LD-HA联合诱导治疗高白细胞性急性非淋巴细胞性白血病

目的：观察小剂量高三尖杉酯碱-阿糖胞苷（LD-HA）联合诱导治疗高白细胞性急性非淋巴细胞性白血病的疗效和不良反应。方法：将78例高白细胞性急性非淋巴细胞性白血病患者随机分为A组（41例）及B组（37例）。A组给予LD-HA（高三尖杉酯碱2mg/日,阿糖胞苷25mg2次/日,D1-14）联合诱导治疗。B组在应用羟基脲降白细胞的基础上进行常规化疗。结果：A组完全缓解（CR）率显著高于B组;死亡率明显降低。骨髓抑制程度两组无明显差异;心、肝、肾、消化道功能损害发生率A组低于B组。结论：LD-HA联合诱导治疗高白细胞性急性非淋巴细胞性白血病疗效好,不良反应轻。     

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。     

Serum levels of angiogenin,basic fibroblast growth factor and endostatin in patients receiving intensive chemotherapy for acute myelogenous leukemia

Angiogenesis seems to be important both in the pathogenesis of acute myelogenous leukemia (AML) and for the susceptibility of AML blasts to chemotherapy. Recent clinical studies even suggest that antiangiogenic therapy can induce disease control in patients with AML relapse. In this context we have investigated the profile of the systemic component of angiogenic regulation in AML by characterizing the serum levels of (i) the angiogenic regulators angiogenin, basic fibroblast growth factor (bFGF) and endostatin; (ii) the endothelial cell marker soluble (s) E-selectin. Patients with untreated AML had increased levels of angiogenin, endostatin and sE-selectin, whereas the levels of bFGF were not significantly altered. The systemic levels of the proangiogenic bFGF, the antiangiogenic endostatin and the endothelial cell marker sE-selectin showed significant correlations, whereas angiogenin and sE-selectin levels were not correlated. Furthermore, intensive chemotherapy resulted in decreased systemic levels of the 2 proangiogenic mediators angiogenin and bFGF, whereas endostatin levels remained high after treatment. Although angiogenin normally is a part of the acute phase reaction, its systemic levels were not altered when patients with chemotherapy-induced cytopenia developed complicating bacterial infections. Our results suggest that intensive chemotherapy can modulate the systemic component of angiogenic regulation in AML patients.     

Flt3 in acute myelogenous leukemia

Flt3 is a tyrosine kinase receptor expressed on hematopoietic cells. Activating mutations of this receptor are encountered in over one-fourth of acute myelogenous leukemia (AML) cases and activate multiple intracellular pathways leading to cell proliferation, inhibition of apoptosis, and blockage of differentiation in leukemic blasts. AML with flt3 mutations has a worse prognosis than AML with normal flt3, at least in younger patients. Sevaral flt3 inhibitors are in various stages of preclinical and clinical development and it is hoped that specific therapies against AML with flt3 mutations will soon be available to the clinician.     

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.     

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.     

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.     

KIT mutation detection in Tunisian patients with newly diagnosed myelogenous leukemia: prevalence and prognostic significance

The KIT gene encodes a class III tyrosine kinase receptor in which specific somatic mutations have been found to be associated with many diseases. In this work, we investigated the prevalence of KIT mutations in patients with chronic and acute myelogenous leukemia (CML and AML) and their prognostic significance. A total of 157 subjects were included in the present study (84 patients with CML, 33 with AML, and 40 healthy controls). Patients were analyzed at the first diagnosis, and the KIT mutations were screened by polymerase chain reaction (PCR) and direct sequencing technologies. The results demonstrated the presence of a G/A transition at codon 796, which is associated with the R796K protein variation. This mutation was detected at 21.42% in the CML subgroup and was absent in both AML patients and healthy controls; however, no correlation was found between this mutation and clinical parameters such as the molecular response to Gleevec. In conclusion, we retain that the KIT gene is highly mutated in the CML subgroup, but its role as a prognostic factor needs to be further elucidated.     

