Brandwein J M, Nayar R, Baker M A, Sutton D M, Scott J G, Sutcliffe S B, Keating A
University of Toronto Autologous Bone Marrow Transplant Program, Toronto Hospital, Ontario, Canada.
Exp Hematol. 1991 Mar;19(3):191-5.
Based on previous observations that granulocyte-macrophage colony-stimulating factor (GM-CSF) promotes granulocyte recovery following chemotherapy, we evaluated the effect of recombinant human GM-CSF on hematopoietic progenitors and clinical outcome in six patients with delayed engraftment (greater than 55 days) after high-dose therapy and autologous bone marrow transplantation (ABMT). Three patients responded to a 14-day course of GM-CSF (10 micrograms/kg body weight/day) with at least a sevenfold rise in circulating granulocytes and a corresponding increase in granulopoietic activity in the bone marrow. A fourth patient died of infection on the 8th day of GM-CSF therapy with no evidence of response, and the remaining two, one of whom received a lower dose of GM-CSF (5 micrograms/kg/day), did not respond. There was no change in platelet or red cell transfusion requirements in any patient during the treatment. In two of the three responders, the granulocyte counts returned to pretreatment levels by 4 and 7 weeks after stopping the drug, respectively. We observed a marked increase in marrow-derived as well as in circulating granulocyte-macrophage progenitors (granulocyte-macrophage colony-forming units, CFU-GM) by the end of the 14-day course of GM-CSF in the three responders. There was no change in the frequency of circulating or marrow-derived erythroid (erythroid burst-forming units, BFU-E) or multilineage (multilineage colony-forming units, CFU-GEMM) progenitors. The results indicate that GM-CSF therapy in patients with markedly delayed engraftment after ABMT may stimulate granulopoiesis, but the effect is transient in some patients.
基于先前的观察结果，即粒细胞巨噬细胞集落刺激因子（GM-CSF）可促进化疗后粒细胞的恢复，我们评估了重组人GM-CSF对6例大剂量治疗及自体骨髓移植（ABMT）后植入延迟（超过55天）患者的造血祖细胞及临床结局的影响。3例患者接受了为期14天的GM-CSF治疗（10微克/千克体重/天），循环粒细胞至少升高了7倍，骨髓中的粒细胞生成活性相应增加。第4例患者在GM-CSF治疗的第8天死于感染，无反应迹象，其余2例患者，其中1例接受了较低剂量的GM-CSF（5微克/千克/天），未出现反应。治疗期间，所有患者的血小板或红细胞输注需求均未改变。在3例有反应的患者中，有2例在停药后4周和7周时粒细胞计数分别恢复到治疗前水平。我们观察到，在3例有反应的患者中，GM-CSF治疗14天疗程结束时，骨髓来源以及循环中的粒细胞巨噬细胞祖细胞（粒细胞巨噬细胞集落形成单位，CFU-GM）显著增加。循环或骨髓来源的红系祖细胞（红系爆式集落形成单位，BFU-E）或多系祖细胞（多系集落形成单位，CFU-GEMM）的频率没有变化。结果表明，ABMT后植入明显延迟的患者接受GM-CSF治疗可能会刺激粒细胞生成，但在一些患者中这种作用是短暂的。
