粒细胞集落刺激因子动员外周血造血干细胞致急性肺损伤1例

患者,女,32岁,确诊非霍奇金淋巴瘤Ⅳ期(非特异性外周T细胞型)2个月,于2002年12月7日入院行自体外周血造血干细胞移植。既往体健。入院后查血常规、胸片、心电图、肺功能等均正常。遂于12月10日开始外周血干细胞动员,方案为NAP(米托蒽醌 阿糖胞苷 泼尼松)化疗及G-CSF(粒细胞集落刺激因子)联合,G-CSF自化疗结束后24h始用,     

低剂量粒细胞集落刺激因子动员健康供者造血干细胞的研究

 目的　探讨低剂量（5 μg·kg-1·d-1）粒细胞集落刺激因子（G-CSF）对健康供者CD+34细胞动员的效果及造血干细胞最佳采集时间。方法　对2006年2月至2009年4月108例健康供者给予G-CSF 5 μg·kg-1·d-1,在动员后的第4天至第6天收集标本,检测相应时间点的外周血白细胞（WBC）计数、采集物单个核细胞（MNC）计数、采集物中CD+34细胞的比例、粒-巨噬细胞集落形成单位（CFU-GM）培养。结果　动员后采集物中第4天至第6天CD+34细胞比例分别为（0.71±0.08）%、（1.09±0.09）%、（0.57±0.08）%,第4天至第6天CFU-GM产率分别为：（93.33±44.51）／105 MNC、（124.61±57.85）／105 MNC和（80.25±49.24）／105 MNC。CD+34细胞比例和CFU-GM产率均在第5天达到峰值（P＜0.05）,第4天次之（P＜0.05）,第6天再次之（P＜0.05）。动员后采集物中第4天至第6天CD+34细胞量分别为（3.33±1.36）×106／kg、（4.14±1.67）×106／kg、（2.79±1.47）×106／kg,第5天达到峰值（P＜0.05）,第4天次之（P＜0.05）,第6天再次之（P＜0.05）。108例供者采集2次（第4天、第5天）均可满足移植标准。所有供者均无严重不良反应发生。结论　单一低剂量G-CSF能够有效动员健康供者造血干细胞。动员后于第4、第5天行干细胞采集优于第5、第6天。     

异基因外周血造血干细胞移植治疗白血症

５例白血病患接受ＨＬＡ相合异基因外周血干细胞移植。外周血干细胞动员采用供连续皮下注射Ｇ－ＣＳＦ（１０μｇ／ｋｇ）５天，于第５天和第６天用ＣＳ３０００Ｐｌｕｓ血细胞分离机分离单个核细胞（ＭＮＣ）。患平均输入ＭＮＣ６．０×１０＾８／ｋｇ，ＣＤ３４＾＋细胞２２．６×１０＾６／ｋｇ，ＣＤ３＾＋细胞４１２×１０＾６／ｋｇ，ＣＤ４＾＋细胞２０５×１０＾６／ｋｇ和ＣＤ８＾８细胞１６２×１０＾６／ｋｇ。移植     

联合化疗加粒细胞集落刺激因素动员外周造血干细胞的作用

目的研究大剂量联合化疗(HDCT)加粒细胞集落刺激因子(G-CSF)对外周血造血干细胞的动员作用。方法8例非霍奇金淋巴瘤(NHL)多周期诱导化疗达完全缓解后,采用大剂量联合化疗,联合应用小剂量G-CSF进行外周造血干细胞的动员。结果动员后外周血WBC及MNC总数明显增加,与动员前比较,差异有显著性。冷冻前后,MNC计数、GFU-G集落总数无明显差异。预处理后,病人中性粒细胞、血小板恢复时间分别平均为(10.5±4)天及(11.5±6)天。结论大剂量联合化疗加小剂量G-CSF联合动员方案是安全有效的,值得推广。     

