Schwartzberg L S, Birch R, Hazelton B, Tauer K W, Lee P, Altemose R, George C, Blanco R, Wittlin F, Cohen J
Clinical Trials Division, Response Technologies, Inc., Memphis, TN 38117.
J Hematother. 1992 Winter;1(4):317-27. doi: 10.1089/scd.1.1992.1.317.
Chemotherapy can serve as a stimulus for mobilizing hematopoietic progenitor cells to the peripheral blood for harvest via leukapheresis. Mobilized peripheral blood stem cells (PBSC) support rapid hematologic reconstitution after bone marrow aplasia induced by intensive myelosuppressive treatments. Our purpose was to develop effective mobilization regimens allowing collection of large quantities of PBSC. We administered high-dose cyclophosphamide (HDC, 4 gm/m2) or cyclophosphamide (4 gm/m2) plus etoposide (600 mg/m2) (HDCE) in a nonrandomized, sequential fashion to 94 patients with breast cancer, lymphoma, and other malignancies with collection of PBSC via leukapheresis during white blood cell (WBC) recovery from nadir counts. Each apheresis product was analyzed for total nucleated cell number, granulocyte-macrophage colony-forming units (CFU-GM) and CD34+ cells. Twenty-four additional patients with comparable pretreatment characteristics received HDCE plus recombinant human granulocyte colony-stimulating factor (HDCE+G) after chemotherapy through the end of apheresis. Patients receiving HDC were matched for age, sex, and disease but were more heavily pretreated. HDCE was superior to HDC in mean daily CFU-GM and CD34+ yield (p < 0.05), even when groups were adjusted for performance status and amount of prior therapy. HDCE+G led to 3.7 times more CFU-GM and 4.7 times more CD34+ cells than HDCE. Target PBSC yield, defined as > 20 x 10(4) CFU-GM/kg and >4 x 10(8) cells/kg, was achieved by 92% of HDCE+G patients after a median of three aphereses, 56% of HDCE patients after five aphereses, and 16% of HDC patients after six apheresis (p < 0.0001). Prior chemotherapy inversely correlated with the quantity of PBSC harvested regardless of regimen utilized. Our results demonstrate effective chemotherapy regimens for harvesting hematopoietic progenitors in a diverse patient population. HDCE+G produced the highest number of progenitors, suggesting that increasing dose intensity and adding rhG-CSF enhances mobilization. Correlation between cumulative CD34+ and CFU-GM allows real-time flow cytometric analysis of the number of aphereses required to harvest target numbers of PBSC.
化疗可作为一种刺激因素，促使造血祖细胞动员至外周血，以便通过白细胞分离术进行采集。动员的外周血干细胞（PBSC）有助于在强化骨髓抑制治疗诱导的骨髓再生障碍后实现快速的血液学重建。我们的目的是制定有效的动员方案，以允许采集大量的PBSC。我们以非随机、序贯的方式，给94例乳腺癌、淋巴瘤及其他恶性肿瘤患者给予大剂量环磷酰胺（HDC，4 g/m²）或环磷酰胺（4 g/m²）加依托泊苷（600 mg/m²）（HDCE），并在白细胞从最低点计数恢复期间通过白细胞分离术采集PBSC。对每份单采产品分析其总核细胞数、粒-巨噬细胞集落形成单位（CFU-GM）和CD34⁺细胞。另外24例具有可比预处理特征的患者在化疗后至单采结束接受HDCE加重组人粒细胞集落刺激因子（HDCE+G）。接受HDC的患者在年龄、性别和疾病方面匹配，但预处理程度更高。HDCE在平均每日CFU-GM和CD34⁺产量方面优于HDC（p<0.05），即使在根据体能状态和既往治疗量对组进行调整后也是如此。HDCE+G产生的CFU-GM比HDCE多3.7倍，CD34⁺细胞多4.7倍。目标PBSC产量定义为>20×10⁴CFU-GM/kg和>4×10⁸细胞/kg，92%接受HDCE+G的患者在中位3次单采后达到，56%接受HDCE的患者在5次单采后达到，16%接受HDC的患者在6次单采后达到（p<0.0001）。无论采用何种方案，既往化疗与采集的PBSC数量呈负相关。我们的结果表明，在不同患者群体中，有有效的化疗方案用于采集造血祖细胞。HDCE+G产生的祖细胞数量最多，表明增加剂量强度和添加重组人粒细胞集落刺激因子可增强动员效果。累积CD34⁺与CFU-GM之间的相关性允许对采集目标数量PBSC所需的单采次数进行实时流式细胞术分析。
