脑脊液中找肿瘤细胞在视网膜母细胞瘤中的应用价值

目的探讨脑脊液中找肿瘤细胞对判断视网膜母细胞瘤(RB)转移及预后的价值。方法选取本院2006年11月-2008年7月临床确诊为RB的患儿256例。男154例,女102例;单眼患儿171例,双眼患儿85例。治疗前常规行腰椎穿刺,并在脑脊液中找肿瘤细胞,观察有无肿瘤细胞及其与预后的关系。对脑脊液中发现肿瘤细胞的患儿予6~9个周期的化疗和8~10次鞘内注射,化疗方案采用CTV(卡铂、替尼泊苷和长春新碱)方案,鞘内注射药物为阿糖胞苷、甲氨蝶呤和地塞米松。随访时间8~23个月,平均14.6个月。结果256例患儿中8例脑脊液中发现肿瘤细胞,其中1例脑膜弥散浸润性转移,死亡;1例发生颅内转移,进一步行大剂量化疗+自体外周血造血干细胞移植,目前病情稳定;余6例随访期间行眼球摘除,病理证实4例侵犯视神经,占67%(4/6例),其中2例累及视神经断端;6例均未发现其他转移证据。结论RB常见的途径是沿视神经向颅内转移;脑脊液检查找肿瘤细胞对于早期判断颅内转移、早期治疗及预后有重要意义。     

CEM为预处理方案的自体外周血造血干细胞移植治疗晚期神经母细胞瘤相关毒性及疗效观察

目的　观察以CEM (卡铂 +VP 16 +马法兰 )为预处理方案的自体外周血造血干细胞移植治疗晚期神经母细胞瘤患儿的毒性和疗效。方法　研究经大剂量放、化疗及手术治疗达完全缓解的IV期神经母细胞瘤患儿 6例 ,采用CEM预处理方案 (卡铂每日 4 2 5mg/m2 共 4d ,VP 16每日 338mg/m2 共 4d ,马法兰每日 70mg/m2 共 3d)的自体外周血造血干细胞移植 ,并依据Bearman标准对预处理毒性进行评价 ,对其造血重建、并发症及预后进行观察。结果　预处理后髓外毒性除 1例为I级肝损害外 ,主要表现在口腔粘膜 (I级 6例 )和胃肠道 (I级 5例 ,II级 1例 )损害。白细胞于移植后 3± 0 .5d达到 0 ,移植后 33± 3.1d稳定于 1× 10 9/L以上。除 1例患儿移植后 11个月颅内转移外 ,余 5例患儿均健康存活。随诊时间分别为 8、10、2 3、36及 4 8个月。结论　以CEM为预处理方案的自体外周血造血干细胞移植可以安全、有效的治疗IV期神经母细胞瘤。     

脐带血异基因造血干细胞移植后噬血细胞性淋巴组织细胞增生症1例临床分析

目的探讨异基因造血干细胞移植后噬血细胞性淋巴组织细胞增生症(HLH)的临床特征、诊断及治疗。方法回顾性分析1例急性髓系白血病非血缘相关脐带血造血干细胞移植(AML-URD-UCBT)患儿术后并发HLH的临床特点并复习相关文献。结果患儿移植术后第6天(+6 d,下同)出现皮肤、肝脏、肠道急性移植物抗宿主病(aGVHD),先后给予糖皮质激素、环孢素A(CsA)、赛尼哌、霉酚酸酯(MMF)、他克莫司(FK506)等免疫抑制治疗后,aGVHD症状好转,但+26 d后出现活动性巨细胞病毒(CMV)感染合并HLH,给予静脉注射用丙种球蛋白、无环鸟苷、更昔洛韦抗CMV治疗,输红细胞、血小板、血浆、纤维蛋白原等支持治疗,参照HLH-2004方案予依托泊苷、糖皮质激素及CsA治疗后,+61 d检测血CMV早期/晚期基质蛋白(CMV-PP65)转阴,+55、+63 d骨髓象未见噬血细胞,呈HLH完全缓解骨髓象,临床症状及血常规等实验室指标好转;+83 d检测血CMV-PP65及CMV脱氧核糖核酸(CMV-DNA)转阳,+86 d因严重肺部感染、肺出血、消化道出血及多器官功能衰竭而死亡。结论异基因造血干细胞移植后aGVHD及抗aGVHD的免疫抑制治疗,是引起移植后CMV感染相关HLH的危险因素;HLH-2004方案未考虑到异基因造血干细胞移植后HLH的特殊性,需进一步研究有针对性的治疗方案,以提高疗效。     

