Baer M R, Christiansen N P, Frankel S R, Brunetto V L, Mrózek K, Bloomfield C D, Herzig G P
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263.
Semin Oncol. 1993 Dec;20(6 Suppl 8):6-12.
This report describes the preliminary results of the remission induction phase of a protocol for previously untreated de novo and secondary acute myeloid leukemia (AML) designed to deliver very intensive therapy over a brief period of time using hematopoietic growth factor support. Remission induction therapy consisted of cytarabine 3 g/m2 (1.5 g/m2 for age > 50 years) intravenously over 1 hour every 12 hours for 12 doses and idarubicin 12 mg/m2 over 30 minutes on days 2, 3, and 4 of cytarabine, followed by 10 micrograms/kg granulocyte colony-stimulating factor subcutaneously daily until the absolute neutrophil count increased to > or = 5.0 x 10(9)/L on 2 consecutive days. Twenty-seven patients received all the planned doses of chemotherapy. The complete remission (CR) rate to a single course of therapy was 65% in 20 patients with de novo AML (median age, 60.5 years; age range, 26 to 78 years); for those aged less than 60 and > or = 60 years, the CR rates were 90% and 40%, respectively. In contrast, only two of 10 patients with secondary AML (median age, 68 years; age range, 35 to 77 years) achieved a CR. The median time from initiation of chemotherapy to recovery of 0.5 x 10(9)/L neutrophils in de novo AML patients achieving CR was 20 days (range, 18 to 23 days). Median times to last platelet transfusion and to 100 x 10(9)/L platelet count were 23 days (range, 18 to 41 days) and 28 days (range, 24 to 97 days), respectively. The major nonhematologic toxicity was transient hyperbilirubinemia, which was observed in 64% of patients. Reversible cerebellar toxicity was seen in three patients. Thus, idarubicin at full dose (12 mg/m2 x 3 days) may be safely administered with high-dose cytarabine, even in elderly patients. The use of granulocyte colony-stimulating factor is associated with rapid neutrophil recovery without obvious toxicity. The CR rate for de novo AML patients treated with a single course of high-dose cytarabine, idarubicin, and granulocyte colony-stimulating factor is at least comparable to CR rates achieved with standard-dose cytarabine and anthracycline regimens. The response of secondary AML patients remains inferior.
本报告描述了一项针对既往未经治疗的初发和继发性急性髓系白血病（AML）方案缓解诱导期的初步结果，该方案旨在使用造血生长因子支持在短时间内进行非常强化的治疗。缓解诱导治疗包括阿糖胞苷3 g/m²（年龄>50岁者为1.5 g/m²），每12小时静脉输注1小时，共12剂，以及在阿糖胞苷治疗的第2、3和4天，伊达比星12 mg/m²静脉输注30分钟，随后每日皮下注射10 μg/kg粒细胞集落刺激因子，直至绝对中性粒细胞计数连续2天升至≥5.0×10⁹/L。27例患者接受了所有计划剂量的化疗。20例初发AML患者（中位年龄60.5岁；年龄范围26至78岁）接受单疗程治疗后的完全缓解（CR）率为65%；年龄小于60岁和≥60岁者的CR率分别为90%和40%。相比之下，10例继发性AML患者（中位年龄68岁；年龄范围35至77岁）中只有2例达到CR。初发AML患者达到CR后，从开始化疗到中性粒细胞恢复至0.5×10⁹/L的中位时间为20天（范围18至23天）。最后一次血小板输注的中位时间和血小板计数达到100×10⁹/L的中位时间分别为23天（范围18至41天）和28天（范围24至97天）。主要的非血液学毒性是短暂性高胆红素血症，64%的患者出现该症状。3例患者出现可逆性小脑毒性。因此，即使在老年患者中，全剂量（12 mg/m²×3天）伊达比星与大剂量阿糖胞苷联合使用可能是安全的。使用粒细胞集落刺激因子可使中性粒细胞快速恢复且无明显毒性。接受单疗程大剂量阿糖胞苷、伊达比星和粒细胞集落刺激因子治疗的初发AML患者的CR率至少与标准剂量阿糖胞苷和蒽环类方案所达到的CR率相当。继发性AML患者的反应仍然较差。
