自体外周血干细胞移植治疗实体瘤中不良反应研究

目的 探讨小儿自体外周血干细胞移植(auto-PBSCT)预处理的不良反应及防治.方法 观察30例实体瘤患儿接受auto-PBSCT的急性相关不良反应.30例中男22例,女8例;其中神经母细胞瘤20例,横纹肌肉瘤3例,原发性神经外胚层瘤(PNET)2例,肝母细胞瘤1例,视网膜母细胞瘤3例,肾母细胞瘤1例.结果 外周血造血干细胞回输后+3～+14 d内不良反应表现为1级21例,Ⅱ级6例,Ⅲ级1例,Ⅳ级2例(死亡1例);经对症处理后于预处理+15～+22 d 25例无不良反应;2例1级,2例Ⅱ级.30例患儿均有不同程度口腔溃疡、呕吐、腹泻及离子紊乱,有心肌损伤、心律不齐及心衰表现5例,出血性膀胱炎Ⅰ例,肝转氨酶升高改变15例,消化道大出血低血容量休克1例,多脏器功能衰竭死亡1例.经过规律抗感染及对症治疗后,30例患儿中+22 d不良反应好转率为86.7%(26/30),+30～+40 d不良反应除2例因病情进展外均好转,移植后1年无病生存率为70.0%(21/30),移植2年后无病生存率为53.3%(16/30).29例患儿于+15～+40 d脏器损伤恢复正常.结论 虽然auto-PBSCT预处理可引起各系统的不良反应,但多可在短期内恢复,对患儿生活质量影响较小.在治疗过程中防治上述不良反应,可有效地提高实体瘤缓解率.     

CIE及IEV方案在恶性实体瘤儿童自体外周血干细胞动员和采集中的应用

目的：自体外周血干细胞移植（APBSCT）是治疗儿童恶性实体瘤的重要方法之一,干细胞动员与采集是决定造血重建的重要因素。本研究采用CIE及IEV动员方案对儿童神经母细胞瘤（NB）及横纹肌肉瘤进行干细胞动员和采集,并对临床效果进行评价。方法：8例IV期NB 患儿采用CIE化疗方案动员,3例III期横纹肌肉瘤患儿采用IEV方案。观察采集干细胞的效果。结果：11例患儿平均采集单个核细胞数（MNC）为(5.55 ±1.43)×108/kg,CD34+ 细胞数为（4.88±2.48）×106/kg,动员并发症少,患儿均能耐受。10例行APBSCT后均获快速造血功能重建,其中1例NB于APBSCT后32 d因合并左心衰竭死亡,余9例患儿APBSCT后60 d复查外周血象稳定。结论：CIE及IEV方案可以安全有效地完成NB及横纹肌肉瘤自体外周血干细胞动员和采集并达到移植要求。     

自体外周血造血干细胞移植在小儿恶性晚期实体肿瘤的临床应用(英文)

目的　小儿晚期实体肿瘤对常规化疗效果欠佳 ,该文探讨大剂量化疗并自体外周血干细胞移植(APBSCT)治疗小儿高危晚期实体瘤的可行性及疗效。方法　 1 3例恶性实体肿瘤患儿 (恶性淋巴瘤 7例、神经母细胞瘤 6例 ) ,在其完全缓解 (1 2例 ) ,部分缓解 (1例 )后进行了APBSCT治疗。移植时病程中位时间 1 0月。 1 1例用化疗加重组人粒 单细胞集落刺激因子 (rhGM CSF)或重组人粒细胞集落刺激因子 (rhG CSF)动员 ,2例采用常规化疗方案作为动员剂。所采集单个核细胞 (MNC)为 (6 .85± 2 .6 5 )× 1 0 8/kg。CD34+ 细胞为 (1 5 .82± 1 2 .93)×1 0 6/kg。CFU GM集落为 (1 7.87± 1 7.94 )个 / 1 0 4细胞。预处理方案中 6例基本方案为全身放疗加环磷酰胺。 7例未用TBI ,仅以马法兰为主做为预处理方案 (马法兰 +卡铂 +足叶乙甙 5例 ,白消胺 +马法兰 2例 )。结果　移植后白细胞 >0 .5× 1 0 9/L、>1 .0× 1 0 9/L、血小板 >2 0× 1 0 9/L的中位时间分别为 1 2天、1 5天、1 9天。中位随访时间4 8月 (1月～ 1 4 4月 )。至今总生存率 77% (1 0 / 1 3) ,死亡率 2 3% (3/ 1 3) ,无移植相关死亡。结论　APBSCT是治疗小儿晚期实体肿瘤 ,明显改善其预后的重要治疗方法。     