外周血造血干细胞移植联合间充质干细胞输注治疗范可尼贫血患儿1例并文献复习

目的分析造血干细胞移植联合间充质干细胞输注对范可尼贫血(FA)患儿的治疗效果。方法通过分析1例.FA患儿外周血造血干细胞移植联合间充质干细胞输注治疗的临床资料,观察此种治疗方法对患儿的治疗效果及预后的影响。结果患儿于移植+13 d中性粒细胞植活,+15 d血小板植活,移植后供受者基因嵌合率为99.83%。移植后1.5个月血清CMV-DNA、EBV-DNA阳性,经免疫抑制剂减量及抗病毒治疗后转阴。移植后2个月出现皮肤GVHD(I度),未调整免疫抑制剂剂量,行间充质干细胞输注治疗4次后GVHD消失。移植后6个月,患儿出现血红蛋白水平下降,复查供受者基因嵌合率为57.8%,考虑出现移植物排斥,逐渐减停免疫抑制剂,供受者基因嵌合率复升至81.83%,血象恢复正常,无GVHD表现。现为移植后1.5年,患儿血象持续正常,供受者基因嵌合率维持在95%以上,FA相关基因检测持续转阴。结论造血干细胞移植是根治FA的重要治疗手段,健康供者骨髓间充质干细胞输注对于本例患儿造血干细胞植入、GVHD控制可能具有重要辅助作用。     

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目的观察全身应用卡铂、替尼泊苷和长春新碱(CTV)方案化疗加鞘内注射治疗脑脊液细胞学检查肿瘤细胞阳性的视网膜母细胞瘤(RB)患儿的疗效。方法6例患儿资料来自首都医科大学附属北京同仁医院2006年11月至2008年7月临床确诊为RB且治疗前行脑脊液细胞学检查发现肿瘤细胞者,对其进行6～9次CTV方案化疗加8～10次鞘内注射治疗,同时结合局部治疗,随访12～20个月,观察疗效。结果6例患儿均完成治疗,病情稳定,复查脑脊液细胞学检查均未发现肿瘤细胞,无复发及死亡。结论全身化疗加鞘内注射是对RB颅内转移有效的治疗方法,由于观察时间较短,长期疗效尚须行观察。     

大剂量化疗结合外周血干细胞移植治疗横纹肌肉瘤疗效分析

目的对采用大剂量化疗结合自体外周血造血干细胞移植及免疫治疗的3例横纹肌肉瘤患儿的疗效进行观察。方法 3例横纹肌肉瘤患儿,年龄为3、10、14岁,强烈化疗5、6、11个周期,平均(7.33±3.21)个疗程;期间进行外周血造血干细胞采集、手术切除,然后进行自体外周血造血干细胞移植,术后行白介素-2治疗,复发者行普通化疗及局部放疗,定期随访。结果均顺利度过移植后骨髓抑制期,造血重建时间为13、14、15d,平均(13.33±0.58)d。术后随访8、12、17个月,3例患儿无病生存2/3,总生存率3/3。结论大剂量化疗、自体外周血造血干细胞移植及白介素-2相结合治疗横纹肌肉瘤,在移植前达到部分缓解时可取得较好疗效,长期生存率较高。     

脑脊液肿瘤细胞阳性视网膜母细胞瘤6例治疗观察

观察全身应用卡铂、替尼泊苷和长春新碱（CTV）方案化疗加鞘内注射治疗脑脊液细胞学检查肿瘤细胞阳性的视网膜母细胞瘤（RB）患儿的疗效。方法　6例患儿资料来自首都医科大学附属北京同仁医院2006年11月至2008年7月临床确诊为RB且治疗前行脑脊液细胞学检查发现肿瘤细胞者,对其进行6～9次CTV方案化疗加8～10次鞘内注射治疗,同时结合局部治疗,随访12～20个月,观察疗效。结果　6例患儿均完成治疗,病情稳定,复查脑脊液细胞学检查均未发现肿瘤细胞,无复发及死亡。结论　全身化疗加鞘内注射是对RB颅内转移有效的治疗方法,由于观察时间较短,长期疗效尚须行观察。     