重组人粒细胞集落刺激因子促进自体造血干细胞移植后造血功能恢复的临床研究

背景与目的:高剂量化放疗联合自体造血干细胞移植(autologoushematopoieticstemcellstransplantation,AHSCT)能够提高某些实体瘤的疗效,该疗法的成功得益于重组人粒细胞集落刺激因子(recombinanthumangranulocytecolony-stimulatingfactor,rhG-CSF)的运用。本研究的目的是观察rhG-CSF对实体瘤患者自体造血干细胞移植后造血功能重建的影响。方法:将接受AHSCT的130例实体瘤患者分为rhG-CSF组和对照组,rhG-CSF组在造血干细胞回输后第6天开始连日给予rhG-CSF250～300μg/d,皮下注射,直至白细胞(whitebloodcell,WBC)≥5.0×109/L为止;对照组在造血干细胞回输后不给予rhG-CSF。结果:130例患者共完成移植132次,其中2例为2次移植。研究早期的24例患者采取自体骨髓移植,其中12例移植后给予rhG-CSF;此后的106例均采用自体外周血造血干细胞移植(2例为2次移植),其中47例移植后给予rhG-CSF。(1)rhG-CSF组和对照组自体骨髓移植患者住无菌病房的中位时间为33天和41天,WBC恢复到1.5×109/L以上的中位时间为14天和24天,两组之间的差异有显著性(P<0.05);两组血小板(platelet,PLT)恢复到20×109/L及50×109/L以上的中位时间均无显著性差异。(2)rhG-CSF组和对照组自体外周血干细胞移植患者住无菌病房的中位时间为17天和20天,     

聚乙二醇化重组人粒细胞集落刺激因子用于多发性骨髓瘤自体造血干细胞动员的研究

目的探讨聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)用于多发性骨髓瘤(MM)患者外周血造血干细胞动员(PBSCM)的效果及药物经济学价值。方法回顾性分析2015年1月至2017年10月在吉林大学第一医院和中国医学科学院血液病医院住院治疗的91例初治MM患者资料。根据患者意愿,采用大剂量化疗结合皮下注射PEG-rhG-CSF或重组人粒细胞集落刺激因子(rhG-CSF)进行干细胞动员,分别为42、49例。分析两组动员后采集单个核细胞(MNC)数、采集物CD34+细胞数、动员中最高中性粒细胞(mANC)数、动员的费用以及移植后白细胞和血小板植入时间。结果PEG-rhG-CSF组和rhG-CSF组的中位采集MNC数分别为5.86×10⁸/kg[(1.08~24.54)×10⁸/kg]和6.61×10⁸/kg[(0.83~33.80)×10⁸/kg],差异无统计学意义(U=883.00,P=0.245);PEG-rhG-CSF组的中位采集物CD34+细胞数高于rhG-CSF组,分别为5.56×10⁶/kg[(0.94~19.90)×10⁶/kg]和4.82×10⁶/kg[(1.12~14.61)×10⁶/kg],差异有统计学意义(U=732.00,P=0.038)。PEG-rhG-CSF组动员期间中位mANC数较rhG-CSF组低,分别为20.50×109/L[(7.26~61.30)×109/L]和32.08×109/L[(6.92~69.99)×109/L],差异有统计学意义(U=490.00,P=0.001)。自体干细胞移植(ASCT)后,PEG-rhG-CSF组白细胞计数(WBC)恢复至1.0×109/L的时间较rhG-CSF组短[(11.59±1.98)d比(12.93±2.83)d],差异有统计学意义(t=-2.395,P=0.019);PEG-rhG-CSF组血小板计数(Plt)恢复至20.0×109/L的时间也较rhG-CSF组有缩短趋势[(12.86±2.62)d比(14.80±5.47)d],但差异无统计学意义(t=-1.749,P=0.085)。PEG-rhG-CSF组的动员总费用与rhG-CSF组差异无统计学意义[(21405.47±7365.98)元比(22976.83±10264.34)元,t=-0.721,P=0.474]。结论PEG-rhG-CSF联合大剂量化疗是MM患者PBSCM的有效方案,其动员费用与rhG-CSF相当。PEG-rhG-CSF可能是MM患者PBSCM的更好选择。     

