High-dose homoharringtonine versus standard-dose daunorubicin is effective and safe as induction and post-induction chemotherapy for elderly patients with acute myeloid leukemia: a multicenter experience from China

The purpose of the study was to compare the antitumor efficacy and safety profile of high-dose homoharringtonine as induction and post-induction therapy compared to either standard-dose homoharringtonine or daunorubicin in elderly patients with newly diagnosed acute myeloid leukemia. A total of 254 patients, age range 60–77 years received induction and post-induction therapy containing daunorubicin, standard-dose homoharringtonine, or high-dose homoharringtonine. After one course of induction therapy, the overall complete remission rate was similar between treatment arms (58.7%, P = .92). Among 161 patients with acute myeloid leukemia (non-M5 subtype), estimated median overall survival was 39, 29, and 37 months, respectively, in the daunorubicin, standard-dose homoharringtonine, and high-dose homoharringtonine treatment groups (P = .53). In the 93 patients with acute myeloid leukemia-M5 subtype, there was a significant difference in estimated median overall survival: 24, 24, and 52 months, respectively, in the daunorubicin, standard-dose homoharringtonine, and high-dose homoharringtonine treatment groups (P = .003). There was no significant difference in drug-related adverse events between treatment arms. High-dose homoharringtonine does not clearly increase the complete remission rate of elderly patients with acute myeloid leukemia. However, in the subset of elderly patients with acute monocytic leukemia, high-dose homoharringtonine as a first-line regimen prolonged overall survival with minimal toxicity.     

小剂量CHG预激方案治疗老年人急性髓系白血病的临床研究

 目的　探讨小剂量CHG预激方案[小剂量阿糖胞苷（Ara-C）、高三尖杉酯碱（HHT）联合粒细胞集落刺激因子（G-CSF）]对老年急性髓系白血病（AML）的治疗疗效和毒副作用。方法　选择 年龄＞60岁的AML初治患者共35例,采用CHG方案治疗：在化疗前12 h皮下注射粒细胞集落刺激因子（G-CSF）200 μg／m2后,应用14 d,HHT 1 mg／m2,第1天至第14天,1次／d;Ara-C 10 mg／m2,第1天至第14天,皮下注射,每12 h 1次。治疗过程中,WBC＞20×109／L时暂停使用G-CSF,但不停化疗,待WBC回落后再继续使用。对完全缓解（CR）者后期可选择不同方案交替巩固化疗。结果　第1个疗程后12例患者获得CR,15例获得部分缓解（PR）,8例未缓解（NR）。第2个疗程后,15例PR患者5例取得CR,8例NR患者有2例获得PR,总有效率83 %（29／35）。17例获得CR的患者中11例按计划巩固强化治疗未复发,生存期为12～34个月,中位生存18个月;6例复发,经过原方案诱导后1例CR、4例 PR、1例NR。CHG方案血液学毒性低,非血液学毒性不明显。结论　初治的老年AML患者采用小剂量CHG预激方案诱导缓解的疗效较好、不良反应可耐受。     

小剂量CHG预激方案治疗老年人急性髓系白血病的临床研究

Objective To explore the efficacy and side effect of inductive chemotherapy with lowdose,cytarabine,homoharringtonine and granulocyte colony-stimulating factor(CHG) in elderly acute myeloid leukemia(AML). Methods Thirty-five elderly patients (age＞60 years) with AML were enrolled for the initial treatment with CHG regimen,The CHG regimen consisted of cytarabine 10 mg/m2 per 12 h by subcutaneous injection,days 1-14,homoharringtonine 1 mg/m2 per day by intravenous continuous infusion,days 1-14,and G-CSF 200 μg/m2 per day by subcutaneous injection 12 h before chemotherapy,days 0-14. G-CSF only was used when white blood cell count(WBC) was less than 20×109/L during the whole course. Results After the first course,12 patients achieved complete response (CR),15 patients achieved partial response(PR),and 8 patients had no response(NR). After the second course,5 of 15 PR patients achieved CR,2 of 8 NR patients achieved PR. The total effective rate was 82 % (29/35). Of those 17 CR patients,eleven patients continued maintenance therapy and remained in remission for 12-34 months with a median CR duration of 18 months,the other 6 patients relapsed and were treated with original regimen,including one achieved CR again,4 achieved PR,and 1 achieved NR. The CHG regimen had mild hematologic toxicities and no severe nonhematologic toxicities. Conclusion CHG regimen is effective and well tolerated in remission for elderly AML.     