伴N-RAS及CBL突变的幼年型粒单核细胞白血病快速急变后单倍体移植1例报告并文献复习

目的减少对幼年型粒单核细胞白血病(JMML)的误诊,探讨单倍体造血干细胞移植治疗急变后未获得完全缓解JMML的可行性,并分析JMML快速急变的原因。方法 3岁患儿历经误诊为免疫性血小板减少症(ITP)和传染性单核细胞增多症后确诊为JMML,伴有N-RAS及CBL基因突变,但快速急变为急性髓细胞性白血病AML-M4型,伴有EVI1阳性表达。患儿接受母亲单倍体(HLA 7/10相合)造血干细胞移植,预处理方案为阿糖胞苷+白舒非+猪抗人T细胞免疫球蛋白+环磷酰胺,移植后采用环孢素A+霉酚酸酯(MMF)+短程甲氨蝶呤+甲基强的松龙方案预防移植物抗宿主病(GVHD)。结果移植后+14d白细胞植活,+18d血小板植活,未发生重度GVHD。移植后2个月减停全部免疫抑制剂,随访至2018年8月1日,患儿无病存活。结论 JMML急变后未获得完全缓解行单倍体造血干细胞移植治疗是可行的,同时存在N-RAS及CBL基因突变且有EVI1阳性可能是患儿快速急变的原因。     

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目的探讨母亲供髓异基因造血干细胞移植(Allo-HSCT)治疗恶性复发非霍奇金淋巴瘤的疗效和供体造血干细胞来源问题。方法2004年1月,第一军医大学南方医院儿科与海军总医院儿科给1例8岁男性淋巴母细胞淋巴瘤(LBL)患儿移植了母亲来源的HLA不全相合、ABO血型不合的骨髓造血干细胞。预处理选用阿糖胞苷、足叶乙苷、环磷酰胺和全身照射。预防移植物抗宿主病(GVHD)采用兔抗人T-淋巴细胞免疫球蛋白、环孢菌素A、甲氨蝶呤和CD25单克隆抗体。移植有核细胞数8.92×108/kg,单个核细胞数为1.89×108/kg,CD34细胞数为1.37×106/kg,CD3细胞数为32.9×107/kg。结果粒细胞绝对数>0.5×109/L的天数是移植后15d(+15d),血小板>30×109/L的天数是+20d,+27d采用荧光原位杂交性染色体检测显示99%为供者型。+37d受者血型由O型转变为供者血型B型。患儿于+19d出现Ⅰ度急性GVHD,给予激素冲击后,口服小剂量维持治疗,渐消退,随访1年余,未发生慢性GVHD。结论母亲来源的骨髓造血干细胞移植对LBL有根治性治疗作用,而且在一定程度上解决造血干细胞来源问题。     

自体外周血造血干细胞移植在小儿视网膜母细胞瘤的临床应用

目的探讨大剂量化疗并自体外周血造血干细胞移植(APBSCT)治疗小儿眼外期视网膜母细胞瘤的可行性及疗效。方法对3例视网膜母细胞瘤眼外转移患儿,在常规化疗后进行APBSCT治疗。大剂量化疗(预处理)方案采用卡铂(250 mg/m2,-7～-3 d),依托泊苷(350 mg/m2,-7～-3 d),环磷酰胺(1.6 g/m2,-6～-3 d)。从第0天开始输入自体外周血造血干细胞。结果3例患儿均获得移植成功,外周血白细胞总数>1.0×109/L的平均时间为10 d,中性粒细胞>0.5×109/L的平均时间为12 d,白细胞总数恢复正常的平均时间为15 d,血小板计数>50×109/L的平均时间为23 d;血红蛋白含量平均在移植后第15天升至100 g/L;随访时间6个月～14个月,至今3例患儿均生存。结论大剂量化疗加自体干细胞移植是治疗眼外转移的视网膜母细胞瘤的有效治疗方法。因观察例数和随访时间有限,其远期效果还有待进一步评估。     

High-dose chemotherapy and autologous blood stem cell transplantation in children with metastatic neuroblastoma