应用粒细胞集落刺激因子动员后异基因外周血干细胞移植供者外周血干细胞与不成熟粒细胞的相关性

 目的　探讨供者应用重组人粒细胞集落刺激因子（rhG-CSF）动员后单采外周血干细胞（PBSC）移植物中的不成熟粒细胞与CD+34 细胞及单个核细胞（MNC）之间的相关性。方法　122例异基因外周血干细胞移植（allo-PBSCT）供者用rhG-CSF 7.25～10 μg·kg-1·d-1进行动员,于动员前及动员后对外周血及PBSC收集物中的MNC和不成熟粒细胞及CD+34 细胞进行检测,并计算出输给患者的MNC、不成熟粒细胞及CD+34 细胞数。结果　动员后白细胞计数及不成熟粒细胞比值逐渐升高,至第5天达高峰;外周血MNC中不成熟粒细胞与CD+34 细胞同步增加有较好的相关性;采集后的PBSC移植物输给患者后,均全部植活并恢复造血功能,为染色体核型或血型及HLA转为供者型所证实,慢性粒细胞白血病患者Ph1染色体转阴。结论　rhG-CSF 7.25～10 μg·kg-1·d-1分两次皮下注射能有效动员PBSC;allo-PBSCT供者经rhG-CSF动员后,外周血MNC中不成熟粒细胞与CD+34细胞数同步增加有较好的相关性,不成熟粒细胞的数量可间接反映干／祖细胞的数量,故MNC与不成熟粒细胞数结合可作为allo-PBSCT的剂量阈标准。     

粒细胞集落刺激因子对供体造血干细胞移植物中树突状细胞的影响

 目的　探讨粒细胞集落刺激因子（G-CSF）对正常异基因造血干细胞移植供者外周血与骨髓移植物中I型树突状细胞（DC1）、Ⅱ型树突状细胞（DC2）的数量及DC2／DC1比例的影响。方法　以G-CSF 每天10 μg／kg动员5 d后,以流式细胞术（FCM）检测11例G-CSF动员的异基因外周血造血干细胞移植物及20例G-CSF动员的异基因骨髓移植物中的DC1、DC2数量及DC2／DC1比例,并与8例正常供者动员前外周血及10例健康者动员前骨髓进行比较。结果　动员前后骨髓DC2由14.37×106／L增至29.68×106／L（t＝2.433,P＝0.022）,而骨髓DC1分别为13.77×106／L和18.88×106／L（t＝0.625,P＝0.541）;DC2／DC1比例在动员后为1.83±0.81,较动员前的1.12±0.32明显升高（t＝2.685,P＝0.013）。正常供者以G-CSF动员前、后移植物中外周血 DC2数量分别为14.92×106／L和26.76×106／L（t＝2.390,P＝0.029）,DC2／DC1比例分别为1.00±0.37和2.02±1.43（t＝2.158,P＝0.044）,但外周血DC1分别为14.21×106／L和18.02×106／L（t＝0.625,P＝0.541）。结论　移植前以 G-CSF动员正常异基因干细胞移植供者,可选择性提高外周血及骨髓移植物中DC2的数量,而DC1数量无明显增加。     

中剂量依托泊苷联合粒细胞集落刺激因子动员恶性淋巴瘤的外周血造血干/祖细胞

 目的　观察中剂量依托泊苷（VP16）和粒细胞集落刺激因子（G-CSF）在恶性淋巴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　31例恶性淋巴瘤患者（非霍奇金淋巴瘤30例,霍奇金淋巴瘤1例）,VP16 1.2 g／m2分3 d静脉滴注,外周血白细胞降至最低点时给予G-CSF每天5 μg／kg,分2次,皮下注射,直至采集结束。结果　VP16应用后12 d（10～15 d）开始采集外周血造血干／祖细胞,获得单个核细胞（MNC）7.8×108／kg[（5.2～11.3）×108／kg],CD+34细胞7.2×106／kg [（5.3～13.1）×106／kg]。18例患者采集1次,13例采集2次。所有患者移植后均恢复造血,外周血粒细胞>0.5×109／L的中位时间为12 d（9～18 d）,血小板>20×109／L的中位时间为14 d（10～21 d）。患者无严重不良反应。结论　中剂量VP16和G-CSF 动员恶性淋巴瘤患者外周血干／祖细胞有效、安全,可获得满意的动员采集效果。     

