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.     

Leukocyte count as a predictor of death during remission induction in acute myeloid leukemia

Acute myeloid leukemia (AML) presenting with a high leukocyte count has been associated with an increase in induction mortality and poor results in a number of other survival measures. However, the level at which an elevated leukocyte count has prognostic significance in AML remains unclear. In this report on a series of 375 adult (non-M3) AML patients undergoing induction chemotherapy at a single institution, leukocyte count analyzed as a continuous variable is shown to be a better predictor of induction death (ID) and overall survival (OS) than a leukocyte count of ≥100×10⁹/L, a value characteristically associated with “hyperleukocytosis” (HL). In this patient cohort, a presenting leukocyte count of ≥30×10⁹/L had high sensitivity and specificity for predicting ID, and both performance status (PS) and leukocyte count more accurately predicted for ID than age. Considering these parameters in newly-diagnosed AML patients may facilitate the development of strategies for reducing induction mortality.     

老年急性髓细胞白血病的临床特点

根据老年急性髓细胞白血病的临床特点,寻求治疗老年急性髓细胞性白血病的有效措施。回顾性分析25例老年急性髓细胞白血病的临床资料,治疗按个体差异分为姑息治疗组、小剂量HA化疗组及标准剂量联合化疗组,并对其治疗效果进行比较。老年急性髓细胞白血病,具有独特的生物学及临床特征;姑息治疗组3例,CR率为0;小剂量HA化疗组7例,CR率28.6%;标准剂量联合化疗组15例,CR率33.3%。标准剂量联合化疗组的CR率及平均存活期均高于小剂量HA化疗组,而诱导期死亡率则低于小剂量HA化疗组,但其差异均无统计学意义。对老年急性髓细胞性白血病的化学治疗应个体化,并辅以积极的综合治疗,才能有望提高疗效。     

Treatment patterns and a prognostic scoring system for elderly acute myeloid leukemia patients: a retrospective multicenter cohort study in China

Objective:Acute myeloid leukemia (AML) is primarily a malignant disorder affecting the elderly. We aimed to compare the outcomes of different treatment patterns in elderly AML patients and to propose a prognostic scoring system that could predict survival and aid therapeutic decisions.Methods:Patients aged ≥ 60 years who had been diagnosed with AML at 7 hospitals in China were enrolled (n = 228). Treatment patterns included standard chemotherapy, low intensity therapy, and best supportive care (BSC).Results:The early mortality rates were 31%, 6.8%, and 6.3% for the BSC, low intensity therapy, and standard chemotherapy groups, respectively. The complete remission rate of the standard chemotherapy group was higher than that of the low intensity therapy group. The median overall survival (OS) was 561 days and 222 days for the standard chemotherapy and low intensity therapy groups, respectively, and were both longer than that of the BSC group (86 days). Based on multivariate analyses, we defined a prognostic scoring system that enabled classification of patients into 3 risk groups, in an attempt to predict the OS of patients receiving chemotherapies and low intensity therapies. Low and intermediate risk patients benefited more from standard chemotherapies than from low intensity therapies. However, the median OS was comparable between standard chemotherapies and low intensity therapies in high risk patients.Conclusions:Our prognostic scoring system could predict survival and help select appropriate therapies for elderly AML patients. Standard chemotherapy is important for elderly AML patients, particularly for those categorized into low and intermediate risk groups.     

A scoring system to predict the risk of death during induction with anthracycline plus cytarabine-based chemotherapy in patients with de novo acute myeloid leukemia

BACKGROUND:

A prognostic index to predict induction death in adult patients receiving induction chemotherapy for de novo acute myeloid leukemia (AML) was developed.

METHODS:

The authors analyzed 570 patients (aged 16‐70 years) included in 2 multicenter trials of the CETLAM Group to develop a scoring system (study cohort). The scoring system was tested in 209 patients from an external single institution (validation cohort). Induction regimens consisted of anthracycline and cytarabine combination with or without etoposide. Induction death was defined as death in the first 42 days without evidence of leukemic resistance.