小剂量CHG预激方案治疗老年人急性髓系白血病的临床研究

Objective To explore the efficacy and side effect of inductive chemotherapy with lowdose,cytarabine,homoharringtonine and granulocyte colony-stimulating factor(CHG) in elderly acute myeloid leukemia(AML). Methods Thirty-five elderly patients (age＞60 years) with AML were enrolled for the initial treatment with CHG regimen,The CHG regimen consisted of cytarabine 10 mg/m2 per 12 h by subcutaneous injection,days 1-14,homoharringtonine 1 mg/m2 per day by intravenous continuous infusion,days 1-14,and G-CSF 200 μg/m2 per day by subcutaneous injection 12 h before chemotherapy,days 0-14. G-CSF only was used when white blood cell count(WBC) was less than 20×109/L during the whole course. Results After the first course,12 patients achieved complete response (CR),15 patients achieved partial response(PR),and 8 patients had no response(NR). After the second course,5 of 15 PR patients achieved CR,2 of 8 NR patients achieved PR. The total effective rate was 82 % (29/35). Of those 17 CR patients,eleven patients continued maintenance therapy and remained in remission for 12-34 months with a median CR duration of 18 months,the other 6 patients relapsed and were treated with original regimen,including one achieved CR again,4 achieved PR,and 1 achieved NR. The CHG regimen had mild hematologic toxicities and no severe nonhematologic toxicities. Conclusion CHG regimen is effective and well tolerated in remission for elderly AML.     

常规剂量与减量化疗治疗老年急性白血病的比较

目的　探讨老年急性白血病最佳化疗方案。方法　对我院 1984年～ 2 0 0 0年收治的 6 4例老年急性白血病进行回顾性分析。根据化疗剂量的选择将患者分为常规剂量组与减量组 ,对两组的治疗效果进行比较。结果　常规剂量组与减量组完全缓解率基本相同 ,诱导期死亡率高于减量组 ,但其差异无显著性。结论　老年急性白血病的治疗方案宜个体化。     

IA方案诱导治疗急性髓系白血病的临床研究

 【摘要】　目的　探讨去甲氧柔红霉素（IDA）联合阿糖胞苷（Ara-C）组成的IA方案诱导治疗不同预后组急性髓系白血病（AML）患者的临床疗效及安全性。方法　回顾性分析60例初治AML患者应用IA方案治疗1个疗程后的临床资料。结果　预后良好组12例,完全缓解（CR）率83.3 %（10／12）,部分缓解（PR）率16.7 %（2／12）,总有效（OR）率100 %（12／12）;预后中等组26例,CR率73.1 %（19／26）,PR率19.2 %（5／26）,OR率92.3 %（24／26）;预后不良组22例,CR率59.1 %（13／22）,PR率13.6 %（3／22）,OR率72.7 %（15／22）;三组患者OR率比较差异无统计学意义（P＝0.113）。随访2年,预后良好组无复发生存（RFS）率100.0 %,预后中等组53.8 %,预后不良组45.5 %,三组间比较差异有统计学意义（P＝0.042）。化疗的不良反应主要为骨髓抑制和粒细胞缺乏所致感染,未见严重的非血液系统不良反应。结论　预后良好组AML使用IA方案诱导化疗OR率和2年RFS率高,可作为首选方案,而预后中等、不良组RFS率较低,应尽早考虑移植治疗。     

Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia

BACKGROUND.: Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, which is explained by the disease itself and by host-related factors. The objective of this study was to determine the prognostic role of comorbidities in this population. METHODS.: For this single-center, retrospective study, the authors analyzed the outcome of 133 patients aged >/=70 years who received induction chemotherapy for nonpromyelocytic AML between 1995 and 2004. Comorbidities were evaluated by using an adapted form of the Charlson comorbidity index (CCI). RESULTS.: The median patient age was 73 years. The CCI score was 0 for 83 patients (68%), 1 for 16 patients (13%), and >1 for 23 patients (19%). The complete remission (CR) rate was 56%, and the median overall survival was 9 months. In multivariate analysis, 4 adverse prognostic factors for CR were identified: unfavorable karyotype, leukocytosis >/=30 g/L, CD34 expression on leukemic cells, and CCI >1. A score could be generated to allow the stratification of patients into low-, intermediate-, and high-risk groups with CR rates of 87%, 63%, and 37%, respectively. The risk of early mortality and the probability of survival also were different in the 3 risk groups (P = .02 and P = .01, respectively). CONCLUSIONS.: The results from this study indicated that associated comorbidities are independent factors that may influence achievement of CR in elderly patients with AML. Such a scoring system may be useful in the prognostic staging systems that are used to identify patients with AML who can benefit from induction chemotherapy.     