地西他滨联合CAG方案治疗老年复发难治性急性髓细胞白血病的临床观察

目的:评价地西他滨结合CAG方案治疗老年复发难治性急性髓细胞白血病效果和药物不良反应.方法:回顾性分析2013年01月至2015年05月扬州大学附属泰兴医院血液科收治的12例老年复发难治性急性髓细胞白血病患者的临床资料,地西他滨结合CAG方案:地西他滨20mg/m2,静滴,第1~5天;阿克拉霉素20mg/m2,第1天、第3天、第5天、第7天;阿糖胞苷10mg/m2,1次/12小时,皮下注射,第1~14天;粒系集落刺激因子300μg,皮下注射,1次/天(依照骨髓抑制情况而调整用药剂量及用药次数).结果:12例患者均出现不同程度的骨髓抑制,在骨髓抑制期间,4例出现不明原因的发热,3例出现肺部感染,1例出现肛周感染,经升白细胞、抗感染治疗后症状得到控制,1例患者肝功能损害,经保肝降酶治疗后恢复,2例出现轻度胃肠道反应,经对症治疗后症状消失.12例病人中,完全缓解者6例,部分缓解3例,总有效率为75%.结论:地西他滨联合CAG方案治疗老年复发难治性急性髓细胞白血病效果确切、临床用药安全,在临床上可以推广应用.     

急性髓细胞白血病早期病死高危因素及高白细胞髓性白血病首交化疗策 …

目的 :探讨急性髓细胞白血病 (acutemyelogenousleukemia ,AML)早期病死 (earlydeath ,ED)的高危因素以及高白细胞髓性白血病 (hyperleukocyticacutemyelogenousleukemia ,HAML)的首次化疗策略。 方法 :采用回顾性病例对照、多因素分析的方法对 30 1例AML、31例HAML进行研究。结果 :白细胞计数 (≥ 10 0× 10 9/L)、骨髓增生度 (极度活跃 )、体温 (≥ 39℃ )、血小板计数 (≤ 2 0× 10 9/L)及白血病类型 (M5)等指标进入Logistic多元回归方程 (P =0 0 0 0 0 ) ,OR值分别约 5 0、4 9、3 3、3 2和 2 2 ;HAML的首次化疗 ,采用常规剂量 (平均相对剂量强度≥ 0 5 )、含蒽环类方案 (DA)化疗发生ED的危险性分别为小剂量 (平均相对剂量强度 <0 5 )、其它方案 (HA或HOAP)化疗的 12倍 (P =0 0 34 6 )和 7 5倍 (P =0 0 479)。结论 :白细胞计数 (≥ 10 0× 10 9/L)、骨髓增生度 (极度活跃 )、体温 (≥ 39℃ )、血小板计数 (≤ 2 0× 10 9/L)及白血病类型 (M5)等 5个指标为AMLED的高危因素 ,其中以HAML最为重要 ,而HAML首次化疗 ,采用小剂量、非蒽环类方案化疗 ,可能有助于降低ED率。     

Estimation of the prevalence of Fanconi anemia among patients with de novo acute myelogenous leukemia who have poor recovery from chemotherapy

We speculated that some individuals with de novo acute myelogenous leukemia (AML) may have undiagnosed Fanconi Anemia (FA). Data from patients enrolled on AML protocol CCG-2961, published FA cohort studies, SEER, and Bayes rule were used to estimate the probability of FA among all newly diagnosed AML cases, and among those who had no or delayed recovery of the absolute neutrophil count following initial chemotherapy. We determined that the probability of undiagnosed FA in patients in a treatment trial for newly diagnosed patients was around 0.18%, and around 0.83% in the subset who had poor marrow recovery. We suggest that FA or other inherited bone marrow failure syndromes be considered prior to treatment, or certainly among those with poor recovery.     