RESULTS:

The cumulative incidence of induction death was 11% in the study cohort and 18% in the validation cohort. Median age was 48 years in the study cohort and 56 years in the validation cohort (P < .001). Multivariate analysis in the study cohort showed the following adverse risk factors for induction death: leukocyte count >100 × 10⁹/L, serum creatinine >1.2 mg/dL, and age ≥50 years. According to these factors, the authors developed a predictive score: low risk (no risk factors), intermediate risk (1 factor), and high risk (2 or 3 factors). The cumulative incidence of induction death in the 3 respective groups was 5%, 13%, and 26% (P < .001). The scoring system was applied in the validation cohort, resulting in cumulative incidence rates of induction death of 6%, 19%, and 32%, for the low‐risk, intermediate‐risk, and high‐risk categories, respectively (P < .001).

CONCLUSIONS:

By using this validated and simple scoring system, the risk of induction death in patients with AML can be predicted accurately. The score may be helpful to design risk‐adapted induction strategies. Cancer 2011;. © 2011 American Cancer Society.     

国产地西他滨治疗老年急性髓系白血病的疗效及安全性

目的:探讨以国产地西他滨为基础的化疗方案治疗老年急性髓系白血病（AML）的临床疗效及安全性。方法:回顾性分析2013年1月-2016年2月收治的老年急性髓系白血病患者29例,根据其是否使用国产地西他滨分组,对比评定疗效。结果:地西他滨组和传统方案组的完全缓解率分别为60.0%（6/10）和35.7%（5/14）,差异有统计学意义（P＜0.05）;同时比较两组的总生存期（OS）,差异有统计学意义（P＜0.05）。80%的老年AML患者在使用以国产地西他滨为基础的化疗方案治疗过程出现不同程度的不良反应,多为Ⅰ-Ⅱ级,少数患者发生了Ⅲ-Ⅳ级不良反应,主要为中性粒细胞减少和血小板减少。结论:以国产地西他滨为基础的化疗方案有较高的缓解率,且延长生存期。     

Adult patients with acute myeloid leukemia who achieve complete remission after 1 or 2 cycles of induction have a similar prognosis

BACKGROUND:

Patients with newly diagnosed acute myeloid leukemia (AML) often have residual leukemia in the bone marrow 10 to 14 days after the start of induction therapy. Some cooperative groups administer a second cycle of similar induction therapy on Day 14 if there is residual leukemia. It is a common perception that the presence of residual leukemia at that point predicts a worse prognosis irrespective of the therapy received. The objective of this study was to determine whether patients who required a second cycle of induction (given on or about Day 14) to achieve complete remission (CR) had a worse prognosis than patients who achieved CR after only 1 cycle, because a worse prognosis may alter postremission therapy.

METHODS:

Patients who were enrolled on 6 consecutive studies for AML that were conducted by the Eastern Cooperative Oncology Group (ECOG) between 1983 to 1993 received induction therapy. If residual leukemia was present in the bone marrow on the Day 14 after the start of induction, then patients were to receive a second cycle of identical induction therapy. All patients who achieved CR after 1 or 2 cycles received the identical postremission therapy.

RESULTS:

In each of the 6 ECOG studies, the long‐term outcome was similar for patients who required 1 or 2 cycles of induction therapy to achieve CR, and their outcome was independent of other prognostic variables, such as age or karyotype.

CONCLUSIONS:

The presence of residual leukemia in bone marrow 10 to 14 days after induction therapy did not predict a worse prognosis if patients received second, similar cycle of induction therapy and achieved CR. Cancer 2010. © 2010 American Cancer Society.     

Outcomes of patients who undergo aggressive induction therapy for secondary acute myeloid leukemia

BACKGROUND:

Response and survival in 96 patients with secondary acute myeloid leukemia (sAML) who received aggressive induction chemotherapy was reviewed.

METHODS:

The median follow‐up of survivors was 2.3 years. A total of 70 (73%) patients achieved a morphologic complete remission (CR) confirmed by absence of leukemic blasts by flow cytometry.

