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环磷酰胺和粒细胞巨噬细胞集落刺激因子动员后采用单次大容量白细胞分离术进行外周血祖细胞采集的预测因素

Predictive factors for peripheral-blood progenitor-cell collections using a single large-volume leukapheresis after cyclophosphamide and granulocyte-macrophage colony-stimulating factor mobilization.

作者信息

Passos-Coelho J L, Braine H G, Davis J M, Huelskamp A M, Schepers K G, Ohly K, Clarke B, Wright S K, Noga S J, Davidson N E

机构信息

Johns Hopkins Oncology Center, Baltimore, MD 21287.

出版信息

J Clin Oncol. 1995 Mar;13(3):705-14. doi: 10.1200/JCO.1995.13.3.705.

Abstract

PURPOSE

(1) To study the ability of mobilized peripheral-blood progenitor cells (PBPC) collected in a single large-volume leukapheresis performed on a predetermined date to accelerate engraftment after high-dose cyclophosphamide and thiotepa; (2) to establish the minimum dose of PBPC associated with early engraftment; and (3) to identify parameters predictive of collection of large numbers of PBPC.

PATIENTS AND METHODS

Twenty-three patients with breast cancer received cyclophosphamide (4 g/m2) and granulocyte-macrophage colony-stimulating factor ([GM-CSF] 5 micrograms/kg/d x 15 days) for PBPC mobilization. A single leukapheresis was performed 15 days after cyclophosphamide administration. Then, patients received high-dose cyclophosphamide and thiotepa followed by reinfusion of PBPC and 4-hydroperoxycyclophosphamide (4HC)-purged bone marrow. PBPC concentration was measured in serial peripheral-blood samples and in the leukapheresis product. Correlation analysis between PBPC dose and engraftment and between leukapheresis yield and patient characteristics was attempted.

RESULTS

A single leukapheresis processed a median 36 L (range, 24 to 46) blood and collected 5 x 10(6) CD34+ cells/kg (< 0.3 to 24) and 6.2 x 10(5) colony-forming units granulocyte-macrophage (CFU-GM)/kg (< 0.001 to 29). All sixteen patients (70%) reinfused with > or = 2.9 x 10(6) CD34+ cells/kg reached a level of greater than 1,000 leukocytes/microL by day 13 and greater than 50,000 platelets/microL by day 15. All of these patients had a percentage of peripheral-blood CD34+ cells > or = 0.5%, and all but one, a level of greater than 100,000 platelets/microL, on the day of leukapheresis. The bone marrow CD34+ cell percentage at study entry predicted the number of CD34+ cells collected after PBPC mobilization (R2 = .42, P = .002). All patients with > or = 2.5% bone marrow CD34+ cells experienced early engraftment.

CONCLUSION

Reinfusion of PBPC collected in a single leukapheresis accelerates engraftment in the majority of patients. Pretreatment bone marrow CD34+ cell content determines PBPC mobilization capacity and may help select hematopoietic rescue strategies.

摘要

目的

(1)研究在预定日期进行的单次大容量白细胞分离术中采集的动员外周血祖细胞(PBPC)加速大剂量环磷酰胺和塞替派后植入的能力;(2)确定与早期植入相关的PBPC最低剂量;(3)识别预测大量PBPC采集的参数。

患者与方法

23例乳腺癌患者接受环磷酰胺(4 g/m²)和粒细胞-巨噬细胞集落刺激因子([GM-CSF]5μg/kg/d×15天)以动员PBPC。在给予环磷酰胺15天后进行单次白细胞分离术。然后,患者接受大剂量环磷酰胺和塞替派,随后回输PBPC和经4-氢过氧环磷酰胺(4HC)净化的骨髓。在系列外周血样本和白细胞分离术产物中测量PBPC浓度。尝试分析PBPC剂量与植入之间以及白细胞分离术产量与患者特征之间的相关性。

结果

单次白细胞分离术处理的血液中位数为36 L(范围24至46),采集到5×10⁶个CD34⁺细胞/kg(<0.3至24)和6.2×10⁵个粒细胞-巨噬细胞集落形成单位(CFU-GM)/kg(<0.001至29)。所有16例回输≥2.9×10⁶个CD34⁺细胞/kg的患者在第13天白细胞计数达到>1000/μL,在第15天血小板计数达到>50000/μL。所有这些患者在外周血CD34⁺细胞百分比≥0.5%,且除1例患者外,在白细胞分离术当天血小板计数均>100000/μL。研究开始时骨髓CD34⁺细胞百分比可预测PBPC动员后采集的CD34⁺细胞数量(R² = 0.42,P = 0.002)。所有骨髓CD34⁺细胞≥2.5%的患者均实现早期植入。

结论

单次白细胞分离术采集的PBPC回输可加速大多数患者的植入。预处理骨髓CD34⁺细胞含量决定PBPC动员能力,并可能有助于选择造血挽救策略。

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