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大剂量环磷酰胺(4或7 g/m²)联合粒细胞集落刺激因子动员多发性骨髓瘤患者外周血祖细胞。

Mobilization of peripheral blood progenitor cells with high-dose cyclophosphamide (4 or 7 g/m2) and granulocyte colony-stimulating factor in patients with multiple myeloma.

作者信息

Goldschmidt H, Hegenbart U, Haas R, Hunstein W

机构信息

Department of Internal Medicine V, University of Heidelberg, Germany.

出版信息

Bone Marrow Transplant. 1996 May;17(5):691-7.

PMID:8733683
Abstract

High-dose cyclophosphamide (HD-CY) has been shown to decrease the tumor mass in multiple myeloma (MM) patients and to be effective in the mobilization of PBPC. By administering hematopoietic growth factor the quantity of progenitor cells in the peripheral blood increased and the hematological toxicity of CY could be reduced. Thirty-two patients with stage II and stage III MM were treated to mobilize and harvest a sufficient amount of PBPC for autologous transplantation. Sixteen patients received 4 g/m2 CY and 16 patients 7 g/m2 CY in divided doses of 1 g/m2 every 2 h. Both patient groups were comparable for disease stages as well as previous therapies. Twenty-four hours after chemotherapy 300 micrograms GCSF were administered subcutaneously once daily until the last day of leukapheresis. Administration of 7 g/m2 HD-CY resulted in statistically significantly higher peak values for CD34+ progenitor cells (47.86/microliters vs 18.75/microliters, P = 0.0198) in the peripheral blood. PBPC autografts containing > 2.5 x 10(6) CD34+ cells/kg BW could be obtained at the first attempt from 14 of 16 patients treated with 7 g/m2 CY as compared to 10 of 16 patients treated with 4 g/m2 CY (P = 0.11). The analysis of potentially malignant CD19+ B cells showed a highly significant lower mean CD19+ cell content/kg BW per leukapheresis in the 7 g/m2 compared to the 4 g/m2 CY group (0.75 vs 1.81 x 10(6), P = 0.001). WHO grade IV treatment-related non-hematologic toxicity was not observed. We prefer the 7 g/m2 CY dosage followed by cytokine administration for the mobilization of PBPC in advanced state MM patients pretreated with alkylating agents.

摘要

大剂量环磷酰胺(HD - CY)已被证明可减少多发性骨髓瘤(MM)患者的肿瘤体积,并有效动员外周血祖细胞(PBPC)。通过给予造血生长因子,外周血中祖细胞数量增加,且环磷酰胺的血液学毒性可降低。32例II期和III期MM患者接受治疗,以动员和采集足够数量的PBPC用于自体移植。16例患者接受4 g/m²环磷酰胺,16例患者接受7 g/m²环磷酰胺,每2小时分剂量给予1 g/m²。两组患者在疾病分期以及既往治疗方面具有可比性。化疗后24小时,皮下注射300微克粒细胞集落刺激因子(GCSF),每日1次,直至白细胞分离术的最后一天。给予7 g/m² HD - CY导致外周血中CD34⁺祖细胞的峰值在统计学上显著更高(47.86/微升 vs 18.75/微升,P = 0.0198)。接受7 g/m²环磷酰胺治疗的16例患者中有14例在首次尝试时可获得每千克体重含> 2.5×10⁶个CD34⁺细胞的PBPC自体移植物,而接受4 g/m²环磷酰胺治疗的16例患者中有10例(P = 0.11)。对潜在恶性CD19⁺ B细胞的分析显示,与4 g/m²环磷酰胺组相比,7 g/m²环磷酰胺组每次白细胞分离术每千克体重的平均CD19⁺细胞含量显著更低(0.75 vs 1.81×10⁶,P = 0.001)。未观察到世界卫生组织(WHO)IV级治疗相关非血液学毒性。对于接受烷化剂预处理的晚期MM患者,我们更倾向于采用7 g/m²环磷酰胺剂量随后给予细胞因子来动员PBPC。

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