RESULTS:

For all 96 patients, the median event‐free survival (EFS) was 8 months, and overall survival (OS) was 13.6 months (range, 1‐119 months). Eight patients died shortly after induction therapy because of disease or side effects, and 13 are currently in continuous first remission. The median disease‐free survival (DFS) for all 70 patients who achieved a morphologic CR was 9 months (range, 1‐51 months), with a 64% chance of surviving 1 year. Patients with AML after previous chemotherapy or radiation therapy had a higher morphologic remission rate compared with those arising from myelodysplastic syndrome or myeloproliferative disease (82% vs 62%; P = .027). However, among the patients from the 2 groups who attained a morphologic remission, there was no difference in terms of CR rate (P = .94), DFS, EFS, or OS (P = .55, .83, and .71, respectively). This is a similar DFS to the group of 7 patients who went directly to ablative allogeneic transplant rather than having induction therapy first. In this population of patients who received aggressive chemotherapy, Charlson comorbidity index or a higher number of factors recognized as high risk in leukemia patients did not affect the chance of OS, DFS, and EFS, although having more recognized leukemia risk factors was related to a lower chance of surviving 1 year. However, it is important to note that those with higher comorbidity indexes were underrepresented in this aggressively treated cohort.

CONCLUSIONS:

The data from the current study demonstrate that many patients with sAML can tolerate aggressive induction therapy and attain remission, but duration of response and the chance of long‐term survival remain poor. Cancer 2009. © 2009 American Cancer Society.     

Impact of remission induction chemotherapy on survival in older adults with acute myeloid leukemia

BACKGROUND: Significant controversy surrounds the use of remission induction chemotherapy (IC) in older adults with acute myeloid leukemia (AML). Earlier clinical trials have yielded conflicting results and possibly a minor survival benefit, often offset by a longer hospitalization time. METHODS: To evaluate the role of IC in patients with AML, a case control study of patients 60 years or older treated at the Cleveland Clinic Taussig Cancer Center between 1997 and 2005 was conducted. Forty-four patients who did not receive IC were matched by a propensity analysis to 138 patients who received an anthracycline-based regimen. RESULTS: The unadjusted median survival of patients who did not receive IC was 53 days, compared with 197 days (P < .001) for those who did. After further adjusting for age, gender, race, leukocyte count at presentation, AML cytogenetics, history of prior hematologic disorder, and assessing for comorbidities, not receiving IC was still associated with worse survival (hazards ratio of 1.88; 95% confidence interval, 1.15-3.05 [P = .01]). Additional predictors of poor outcomes in older adults with AML included higher leukocyte count at presentation, poor-risk cytogenetics, and African-American race (compared with Caucasians). CONCLUSIONS: The study suggests improved outcomes in older adults with AML who undergo remission induction therapy.     

影响老年急性髓系白血病患者预后的危险因素分析

目的 探讨影响老年急性髓系白血病患者预后的危险因素.方法 回顾性分析121例老年急性髓系白血病患者的临床资料.对比不同临床资料患者的完全缓解率和中位生存期.通过多因素Cox模型分析统计影响老年急性髓系白血病患者预后的危险因素.结果 本研究患者的中位生存期为131 d(95%可信区间109~154 d),诱导化疗后的完全缓解率为29.75%.年龄≤70岁、PS评分﹤2分、原发急性髓系白血病、骨髓原始细胞比例≤50%、接受标准化疗以及白细胞CD34表达阴性患者的完全缓解率升高(P﹤0.05);年龄≤70岁、PS评分﹤2分、原发急性髓系白血病、初治时的白细胞计数≤50×109/L、骨髓原始细胞比例≤50%、接受标准化疗以及白细胞CD34表达阴性患者的中位生存期延长(P﹤0.05);多因素Cox模型分析结果显示,年龄、PS评分、初治时白细胞计数以及治疗方案是影响老年急性髓系白血病患者预后的危险因素(P﹤0.05).结论 年龄、PS评分、初治时白细胞计数以及治疗方案是影响老年急性髓系白血病患者预后的危险因素.临床应通过整体评估,制定个体化的化疗方案,以改善患者的预后.     