High-dose chemotherapy (HDC) followed by autologous blood stem cell transplantation (ABSCT) was performed to improve the prognosis of children with metastatic neuroblastoma over 1 year of age at diagnosis. Seven stage IV neuroblastoma patients with a median age of 3.9 years (range 1.6–11.4 years) received conventional chemotherapy before leukapheresis for ABSCT. The median duration of chemotherapy before harvest was 8 months (range 3–23 months). Peripheral blood stem cells (PBSC) were harvested from them after the use of cytotoxic drugs plus granulocyte colony-stimulating factor. The median number of granulocyte-macrophage colony forming units collected after harvest was 23.2 × 10⁴/kg (range 10.1–45.3 × 10⁴/kg). The patients were administered HDC consisting of carboplatin, etoposide, and melphalan followed by ABSCT. Hematopoietic reconstitution after ABSCT was favorable; recovery of granulocytes count > 0.5 × 10⁹/L occurred within 2 weeks and stable platelet engraftment occurred at a median duration of 23 days (range 7–33 days). The toxicity of ABSCT was well tolerable. Two of the four patients who received ABSCT at their first complete remission remained in remission 67 and 68 months after ABSCT. One with partial remission also showed a good response for 8 months. The other two at first relapse showed a transient regression of the tumor. The prognosis of seven patients who received ABSCT was significantly better than that of 13 patients who received conventional therapy alone. These findings suggest that HDC followed by ABSCT is safe and useful as consolidation therapy for the treatment of patients with metastatic neuroblastoma.     

Ommaya储液囊在儿童急性梗阻性脑积水中的应用

目的 探讨Ommaya储液囊在儿童急性梗阻性脑积水中的应用.方法 回顾性分析我科2006至2009年22例晚发维生素K依赖因子缺乏性脑室出血和结脑致急性梗阻性脑积水患儿,行Ommaya储液囊植入手术,观察脑室大小、脑脊液细胞数、蛋白含量变化.结果 结核性脑膜炎7例经储液囊植入行泵内多次注射抗生素,治疗2～4个月、随访脑脊液恢复正常,6例脑积水消失;晚发维生素K依赖因子缺乏性脑室出血伴脑积水15例植入脑室内行泵内穿刺冲洗引流,1～2周头颅CT复查脑室积血消失,脑积水减轻,2例行侧脑室腹腔分流术,无一例发生颅内感染.结论 Ommaya储液囊植入术治疗儿童急性梗阻性脑积水效果良好,手术简便、创伤小、并发症少,值得临床广泛应用.

Abstract：

Objective To review the Ommaya pump application in acute obstructive hydrocephalus in children. Methods We carried out a retrospective analysis of 22 children with obstructive hydrocephalus admitted into our department between 2006 2009. The causes of hydrocephalus included intraventricular hemorrhage secondary to vitamin K deficiency and tuberculous meningitis. Ommaya pump were implanted and the ventricle size and cerebrospinal fluid cell count, protein content were studied. Results Seven children had intracranial infection and treated with antibiotic injection into pump for 2-4 months. Follow-up revealed no recurrence. Fifteen children with ventricle hemorrhage and hydrocephalus underwent drainage from the pump. CT scan after 1-2 weeks demonstrated disappearance of ventricle hemorrhage. There was, no intracranial infection. Conclusions Ommaya pump for the treatment of acute obstructive hydrocephalus produces good result. The surgery is simple. It incurs less trauma and has less complications.     

Ommaya储液囊在儿童急性梗阻性脑积水中的应用

目的 探讨Ommaya储液囊在儿童急性梗阻性脑积水中的应用.方法 回顾性分析我科2006至2009年22例晚发维生素K依赖因子缺乏性脑室出血和结脑致急性梗阻性脑积水患儿,行Ommaya储液囊植入手术,观察脑室大小、脑脊液细胞数、蛋白含量变化.结果 结核性脑膜炎7例经储液囊植入行泵内多次注射抗生素,治疗2～4个月、随访脑脊液恢复正常,6例脑积水消失;晚发维生素K依赖因子缺乏性脑室出血伴脑积水15例植入脑室内行泵内穿刺冲洗引流,1～2周头颅CT复查脑室积血消失,脑积水减轻,2例行侧脑室腹腔分流术,无一例发生颅内感染.结论 Ommaya储液囊植入术治疗儿童急性梗阻性脑积水效果良好,手术简便、创伤小、并发症少,值得临床广泛应用.     

