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.     

急性髓系白血病预后相关因素分析

目的 探讨成年急性髓系白血病(AML)患者的预后影响因素.方法 回顾性分析182例初治AML患者临床资料,探讨患者性别、年龄(以60岁为界)、初治白细胞计数(≥30× 109/L)、骨髓细胞学免疫表型、细胞遗传学、异基因造血干细胞移植(allo-HSCT)和治疗1个疗程获得完全缓解(CR)等因素与总生存(OS)及无事件生存(EFS)的关系.结果 182例AML患者的中位年龄49岁(14～ 80岁),中位随访时间9.7个月(0.5～75.5个月),首次化疗达CR 107例,总有效率为65.9％(120/182),年龄≥60岁、CD64阴性、染色体高危组及首次诱导未达CR患者的总CR率低于无上述因素者.单因素生存分析提示年龄≥60岁、细胞遗传学高危组、CD19阴性、CD11b阳性、CD64阴性、未行allo-HSCT、首次诱导未达到CR的患者OS及EFS较短(P＜0.05),多因素分析显示年龄、细胞遗传学表达、CD11b、CD64、是否行allo-HSCT、首次诱导能否达CR是患者OS的独立预后因素,细胞遗传学表达、CD64表达、是否行allo-HSCT及首次诱导能否达CR是患者EFS的独立预后因素.结论 根据AML相关因素进行预后分析判断,有利于临床医生早期制订个体化治疗方案,对于延长患者生存期有重要意义.     

成人急性髓系白血病的免疫学特点及预后

目的：探讨急性髓细胞白血病（AML）的免疫表型特点。方法：使用淋系和髓系单抗,用间接免疫荧光法对70例原发性AML进行免疫表型分析。结果：所有AML患者的细胞至少被1种髓系单抗标记,各髓系抗原的表达率依次为CD33＞CD13＞CD15。所有M3患者CD9为阳性。16／70例（30％）表达CD34抗原、CD34^ AML组在年龄、外周血象及骨髓原始、幼稚细胞比例等方面与CD34^-组相比较无显著差别,但表达CD34抗原的AML常伴有HLA－DR、CD38、CD7等不成熟细胞表面标记的表达,而较成熟的髓系细胞表面标记CD15则不表达。70例AML中有16例表达淋系抗原,CD4^ 例（13．8％,M2为8．8％,M460％）;CD7^ 9例（16．9％,M1为50％,M218％,M5b16．7％）。CD4^ 的AML患者CD34为低表达,CD33表达。结论：CD9^ 、CD34^-、HLA－DR^-及CD13^ 、CD15^ 是典型M3的免疫表型特点。CD34^ AMLgn AML-M1有着密切的关系,且对化疗反应较差,证明CD34^ 的AML是一组分化程度较差的类型;提示CD7^ 和CD4^ 的AML预后差,CD7^ 的AML的一种独特类型。     

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。     

急性髓细胞白血病预后因素研究进展

正急性髓细胞白血病(acute myelocytic leukemia,AML)作为最常见的血液系统肿瘤,是一大类异质性疾病。对该病的治疗,尤其是巩固治疗方案和移植时机的选择,依赖于对其预后的准确判断。与该病预后相关的因素具体可归纳为临床指标、白血病类型、细胞遗传学因素、分子生物学因素、治疗反应及微小残     

儿童急性髓系白血病M6型转化为M2型一例

患者男,3岁。因“间断发热7d,发现血象异常1d”于2012年2月29日入我院。患者7d前无明显诱因发热,峰值38．3℃,伴阵发性咳嗽,咳少量白痰、食欲缺乏、乏力,按“上呼吸道感染”治疗效果欠佳。既往体健,无血液及其他系统疾病史,无化学毒物及放射性物质接触史,否认家族有类似疾病史。     

