Haas R, Ho A D, Del Valle F, Fischer J T, Ehrhardt R, Döhner H, Witt B, Huberts H, Kaplan E, Hunstein W
Department of Internal Medicine, University of Heidelberg, Germany.
Semin Oncol. 1993 Dec;20(6 Suppl 8):20-6.
Since January 1989, 56 patients (31 females and 25 males) with de novo acute myelogenous leukemia have been included in the study. Their median age was 43 years (range, 15 to 60 years) with a distribution according to French-American-British morphologic subtypes as follows: six M1, 14 M2, four M3, 19 M4, nine M5, two M6, and two M7. The induction regimen (IDAC) consisted of idarubicin (12 mg/m2/d intravenously [IV] days 1 to 3) in combination with cytarabine (100 mg/m2/d continuous IV days 1 to 7). Patients achieving complete remission (CR) or partial remission received another cycle of IDAC followed by NOVE (mitoxantrone 10 mg/m2/d IV days 1 to 5 and etoposide 100 mg/m2/d IV days 1 to 5). Fifty-four patients are evaluable for response: after two cycles of IDAC, 42 patients had attained CR (78%), while 76% of these had already reached CR after the first cycle. Of the initial 11 nonresponders to IDAC, four obtained CR after NOVE. Thus, 46 of 54 patients (85%) achieved CR after sequential treatment with IDAC and NOVE. In the last 17 patients who entered CR or partial remission after the first cycle of IDAC, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; 3 micrograms/kg/d) was administered for 6 days starting 3 days prior to the second cycle of IDAC. For consolidation with NOVE, rhGM-CSF was given according to the same dosage schedule. After 72 hours of rhGM-CSF treatment, the white blood cell count showed a median 3.9-fold increase, without appearance of myeloblasts in the peripheral blood. During sequential chemotherapy, no significant complications (in particular, no major cardiac toxicity) were observed. Postremission, patients were either given bone marrow transplants, received late consolidation with high-dose cytarabine/mitoxantrone, or were followed up without any further treatment. Of the 46 patients evaluable for disease-free survival, 21 patients (45%) remain in CR with a 34% probability of disease-free survival at 37 months. The response-adapted treatment with IDAC/NOVE is effective and very well tolerated. To define the therapeutic impact of rhGM-CSF, a randomized trial will be required.
自1989年1月起，56例初发急性髓性白血病患者（31例女性，25例男性）被纳入本研究。他们的中位年龄为43岁（范围15至60岁），按照法美英形态学亚型分布如下：M1型6例，M2型14例，M3型4例，M4型19例，M5型9例，M6型2例，M7型2例。诱导方案（IDAC）由伊达比星（12mg/m²/d静脉注射[IV]，第1至3天）联合阿糖胞苷（100mg/m²/d持续静脉滴注，第1至7天）组成。达到完全缓解（CR）或部分缓解的患者接受另一周期的IDAC，随后接受NOVE方案（米托蒽醌10mg/m²/d静脉注射，第1至5天；依托泊苷100mg/m²/d静脉注射，第1至5天）。54例患者可评估疗效：经过两个周期的IDAC治疗后，42例患者达到CR（78%），其中76%的患者在第一个周期后就已达到CR。最初对IDAC无反应的11例患者中，4例在接受NOVE方案后获得CR。因此，54例患者中有46例（85%）在序贯接受IDAC和NOVE治疗后达到CR。在最初接受IDAC第一个周期治疗后进入CR或部分缓解的最后17例患者中，从IDAC第二个周期前3天开始给予重组人粒细胞巨噬细胞集落刺激因子（rhGM-CSF；3μg/kg/d），持续6天。为进行NOVE巩固治疗，rhGM-CSF按照相同的剂量方案给药。rhGM-CSF治疗72小时后，白细胞计数中位数增加3.9倍，外周血中未出现原始粒细胞。在序贯化疗期间，未观察到明显并发症（特别是无严重心脏毒性）。缓解期后，患者要么接受骨髓移植，要么接受大剂量阿糖胞苷/米托蒽醌的晚期巩固治疗，要么不进行任何进一步治疗而接受随访。在可评估无病生存的46例患者中，21例患者（45%）仍处于CR状态，37个月时无病生存概率为34%。IDAC/NOVE的适应性治疗有效且耐受性良好。为明确rhGM-CSF的治疗效果，需要进行一项随机试验。