134例老年急性髓系白血病的临床特点及预后分析

  目的  分析老年急性髓系白血病（acute myeloid leukemia,AML）（非早幼粒细胞白血病）的临床特点,治疗方式以及疗效和预后特点。  方法  收集2015年1月至2023年2月北京大学国际医院收治的134例老年AML患者资料,回顾性分析患者初诊时的白细胞计数、骨髓原始细胞计数、细胞遗传学及分子学特点、ELN危险分层,根据不同治疗方案将患者分为高强度化疗组和低剂量治疗组,观察在治疗过程中强化疗是否能给患者带来生存获益以及影响老年患者生存的因素。  结果  高强度化疗患者36例,22例完全缓解（complete response,CR）（61.1%）,低剂量治疗90例中46例获得CR（51.1%）,其中19例阿扎胞苷（AZA）联合维奈克拉（VEN）治疗换着中14例获得CR（73.7%）;高强度化疗与低剂量治疗的总生存期（overall survival,OS）分别为15个月和14.5个月（P=0.226）。欧洲白血病网（ELN）危险分层低、中、高危组患者OS分别为18、14、9个月（P=0.009）,低危组高强度化疗和低剂量治疗的OS分别为22个月和15个月（P=0.745）,中危组分别为9个月和15个月（P=0.783）,高危组分别为9个月和8个月（P=0.739）。强化疗（36例）与阿扎胞苷+维奈克拉治疗（19例）相比OS分别为15个月和17个月（P=0.689）。TP53基因突变者6例,预后明显差于无突变者,中位生存期分别为2个月和14个月（P=0.004）。低、中、高危患者的1年生存率为79%、53%和44%,3年生存率分别为41%、20%和3%。多因素分析显示外周血高白细胞计数（P=0.034）、ELN危险分层（P=0.002）、合并症（P=0.017）与OS相关,而治疗强度、年龄、性别、骨髓原始细胞计数与OS 无明显相关性。  结论  高强度化疗在老年AML中没有显示明显的生存获益,但这一结果在低危患者中有待于进一步观察。TP53突变者预后较差。多因素分析预测老年AML的生存期时,基线的分子学特征、白细胞计数、合并症比治疗强度更重要。     

Therapy‐related acute myelogenous leukemia and myelodysplastic syndrome in patients with acute lymphoblastic leukemia treated with the hyperfractionated cyclophosphamide,vincristine, doxorubicin,and dexamethasone regimens

BACKGROUND:

Secondary malignancies including myeloid neoplasms occur infrequently in acute lymphoblastic leukemia (ALL) and to the authors' knowledge have not been as well documented in adults as in children.

METHODS:

A total of 641 patients with de novo ALL who were treated with the hyper‐CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) regimen or its variants were analyzed.

RESULTS:

Sixteen patients (2.49%) developed secondary acute myelogenous leukemia (AML) (6 patients) or myelodysplastic syndrome (MDS) (10 patients). At the time of ALL diagnosis, the median age was 53 years; cytogenetics were normal in 11 patients, pseudo‐diploidy with del(2) in 1 patient, t(9;22) in 1 patient, and unavailable in 3 patients. Frontline therapy included hyper‐CVAD in 7 patients, hyper‐CVAD with rituximab in 8 patients, and hyper‐CVAD with imatinib in 1 patient. Karyotype at time of AML/MDS diagnosis was ?5, ?7 in 9 patients, normal in 1 patient, complex in 1 patient, inv(11) in 1 patient, t(4;11) in 1 patient, del(20) in 1 patient, and unavailable in 2 patients. Secondary AML/MDS developed at a median of 32 months after ALL diagnosis. Cytarabine plus anthracycline–based treatment was given to 12 patients with AML and high‐risk MDS. One patient with MDS received arsenic trioxide, 1 received clofarabine, and 2 received decitabine. Response to treatment was complete remission in 3 patients, partial remission in 6 patients, and no response in 6 patients; 1 patient was untreated. Eight patients (1 with AML and 7 with MDS) underwent allogeneic stem cell transplantation, and all but 2 died at a median of 3 months (range, 0.5–11 months) after transplantation. The median overall survival after a diagnosis of secondary AML and MDS was 9.25 months (range, 1+ to 26+ months).

