Elias A D, Ayash L, Tepler I, Wheeler C, Schwartz G, Mazanet R, Schnipper L, Frei E, Antman K
Dana Farber Cancer Institute, Harvard Medical School, Boston, MA 02115.
J Hematother. 1993 Fall;2(3):377-82. doi: 10.1089/scd.1.1993.2.377.
High dose chemotherapy with autologous bone marrow support (ABMT) can achieve prolonged relapse-free survival in relapsed lymphomas, leukemias, and certain solid tumors. The principal morbidity and mortality relate to the infectious complications that occur during the 3-4 week aplasia until the marrow autograft recovers. Progenitor cells can be mobilized into the peripheral blood compartment by hematopoietic growth factors, used alone or after chemotherapy. We describe four trials using cytokine-mobilized peripheral blood progenitor cells (PBPC). In the first trial, PBPC collected after GM-CSF administration were used to augment marrow. Reconstitution of trilineage marrow function occurred promptly, resulting in short hospital stays and fewer platelet transfusions. In a second study, GM-CSF/chemotherapy-mobilized PBPC were used as the sole hematopoietic support during high dose chemotherapy. Granulocyte and platelet reconstitution was rapid. Time to hematopoietic recovery, transfusion requirements, and duration of hospital stay were all significantly improved for the patients receiving PBPC compared with similar patients receiving marrow alone. While most patients experienced prompt hematopoietic recovery they showed sluggish platelet engraftment. The next two trials built on the observation that a few PBPC alone could support both granulocyte and platelet recovery and were designed to test the feasibility of sequential high-dose therapies. In one trial, PBPC given with and without marrow made it possible to deliver two sequential cycles of high-dose therapy. The second trial utilized PBPC plus cytokines to deliver four cycles of dose-intensive chemotherapy at doses that could not be given with cytokine support alone.(ABSTRACT TRUNCATED AT 250 WORDS)
大剂量化疗联合自体骨髓支持(ABMT)可使复发的淋巴瘤、白血病及某些实体瘤患者获得较长的无复发生存期。主要的发病和死亡原因与骨髓移植后3 - 4周再生障碍期发生的感染并发症有关。造血生长因子可单独使用或在化疗后使用,将祖细胞动员至外周血中。我们描述了四项使用细胞因子动员外周血祖细胞(PBPC)的试验。在第一项试验中,给予粒细胞巨噬细胞集落刺激因子(GM - CSF)后采集的PBPC用于增强骨髓功能。三系骨髓功能迅速恢复,住院时间缩短,血小板输注减少。在第二项研究中,GM - CSF/化疗动员的PBPC被用作大剂量化疗期间唯一的造血支持。粒细胞和血小板迅速恢复。与仅接受骨髓移植的类似患者相比,接受PBPC的患者造血恢复时间、输血需求和住院时间均显著改善。虽然大多数患者造血迅速恢复,但血小板植入缓慢。接下来的两项试验基于少数PBPC单独即可支持粒细胞和血小板恢复的观察结果设计,旨在测试序贯大剂量治疗的可行性。在一项试验中,给予或不给予骨髓的PBPC使得进行两个序贯大剂量治疗周期成为可能。第二项试验使用PBPC加细胞因子进行四个周期的剂量密集化疗,其剂量是单独使用细胞因子支持无法给予的。(摘要截短至250字)