含高三尖杉酯碱的预激方案诱导治疗高危MDS或MDS转化为AML的疗效及其与CAG、HA方案的比较

Efficacy of Induction Chemotherapy for Patients with High-risk Myelodysplastic Syndrome(MDS) or MDS-transformed Acute Myeloid Leukemia with CHG Regimen and Its Comparison with Regimen GAG and HA

本研究旨在探讨高三尖杉酯碱(HHT)、阿糖胞苷(Ara-C)合并使用粒细胞集落刺激因子(G-CSF)的低强度化疗方案(CHG方案)对高危骨髓增生异常综合征(MDS)或MDS转化的急性髓细胞白血病(AML)的疗效。30例未接受过化疗的高危MDS或MDS转化的AML患者入选CHG方案组,HHT和Ara-C每天1mg和25mg分别静脉滴注,连续14天,G-CSF300μg每天1次皮下注射,于化疗前12小时开始,持续使用至化疗结束或外周血白细胞计数>20×109/L。使用本方案1疗程后若取得完全缓解(CR),则给予常规化疗方案巩固并强化。33例高危MDS患者和MDS转化的AML患者入选CAG方案组,阿克拉霉素(Acla)每天10mg,连续8天,Ara-C每天25mg,连续14天,分别静脉滴注,G-CSF用法用量,同CHG方案。33例高危MDS和MDS转化的AML患者入选HA方案组,HHT每天2-3mg,Ara-C每天100-150mg,分别静脉滴注,连续7天。外周血白细胞计数<4×109/L时,给以G-CSF,白细胞计数>4×109/L时停用。结果表明:(1)CHG方案组1疗程后14例患者达到CR(46.67%),7例患者达到部分缓解(PR)(23.33%),总有效率为70%。CAG方案组1疗程后14例CR(42.4%),9例PR(27.3%),总有效率69.7%。HA方案组1疗程后11例CR(33.3%),3例PR(9.1%),总有效率42.4%。经统计学检验,CHG与CAG方案组比较p>0.05,CHG与HA方案组比较p<0.05。(2)30例接受CHG诱导的患者在治疗期间发生粒细胞缺乏的比例为40%(12例),平均持续时间8天,无治疗相关死亡发生。(3)14例经CHG方案1疗程取得CR病人,1人失访,其他9例复发。平均复发时间为8.2月;复发者再重复使用该方案未能取得再次缓解。(4)CHG方案组中14例CR患者中除1例失访外,6例仅接受HA/DA方案巩固及强化,已全部复发,平均CR持续时间6.1个月。另外7名患者除接受HA/DA方案外,还交替接受AA/TA/MA/IA等方案巩固及强化,平均CR时间已达10.6月,仍有4例处于持续缓解中。结论:CHG方案能取得较高的1疗程缓解率,与CAG方案相仿,高于HA方案。CHG方案骨髓抑制较轻,临床应用较安全。但取得CR后应加强巩固/强化治疗,避免早期复发。

This study was aimed to investigate the efficacy of moderate intensity regimen, CHG （homoharringtonine, cytarabine and granulocyte colony-stimulating factor （G-CSF） ） on the patients with high-risk MDS or MDS-transformed acute myeloid leukemia. 30 newly diagnosed adult patients with high-risk MDS or MDS-transformed AML were enrolled in this clinical trial to evaluate the efficacy of sequential low-dose homoharringtonine / cytarabine chemotherapy combined with G-CSF priming. Homoharringtonine and Ara-C were injected intravenously at doses of 1 mg and 25 mg daily for 14 consecutive days respectively, G-CSF was injected subcutaneously once daily at a dose of 300μg on 12 hours prior to chemotherapy and continued given until the end of chemotherapy or when the peripheral WBC count reached 〉 20×10^9/L. This regimen was given only for one course, and followed by conventional chemotherapy as maintenance or consolidation therapy when CR achieved. 33 patients with highrisk MDS and MDS-transformed AML were injected actarubicin / Ara-C intravenously at doses of 10 mg and 25 mg for 8 and 14 consecutive days respectively, G-CSF was used at the same dose and the same way as the CHG regimen. 33 patients with high-risk MDS and MDS- transformed AML were treated with HHT / Ara-C intravenously at doses of 2 - 3 mg and 100 - 150 mg daily for 7 consecutive days respectively, G-CSF was injected when WBC count was below 4 ×10^9/L, and it was stopped to be used when WBC count was 〉4 ×10^9/L. The results showed that （ 1 ） 14 patients achieved complete remission （CR） （46.67 % ） and 7 patients achieved partial remission （PR） （23. 33 % ） with one course of CHG regimen, total effective rate was 70% ; 14 patient achieved CR （42.4%） and 9 patients achieved PR （27.3%） with one course of CAG regimen, total effective rate was 69.7% ; 7 patient achieved CR （33.3%） and 3 patients achieved PR （9.1%） with one course of HA regimen, total effective rate was 42.4%. There was no statistical difference between the effective rate of CHG and CAG, but difference was significant between CHG and HA. （2） Agranulocytosis （ neutrophil 〈0.5 x 109/L ） occurred in 12 cases （ 40% ） of CHG-treated patients with a mean 8 days of agranulocytic period, so the infectious complications were less serious and tolerable without treatment-related death. （3） Among 14 out of 30 patients with CR, 9 relapsed, the mean duration from CR to replase was 8.2 months. All relapsed patients reusing CHG regimen did not achieved CR again. （4） Among 13 cases with CR, 6 patients just received HA or DA regimens as consolidatory and intensive chemotherapy after CR have relapsed, the mean CR time was only 6.1 months. Otherwise, the mean CR time of 7 CR patients received altemative succeeded chemotherapy containing mitoxantrone/ idarubicin/ THP/ homoharringtonine! daunorubicin/aclarubicin after CR was 10.6 months ; and among them 4 are still in continuous CR. It is concluded that the CHG chemotherapy regimen has a similar effect with CAG but better than HA, and in a salt chemotherapy regimen with slight myelosuppresion in clinical application, strong and alternative succeeded chemotherapy is necessary for CR patients to keep longer CR and survival.