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在细胞毒性化疗后给予重组人粒细胞和粒细胞巨噬细胞集落刺激因子(G-CSF和GM-CSF),它们动员外周血干细胞的能力相似。

Recombinant human granulocyte and granulocyte-macrophage colony-stimulating factor (G-CSF and GM-CSF) administered following cytotoxic chemotherapy have a similar ability to mobilize peripheral blood stem cells.

作者信息

Hohaus S, Martin H, Wassmann B, Egerer G, Haus U, Färber L, Burger K J, Goldschmidt H, Hoelzer D, Haas R

机构信息

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

出版信息

Bone Marrow Transplant. 1998 Oct;22(7):625-30. doi: 10.1038/sj.bmt.1701422.

Abstract

The availability of hematopoietic growth factors has greatly facilitated the mobilization and collection of peripheral blood stem cells (PBSC). It was the aim of this double-blind study to compare the PBSC-mobilizing efficacy of recombinant human G-CSF and GM-CSF when administered post-chemotherapy. Twenty-six patients with relapsed Hodgkin's disease were included in the study. Their median age was 31 years (range, 22-59) and 14 patients were males and 12 were females. Patients were pretreated with a median of eight cycles of cytotoxic chemotherapy, while 18 patients had undergone extended field irradiation. The patients received dexamethasone 24 mg days 1-7, melphalan 30 mg/m2 day 3, BCNU 60 mg/m2 day 3, etoposide 75 mg/m2 days 4-7, Ara-C 100 mg/m2 twice daily days 4-7 (Dexa-BEAM). Twelve patients were randomized to receive 5/microg/kg/day G-CSF and 14 patients to receive 5 microg/kg/day GM-CSF, both administered subcutaneously starting on day 1 after the end of Dexa-BEAM. Primary endpoints of the study were the number of CD34+ cells harvested per kg body weight on the occasion of six consecutive leukaphereses and the time needed for hematological reconstitution following autografting. Twenty-one patients completed PBSC collection, and six patients of the G-CSF group and nine of the GM-CSF group were autografted. No difference was observed with respect to the median yield of CFU-GM and CD34+ cells: 32.5 x 10(4)/kg vs 31.3 x 10(4)/kg CFU-GM, and 7.6 x 10(6)/kg vs 5.6 x 10(6)/kg CD34+ cells, for G-CSF and GM-CSF, respectively (U test, P= 0.837 and 0.696). High-dose chemotherapy consisted of cyclophosphamide 1.7 g/m2 days 1-4, BCNU 150 mg/m2 days 1-4, etoposide 400 mg/m2 days 1-4. All patients transplanted with more than 5 x 10(6) CD34+ cells/kg had a rapid platelet recovery (20 x 10(9)/l) between 6 and 11 days and neutrophil recovery (0.5 x 10(9)/1) between 9 and 16 days, while patients transplanted with less than 5 x 10(6)/kg had a delayed reconstitution, regardless of the kind of growth factor used for PBSC mobilization. In conclusion, our data indicate that in patients with Hodgkin's disease G-CSF and GM-CSF given after salvage chemotherapy appear to be not different in their ability to mobilize PBSC resulting in a similar time needed for hematological reconstitution when autografted following high-dose therapy.

摘要

造血生长因子的可获得性极大地促进了外周血干细胞(PBSC)的动员和采集。本双盲研究的目的是比较化疗后给予重组人粒细胞集落刺激因子(G-CSF)和粒细胞-巨噬细胞集落刺激因子(GM-CSF)对PBSC的动员效果。26例复发性霍奇金淋巴瘤患者纳入本研究。他们的中位年龄为31岁(范围22 - 59岁),男性14例,女性12例。患者接受了中位8个周期的细胞毒性化疗预处理,其中18例患者接受了扩大野照射。患者在第1 - 7天接受地塞米松24mg、第3天接受美法仑30mg/m²、第3天接受卡莫司汀(BCNU)60mg/m²、第4 - 7天接受依托泊苷75mg/m²、第4 - 7天接受阿糖胞苷(Ara-C)100mg/m²每日2次(Dexa - BEAM方案)。12例患者随机接受5μg/kg/天的G-CSF,14例患者接受5μg/kg/天的GM-CSF,均在Dexa - BEAM方案结束后的第1天开始皮下注射。本研究的主要终点是连续6次白细胞单采时每千克体重采集的CD34⁺细胞数量以及自体移植后血液学重建所需的时间。21例患者完成了PBSC采集,G-CSF组6例患者和GM-CSF组9例患者进行了自体移植。在CFU - GM和CD34⁺细胞的中位产量方面未观察到差异:G-CSF组和GM-CSF组的CFU - GM分别为32.5×10⁴/kg对31.3×10⁴/kg,CD34⁺细胞分别为7.6×10⁶/kg对5.6×10⁶/kg(U检验,P = 0.837和0.696)。大剂量化疗包括第1 - 4天给予环磷酰胺1.7g/m²、第1 - 4天给予BCNU 150mg/m²、第1 - 4天给予依托泊苷400mg/m²。所有移植的CD34⁺细胞超过5×10⁶/kg的患者在6至11天内血小板快速恢复(≥20×10⁹/L),在9至16天内中性粒细胞恢复(≥0.5×10⁹/L),而移植的CD34⁺细胞低于5×10⁶/kg的患者血液学重建延迟,无论用于PBSC动员的生长因子类型如何。总之,我们的数据表明,在霍奇金淋巴瘤患者中,挽救性化疗后给予G-CSF和GM-CSF在动员PBSC的能力方面似乎没有差异,在大剂量治疗后自体移植时血液学重建所需时间相似。

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