Damon Lloyd, Rugo Hope, Tolaney Sara, Navarro Willis, Martin Thomas, Ries Curt, Case Delvyn, Ault Kenneth, Linker Charles
University of California, San Francisco, San Francisco, California 94143-0324, USA.
Biol Blood Marrow Transplant. 2006 Mar;12(3):316-24. doi: 10.1016/j.bbmt.2005.10.021.
We evaluated the efficiency of high doses of cyclophosphamide (6 g/m2) and etoposide (2 g/m2) plus filgrastim (granulocyte colony-stimulating factor; G-CSF) to mobilize autologous hematopoietic progenitor cells in patients with non-Hodgkin lymphoma, multiple myeloma, and Waldenström macroglobulinemia. We also evaluated the safety of this regimen and the engraftment kinetics after myeloablative chemotherapy. Seventy-nine patients with high-risk or relapsed/primary refractory non-Hodgkin lymphoma, multiple myeloma, or Waldenström macroglobulinemia were treated. The mobilizing regimen was as follows: cyclophosphamide 600 mg/m2 twice daily for 10 doses, etoposide 200 mg/m2 twice daily for 10 doses (continuous; n=57) or 2 g/m2 over 10 hours on day 5 of etoposide (bolus; n=22), and G-CSF 5 microg/kg/d beginning day 14. Fifty-nine percent of patients achieved the primary end point (a CD34 cell dose of 5 million per kilogram with a single leukapheresis). More bolus etoposide patients achieved the primary end point (86%) compared with continuous etoposide patients (47%; P<.0001). The CD34 cell dose collected was greater in bolus etoposide patients (44 million per kilogram) than in continuous etoposide patients (10.9 million per kilogram; P<.0001). Patients took 3 weeks to recover >500/microL neutrophils and >20000/microL platelets after cyclophosphamide and etoposide. The overall response rate was 69% for non-Hodgkin lymphoma patients and 71% for multiple myeloma/Waldenström macroglobulinemia patients. The treatment-related mortality was 2.5%. Sixteen percent of surviving patients experienced grade>or=3 nonhematologic toxicity. Patients receiving bolus etoposide had significantly less grade>or=2 oral mucositis, less use of total parenteral nutrition, and less need for red blood cell and platelet transfusions. Sixty-four patients (81%) underwent autologous hematopoietic progenitor cell transplantation, with prompt engraftment. Four patients (5%) did not undergo autologous hematopoietic progenitor cell transplantation because of toxicity from high-dose cyclophosphamide and etoposide. We conclude that high doses of cyclophosphamide and etoposide combined with G-CSF are an efficient and safe mobilizing regimen for the collection of hematopoietic progenitor cells during aggressive cytoreduction of tumor burden in patients with lymphoid malignancies.
我们评估了大剂量环磷酰胺（6 g/m²）、依托泊苷（2 g/m²）加非格司亭（粒细胞集落刺激因子；G-CSF）用于动员非霍奇金淋巴瘤、多发性骨髓瘤和华氏巨球蛋白血症患者自体造血祖细胞的效果。我们还评估了该方案的安全性以及清髓性化疗后的植入动力学。79例高危或复发/原发难治性非霍奇金淋巴瘤、多发性骨髓瘤或华氏巨球蛋白血症患者接受了治疗。动员方案如下：环磷酰胺600 mg/m²，每日2次，共10剂；依托泊苷200 mg/m²，每日2次，共10剂（持续给药；n = 57）或在依托泊苷第5天10小时内给予2 g/m²（大剂量给药；n = 22），从第14天开始给予G-CSF 5 μg/kg/d。59%的患者达到主要终点（单次白细胞分离术采集的CD34细胞剂量为每千克500万）。与持续给予依托泊苷的患者（47%；P<0.0001）相比，更多接受大剂量依托泊苷的患者达到主要终点（86%）。大剂量依托泊苷患者采集的CD34细胞剂量（每千克4400万）高于持续给予依托泊苷的患者（每千克1090万；P<0.0001）。环磷酰胺和依托泊苷治疗后，患者需3周时间才能使中性粒细胞恢复至>500/μL、血小板恢复至>20000/μL。非霍奇金淋巴瘤患者的总体缓解率为69%，多发性骨髓瘤/华氏巨球蛋白血症患者为71%。治疗相关死亡率为2.5%。16%的存活患者出现≥3级非血液学毒性。接受大剂量依托泊苷的患者≥2级口腔黏膜炎明显较少，全胃肠外营养的使用较少，红细胞和血小板输注需求也较少。64例患者（81%）接受了自体造血祖细胞移植，植入迅速。4例患者（5%）因大剂量环磷酰胺和依托泊苷的毒性未接受自体造血祖细胞移植。我们得出结论，在对淋巴恶性肿瘤患者进行积极的肿瘤负荷细胞减灭期间，大剂量环磷酰胺和依托泊苷联合G-CSF是一种有效且安全的造血祖细胞采集动员方案。