淋系抗原表达对急性髓系白血病预后的价值

目的:探讨淋系抗原表达在急性髓系白血病（acute myeloid leukemia,AML）预后方面的临床意义。方法:应用流式细胞术检测我院101例初诊AML患者的免疫表型,以CD7-CD19-CD56-AML为对照组,将CD7+AML组、CD19+AML、CD56+AML组与对照组的临床特征、疗效进行分析比较,随访并观察生存曲线的差异。结果:101例AML患者中淋系抗原表达者52例(51.5%),CD7抗原表达29例（28.7%）,CD56抗原表达29例（28.7%）,CD19抗原表达13例（12.8%）;CD7+AML、CD19+AML、CD56+AML患者与对照组间的发病年龄、肝脾大、髓外浸润、白细胞计数、血红蛋白、骨髓原始细胞比例差异无统计学意义（P＞0.05）,CD7+AML组血小板计数偏低（P＜0.05）;CD56+AML组首次完全缓解率（CR）率及总CR率均低于对照组（P＜0.05）;CD7+AML、CD19+AML组首次CR率及总CR率与对照组相比差异均无统计学意义（P＞0.05）;与对照组相比,CD56+AML组无复发生存期（RFS）缩短（P＜0.05）,CD7+AML、CD19+AML组RFS与对照组差异无统计学意义（P＞0.05）。结论:CD56+AML患者常规化疗不敏感,疗效差,CD56抗原可能是AML患者的预后不良因素;CD7、CD19抗原不影响AML患者的预后。     

少见急性髓系粒-巨核细胞白血病及其归属探讨(附2例报告)

国外曾有多例粒巨双表型急性白血病报道,国内也有急性粒巨核细胞白血病和伴有巨核细胞异常增生的急性粒单核细胞白血病的报道[1,2].     

儿童急性髓系白血病免疫表型特点分析

目的:分析儿童急性髓系白血病(AML)免疫表型特征,探讨其临床意义.方法:采用四色流式细胞术CD45/SSC双参数散点图设门方法,对127例儿童AML患者幼稚细胞进行免疫表型检测,对抗原表达情况进行分析.结果:在127例儿童急性髓系白血病患者中,髓系特异性抗原CD33、CD13和CD117的表达最常见,分别达95.3%、90.6%、90.6%.造血干/祖细胞抗原CD34、HLA-DR、CD38阳性率分别达53.5%、71.6%和97.6%.有65.4%的病例伴有淋系抗原的表达,其中以CD56的表达最常见占38.6%,其次为CD7占21.3%.有淋系抗原表达(LymAg+)患者早期抗原CD34和HLA-DR抗原表达阳性率明显高于无淋系抗原表达(LymAg-)患者(P<0.05).结论:免疫分型对儿童AML的诊断和不同亚型鉴别具有重要意义.     

免疫疗法治疗急性髓系白血病的新进展

急性髓系白血病（acute myeloid leukemia,AML）是最常见的白血病,发病率居高不下,尽管随着科技的发展,可以延长其生存期,但对新型治疗方法的需求仍十分紧迫。当前的癌症免疫学和免疫疗法概念具有相关性,因此可以考虑从免疫治疗的角度上治疗AML,但在设计针对这种白血病的合理免疫疗法时,还应考虑AML免疫失调的独特方面。本文主要从改善免疫系统和白血病靶标之间的平衡,直接针对白血病的抗体,T细胞和NK细胞进行干预,使用呈递白血病抗原的增强抗原呈递细胞重新设计并重新激活患者T细胞的疫苗三方面进行综述。     

CD56+表达对急性单核细胞白血病儿童的临床特征、疗效及预后的影响

目的探讨CD56⁺表达对急性单核细胞白血病(AML-M5)儿童临床特征、疗效及预后的影响。方法对84例14岁以下AML-M5患儿临床资料进行回顾性分析,分析CD56的表达与临床特征、疗效及预后的关系。结果CD56⁺表达率为32.14%,白细胞计数(73.21±12.93)×10⁹/l,高白细胞血症占51.85%,髓外浸润占59.26%;CD56^-表达率为67.86%,白细胞计数(54.21±10.64)×10⁹/l,高白细胞血症占15.79%,髓外浸润占29.82%,比较差异具有统计学意义(P<0.05)。CD56+患儿治疗完全缓解率为62.96%、死亡率为7.41%,CD56^-患儿完全缓解率66.67%、死亡率8.77%,比较差异无统计学意义(P>0.05);CD56⁺达完全缓解的患儿随访期间复发率76.47%、持续缓解率为23.53%,平均生存时间(10.92±4.71)个月,CD56^-患儿复发率28.95%、持续缓解率为71.05%、平均生存时间(15.15±8.12)个月,比较差异具有统计学意义(P<0.05)。结论CD56⁺表达的14岁以下AML-M5患儿高白细胞血症、髓外浸润发生及复发率较高,平均生存时间较短。CD56表达能够为患儿的治疗及预后提供指导信息。     