促红细胞生成素,粒细胞及粒—巨噬细胞集落刺激因子对慢性粒细胞白血病急性

为了解外源性细胞因子对慢性粒细胞白血病急变细胞增殖的影响，观察了促红细胞生成素，粒细胞集落刺激因子和粒－巨噬细胞集落刺激因子在体外对慢性急变细胞生长的影响，实验结果显示慢粒急变细胞的增殖不受这些外源性细胞生长因子的影响，提示急变期细胞的生长特性发生了改变，同时这一结果也对细胞生长因子的临床应用有一定的意义。     

异基因外周血和骨髓干细胞联合移植治疗白血病的初步研究

 目的 探讨异基因造血干细胞移植治疗白血病的新方法。方法 23例白血病患者,HLA 配型全相合9例,1～3个位点不相合14例,采用粒细胞集落刺激因子（G-CSF）动员的骨髓和外周血干细胞联合移植,采用环孢素A（CsA）和霉酚酸酯（MMF）及短程甲氨蝶呤（MTX）方案预防移植物抗宿主病（GVHD）。结果 1例植入失败,22例完全植入,HLA全相合受者未发生急性GVHD,13例HLA不全相合受者中Ⅱ～ Ⅳ度急性GVHD发生率46.2 %。20例可评估的患者中,慢性 GVHD 13例,广泛型5例,累积发生率65 %。随访6至32个月,预期一年生存率86.6 %。结论 骨髓和外周血联合移植对HLA配型全相合和部分相合患者是安全、有效的移植方法。     

Increased hematopoietic progenitor cell maintenance in long-term bone marrow cultures containing minimal numbers of contaminating breast cancer cells

The maintenance of hematopoietic progenitor cells as assayedin the mixed colony (CFU-GEMM) assay in humanlong-term bone marrow cultures was compared between normalallogeneic marrow transplantation donor collections and those fromcandidates for high-dose therapy and autologous bone marrowtransplantation (ABMT). To be eligible for ABMT, patientswere required to have a histologically normal appearingbone marrow and therefore any tumor contamination wasat minimal levels and detectable only after evaluationof the cultured harvests. Marrow from 15 normaldonors, 36 patients with breast cancer, and 30patients with Hodgkin's disease was evaluated. The numberof mononuclear cells placed in culture was standardized.In all groups, significantly more progenitor cells wererecovered at 4–6 weeks of culture than at12–14 weeks. At 4–6 and 12–14 weeks, therewere no significant differences in the number ofprogenitor cells recovered from the cultures of normaldonors and tumor negative cultures of breast canceror Hodgkin's disease patients. However, following 4–6 and12–14 weeks of culture, progenitor cell numbers ofcultures which contained breast cancer cells were significantlyhigher than the pooled values for cultures fromthe concurrent normal controls, and those from breastcancer and Hodgkin's disease patients with tumor negativecultures. These results suggest that minimal breast cancercell contamination of the bone marrow can influencethe production of marrow progenitor cells. Exposure toprior chemotherapy or radiation therapy does not appearto be the cause of this effect. Themost likely mechanism is the local production ofcytokines by the tumor cells, although a processinvolving direct adhesive contact of the tumor cellswith hematopoietic cells, which is sometimes observed insemisolid cultures, cannot be excluded.     