微移植联合化疗治疗老年急性髓系白血病临床观察

目的:观察微移植联合化疗治疗老年急性髓系白血病患者的临床疗效及安全性.方法:回顾性分析我院35例老年急性髓系白血病患者经单纯诱导化疗(n=16)或联合微移植(n=19)的治疗过程及转归情况.结果:微移植联合化疗组14例(73.7%)完全缓解(CR),单纯诱导化疗组6例(37.5%)CR;微移植组中性粒细胞、血小板中位恢复时间分别为11.5 d、16 d,而单纯诱导化疗组则分别为15 d、22 d(P<0.05);微移植组无重症感染及相关死亡发生,单纯化疗组因重症感染死亡3例.结论:微移植联合化疗治疗老年急性髓系白血病提高了疾病缓解率,降低了化疗相关死亡率.     

口服青黄散与低强度化疗治疗老年人急性髓系白血病生存情况比较

目的 探讨口服青黄散与低强度化疗治疗老年人急性髓系白血病(AML)的生存情况.方法 对2015年1月至2017年12月在中国中医科学院西苑医院接受治疗的42例老年AML患者临床资料进行回顾性分析,其中20例接受口服青黄散治疗(青黄散组),22例接受低强度化疗(低强度化疗组),比较两组患者的生存情况.结果 低强度化疗组和青黄散组中位生存期(13.0个月比13.5个月,x2=0.096,P=0.757)、1年生存率(59.1％比70.0％,x 2=0.543,P=0.461)、2年生存率(13.6％比15.0％,x 2=0.016,P＞0.05)、3年生存率(4.6％比5.0％,x2=0.005,P＞0.05)比较,差异均无统计学意义.分层分析显示,低强度化疗组和青黄散组年龄≥75岁(12个月比12.5个月,x 2=1.317,P=0.251)、体能状况评分＞2分(12个月比12个月,x2=0.834,P=0.361)、继发AML(10个月比14个月,x2=1.552,P=0.213)、造血干细胞移植合并疾病指数＞2(12个月比13个月,x2=1.726,P=0.189)以及差的遗传学特征(12个月比8个月,x2=0.479,P=0.489)患者中位生存期比较,差异均无统计学意义.结论 口服青黄散与低强度化疗治疗老年AML患者的生存期相似.不愿接受低强度化疗的老年AML患者,尤其75岁以上患者,可以选择口服青黄散治疗.     

Double intensive consolidation chemotherapy in adult acute myeloid leukemia

Of 115 adult patients with de novo acute myeloid leukemia (AML), 87 (75.5%) achieved complete remission (CR) after induction treatment with zorubicin and conventional doses of cytarabine (Ara-C). Patients under age 45 years with histocompatibility locus antigen-identical sibling underwent bone marrow transplantation (BMT). The others were treated with two courses of intensive consolidation chemotherapy (ICC): course 1 with 4 days of high-dose Ara-C and 3 days of amsacrine (m-AMSA); course 2 with carmustine (BCNU), Ara-C, cyclophosphamide, and etoposide. Forty-two patients received both planned courses, 15 received only the first, and 13 patients could only support conventional maintenance therapy. Four patients died during consolidation. With a median follow-up of 60 months, the disease-free survival (DFS) after ICC at 5 years is 40.3% (+/- 6.5%), with no statistically significant difference between patients receiving one or two courses. The DFS for the 17 transplanted patients is comparable (P = .72) and is lower for the 13 excluded patients (23% +/- 11.5%, P = .046). Age did not influence the probability of remaining in CR. In univariate analysis, three parameters had a negative impact on the 5-year DFS: a high initial WBC count (52% for patients with less than 30 x 10(9) WBC/L v 12% for patients with greater than 30 x 10(9) WBC/L, P = .01), a long delay between induction treatment and course 1 (+/- 60 days; 63% v 29%, P = .01), and a long delay between course 1 and course 2 (+/- 60 days, 61.5% v 28.5%, P = .05). In multivariate analysis (Cox model), only the WBC count remained significant. This study confirms the value of intensive postremission chemotherapy, which can be compared in AML with allogeneic or autologous BMT. It also demonstrates the prognostic value of the initial WBC count. The optimal modalities of ICC remain to be defined by further studies.     