CONCLUSIONS:

Secondary AML and MDS occur infrequently in adult patients with de novo ALL treated with the hyper‐CVAD regimens, and response to therapy is poor. Cancer 2009. © 2008 American Cancer Society.     

复发/难治急性髓系白血病患者P-糖蛋白的表达及功能分析

 目的 研究复发／难治急性髓性白血病（AML）患者P-糖蛋白表达及其功能。方法 用免疫组化方法检测CD34表达,RT-PCR方法检测P-gp的表达,用流式细胞术检测P-gp的功能。结果 CD34表达与P-gp表达、功能呈正相关（r =0.621,P＜0.001;r =0.496,P＜0.001）,P-gp表达与功能呈正相关（r = 0.574,P＜0.01）;复发／难治组CD34阳性率（66.7 %）高于初治组（32.6 %）（P＜0.05）;复发／难治组P-gp功能阳性率（66.7 %）高于初治组（25.6 %）（P＜0.01）。结论 CD34表达、P-gp表达和P-gp功能三者间呈正相关;复发／难治AL组 CD34阳性率、P-gp功能阳性率高于初治组;P-gp功能的检测更具有临床指导意义。     

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。     

依马替尼对c-Kit+急性髓细胞白血病凋亡机制的作用

 目的 观察依马替尼（STI571）体外对干细胞受体阳性（c-Kit+）急性髓细胞白血病（AML）患者骨髓细胞凋亡的作用。方法 用RT-PCR法检测c-Kit+ AML细胞抑凋亡基因Survivin mRNA和促凋亡基因Smac mRNA的表达水平。结果 抑凋亡基因Survivin mRNA的表达水平下降，促凋亡基因Smac mRNA的表达水平上升。结论 STI571能诱导c-Kit+ AML细胞促凋亡基因 Smac mRNA上调，抑凋亡基因Survivin mRNA的表达水平下降，发挥促凋亡作用。     

化疗对老年肿瘤患者生活质量的影响

目的研究化疗对65岁以上的老年肿瘤患者生活质量的影响。方法采用欧洲癌症研究和治疗组织的生命质量测定量表QLQ-C30（V3．0）中文版对我院94例≥65岁的老年肿瘤患者进行问卷调查,同时进行卡氏行为状态评分。其中辅助组38例,姑息组56例。在化疗前、化疗第3个周期后分别进行测定并进行比较。结果全体患者化疗3个周期后生活质量评分显示：恶心呕吐、便秘的症状较治疗前有显著性加重评分增高,但疼痛减轻评分下降（P〈0．05）;5项功能（躯体功能、角色功能、认知功能、情绪功能、社会功能）、其他症状（疲乏、睡眠、食欲下降、呼吸困难、腹泻、经济困难）和整体生活质量在治疗前后均无显著变化。与化疗前相比,辅助组患者化疗后恶心呕吐、食欲减退、便秘的症状加重（P〈0．05）。姑息组患者化疗后恶心呕吐的症状明显加重、但疼痛减轻（P〈0．05）。在化疗前后卡氏行为状态评分均未显示出明显的差别。化疗后辅助化疗组与姑息化疗组相比,姑息组在疼痛、便秘症状和经济困难的评分明显高于辅助组,姑息组的总体生活质量评分明显低于辅助组,均有统计学意义（P〈0．05）。结论老年肿瘤患者的躯体、角色、认知、情绪、社会功能受化疗的影响较小,化疗后会出现消化道症状加重,疼痛减轻,总体生活质量下降不明显。卡氏行为状态评分不能全面反映患者化疗时的生活质量,QLQ-C30（V3．0）中文版评估量表对中国老年肿瘤患者测评生活质量优于卡氏行为状态评分。