得力生联合化疗治疗急性髓性白血病疗效观察

目的:观察得力生注射液联合化疗治疗急性髓性白血病的疗效。方法:将62例患者随机分为治疗组和对照组,治疗组给予得力生注射液联合化疗,对照组单用化疗,观察临床疗效及造血恢复时间。结果:在第一疗程化疗后完全缓解率、部分缓解率、总有效率两组无显著性差别;达到完全缓解所需时间两组分别为25.9±6.6天、30.0±7.6天,治疗组短于对照组(P<0.05);治疗组骨髓抑制期也明显短于对照组(P<0.05)。结论:得力生注射液可提高急性髓性白血病的化疗效果,保护骨髓、促进造血恢复。     

Potential cure of acute myeloid leukemia : analysis of 1069 consecutive patients in first complete remission

BACKGROUND: Potential cure of acute myeloid leukemia (AML) is now a widely accepted idea, but it is uncertain whether there is heterogeneity in the failure rate in patients once they have been in complete remission (CR) for various periods of time. METHODS: The long-term outcomes were analyzed in 1069 consecutive AML patients in first CR who were diagnosed and treated at the University of Texas M. D. Anderson Cancer Center between 1991 and 2003. RESULTS.: The failure rates as yearly risk of treatment failure were 69.1 in the first year, 37.7 in the second year, 17.0 in the third year, 7.6 in the fourth year, and 6.6 in the fifth year, suggesting that 3 years from the CR date is a convenient time to consider patients potentially cured. The effect of cytogenetics on relapse-free survival (RFS) remained constant throughout the first 3 years, whereas the effect of age increased with time. The probability of RFS for patients alive without disease recurrence at 3 years was 84.0% at 6 years. When the interaction between age and cytogenetics was examined for these patients, the outcomes of those with favorable cytogenetics were found to be excellent regardless of age. However, in the intermediate cytogenetic group, although patients aged <60 years had excellent outcomes, those aged > or =60 years were found to be at a substantial risk of disease recurrence even after 3 years of CR, with a 6-year RFS rate of 56.5%. There were only 6 patients with adverse cytogenetics in this cohort. CONCLUSIONS: The results of the current study demonstrate that the risk of treatment failure differs over time according to a combination of cytogenetics and age.     

Multicentre study on intensified remission induction therapy for acute myeloid leukemia

In a cooperative study at 13 centres in the Federal Republic of Germany, 213 adult patients with AML were treated for remission induction by a 9-day regimen consisting of cytosine arabinoside, daunorubicin and thioguanine (TAD) according to previously described sequencing. Complete remission was achieved in 70% of all patients. Complete remission rate was 57% in the 49 patients 60 years of age and older and 74% in the 164 patients under 60 years. Sixty-eight per cent of all complete remissions and 75% of those in the higher age group were induced by one induction course. Median survival was 10 months for all patients treated and 16 months for responders. Median remission duration was 13 months with 72 patients still in continuous remission for 1–31 months. Remission duration was not significantly different for patients treated either by monthly maintenance therapy or induction type consolidation without further therapy. However, patients completing two consolidation courses had a significantly longer remission duration of 22 months. Compared to similar multicentre studies on AML therapy the intensified induction regimen applied in this study shows an improvement even in older patients.     

吡喃阿霉素方案治疗初治年轻患者急性髓性白血病

背景与目的：含有蒽环类抗生素的方案已经成为了治疗急性髓性白血病的标准治疗。本研究以米托蒽醌方案为对照,探讨了含有吡哺阿霉素（perarubicin,THP）的联合化疗方案在年轻急性髓性白血病的患者治疗中的疗效与毒性。方法：129例初治急性髓性白血病人组,年龄≥16岁而〈60岁,诱导化疗给予常规剂量的阿糖胞苷及THP或米托蒽醌（MIT）。完全缓解（CR）后,患者接受两个疗程的原诱导方案的化疗：此后,交替应用含有THP及MIT的方案进行巩固治疗,三周一个疗程,共四个疗程。在持续缓解的情况下,维持治疗共三年。结果：在42例接受THP诱导缓解治疗的患者中,26例（61．90％）患者达到CR;73例以MIT作为诱导缓解治疗的患者中,有48例（65．75％）达到CR。两者比较,无显著的统计学意义（P〉0．05）。在THP进行诱导治疗的患者中,9例（34．61％）患者在一年内出现复发;而MIT治疗的患者其一年内的复发率为22．92％;但经统计分析后发现,两者之间无统计学意义（P=0．28）。对诱导化疗中两种方案阿糖胞苷（Ara—C）加THP或Ara．C加MIT的副作用进行比较发现,除脱发发生率THP组（26．19％）低于MIT组（42．47％）外（P〈0．01）,其它毒副反应如感染、恶心、呕吐及心脏事件,发生率几乎相同（P〉O．05）。结论：THP加Ara—C的方案能够用于年轻成人的初治白血病的诱导化疗,但其并不优于含有MIT的方案：在完全缓解后,THP和MIT可用于巩固治疗中。     