Prognostic Factors in Acute Promyelocytic Leukemia: A Retrospective Study of 67 Cases

In a cohort of 67 adult patients with newly diagnosed untreated acute promyelocytic leukemia (APL), the initial clinical and biological parameters were submitted to multivariate analysis for potential prognostic significance. Median age of the patients was 40 years and the hematologic characteristics of the patients were those regularly seen. Complete remission (CR) was achieved in 43 cases (64%). Fourteen patients died within 4 weeks of diagnosis, due to severe hemorrhage. Factors predictive of hemorrhagic death in the multivariate analysis were hyperuricemia (p = 0.001), splenomegaly (p = 0.009), anemia (p = 0.02), high serum levels of LDH (p = 0.02), increased prothrombin time (p = 0.04), and hypercreatininemia (p = 0.05). Pretreatment patient characteristics for poor prognosis and achieving CR were hyperuricemia (p = 0.0002), splenomegaly (p = 0.01), anemia (p = 0.02), and lymphadenopathy (p = 0.04). The median disease-free survival (DFS) was 15.6 months. Poor prognostic factors for DFS were hyperuricemia (p = 0.007), and splenomegaly (p = 0.03). Maintenance chemotherapy had no statistically significant impact on CR duration. Median survival duration was 10 months. Poor prognostic factors for survival were hyperuricemia (p = 0.0005), and elevated serum LDH levels (p = 0.01).     

Clofarabine in the Treatment of Elderly Patients with AcuteMyeloid Leukemia

Background: Elderly patients with acute myeloid leukemia (AML) have a poor outcome because of comorbidities,poor tolerance to intensive chemotherapy and inherently more resistant disease. Clofarabine is asecond generation nucleoside analogue which has shown promising activity in elderly patients with AML. Thisstudy was conducted to review the outcome of treatment with clofarabine in a group of such patients. Methods:The records of 5 elderly patients who were diagnosed to have AML and treated with clofarabine over a 12month period were reviewed retrospectively. Results: There were 2 female and 3 male patients with a medianage of 68 years (range 65-82). At the time of treatment, 2 patients had newly diagnosed AML not consideredsuitable for intensive therapy, while 3 patients had partial or no response to conventional chemotherapy. Theoverall response rate was 100%, all patients achieving a complete remission. Induction and consolidation werewell tolerated. All patients developed neutropenia with a median duration of 20 days (range 17-42). One patientdeveloped hand and foot syndrome and a generalized rash but recovered. There was no mortality and all patientsremained in remission after a median follow-up of 5.2 months (Range 3-10). Conclusion: Clofarabine (alone orin combination) is active in elderly AML patients with an acceptable safety profile and should be considered apotential option in this group.     

Correlation between Intracellular and Extracellular Lysozyme in Acute (Myelo)Monocytic Leukemia

The localization of myeloperoxidase (MPO) or lysozyme was studied in leukemic cells by electron microscopy in an attempt to investigate why the level of lysozyme activity increases in the serum of patients with acute (myelo)monocytic leukemia. The specimens were obtained from 3 patients with acute monocytic leukemia and 4 with acute myelomonocytic leukemia with extremely elevated serum lysozyme levels (more than 100 μg/ml, normal: ∼10µg/ml). The granules containing MPO or lysozyme, surrounded by microfilaments, were observed in the periphery of the cytoplasm. MPO positive granules were considered tot contain lysozyme. Some granules appeared to be degranulation from the cell-membrane of viable leukemic cells. This observation supports the concept that there is a mechanism by which lysozyme-positive granules degranulation from viable leukemic cells and as a result the level of lysozyme activity becomes elevated in the serum. It also appears that MPO is discharged into the serum at the same time as lysozyme: is released.     

地西他滨联合参麦注射液治疗儿童急性髓系白血病的临床研究

目的 探讨地西他滨联合参麦注射液治疗儿童急性髓系白血病的疗效、安全性.方法 将急性髓系白血病患儿80例随机分为对照组40例和治疗组40例.对照组给予地西他滨和减量FLAG联合方案.治疗组在对照组基础上予参麦注射液20 mL,1次/天,连续21 d.比较2组中医证候积分、不良反应情况、临床疗效及死亡率等.结果 治疗后,治疗组患儿的发热、口干和乏力积分明显少于对照组(P＜0.01).治疗组患儿的不良反应发生率均少于对照组,其中中性粒细胞减少和肝损伤明显少于对照组(P＜0.05).治疗组的总有效率为77.5％,显著高于对照组为55.0％(P＜0.05).治疗组患儿的复发率和死亡率分别为22.5％和17.5％,均明显少于对照组的47.5％和40.0％ (P ＜0.01).结论 地西他滨联合参麦注射液治疗儿童急性髓系白血病具有增效减毒的作用,且可降低死亡率,值得临床借鉴.     

