臺灣博碩士論文加值系統

高劑量化學治療 ( High Dose Chemotherapy, HDC ) 加上血液幹細胞移植 ( Stem Cells Transplantation, SCT ) 已成為許多血液腫瘤與固形瘤臨床治療的重要方法；部份傳統的治療無法治癒的病人，經由 HDC & SCT 能再次地達到長期的緩解與存活。近十幾年來自體(autologous)或異體(allogeneic)週邊血液幹細胞移植(Peripheral Blood Stem Cells Transplantation, PBSCT )逐漸取代自體或異體骨髓移植，也因此週邊血液幹細胞之收集也成為PBSCT中重要的過程，為探討PBSCs收集之因素，本研究比較兩種不同血球分離機收集週邊血液單核細胞濃厚液之效率與分析其他相關資料，並評估自體與異體週邊血液幹細胞收集之表現如週邊血液幹細胞液中細胞分類 34 陽性(cell differentiation CD34+ )細胞濃度收集前白血球數量、短期細胞培養等資料及與臨床病人血液恢復之相關。
本研究自民國83年5月起至89年2月止，在高雄醫學大學血液腫瘤內科收集不同自體與異體週邊血液幹細胞移植案例作為研究對象。共有自體週邊血液幹細胞移植40例，包括男性21例、女性19例，平均年齡為33.5歲 (範圍15-62歲)；疾病類別分別為Non-Hodgkin''s Lymphoma (NHL) 12例、Hodgkin''s Disease (HD) 2例、Nasopharyngeal Carcinoma ( NPC ) 8例、Breast Cancer 6例、Lung Cancer 3例、Sarcoma 3例、Acute MyeloblasticLeukemia ( AML ) 3例、Acute Lymphoblastic Leukemia ( ALL ) 2例、Germ Cell Tumor 1例；總計施術白血球分離術( Leukapheresis )112次。異體週邊血液幹細胞移植共15例，包括男性6例、女性9例；平均年齡24.4歲(範圍9-36歲)；總計施術血球分離術31次。其中COBE SPECTRA ( COBE BCT Inc.)施術者共107次，包括在自體組施術88次，異體組施術19次；以MCS3P( HAEMONETICS)施術共45次，其中在自體組施術24次，異體組施術21次。本研究結果顯示不論在自體或異體週邊血液幹細胞收集在施術總血量與抗凝劑使用量，COBE系統皆比MCS3P系統多。在施術時間上，MCS3P系統則需較長時間；而在收集液中COBE系統比MCS3P系統有較低紅血球之收集率(有顯著差異p 值皆小於0.001)。而在白血球之收集與CD34+ 細胞濃度上，這兩種血球分離機沒有顯著差異。在收集過程中COBE血球分離機不論在自體組或異體組施術中發生發燒、嘔吐、噁心、麻木等副作用之頻率遠大於MCS3P (頻率分別為16%、78% > 4%、0 % )。
本研究結果亦顯示自體與異體兩組收集之CD34 (+) 細胞濃度與細胞培養之CFU-GM (r 值分別為0.909、0.649 )或BFU-E ( r 值分別為0.788、0.600 )皆呈現有意義的相關。在自體週邊血液幹細胞移植之血液系統恢復方面；當PBSCs輸回給病人時在白血球恢復>1000/ul與血小板恢復>20000/ul平均需要分別為11.2天 、13.9天 ，在異體週邊血液幹細胞移植病人血球恢復平均需要9.8天，11.5天；所輸回給病人CD34 (+)細胞數目與血球重建需要天數呈現負相關。比較自體與異體兩組之收集週邊血液幹細胞CD34 (+) 細胞濃度並沒有顯著差異，但是在病人體重每公斤輸入CD34 (+) 細胞總數異體組就很明顯比自體組多，這種情形可能是因為自體組接受化學治療或電療而導致骨髓性傷害，CD34 (+)細胞之收集明顯比正常捐贈者少。本研究也發現在自體組PBSC收集CD34 (+) 細胞濃度與病人年齡呈負相關( r = - 0.333)，年齡分成兩組結果發現年輕一組 ( ≦30 歲) 收集較多之CD34 (+) 細胞很明顯多於30歲以上者(p= 0.001)，而以最後一次rhG-CSF 注射至開始收集週邊血液幹細胞之時間作比較，我們發現在6小時內者收集比超過6小時收集血液幹細胞有較好之結果。
由上述結果得知，COBE與MCS3P兩個收集系統雖然具有相同收集白血球與血液幹細胞效率，但在紅血球污染上COBE系統有較低之趨勢，因此建議在血型不同之異體週邊血液幹細胞移植以使用COBE系統為佳。另外收集之時間宜在最後一次注射G-CSF後6小時內施行，不宜在超過6小時之後再收集。本研究經驗希望能與國內其他臨床週邊血液幹細胞收集經驗互相交流，以提升臨床實驗診斷技術品質。