脐带血血清体外培养的人骨髓间充质干细胞对干细胞移植病人造血重建的影响

目的：观察脐带血血清体外培养体系培养的人骨髓间充质干细胞对干细胞移植病人造血重建的影响及不良反应。方法：用10%脐带血血清体外培养体系培养的人骨髓间充质干细胞联合自体外周血干细胞移植治疗3例恶性淋巴瘤患者,计数BM-MSC的数目,观察其造血重建时间、不良反应。结果：采用10%脐带血血清培养体系培养BM-MSC,回输时达到2.82-3.96×106/kg,3例患者中性粒细胞〉0.1×109/L的时间为移植后第9-12天,血小板〉20×109/L的时间为移植后第9-15天,无明显不良反应。结论：10%脐带血血清培养体系是一种基于临床移植需要的分离、培养人BM-MSC的方法,此法培养的BM-MSC联合APBSC移植治疗恶性淋巴瘤患者,加速了造血重建,未见明显不良反应,具有临床应用价值。     

Clinical outcome of peripheral blood stem cell support

Two clinical results of peripheral blood stem cell support are commonly considered: (1) the effect on hematopoietic recovery and (2) the effect on the underlying malignancy. The dynamics of hematopoietic recovery after autoiogous bone marrow transplantation and after autologous peripheral blood stem cell transplantation in a clinical setting are similar if no exogenous cytokines are administered and the peripheral stem ceils are collected while their numbers are not deliberately increased (mobilised). If mobilized peripheral stem cells are transplanted, hematopoietic recovery is accelerated. In some circumstances, patients who receive peripheral stem cell transplantation may experience an improved progression-free survival after high-dose therapy when compared with similar patients who receive autologous bone marrow transplantation. Explanations for such a survival advantage might include (1) a lower likelihood of occult tumor cells capable of restoring disease in peripheral stem cell autograft products than in bone marrow harvests, (2) a greater number of cytotoxic effector cells capable of destroying occult tumor ceils in the peripheral stem cell collections than in bone marrow harvests, and (3) a different and advantageous pattern of immunologic recovery following autologous peripheral stem cell transplant compared to autologous bone marrow transplant.     

Allogeneic transplants with peripheral blood progenitor cells: a report of six cases

Six patients with high-risk leukaemia received a myeloablative regimen followed by allogeneic peripheral blood progenitor cells transplantation (PBPCT) from an HLA-identical sibling donor. Donors received 10-12 pg/kg/day of G-CSF subcutaneously for 5 days. G-CSF was well tolerated except for moderate bone pain. Peripheral blood leukapheresis product contained 14 times, more CD34+ cells and approximately a log more of T lymphocytes than marrow grafts from normal donors. In the two first cases the leukapheresis product was partially depleted of T-lymphocytes using counterflow centrifugation. No growth-factors were administered post-transplant. GVHD prophylaxis consisted of cyclosporin A (CyA) in one case, and CyA and methotrexate in five cases. All patients engrafted with a neutrophil count reaching more than 0.5 × 10⁹/L by day 12 to 21 post-transplant and a platelet count above 20 × 10⁹L by day 6 to 41 post-transplant. Acute GVHD was clinical grade 0 (n = 2). I (n = 1), II (n = 1), grade III (n = 1) and grade IV (n = 1). One case presents an extensive chronic cutaneous GVHD and is currently being treated with methylprednisolone. In conclusion, allogeneic transplants using PBPC can be performed safely. This may result in a rapid neutrophil and platelet engraftment, without an apparent increased risk of GVHD.     

检测细胞角蛋白在食管癌外周血和骨髓微转移中的意义

目的：探讨食管癌患者外周血和骨髓中CK18mRNA基因表达及临床意义。方法：采用巢式RT—PCR方法检测50例M0、10例M0的食管癌患者及10例食管良I生病变患者外周血及肋骨骨髓中细胞角蛋白CK18mRNA基因的表达。结果：50例M0食管癌患者外周血、骨髓中CK18mRNA阳性表达率分别为38．0％（19／50）和42．0％（21／50）;10例M,的食管癌患者外周血、骨髓中CK18mRNA阳性表达率分别为90．0％（9／10）、100％（10／10）;食管良性病变患者的外周血和骨髓中K18mRNA阳性表达率均为0％（0／10）,CK18mRNA阳性表达在三组间差异有显著性（P〈0．01）。CK18mRNA在Ⅳ期食管癌患者外周血和骨髓中阳性表达率与III期以前患者相比,有显著性差异（P〈0．05）。CK18mRNA在外周血和骨髓中表达无差异（P〉0．05）,但呈正相关性（r=0．704,P〈0．01）。结论：应用RT—PCR法检测食管癌患者外周血或骨髓中CK18mRNA微转移有助于食管癌的分期和预后的判断。     