Prognostic Relevance of DNMT3A,FLT3 and NPM1 Mutations in Syrian Acute Myeloid Leukemia Patients

Objective: Among all types of hematological neoplasms, acute myeloid leukemia (AML) has the highest death rate. Recently, cytogenetic and molecular genetics are crucial in the management, as a consequence of their effect on AML pathogenesis, classification, risk-stratification, prognosis and treatment. Methods: 100 Syrian adults with Normal Karyotype (NK) newly diagnosed  AML patients were included in this study, all cases confirmed histologically and immunohistochemically. Patients were divided into six subgroups using flow cytometry and cytological results. Polymerase chain reaction (PCR) was performed on exon 11-12 for FMS-like tyrosine kinase-3 internal tandem duplication (FLT3-ITD), exon 12 for Nucleophosmin1 (NPM1), and exon 23 for DNA methyltransferase 3A (DNMT3A) using target primers, the electropherograms were analyzed for gene mutations by comparing with the reference DNA sequence. Data were compared and aligned with different sequences using the NCBI BLAST Assembled Genomes tool. Results: FLT3-ITD, NPM1 and DNMT3A were detected in 24%, 22 % and 4%  patients respectively. M2 subtype had the most frequent incidence of diagnosis in AML. FLT3-ITD mutation patients had the highest mean of death cases, while the DNMT3A mutation patients had the lowest. On the other hand, the highest mean of remission was in patients with NPM1 mutation and the lowest in the carriers of the FLT3-ITD mutation. It was observed that the mean relapsed patients with FLT3-ITD and DNMT3A mutation was 3.4 and 2 months respectively, with no significant differences between (FLT3-ITD and DNMT3A) carriers and non-carriers relapsed. On the contrary,  the mean relapsed for NPM1 mutation carriers was 2.4  months with significant statistical differences. The mean survival time for patients with FLT3-ITD and NPM1  mutation was 5.9 months and 5.85 months respectively, with significant correlation. Between it was 5.88 months in DNMT3A patients with no significant differences. Finally, It was noted that the mean event free survival (EFS) of FLT3-ITD mutation patients was 4.818 months and the mean EFS of NPM1 mutation patients was 4.805 months, with significant statistical differences (p<0.05) between the mutation patients and non-mutated patients regarding to EFS, While this mean was not statistically significant in patients carrying DNMT3A mutation. Conclusion: Patients with FLT3-ITD and NPM1 mutations have the worst prognosis, where the presence of those mutations was significantly related to overall survival (OS) and EFS. Our study reflects that DNMT3A was not an extremely bad prognostic effect as an independent factor. We can declare according to this study that genetic mutation and variants detection could easily be incorporated into the regimen evaluation of AML patients.     

WT1 Expression in Peripheral Blood at Diagnosis and During the Course of Early Consolidation Treatment Correlates With Survival in Patients With Intermediate and Poor-Risk Acute Myeloid Leukemia

BackgroundUp to 55% of non-APL acute myeloid leukemias (AML) lack a molecular target suitable for standardized disease monitoring. We aimed to evaluate the prognostic significance of WT1 gene expression at early stages of intensive treatment.Patients and MethodsA total of 106 consecutive patients with intermediate and high-risk AML who had WT1 expression at diagnosis >500 copies/10⁴ ABL and who achieved remission after 1 to 2 cycles of induction treatment were analyzed. WT1 expression was measured in peripheral blood using a standardized European LeukemiaNet method. Overexpression was defined as >50 copies/10⁴ ABL. The median follow-up was 30 months.ResultsPatients with normal versus high WT1 expression after 2 cycles of chemotherapy had overall survival (OS) at 3 years of 66% versus 41% (P = .01); event-free survival (EFS) 45% versus 22% (P = .01). Prognostic significance of WT1 expression after 2 cycles of treatment was maintained in the group of patients treated with chemotherapy alone without hematopoietic stem cell transplantation in first line treatment (OS 70% vs. 36%, P = .02; EFS 35% vs. 0%, P = .03). Significant prognostic factors for EFS on multivariate analysis were the achievement of molecular remission (<50 copies of WT1) at any time during treatment (hazard ratio [HR] 0.47, P = .04) and increased WT1 expression after 2 cycles of chemotherapy (HR 2.0, P = .03).ConclusionIncreased WT1 expression after 2 cycles of chemotherapy is a negative prognostic factor for survival. WT1 remains a valuable molecular marker in AML without any leukemia-specific mutation, especially if next generation sequencing and/or digital polymerase chain reaction are not routinely available.     

