Büchner T, Hiddemann W, Koenigsmann M, Zühlsdorf M, Wörmann B, Boeckmann A, Freire E A, Innig G, Maschmeyer G, Ludwig W D
Department of Hematology/Oncology, University of Münster, Germany.
Blood. 1991 Sep 1;78(5):1190-7.
To reduce critical neutropenia after chemotherapy (CT) for acute myeloid leukemia (AML) we administered recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) to patients over the age of 65 years with newly diagnosed AML and to patients with early or second relapse. CT was 9-day 6-thioguanine, ara-C, and daunorubicin (TAD9) in newly diagnosed AML and sequential high-dose ara-C and mitoxantrone (S-HAM) for relapse. In patients whose bone marrow was free from blasts a continuous intravenous infusion of GM-CSF 250 micrograms/m2/d started on day 4 after CT. Thirty-six patients entered the study and 30 of them did receive GM-CSF. For comparison, a historical control group of 56 patients was used. Complete remission rate was 50% (18 of 36) versus 32% in controls (P = .09), and early death rate was 14% versus 39% (P = .009). Treatment with GM-CSF was not associated with major adverse events. Two patients showed a marked leukemic regrowth that was completely reversible in one patient and appeared to be GM-CSF independent in the other patient. Remission duration does not seem to be reduced after GM-CSF. Under GM-CSF the blood neutrophils recovered 6 and 9 days earlier in the TAD9 (P = .009) and S-HAM (P = .043) groups associated with a rapid clearance of infections in most patients. We conclude that GM-CSF was of therapeutic benefit to our patients and this provides a basis for larger controlled trials.
为降低急性髓系白血病（AML）化疗（CT）后严重中性粒细胞减少的发生率，我们对65岁以上新诊断的AML患者以及早期或二次复发的患者给予重组人粒细胞巨噬细胞集落刺激因子（GM-CSF）。新诊断AML患者的CT方案为9天的6-硫鸟嘌呤、阿糖胞苷和柔红霉素（TAD9），复发患者采用序贯大剂量阿糖胞苷和米托蒽醌（S-HAM）。对于骨髓无原始细胞的患者，在CT后第4天开始持续静脉输注GM-CSF 250微克/平方米/天。36例患者进入研究，其中30例确实接受了GM-CSF治疗。作为对照，使用了一个由56例患者组成的历史对照组。完全缓解率为50%（36例中的18例），而对照组为32%（P = 0.09），早期死亡率为14%，而对照组为39%（P = 0.009）。GM-CSF治疗与主要不良事件无关。2例患者出现明显的白血病细胞再生，其中1例患者完全可逆，另一例患者似乎与GM-CSF无关。GM-CSF治疗后缓解期似乎并未缩短。在GM-CSF作用下，TAD9组（P = 0.009）和S-HAM组（P = 0.043）的血液中性粒细胞分别提前6天和9天恢复，大多数患者感染得以快速清除。我们得出结论，GM-CSF对我们的患者具有治疗益处，这为更大规模的对照试验提供了依据。