美罗培南与万古霉素联用治疗自体外周血干细胞移植患儿合并感染的疗效观察

目的评价美罗培南与万古霉素联用治疗实体瘤患儿自体外周血干细胞移植过程中合并中重度感染的临床疗效及安全性。方法剂量为美罗培南10~20 mg/(kg.次),万古霉素10~20 mg/(kg.次),均为1次/12 h静脉滴注。结果美罗培南与万古霉素联用有效率为78.4%,4例合并败血症患儿中2例有效,不良反应发生率为8.1%。结论美罗培南与万古霉素联用治疗自体外周血干细胞移植过程中合并中重度感染疗效显著,而且安全性好。     

Primary intraspinal primitive neuroectodermal tumor treated with autologous stem cell transplantation: case report and review of the literature

The authors describe the case of a 19-year-old female patient with a primary primitive neuroectodermal tumor (PNET) of the thoraco-lumbar spinal cord, who presented with acute urinary retention and back pain for 2 months. Magnetic resonance imaging revealed an intradural extramedullary tumor, 6.5 cm long, in the region of the conus medullaris. Histological examination disclosed a small round cell tumor with immunohistochemical characteristics of a peripheral PNET. Metastatic workup showed no evidence of an intracranial tumor or metastases outside the neuroaxis. The patient received multidisciplinary treatment, including surgical excision, irradiation of the entire cranio-spinal axis, and high-dose chemotherapy with autologous stem cell rescue. Presently, 24 months after diagnosis, the patient remains in complete remission.     

自身造血干细胞移植治疗儿童晚期恶性实体肿瘤

目的　评价自身干细胞移植治疗儿童晚期恶性实体肿瘤的安全性及疗效。方法13例次患儿直接采集骨髓 ,另 15例患儿经粒细胞集落刺激因子 (G CSF)动员后从外周血获取单个核细胞 ,对 1例疑有肿瘤细胞浸润的采集物经CliniMACS进行了CD 3 4 细胞分选的净化处理。除 2例霍奇金淋巴瘤患儿经CBV方案 (CTX BCNU VP16 ) (环磷酰氨、卡氮芥及依托泊甙 )治疗外 ,其余患儿均采用VP16 卡铂 马法兰的预处理方案。结果　采集骨髓及外周血得到的单个核细胞分别为 ( 5 4± 2 1)× 10 8/kg和 ( 4 1± 1 9)× 10 8/kg。所有患儿移植后均获得造血重建 ,中性粒细胞恢复至 0 5×10 9/L的时间为 ( 11 8± 5 7)d ,血小板大于 2 0× 10 9/L的时间为 ( 2 1 0± 9 3)d。移植过程中 3例患儿分别合并表皮葡萄球菌、腐生葡萄球菌和枯草杆菌败血症 ,无一例因移植相关并发症而死亡。但 1例出现急性肾功能不全、肺水肿、心包积液并发展为呼吸窘迫综合征 ,经机械通气、应用肺表面活性物质等积极治疗后康复 ;另 1例出现BCNU相关的肺损伤 ,导致严重的肺动脉高压、嗜酸性细胞增多 ,经皮质激素等治疗后逐渐好转。本组平均随访 13个月 ,2 7例患儿中 5例移植后 5个月内因疾病复发而死亡 ;1例非霍奇金淋巴瘤患儿移植后 3个月中枢神经系统复     

Outcome for children <4 years of age with malignant central nervous system tumors treated with high-dose chemotherapy and autologous stem cell rescue

BACKGROUND: Children <4 years of age (yo) with malignant central nervous system (CNS) tumors have a dismal prognosis. In an attempt to delay or obviate radiation therapy (XRT) and improve outcome, our institution has treated children <4 yo with newly diagnosed malignant CNS tumors with high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) followed by selective XRT. PROCEDURE: Fifteen children (age 4-38 months) with malignant CNS tumors have completed treatment with HDC/ASCR. All patients received three cycles of induction chemotherapy (cisplatin 3.5 mg/kg- day 0, cyclophosphamide 60 mg/kg- day 1 and 2, etoposide 2.5 mg/kg- day 0-2, vincristine 0.05 mg/kg, day 0, 7, 14) followed by three cycles of HDC (carboplatin 17 mg/kg and thiotepa 6 mg/kg, day 0 and 1) with ASCR. Histology included five medulloblastomas, four primitive neuroectodermal tumors (PNET), five malignant gliomas, and one ependymoma. Outcome and treatment toxicities were evaluated by retrospective chart review. RESULTS: Median follow-up time of the 15 patients is 22 months (range 8-82 months). The 1- and 2-year progression-free survival (PFS) is 86.1% and 52.2% and overall survival (OS) 91.6% and 72.1%, respectively. Ten patients are alive and disease free 3-77 months (median 18 months) after having completed HDC/ASCR, thereoff five received XRT. Toxicity was primarily myelosuppression. There was no treatment mortality. CONCLUSIONS: We are encouraged by the outcome of 15 children <4 yo with malignant CNS tumors treated with tandem cycles of HDC and ASCR at our institution. The treatment regimen is relatively well tolerated.     

