Elias A D, Ayash L, Anderson K C, Hunt M, Wheeler C, Schwartz G, Tepler I, Mazanet R, Lynch C, Pap S
Department of Medicine, Dana-Farber Cancer Institute, Boston, MA.
Blood. 1992 Jun 1;79(11):3036-44.
High-dose therapy with autologous marrow support results in durable complete remissions in selected patients with relapsed lymphoma and leukemia who cannot be cured with conventional dose therapy. However, substantial morbidity and mortality result from the 3- to 6-week period of marrow aplasia until the reinfused marrow recovers adequate hematopoietic function. Hematopoietic growth factors, particularly used after chemotherapy, can increase the number of peripheral blood progenitor cells (PBPCs) present in systemic circulation. The reinfusion of PBPCs with marrow has recently been reported to reduce the time to recovery of adequate marrow function. This study was designed to determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPCs alone (without marrow) would result in rapid and reliable hematopoietic reconstitution. Sixteen patients with metastatic breast cancer were treated with four cycles of doxorubicin, 5-fluorouracil, and methotrexate (AFM induction). Patients responding after the first two cycles were administered GM-CSF after the third and fourth cycles to recruit PBPCs for collection by two leukapheresis per cycle. These PBPCs were reinfused as the sole source of hematopoietic support after high doses of cyclophosphamide, thiotepa, and carboplatin. No marrow or hematopoietic cytokines were used after progenitor cell reinfusion. Granulocytes greater than or equal to 500/microL was observed on a median of day 14 (range, 8 to 57). Transfusion independence of platelets greater than or equal to 20,000/microL occurred on a median day of 12 (range, 8 to 134). However, three patients required the use of a reserve marrow for slow platelet engraftment. In retrospect, these patients were characterized by poor baseline bone marrow cellularity and poor platelet recovery after AFM induction therapy. When compared with 29 historical control patients who had received the same high-dose intensification chemotherapy using autologous marrow support, time to engraftment, antibiotic days, transfusion requirements, and lengths of hospital stay were all significantly improved for the patients receiving PBPCs. Thus, autologous PBPCs can be efficiently collected during mobilization by chemotherapy and GM-CSF and are an attractive alternative to marrow for hematopoietic support after high-dose therapy. The enhanced speed of recovery may reduce the morbidity, mortality, and cost of high-dose treatment. Furthermore, PBPC support may enhance the effectiveness of high-dose therapy by facilitating multiple courses of therapy.
对于某些复发的淋巴瘤和白血病患者，传统剂量治疗无法治愈，而采用自体骨髓支持的高剂量治疗可使其获得持久的完全缓解。然而，在重新输注的骨髓恢复足够的造血功能之前，会有3至6周的骨髓再生障碍期，这会导致相当高的发病率和死亡率。造血生长因子，特别是在化疗后使用时，可增加全身循环中存在的外周血祖细胞（PBPC）数量。最近有报道称，将PBPC与骨髓一起重新输注可缩短骨髓功能恢复的时间。本研究旨在确定单独使用粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）动员的PBPC（不使用骨髓）是否会导致快速且可靠的造血重建。16例转移性乳腺癌患者接受了四个周期的阿霉素、5 - 氟尿嘧啶和甲氨蝶呤治疗（AFM诱导）。在前两个周期有反应的患者在第三和第四周期后给予GM - CSF，以募集PBPC，每个周期通过两次白细胞分离术进行采集。这些PBPC在大剂量环磷酰胺、噻替派和卡铂治疗后作为唯一的造血支持来源进行重新输注。祖细胞重新输注后未使用骨髓或造血细胞因子。在第14天（范围为8至57天）的中位数时观察到粒细胞≥500/μL。血小板≥20,000/μL时无需输血的情况在第12天（范围为8至134天）的中位数时出现。然而，有3例患者需要使用备用骨髓以促进血小板缓慢植入。回顾来看，这些患者的特点是基线骨髓细胞计数低以及AFM诱导治疗后血小板恢复不佳。与29例接受相同高剂量强化化疗并使用自体骨髓支持的历史对照患者相比，接受PBPC的患者在植入时间、抗生素使用天数、输血需求和住院时间方面均有显著改善。因此，自体PBPC可在化疗和GM - CSF动员期间有效采集，并且是高剂量治疗后造血支持的一种有吸引力的骨髓替代物。恢复速度的加快可能会降低高剂量治疗的发病率、死亡率和成本。此外，PBPC支持可能通过促进多疗程治疗来提高高剂量治疗的有效性。