Prognostic Factors in Children with Acute Lymphoblastic Leukemia -- Part I: Univariate Analysis --

The pretreatment characteristics of 158 children with previouslyuntreated acute lymphoblastic leukemia diagnosed April 1972to June 1978 were analyzed for their ability to predict prognosis.The children were treated according to therapeutic protocols721, 745 and 765, by members of the Japanese Children's Cancerand Leukemia Study Group. A univariate analysis was performed to determine the relationshipbetween the characteristics and the duration of the patients'survival. The following characteristics were analyzed: initialwhite blood cell (WBC) count, age at diagnosis, initial hemoglobinlevel, initial platelet count, sex, organomegaly. and treatmentregimen that was provided. Favorable prognosis was exhibited only by those patients withinitial WBC counts of less than 50,000/mm³, with age at onsetbetween 2 and 6 years, without splenomegaly, and with hemoglobinlevels between 5 and 10 g/dl. The most significant contributions among the various individualprognostic factors were initial WBC count (p < 0.001) andthe age at diagnosis (p < 0.01).     

MDR1 RNA Expression as a Prognostic Factor in Acute Myeloid Leukemia: An Update

In order to confirm our initial report on the negative impact of MDR1 gene expression on the outcome of de novo acute myeloid leukemia (AML), we present an update of our prospective study with a larger number of patients and a longer duration of follow-up. At diagnosis, MDR1 RNA expression of the leukemic cells was negative in 37% and positive in 63% of the patients (N = 79). The complete remission rate of induction chemotherapy was 76% for MDR1 RNA negative and 54% for MDR1 RNA positive patients (p = 0.05). At a median observation duration of 33 months, the duration of overall survival was 19 months for the MDR1 RNA negative patients but only 8 months for the patients with MDR1 gene expression (p = 0.02). Thus the long-term data also indicate that MDR1 gene expression is an unfavourable prognostic factor in AML.     

Acute Myeloid Leukemia Possibly Producing Thrombopoietic Factor(s)

A 75-year-old man developed a cluster of differentiation (CD)4-positivebut human T-cell lymphotropic virus type I (HTLV-I)-negativeT lymphoid neoplasm with overwhelming cutaneous involvementand mild thrombocytosis. Twelve courses tetrahydropyranyl adriamycin,cyclophosphamide, vincristine and predonisone (THP-COP) combinationchemotherapy led him to complete remission. After four monthsof complete remission, however, atypical immature cells (blasts)appeared in peripheral blood and bone marrow. Surface markeranalysis revealed the blasts to be CD2–, CD3–, CD4–,CD5–, CD7+, CD8–, CD10, CD13±, CD19–,CD20–, CD25–, CD33+ and human leukocyte antigen-DR(HLA-DR+). Staining for myeloperoxidase, esterases, PAS andplatelet peroxidase were all negative. The patient was diagnosedas having both CD7 and CD33 positive acute myeloid leukemia(AML). The relation between the T cell lymphoid neoplasm andAML was not clear. Thrombocytosis became more marked after acuteleukemia occurred and the platelet count varied in parallelwith the blast cell count in peripheral blood. When the leukemiccell count was high, thrombopoietic activity could be detectedin the serum. In addition, conditioned medium obtained fromprimarily-cultured blasts had detectable thrombopoietic activity,which implied the blasts directly to produce a thrombopoieticfactor(s). Analysis of the serum concentration for cytokineswith associated thrombopoietic activity indicated that the blastspossibly produced a thrombopoietic factor(s) distinct from interleukin(IL)6, IL3, leukemia inhibitory factor (LIF), erythropoietinand granulocyte macrophagecolony stimulating factor. To ourknowledge, this is the first reported case of an acute myeloidleukemia with marked thrombopoiesis (more than 2000x10³/µlof maximum platelet count in peripheral blood).