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.     

大剂量化疗结合自体外周血干细胞移植治疗神经外胚层来源的儿童实体瘤疗效分析

目的：探讨大剂量化疗结合自体外周血造血干细胞移植（APBSCT）治疗神经外胚层来源晚期实体瘤的疗效。方法：选择神经外胚层来源的肿瘤患儿23例,平均年龄5.8±3.5岁。移植前化疗8.0±4.3疗程。其中IV期神经母细胞瘤20例,移植时完全缓解9例,部分缓解7例,处于肿瘤进展期4例;原始神经外胚叶肿瘤2例,移植期间为完全缓解。视网膜母细胞瘤1例,移植时部分缓解。进行外周血造血干细胞采集、手术切除,然后进行APBSCT。结果：①20例神经母细胞瘤患儿中,19例移植后造血功能获得满意重建,重建时间为16.5±0.9 d。术后中位随访时间为15.8月。移植前获完全缓解的患儿生存率为100%,部分缓解患儿为57%,进展期患儿为0（P<0.05）。3组15.8月总生存率67%。②视网膜母细胞瘤患儿随访6个月获完全缓解。③原始神经外胚叶肿瘤患儿于术后5~8个月原发灶复发,1年内均死亡。结论：大剂量化疗结合APBSCT治疗神经外胚层来源实体瘤,在移植前达到完全缓解者可取得较好疗效,部分缓解者可提高缓解率。其中原始神经外胚叶肿瘤预后最差,即使在完全缓解时移植死亡率仍高。［中国当代儿科杂志,2010,12（4）：244-247］     

High‐dose chemotherapy followed by autologous peripheral blood stem cell transplantation for recurrent primary mediastinal malignant germ cell tumor: A case report

A 15‐yr‐old boy presented with an anterior mediastinal mass, multiple lung metastases and obstruction of the left brachiocephalic vein, the superior vena cava and the subclavian vein. Tumor biopsy by CT guidance confirmed a diagnosis of GCT. Five courses of BEP therapy were performed, and CT of the chest revealed reduction in the anterior mediastinal mass and disappearance of the multiple lung metastases. We performed the anterior mediastinal mass extraction followed by adjuvant chemotherapy consisting of ICE and TIP. However, the AFP levels became elevated soon after. Abnormal accumulation was observed in the right upper lung by DW‐MRI. After the operation, two courses of TI chemotherapy and two courses of HDCT followed by auto‐PBSCT were performed. He was complicated with auditory disorder and renal dysfunction. Although HDCT followed by auto‐PBSCT was effective for the relapsed primary mediastinal GCT, a treatment strategy avoiding late complications is warranted.     

Evans syndrome after autologous peripheral blood stem cell transplantation for recurrent Hodgkin lymphoma

There have been a number of recent reports on the occurrence of autoimmune conditions after autologous hematopoietic stem cell transplantation. We describe a rare case of Evans syndrome (ES) that developed in a 16‐year‐old patient >1 year after autologous peripheral blood stem cell transplantation for recurrent Hodgkin lymphoma. ES is a rare and frequently refractory condition. No therapy for the condition has been established, and it can often be fatal. In the present case, i.v. cyclosporine A injection was significantly effective against the ES, which has not recurred.     

