自身造血干细胞移植治疗儿童晚期恶性实体肿瘤

Treatment of advanced malignant solid tumors in children with autologous hematopoietic stem cell transplantation

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

Objective To investigate the efficacy of autologous hematopoietic stem cell transplantatation in children with advanced solid tumors. Methods Bone marrow was collected from the anterior crista of iliac in both sides in 13 cases while peripheral mononuclear cell was harvested with CS-3000 cell separator in other 15 patients after G-CSF mobilization. Since one of them was suspected to have bone marrow involvement of the neuroblastoma cells, the autograft was purged with CliniMACS based on the CD34 positive selection. Conditioning regimen was CBV protocol (cyclophosphamide+bischloro-nitrosourea,i.e.,BCNU+etopside) in two children with Hodgkin′s disease and etopside plus carboplatin plus melphalan in others. Results The number of mononuclear cells collected from bone marrow or peripheral blood was equal to (5.4±2.1)×10 8/kg and (4.1±1.9)×10 8/kg, respectively. Hematopoietic reconstitution was achieved in all patients. Mean time of the neutrophil count recovery to 0.5×10 9/L and mean time of platelet recovery over 2.0×10 9/L were 11.8±5.7 and 21.0±9.3 days, respectively. Three units of packed red blood cells and three units of platelet products were transfused in the course of transplantation on average. A total of 12 children developed neutropenic fever and 3 of them had positive blood culture, including staphylococcus epidermal, staphylococcus saprophyte and bacillus subtilis. None of the children died of transplantation-associated complication. One child developed acute renal failure, pulmonary edema and pericardial effusion followed by respiratory distress syndrome. Mechanical ventilation and pulmonary surfactant were used and the patient recovered at last. Another patient developed BCNU associated pulmonary injury, severe pulmonary hypertension and eosinophilosis and recovered after treatment. The mean follow up time was 13 months. Among the 27 children, five died of relapse 5 months after transplantation, and one case of NHL had CNS involvement 3 months after transplantation but has got 17 months of survival till now. The remaining twenty one children were in status of disease-free survival. Conclusion Autologous stem cell transplantation might be effective in the treatment advanced solid tumors in children.