Dose‐intensified bendamustine followed by autologous peripheral blood stem cell support in relapsed and refractory multiple myeloma with impaired bone marrow function

Therapeutic options in heavily pretreated relapsed/refractory multiple myeloma patients are often very limited because of impaired bone marrow function. Bendamustine is effective in multiple myeloma and has a favourable toxicity profile. We hypothesized that dose‐intensified bendamustine (180 mg/m², day 1 and 2) followed by autologous blood stem cell support (ASCS) would improve bone marrow function with low post‐transplant toxicity in patients with severely impaired haematopoiesis. We analyzed 28 consecutive myeloma patients, with a median of three prior lines of therapy (range 2–7), who had relapsed from the last treatment with very limited bone marrow function and were therefore ineligible for conventional chemotherapy, novel agents or trial enrolment. Dose‐intensified bendamustine with ASCS improved haematopoiesis as reflected by increased platelet counts (median 40/nl vs 94/nl, p = 0.0004) and white blood cell counts (3.0/nl vs 4.8/nl, p = 0.02) at day +100. The median time until engraftment of platelets (>50/nl) was 11 days (0–24 days) and of white cell counts (>1.0/nl) 0 days (0–24 days). At least, a minimal response was achieved in 36% of patients. The disease stabilization rate was 50% while the median progression‐free survival rate was limited to 2.14 months. Most importantly, patients were once again eligible for alternative treatments including enrolment into clinical trials. We conclude that dose‐intensified bendamustine followed by ASCS is safe and feasible for multiple myeloma patients with very limited bone marrow reserve. Copyright © 2015 John Wiley & Sons, Ltd.     

High-dose therapy with peripheral blood progenitor cell transplantation in multiple myeloma

Background: The objective of our study was to evaluate the efficacyand toxicity of a high-dose melphalan-based (HD-Mel) therapy with or withouttotal body irradiation (TBI) followed by peripheral blood progenitor (PBPC)transplantation in patients with multiple myeloma (MM).Patients and methods: Between June 1992 and May 1996, 100 patients(67 males/33 females) with a median age of 51 years (range 30–65) weretransplanted at our centre. PBPC were collected during G-CSF-enhancedleukocyte recovery following high-dose chemotherapy. Fifty patients weretreated with TBI + melphalan 140 mg/m², while 50 patientsreceived melphalan 200 mg/m².Results: Following PBPC autografting, the median time to reachplatelets 20 × 10⁹/l and neutrophils 0.5 ×10⁹/l was 11 and 14 days with no difference between thetreatment groups. In the TBI group significantly longer periods of totalparenteral nutrition were required due to severe mucositis. Two patients fromthe TBI group died due to transplantation-related complications. Followinghigh-dose treatment, remission state improved in 43 out of 98 patients. Nostatistically significant advantage in reaching CR or PR was observed with TBI+ HD-Mel compared to the treatment with HD-Mel alone.Conclusion: Dose-escalated treatments, with particular regard to theinclusion or omission of TBI, should be prospectively investigated to find thebest high-dose regimen.     

造血干细胞移植治疗恶性血液病的临床观察

目的:观察我院骨髓移植治疗恶性血液病的疗效、探讨移植相关并发症的预防及处理等问题。方法:4例行HLA相合的同胞间异基因外周干细胞移植(Allo-PBSCT)、2例行自体外周干细胞移植(APBSCT)和1例行自体骨髓移植(Au-to-BMT)。结果:全部病例均成功造血重建。中性粒细胞≥0·5×109/L平均时间为11天;血小板≥20×109/L平均时间为16天;发生Ⅱ~Ⅲ度aGVHD1例,cGVHD1例,溶血性贫血2例,间质性肺炎2例,中位随访时间18(6~42)月,全部病例现均存活。结论:骨髓移植治疗恶性血液病有较好疗效。