Demirer T, Buckner C D, Gooley T, Appelbaum F R, Rowley S, Chauncey T, Lilleby K, Storb R, Bensinger W I
Fred Hutchinson Cancer Research Center, Seattle, WA 98104, USA.
Bone Marrow Transplant. 1996 Jun;17(6):937-41.
This study was performed to determine the factors influencing the collection of autologous peripheral blood stem cells (PBSC) in patients with multiple myeloma (MM) who had disease which had progressed after an initial response or who had refractory disease. Fifty-seven patients with MM underwent PBSC collections following recombinant human granulocyte colony stimulating factor (G-CSF) alone (n = 19) (16 micrograms/kg/day), cyclophosphamide (CY) (4 gm/m2 x 1) with either G-CSF (10 micrograms/kg/day) (n = 7) or granulocyte-macrophage colony-stimulating factor (GM-CSF) (500 micrograms/m2/day) (n = 7) or cyclophosphamide (4 gm/m2 x 1) and etoposide (200 mg/m2/day x 3) (CE) with G-CSF (10 micrograms/kg/day) (n = 24). The goal was to collect 5 x 10(6) CD34+ cells/kg. Fifty of 57 patients underwent autologous transplantation with PBSC alone (n = 39) or PBSC + marrow (n = 11). The median yield of CD34+ cells was 7 x 10(6)/kg (range 0-178.3). Thirty-nine of 57 patients (68%) achieved the target level of 5 x 10(6) CD34+ cells/kg in a median of three (range 1-8) collections. Eighteen (32%) patients yielded < 5 x 10(6) CD34+ cells/kg with the first collections. Thirteen of these 18 patients yielded < 2.5 x 10(6) and five yielded 2.5-4.95 x 10(6) CD34+ cells/kg. Of the 18 patients with less than optimal CD34+ cell yields, five with CD34+ yields of 2.5-4.95 x 10(6)/kg received PBSC alone at transplant, six underwent marrow storage to augment the PBSC dose and received PBSC plus marrow and seven patients underwent secondary collections. Of seven patients who underwent second (n = 5) or third (n = 2) cycles of PBSC collections using G-CSF 16 (n = 4) or 32 (n = 3) micrograms/kg/day, > 2.5 x 10(6) CD34+ cells/kg were collected in four patients. Two patients achieved < 0.18 CD34+ cells following three cycles of mobilization. In a linear regression model, an increased percentage of marrow involvement and prior radiotherapy (RT) were statistically significantly associated with a low CD34+ cell collection yield (P = 0.003, and 0.01, respectively). A mobilization regimen of CE plus G-CSF was associated with a significantly higher yield of CD34+ cells as compared to patients receiving G-CSF alone (P = 0.02). CY with G or GM-CSF was not significantly different than G-CSF alone (P = 0.49). Twenty-two of 24 (92%) patients receiving CE with G-CSF achieved a target level of 5 x 10(6) CD34+ cells/kg or more as compared to 11 of 19 (58%) patients receiving G-CSF alone (P = 0.01) and six of 14 (43%) patients receiving CY with G or GM-CSF (P = 0.001). These data suggest that percentage of marrow involvement, prior radiotherapy, and number of prior chemotherapy regimens are important predictors of PBSC yield in patients with MM. These data also suggest that CE plus G-CSF is superior to G-CSF alone or CY plus G/GM-CSF based on mean daily CD34+ cell collection yield. Higher doses of G-CSF (16-32 micrograms/kg/day) can result in adequate CD34+ cell collections in some secondary attempts in patients with MM failing an initial mobilization regimen.
本研究旨在确定影响多发性骨髓瘤(MM)患者自体外周血干细胞(PBSC)采集的因素,这些患者的疾病在初始缓解后进展或患有难治性疾病。57例MM患者在接受重组人粒细胞集落刺激因子(G-CSF)单药治疗(n = 19)(16微克/千克/天)、环磷酰胺(CY)(4克/平方米×1)联合G-CSF(10微克/千克/天)(n = 7)或粒细胞-巨噬细胞集落刺激因子(GM-CSF)(500微克/平方米/天)(n = 7)或环磷酰胺(4克/平方米×1)和依托泊苷(200毫克/平方米/天×3)(CE)联合G-CSF(10微克/千克/天)(n = 24)后进行了PBSC采集。目标是采集5×10⁶个CD34⁺细胞/千克。57例患者中有50例接受了单独PBSC(n = 39)或PBSC+骨髓(n = 11)的自体移植。CD34⁺细胞的中位产量为7×10⁶/千克(范围0 - 178.3)。57例患者中有39例(68%)在中位3次(范围1 - 8次)采集中达到了5×10⁶个CD34⁺细胞/千克的目标水平。18例(32%)患者首次采集时CD34⁺细胞产量<5×10⁶个/千克。这18例患者中有13例产量<2.5×10⁶个,5例产量为2.5 - 4.95×10⁶个CD34⁺细胞/千克。在18例CD34⁺细胞产量未达最佳的患者中,5例CD34⁺产量为2.5 - 4.95×10⁶/千克的患者在移植时仅接受了PBSC,6例进行了骨髓储存以增加PBSC剂量并接受了PBSC加骨髓,7例患者进行了二次采集。在7例使用16(n = 4)或32(n = 3)微克/千克/天的G-CSF进行第二次(n = 5)或第三次(n = 2)PBSC采集周期的患者中,4例患者采集到了>2.5×10⁶个CD34⁺细胞/千克。2例患者在三个动员周期后CD34⁺细胞<0.18个。在一个线性回归模型中,骨髓受累百分比增加和既往放疗(RT)与低CD34⁺细胞采集产量在统计学上显著相关(P分别为0.003和0.01)。与仅接受G-CSF的患者相比,CE加G-CSF的动员方案与显著更高的CD34⁺细胞产量相关(P = 0.02)。CY联合G或GM-CSF与单独使用G-CSF无显著差异(P = 0.49)。接受CE联合G-CSF的24例患者中有22例(92%)达到了5×10⁶个CD34⁺细胞/千克或更高的目标水平,而仅接受G-CSF的19例患者中有11例(58%)(P = 0.01),接受CY联合G或GM-CSF的14例患者中有6例(43%)(P = 0.001)。这些数据表明,骨髓受累百分比、既往放疗和既往化疗方案的数量是MM患者PBSC产量的重要预测因素。这些数据还表明,基于平均每日CD34⁺细胞采集产量,CE加G-CSF优于单独使用G-CSF或CY加G/GM-CSF。更高剂量的G-CSF(16 - 32微克/千克/天)在一些初始动员方案失败的MM患者的二次尝试中可导致足够的CD34⁺细胞采集。