Treatment with linezolid in a neonate with meningitis caused by methicillin-resistant Staphylococcus epidermidis

Recent findings have focused on the possible role of linezolid (LZD) as a suitable candidate for the treatment of central nervous system infections. LZD treatment for meningitis has been sporadically reported in adults, but there are no reports in neonates or infants. We report a case of meningitis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) in a neonatal girl. The patient had intraventricular hemorrhage on postnatal day 1 and was treated with ventricular drainage. Twenty-two days after drainage, the patient developed a fever and seizure. Although ampicillin and ceftriaxone were given empirically for meningitis, an increased cell count and protein were observed in cerebrospinal fluid (CSF). Vancomycin (VCM) was administered intravenously because MRSE was detected from CSF 2 days after the administration of ampicillin and ceftriaxone. However, intravenous administration of VCM did not show any effect. Subsequent treatment of LZD successfully reduced the cell count and protein in CSF. Conclusion: LZD may be a treatment option for neonates and infants for drain-associated meningitis caused by MRSE.     

Lumbar CSF shunting preferentially drains the cerebral subarachnoid over the ventricular spaces: implications for the treatment of slit ventricle syndrome

Based on a proposed pathophysiology of slit ventricle syndrome (SVS), we have hypothesized that lumboperitoneal shunting exerts effects in SVS patients by increasing the buffering capacity for raised intracranial pressure (ICP) via an increase in cerebrospinal fluid drainage from the cerebral subarachnoid space (SAS). We describe 3 SVS patients with patent lumbar subarachnoid drainage but under-functioning ventriculoperitoneal shunts (VPS) who presented with ventriculomegaly (not SVS), and persistence of shunt malfunction like symptoms. Revision of the VPS resulted in complete resolution of symptoms despite a finding of low pressure in the ventricular space. This supports the hypothesis that lumboperitoneal shunting preferentially drains the SAS over the intraventricular space and in these cases allows the 'SVS' ventricles to enlarge by creating a pressure gradient from ventricles to SAS through the cortical mantle.     

粒－单细胞集落刺激因子在自体外周血干细胞移植中的临床应用

报告小儿自体外周血干细胞移植及化疗中粒。单细胞集落刺激因子（ＧＭ－ＣＳＦ）的临床应用研究，共２０例（２４次），并设对照组比较。结果：移植前用作动员剂９例。粒、单系祖细胞（ＣＦＵ－ＧＭ）产率提高平均２９倍，自体外周血每次采集的ＣＦＵ－ＧＭ数较对照组有显著提高（Ｐ＜０．０５）；用于移植后早期４例（６次），白细胞恢复天数较对照组明显缩短（Ｐ＜０．０５）；用于移植后中期及恢复期３例（４次），２例造血恢复，１例（２次）有短期疗效。用于化疗后白细胞减低者效果显著，副反应轻。认为ＧＭ－ＣＳＦ有明显动员外周血干细胞作用，用于移植后可促进造血功能恢复，提高移植的安全性。     

胶质细胞源性神经营养因子联合神经干细胞移植治疗脑室周围白质软化新生大鼠的疗效观察

目的 探讨在移植物中加入胶质细胞源性神经营养因子(glial cell line derived neurotrophic factor,GDNF),能否增强外源性神经干细胞(neural stem cells,NSCs)经脑室移植治疗脑室周围白质软化(periven-tricularleukomalacia,PVL)新生大鼠的移植效果.方法 采用E14胎鼠大脑皮质制备NSCs.2日龄新生大鼠随机分为PVL对照组(PVL组),PVL+NSCs移植组(PVL+NSCs组),PVL+NSCs移植+GDNF组(PVL+NSCs+GNDF组),假手术对照组(Sham组).Sham+NSCs移植组(Sham+NSCs组),以及Sham+NSCs移植+GDNF组(Sham+NSCs+GDNF组).对PVL新生大鼠在建模后72 h进行立体定位仪下经脑室NSCs移植,分别于移植术后7、14、21 d进行免疫荧光、光镜及电镜病理检测,评估在NSCs中加入GDNF对移植效果的可能影响.结果 经脑室植入的外源性NSCs在脑内具有良好的迁移能力,3 d内大部分移行至脑室周围,2周左右在脑室周围主要分化为少突胶质细胞前体,部份分化为神经元及星形胶质细胞.三种分化细胞在加入GDNF移植组显著多于未加GDNF移植组(P均<0.05).移植后21 d光镜下脑病理显示,两个移植组的脑白质病理均获明显改善,尤其加人GDNF移植组的脑白质重度病变发生率较未加GDNF移植组下降了25.5%(P<0.01).移植后21 d的电镜显示,PVL组罕见髓鞘形成,两个移植组的髓鞘形成明显增加,尤其加入GDNF移植组的髓鞘形成明显多于未加GDNF移植组.结论 在外源性NSCs移植物内加入GDNF,可明显增强NSCs经脑室移植治疗PVL新生大鼠的移植疗效.     

