer chemotherapy. Older age and certain comorbidities significantly increase the risk of febrile neutropenia and its consequences. Three new clinical practice guidelines for the use of the myeloid growth factors have been published by major professional oncology organizations including the American Society of Clinical Oncology, the European Organization for Research and Treatment of Cancer and the National Comprehensive Cancer Network. The recommendations and evidence basis for these guidelines are presented here. All three new or updated guidelines recommend prophylactic use of the myeloid growth factors in cancer patients receiving chemotherapy at 20% or greater risk of febrile neutropenia and in those with important variables that increase individual risk of neutropenic complications. SUMMARY: Consistent clinical practice guidelines based on multiple randomized control trials and meta-analyses should further guide the appropriate and cost-effective use of these agents.     

基因重组人粒细胞集落刺激因子在急性白血病化疗后的临床应用

目的：急性白血病,大剂量化疗后,白细胞平均降至１ ．０３３ ×１０９／Ｌ 时,应用重组人粒细胞集落刺激因子（ｒｈＧ－ ＣＳＦ） , 使白细胞恢复。方法： 每天２５０μｇ 皮下注射, 直至连续两次复查中性粒细胞绝对计数（ＡＮＣ） 超过１ ．５ ×１０９／Ｌ 后停药,平均用药时间５ ．９ 天。结果：与未采用ｒｈＧ－ ＣＳＦ 治疗的对照组１３ ．２ 天ＡＮＣ 超过１ ．５ ×１０９／Ｌ 相比,粒细胞缺乏的恢复时间明显缩短。ｒｈＧ－ ＣＳＦ 能够明显增加白血病患者化疗后白细胞的恢复,缩短白细胞减少症的恢复时间。结论：ｒｈＧ－ ＣＳＦ 能够保证白血病患者接受并完成强烈化疗,从而提高患者生存率。