Decitabine for acute myeloid leukemia

Decitabine (Dacogen^®, Eisai Inc., NJ, USA) is a nucleoside analogue DNA methyltransferase inhibitor first synthesized and documented to have antileukemic efficacy over 40 years ago. Over the years, the dosing of decitabine has been refined, such that for acute myeloid leukemia, a 5-day schedule of 20 mg/m² is now commonly utilized. Owing to its relatively modest nonhematologic toxicity when administered in this manner, single agent decitabine has shown the greatest promise in antileukemic efficacy for the management of older individuals and others who are not candidates for more intensive therapy. Whether or not single-agent decitabine is more safe and effective than existing therapies for older individuals, which markers best predict for response, and what drugs combine most effectively with decitabine, are all areas of active investigation at this time.     

Independent prognostic impact of CD15 on complete remission achievement in patients with acute myeloid leukemia

The prognostic role of CD15 in acute myeloid leukemia (AML) has been tested in different studies with conflicting results. To address this issue, we retrospectively evaluated a cohort of 460 AML patients of all ages with the exclusion of acute promyelocytic leukemia (M/F 243/217, median age 50.6 years [range 0.9‐81.2]) intensively treated at our institute between January 1999 and December 2010. CD15 positivity was found in 171 of 406 evaluable patients (42.1%). Complete remission (CR) was achieved by 334 patients (72.6%), while 82 (17.8%) were resistant and 44 (9.6%) died during induction: the median CR duration was 15.5 months (range 0.6‐176.0), with 2‐year disease‐free survival rate of 45.1% (95% confidence interval 39.6‐50.6). The median overall survival was 14.4 months (range 0.3‐177.0), with 2‐year overall survival rate of 42.2% (95% confidence interval 37.5‐46.9). At univariate analysis for CR achievement, age < 60 years (P < .001), World Health Organization classification (P = .045), low‐risk karyotype (P < .001), no high‐risk karyotype (P = .006), positivity for AML‐ETO (P = .004)/CBFβ‐MYH11 (P = .003)/CD15 (P = .006)/CD11b (P = .013), negativity for FLT3‐ITD (P = .001), Hb > 8 g/dL (P = .020), and white blood cell < 50 × 10⁹/L (P = .034) had a favorable impact. At a multivariate logistic regression model, CD15 positivity (P = .002), age < 60 years (P = .008), white blood cell < 50 × 10⁹/L (P = .017), and low‐risk/no high‐risk karyotype (P = .026/P = .025) retained an independent prognostic role on CR achievement . The baseline assessment of CD15 positivity appears to have a role in the risk evaluation for CR achievement in AML patients undergoing intensive chemotherapy and should be assessed in prospective studies together with other clinical and biologic features already reported.     

Invasive fungal diseases during first induction chemotherapy affect complete remission achievement and long-term survival of patients with acute myeloid leukemia

We retrospectively evaluated, in a logistic-regression-model, the role of proven/probable invasive fungal diseases (PP-IFD), occurring during first induction chemotherapy, on the achievement of complete remission (CR) and overall survival (OS) in 198 acute myeloid leukemia (AML) patients. A PP-IFD was documented in 34 (17.2%) patients. Younger age, good performance status at AML diagnosis and no development of a PP-IFD (OR 4.09, 95% CI 1.71–9.81, p < 0.0001) were independent factors associated to CR achievement. Younger age, good performance status, favorable genetic risk and no development of PP-IFD (HR 1.86, 95% CI 1.20–2.88, p = 0.005) were independent factors associated to OS at 3 years.