Cremer F W, Kiel K, Wallmeier M, Haas R, Goldschmidt H, Moos M
Department of Internal Medicine V, University of Heidelberg, Germany.
Exp Hematol. 1998 Sep;26(10):969-75.
High-dose therapy with autografting of peripheral blood stem cells (PBSCs) has become an accepted treatment modality. However, gene-marking studies in patients with acute myeloid leukemia and neuroblastoma have revealed that malignant cells reinfused along with leukapheresis products (LPs) contribute to relapse. Thus, a reduction in the number of malignant cells in autografts is desirable. We analyzed the percentage of malignant cells and the number of CD34+ PBSCs in LPs mobilized by granulocyte colony-stimulating factor (G-CSF) alone (LP-S) compared with high-dose cyclophosphamide plus G-CSF (LP-CY) in patients with multiple myeloma (MM). A quantitative polymerase chain reaction assay involving CDR3-specific primers based on the method of limiting dilutions was used to determine the tumor loads of LPs. Sixteen LPs from eight patients with MM were analyzed intraindividually in matched pairs. The percentage of malignant cells was lower in LP-CY (p = 0.017; median 0.0067 vs. 0.009%), whereas the number of CD34+ cells was higher (p = 0.012; median 0.3 vs. 0.095%). The calculated number of malignant cells per CD34+ cell was significantly lower in LP-CY as well (p = 0.017). We conclude that mobilization by cyclophosphamide plus G-CSF leads to a lower number of malignant cells per CD34+ cell in LPs compared with G-CSF alone.
高剂量外周血干细胞(PBSCs)自体移植疗法已成为一种被认可的治疗方式。然而,针对急性髓系白血病和神经母细胞瘤患者的基因标记研究显示,与白细胞分离产物(LPs)一起回输的恶性细胞会导致复发。因此,减少自体移植物中恶性细胞的数量是很有必要的。我们分析了多发性骨髓瘤(MM)患者中,单独使用粒细胞集落刺激因子(G-CSF)动员的LPs(LP-S)与高剂量环磷酰胺加G-CSF动员的LPs(LP-CY)中恶性细胞的百分比以及CD34+ PBSCs的数量。采用基于有限稀释法的涉及CDR3特异性引物的定量聚合酶链反应测定法来确定LPs的肿瘤负荷。对8例MM患者的16份LPs进行个体内配对分析。LP-CY中恶性细胞的百分比更低(p = 0.017;中位数0.0067%对0.009%),而CD34+细胞的数量更高(p = 0.012;中位数0.3对0.095%)。计算得出的每个CD34+细胞中恶性细胞的数量在LP-CY中也显著更低(p = 0.017)。我们得出结论,与单独使用G-CSF相比,环磷酰胺加G-CSF动员导致LPs中每个CD34+细胞的恶性细胞数量更低。