Outcomes after induction chemotherapy in patients with acute myeloid leukemia arising from myelodysplastic syndrome

BACKGROUND:

Secondary acute myeloid leukemia (AML) from an antecedent myelodysplastic syndrome (MDS)/myeloproliferative neoplasm is associated with a poor prognosis. The authors evaluated predictive factors in patients with secondary AML treated with anthracycline‐based induction therapy.

METHODS:

This was a retrospective review of secondary AML patients treated with induction therapy. Age, International Prognostic Scoring System, Eastern Cooperative Oncology Group performance status, cytogenetics, duration of MDS/myeloproliferative neoplasm, and prior MDS/myeloproliferative neoplasm treatment were evaluated for their impact on complete response (CR), CR with low platelets, and overall survival (OS).

RESULTS:

The authors evaluated 61 secondary AML patients who received induction chemotherapy; 59% (36 patients) achieved CR/CR with low platelets (95% confidence interval [CI], 46%‐71%), and median OS was 6.5 (95% CI, 3.9‐8.1) months. Three factors were associated with lower CR/CR with low platelets and OS: poor risk cytogenetics, prior treatment with hypomethylating agents or lenalidomide, and longer time to transformation to AML. Of those treated with hypomethylating agents or lenalidomide, 32% achieved CR/CR with low platelets versus 78% in the group not treated with a hypomethylating agent or lenalidomide (odds ratio [OR], 0.13; 95% CI, 0.04‐0.42). Median OS for those treated with a hypomethylating agent or lenalidomide was 3.7 versus 10.5 months for those not treated with a hypomethylating agent or lenalidomide (P < .0001). The CR/CR with low platelets rate for those with intermediate risk cytogenetics was 70% versus 35% for those with poor risk (OR, 4.33; 95% CI, 1.38‐13.6). Those with poor risk cytogenetics had a median OS of 2.8 versus 7.5 months for those with intermediate risk (P = .01).

CONCLUSIONS:

Prior treatment with hypomethylating agents or lenalidomide, poor risk cytogenetics, and longer time to transformation to AML are independent negative predictive factors for response and OS in patients with secondary AML after induction therapy. Cancer 2011. © 2010 American Cancer Society.     

地西他滨联合减剂量MAG方案治疗老年急性髓系白血病的疗效及安全性北大核心

目的:评价地西他滨联合减剂量MAG方案[米托蒽醌(MTN)+阿糖胞苷(Ara-C)+粒细胞集落刺激因子(G-CSF)]治疗老年急性髓系白血病(acute myeloid leukemia,AML)患者的疗效及安全性。方法:本研究回顾性分析2016年06月至2020年12月收治的50例初诊老年急性髓系白血病患者,使用地西他滨联合MAG方案进行2个周期化疗,评估其疗效及安全性。结果:50例患者均完成2个周期化疗,骨髓造血恢复后进行评估。其中完全缓解(complete response,CR)29例(58.00%),部分缓解(partial response,PR)14例(28.00%),总缓解率(overall response rate,ORR)为86.00%(43/50)。所有患者均出现Ⅲ-Ⅳ级血液学毒性,其中24例(48.00%)患者粒细胞缺乏期出现感染,16例(32.00%)出现Ⅱ度出血。31例(62.00%)出现Ⅰ-Ⅱ级恶心、呕吐、脏器损害等非血液学毒性,但均可耐受,无治疗相关死亡病例。性别、年龄、KPS评分对完全缓解率无明确影响(P>0.05)。细胞遗传学良好者较细胞遗传学不良者缓解率高,差异具有统计学意义(P<0.05)。结论:地西他滨联合减剂量MAG方案治疗老年急性髓系白血病疗效确切,缓解率高,毒副反应可耐受,适用于临床广泛应用。     