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。     

自体外周血干细胞移植治疗难治性学龄前儿童风湿病

目的探讨自体外周血干细胞移植（auto-PBHSCT）治疗难治性学龄前儿童风湿病的可行性、安全性和有效性。方法幼年皮肌炎（JDM）、幼年系统性红斑狼疮（JSLE）、幼年类风湿关节炎（JRA）各1例,均为男性患儿,年龄分别为3、6,6岁,病程分别为14、3．6、22个月,常规治疗中病情进展,库欣征明显,患病后患儿身高均无增长。JDM患儿肌力Ⅱ级,吞咽肌和呼吸肌受损,明显Gottron’s征和向阳性皮疹;JSLE患儿表现为蝶形红斑、蛋白尿、贫血,脑MRI显示脱髓鞘病变,系统性红斑狼疮疾病活动性指数（SLEDAI）≥12分;JRA患儿双膝、踝、腕、肘严重多关节炎。以环磷酰胺（CTX）＋粒细胞集落刺激因子（G-CSF）进行外周造血干细胞动员,经CliniMACS细胞分选仪分选CD34‘细胞。预处理方案：JSLE和JRA为卡氮芥（BCNU）＋足叶乙甙（VP16）＋阿糖胞苷（Ara-C）＋马法兰（MEL）及抗胸腺球蛋白（ATG）;JDM为CTX＋Mel及ATG。回输CD34^＋细胞数分别为9．45×10^6／kg、5．46×10^6／kg和9．60×10^6／kg。观察移植治疗前后风湿病状态和免疫学指标的变化。结果3例患儿移植后分别于＋9d、＋13d、＋11d粒细胞≥0．5×10^9／L,＋14d、＋18d和＋13d血小板≥20×10^9／L。CIM处于低水平,CD4／CD8倒置。JDM移植后1个月皮疹消失,肌力Ⅴ级,移植后2个月血清肌酶、肌电图恢复正常。JSLE移植后3个月皮疹消退,无蛋白尿,脑MRI病变吸收,移植后8个月自身抗体转阴性,SLEDAI为2～3分。JRA移植后3周关节炎好转,移植后3个月无关节肿胀及活动受限。均停用激素和免疫抑制药物,库欣征消退,18个月身高增长10～15cm,均已上小学或学前班,随访25～27个月无复发。结论auto-PBHSCT治疗难治性学龄前儿童风湿病近期疗效显著,安全性及远期疗效有待进一步观察。     

Pediatric malignant germ cell tumors: A comparison of the neuro‐oncology and solid tumor experience

Malignant germ cell tumors (GCT) arise from abnormal migration of primordial germ cells and are histologically identical whether they occur inside or outside the central nervous system (CNS). However, the treatment strategy for GCTs varies greatly depending on the location of the tumor. These differences are in part due to the increased morbidity of surgery in the CNS but may also reflect differential sensitivity of the tumors to chemotherapy and radiation therapy (RT) or not‐yet‐understood biologic differences between these tumors. Historically, specialists caring for extracranial and intracranial GCT in the United States have practiced separately without much cross communication. The focus of this review is a discussion of differences between the management of CNS and extra‐CNS GCTs and opportunities for collaboration and future research.     

High-dose chemotherapy and autologous stem cell rescue in children with newly diagnosed high-risk or relapsed medulloblastoma or supratentorial primitive neuroectodermal tumor

BACKGROUND: Single or tandem double high-dose chemotherapy (HDCT) was used to treat children with newly diagnosed high-risk or relapsed medulloblastoma and supratentorial primitive neuroectodermal tumor (MB/sPNET) in order to defer or avoid radiotherapy in young children. PROCEDURE: Thirty-seven HDCTs were given to 25 children with newly diagnosed high-risk or relapsed MB/sPNET. Tandem double HDCT was used for 12 of 15 patients initially intended to receive double HDCT. RESULTS: Three-year EFS (+/-SE) in 6 newly diagnosed high-risk (>3 years old), 8 newly diagnosed (<3 years old), and 11 relapsed MB/sPNET was 83.3 +/- 15.2%, 62.5 +/- 20.5%, and 29.1 +/- 15.7%, respectively. Three-year EFS for patients in CR or PR and in less than PR at first HDCT was 67.4 +/- 11.0% and 16.7 +/- 15.2%, respectively (P = 0.001). Three-year EFS in patients initially intended to receive double HDCT and single HDCT was 66.0 +/- 12.4% and 40.0 +/- 15.5%, respectively. For 19 patients in CR or PR at first HDCT, 3-year EFS was 88.9 +/- 10.5% in tandem double HDCT group, and 44.4 +/- 16.6% in single HDCT group, respectively (P = 0.037). Although four treatment-related mortalities (TRMs) occurred during 25 first HDCTs, no TRM occurred during 12 second HDCTs. In four of eight young children, craniospinal radiotherapy was successfully withheld without subsequent relapse. CONCLUSIONS: High-dose chemotherapy may improve the survival of children with newly diagnosed high-risk MB/sPNET, and, to some extent, the survival of those with relapsed MB/sPNET. Further study is necessary to elucidate the efficacy of tandem double HDCT.