Peripheral blood stem cells transplantation ( PBSCT ) has been used increasingly to treat various malignancies and has replaced autologous bone marrow transplantation ( Auto-BMT ) and allogeneic bone marrow transplantation ( Allo-BMT ), which has advantages over ABMT especially in terms of faster hematopoietic recovery, less tumor cells contamination and less side effects etc. The purpose of this study is to report our clinical experience to evaluate two different cells separator i.e. COBE Spectra and MCS3P in the efficiency of collecting stem cells. The correlation between CD34 (+) cells in the PBSCs collect and its cell cultures, i.e. CFU-GM, CFU-GEMM, and BFU-E and the clinical characteristics, hematopoietic recovery of patients following PBSCT were also studied.
A total of 40 patients undergone autologous PBSCT with 112 apheresis procedures (88 with COBE system and 24 with MCS3P system), and 15 allogeneic donors with 31 apheresis procedures (19 with COBE system and 12 with MCS3P system) were analyzed. Our results revealed the COBE system collecting more total nucleated cells and less red cell contamination in PBSCs than those of MCS3P system. The COBE system had also higher blood volume processed and anticoagulant volume used, but less operation time than those did in MCS3P system. As to CD34+ cells collection, there was no significant difference in both systems in terms of CD34 (+) percentage, although the total number of CD34 (+) cells collected were slightly higher in the COBE system than in the MCS3P system. The CD34(+)cellsharvested in patients with acute leukemia were significantly higher than those in other patients with solid tumors, e.g. breast cancer, nasopharyngeal carcinoma, and malignant lymphoma. We correlated CD34 (+) % of PBSCs collects with patient''s age and cell cultures including BFU-E, CFU-GM and CFU-GEMM. We found the CD34 (+) % were significantly positive correlated with CFU-GM, and weakly negative related with patient''s age. Clinically, we also noted the more CD34(+) cells dose infused back to the patients, the faster hematopoeitic recovery. Besides, we also found the proper harvesting time following the last dose of G-CSF injection was very important. In our study, we showed poor results of CD34(+) cells collection if the apheresis were performed 6 hours after the last dose of G-CSF injection. As to the patient''s side effects during apheresis, we noted the COBE system had higher incidence of side effects than that of MCS3P system both autologous and allogeneic harvesting.
Based on above results, we concluded that the harvesting efficiency was no significant difference between COBE and MCS3P system in terms of CD34(+) cells collection, however, the COBE systems had higher incidence of side effects during apheresis than that of MCS3P system.

一、 中文摘要………………………………….. 1
二、 前言及文獻回顧…………………………...4
三、 材料與方法………………………………...8
四、 結果………………………………………..15
五、 討論………………………………………..20
六、 結論與建議………………………………..29
七、 未來研究…………………………………..31
八、 參考文獻…………………………………..32
九、 附圖與附表…………………..…………..43
十、 英文摘要……………………………………72

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