HA联合替尼泊苷或表柔比星治疗急性髓系白血病疗效观察

目的:探讨高三尖杉脂碱+阿糖胞苷联合替尼泊苷（HAT）或表柔比星（HAE)治疗急性髓系白血病（AML)的疗效及毒副反应。方法:回顾性分析了初治急性髓系白血病患者以HAT或HAE方案进行诱导化疗的疗效和毒性反应。统计完全缓解率（CR）及总生存（OS）率分析。结果:初治AML患者在HAT和HAE组一疗程诱导化疗CR率分别为90%和81%。两组中CR患者3年实际OS率分别为33.3%和53.8%。至随访结束HAT组无复发生存22.2%,HAE组30.7%。预期5年总生存率HAT组为20%,HAE组为44%。化疗相关的毒副反应主要为造血抑制和感染,患者可以耐受。结论:HA联合替尼泊苷或表柔比星诱导化疗疗效满意,不良反应可以耐受,可以作为一线诱导化疗方案。     

以地西他滨为主方案治疗初发老年人急性髓系白血病近期疗效分析

目的 探讨以地西他滨为主方案治疗初发老年人急性髓系白血病(AML)的临床安全性和有效性.方法 选择2014年6月至2015年12月首都医科大学附属北京潞河医院收治的12例初发老年AML患者,应用地西他滨单药或联合低剂量化疗方案治疗,对12例患者临床资料进行回顾性分析.结果 12例患者中1个疗程达完全缓解(CR)者6例,部分缓解(PR)者5例,未缓解(NR)者1例.6例CR患者中1例在第6个疗程后复发,其余在随访中仍CR;5例PR患者中2例经2个疗程化疗后达CR,1例在第2个疗程化疗后复发,2例在第3个疗程化疗后复发.1例患者经2个疗程化疗后NR,因肺部感染死亡.4例复杂核型患者中3例疗效差,1例达CR,但最终仍复发;其余8例+8、-X或正常核型患者中7例短期达CR.主要不良反应为骨髓抑制和感染,所有患者均能耐受.结论 地西他滨单药或联合低剂量化疗方案治疗初发老年人AML近期疗效好,耐受性好,安全性高,可作为一线治疗方案.     

HAG方案治疗老年急性髓系白血病临床观察

目的:探讨HAG方案治疗老年急性骨髓系白血病(AML)的疗效及不良反应.方法:选择老年急性骨髓系白血病26例,治疗组14例采用HAG方案诱导治疗.对照组12例采用传统HA治疗.结果:治疗组CR64.2%,有效率75.8%,治疗相关死亡率7.1%;对照组CR58.3%,有效率75%,治疗相关死亡率16.6%.两组间完全缓解率、有效率差异无统计学意义(P＞0.05). 治疗相关死亡率两组间差异有统计学意义(P＜0.05).两组间骨髓恢复时间,所需浓缩红细胞及单采血小板数差异有统计学意义(P＜0.05).结论:HAG方案治疗老年急性骨髓系白血病与传统HA方案对比,不仅完全缓解率及有效率高,而且可降低并发症及治疗相关死亡率,骨髓抑制时间短,输血量少,易为患者接受.     

High-dose cytarabine induction is well tolerated and active in patients with de novo acute myeloid leukemia older than 60 years

BACKGROUND:

High‐dose cytarabine (HiDAC) is safe and very effective in younger patients with acute myeloid leukemia (AML), but it generally is not well tolerated in the elderly.

METHODS:

The authors explored the safety and tolerability of a modified HiDAC induction regimen consisting of 6 daily doses of cytarabine at 2 g/m² in combination with 3 daily doses of daunorubicin at 45 mg/m² in 59 consecutive patients aged >60 years who had de novo AML diagnosed between July 1996 and February 2005.

RESULTS:

The median patient age was 68 years (range, 60‐86 years). The regimen was well tolerated. Infections were common and occurred in 39% of patients, but cerebellar toxicities occurred in only 7% of patients and were reversible. The day‐30 induction‐related mortality rate was 10%. Overall, 69% of patients achieved complete remissions (CR), and 80% received up to 3 consolidations with HiDAC. The median follow‐up for surviving patients was 53 months (range, 17‐114 months). The median overall survival was 15.3 months (range, 1‐114 months), and the relapse‐free survival was 13.8 months (range, 1‐113 months). Survival for patients who achieved CR was 27 months (range, 2‐114 months).

CONCLUSIONS:

The modified HiDAC regimen was well tolerated in patients aged >60 years with AML and was associated with low induction mortality and high rates of CR. Nevertheless, these high remissions still were associated with poor overall outcomes. Cancer 2011;. © 2011 American Cancer Society.