Prediction of target CD34 positive cells following leukopheresis in children with neuroblastoma

BACKGROUND: Myeloablative chemotherapy followed by autologous stem cell transplantation (ASCT) may improve long-term survival in children with disseminated neuroblastoma. In children it is important to be able to ascertain when to start the leukopheresis in order to keep the number of procedures to a minimum. PROCEDURE: Twenty-three children with high-risk neuroblastoma with a median weight of 13 kg (range 8-16 kg). Stem cell collection was planned to start at day 14 after the start of the preceding induction standard chemotherapy and after 4 days of G-CSF treatment at 10 microg/kg body weight once daily subcutaneously. Normal volume leukopheresis (median 2.2 times the blood volume of the child) was carried out using a CS-3000 Plus Blood Cell Separator. A pre-collection peripheral blood CD34+ count of >20/microl was a prerequisite for initiating the stem cell collection. RESULTS: Timely leukopheresis was carried out in 19/23 patients. In 17 (74%) of the patients the target number of CD34+ cells/kg body weight was obtained in one procedure; in the remaining the target number of stem cells was obtained after leukopheresis on the following day. A highly significant correlation was found between the pre-harvest CD34+ count from the peripheral blood and the total number of collected CD34+ cells/kg (r = 0.79, P < 0.001). CONCLUSION: When the pre-harvest CD34+ count was >40/microl, a sufficient number of CD34+ stem cells was collected in a single procedure in 15 out of 16 cases.     

Extracranial outflow of particles solved in cerebrospinal fluid: Fluorescein injection study

Cerebrospinal fluid is thought to be mainly absorbed into arachnoid granules in the subarachnoid space and drained into the sagittal sinus. However, some observations such as late outbreak of arachnoid granules in fetus brain and recent cerebrospinal fluid movements study by magnetic resonance images, conflict with this hypothesis. In this study, we investigated the movement of cerebrospinal fluid in fetuses. Several kinds of fluorescent probes with different molecular weights were injected into the lateral ventricle or subarachnoid space in mouse fetuses at a gestational age of 13 days. The movements of the probes were monitored by live imaging under fluorescent microscope. Following intraventricular injection, the probes dispersed into the 3rd ventricle and aqueduct immediately, but did not move into the 4th ventricle and spinal canal. After injection of low and high molecular weight conjugated probes, both probes dispersed into the brain but only the low molecular weight probe dispersed into the whole body. Following intra‐subarachnoid injection, both probes diffused into the spinal canal gradually. Neither probe dispersed into the brain and body. The probe injected into the lateral ventricle moved into the spinal central canal by the fetus head compression, and returned into the aqueduct by its release. We conclude this study as follows: (i) The movement of metabolites in cerebrospinal fluid in the ventricles will be restricted by molecular weight; (ii) Cerebrospinal fluid in the ventricle and in the subarachnoid space move differently; and (iii) Cerebrospinal fluid may not appear to circulate. In the event of high intracranial pressure, the fluid may move into the spinal canal.     

环磷酰胺对小鼠骨髓造血干/祖细胞作用及机制研究

目的探讨环磷酰胺(CY)对小鼠骨髓造血干/祖细胞损伤的作用特点与机制。方法分别以大(380mg/kg)、中(200mg/kg)、小(100mg/kg)三种剂量CY腹腔注射BALB/C小鼠,注射后一周内动态检测外周血白细胞(WBC)、骨髓及外周血CD34+细胞含量、骨髓有核细胞数(NC)与细胞凋亡及病理学改变。结果①在CY处理后3～4d内,骨髓病理损伤逐渐加重,外周血WBC和骨髓NC逐渐下降直至最低值,受抑程度与CY剂量呈显著正相关。②外周血CD34+细胞与骨髓CD34+细胞水平变化基本一致,均在CY注射后1～3d进行性降低,随后中、小剂量组先一过性迅速上升至高出正常水平,然后再下降,而大剂量组则一直处于缓慢回升。③CY处理后1～3d内骨髓细胞凋亡明显增加。结论CY短期内对小鼠造血干/祖细胞损伤存在剂量—时间效应关系,中、小剂量起“动员”作用,大剂量起“摧毁”作用,诱导细胞凋亡是造血损伤的机制之一。