688例儿童急性白血病群体生物学特征现况调查——单中心小样本研究

目的：通过单中心小样本研究,探讨我国北方地区儿童急性白血病群体生物学特征。方法：对2003年10月至2006年6月于中国医学科学院血液病医院就诊的688例急性白血病患儿发病情况进行回顾性分析。结果：400例急性淋巴细胞白血病(ALL)患儿的发病高峰为1~4岁,其中B-ALL 218例,T-ALL 34例。154例ALL患儿中高超二倍体占13.0%,低超二倍体占3.9%,假二倍体占5.2%,亚二倍体占5.8%,E2A-PBX1阳性B-ALL占3.9%。222例急性髓系白血病（AML）患儿的发病高峰年龄为10~15岁,以AML-M2最多见。急性杂合性白血病（AHL）占4.2%,中位年龄9岁,74% AHL的患儿在髓系积分中主要以CD13、CD33阳性为主。结论：我国北方地区儿童急性白血病的生物学特性与其他地区及种族之间存在差异,提示在不同环境因素作用下的急性白血病的发生可能存在差别。［中国当代儿科杂志,2009,11（10）：793-796］     

Chromosomal aberrations in differential diagnosis and prognosis in childhood acute leukaemias

The purpose of our study was to determine the frequency of specific, somatic chromosomal abnormalities in children with acute leukaemia and to evaluate the usefulness of cytogenetic study and DNA analysis as diagnostic and prognostic tools in these diseases. Among 63 children with acute lymphoblastic leukaemia (ALL) and 13 with de novo acute myeloblastic leukaemia (AML), hyperdiploidy was found in 25% and hypodiploidy in 6% of patients. Normal karyotype was found in 44% whereas pseudodiploidy in 25% of children with ALL. In the group of children with AML, pseudodiploidy was found in 2 cases and normal karyotype in 11. Translocations t(12;21), t(4;11), t(6;11) and t(9;11) failed to be detected by conventional cytogenetics. They were found by molecular methods. On the other hand, the t(1;14) and t(8;14) translocations were detected exclusively by karyotype analysis. The probability of event-free survival (EFS) in the group of children with ALL and genetic abnormalities of favourable prognosis was 96% whereas in the group of children with unfavourable prognosis it was 55%. Classical cytogenetic methods together with more sensitive molecular tests allow to detect diagnostically and prognostically relevant chromosomal aberrations in childhood acute leukaemias.     

Acute myelogenous leukaemia in children

Acute myelogeneous leukaemia in childhood is considerably more resistant to chemotherapy than the acute lymphocytic leukaemias. Recently, more aggressive therapy has improved the outlook for children with this difficult form of leukaemia. Long-term disease-free survival of children achieving remission has been reported to be more than 40% in some studies. This paper reviews both the present concept of leukaemogenesis as well as some of the more recent therapeutic studies on childhood AML.Abbreviations ALL acute lymphocytic leukaemia - AML acute myelogenous leukaemia - Ara-C cytosine arabinoside - BMT bone marrow transplantation - CFU colony forming unit - CSF colony stimulating factor - G granulocyte - M macrophage - MDS myelodysplastic syndrome     

Relapsed Acute Leukemia in Children: Oman Experience

Acute leukemia (AL) is the most common malignancy in children in Oman. It accounts for over one-third of all childhood cancers, most of which (～75%) are acute lymphoblastic leukemia (ALL). Over a decade, a total of 128 cases of childhood acute leukemia have been diagnosed and managed at Paediatric Haematology/Oncology Unit, Sultan Qaboos University Hospital, which is the national referral center of pediatric leukemia cases. A retrospective review of case notes was used to study all children with a diagnosis of acute leukemia from January 1993 to January 2003. All the cases were diagnosed using a bone marrow aspirate with morphological and immunophenotypic classification. Over this period, 24 cases relapsed. They were classified as per BFM group as “very early,” “early,” and “late” according to the time from diagnosis to first relapse and were divided into isolated bone marrow (BM), extramedullary site, and combined relapse. Sixteen percent of ALL cases and 58.6% of acute myeloid leukemia (AML) cases so far relapsed. Most of the AML cases relapsed very early on in treatment. Eleven patients had combined relapse in BM and extramedullary site (9 in the central nervous system, 1 in the testicles, and 1 in the eye). The overall outcome of these patients is very poor, and only 6 patients out of 24 are still alive. In conclusion, the relapse rates of childhood AL are more or less similar to those of other reports but the overall outcome is very poor. A large majority of the patients in this study are either very early or early relapsers. Future studies including genetic and molecular analysis may be able to explain the difference in clinical outcome of these relapsed AL cases.     

儿童急性淋巴细胞白血病常见融合基因的检测及意义

目的建立逆转录-巢式PCR检测融合基因的方法,检测4种常见融合基因在儿童急性淋巴细胞白血病中阳性率,并对阳性患儿进行初步临床资料分析。方法对收治的92例初发的急性淋巴细胞白血病(ALL)患儿,于化疗开始前抽取骨髓标本1.5～2.0 ml,采用巢式RT-PCR方法检测最常见的4种融合基因:TEL/AML1、E2A/PBX1、m-BCR/ABL和AF4/MLL。结果92例ALL患儿中TEL/AML1阳性21例,阳性率22.8%,占B细胞性ALL的24.7%(20/81例);6例E2A/PBX1阳性(6.5%),在前B细胞性ALL中占20.0%(3/15例);2例AF4/MLL阳性(2.2%),在婴儿ALL中占33.3%(2/6例);仅检测到1例m-BCR/ABL阳性(1.1%)。结论巢式RT-PCR方法是检测融合基因有效、敏感的方法。TEL/AML1在儿童ALL中阳性率最高,尤其是在B细胞性ALL中,该融合基因阳性的患儿病情较轻。     

福建医科大学附属协和医院住院儿童白血病初发病例资料分析

目的分析2000年至2007年福建医科大学附属协和医院住院儿童白血病的初发病例资料,为儿童白血病的防治提供参考依据。方法采用SPSS13.0分析软件对收集到的2000年至2007年福建医科大学附属协和医院初发儿童白血病资料进行统计分析。结果儿童白血病初发病例数由2000年66例上升到2007年的91例,平均年增长速度为4.1%。初发病例数的增加可能与环境因素的变化有关。2000年至2007年初发病例共597例,型别最多为ALL(65.7%),其次为AML(29.5%),CML(4.0%);ALL初发例数呈现逐年上升趋势,初发ALL的年龄分布以2～7岁组最多,AML则以8～14岁居多;白血病类型在性别及季节上差异无显著性。结论我院儿童白血病的初发病例数呈逐年上升趋势,提示加强儿童白血病的防治越显重要。     

Development of acute lymphoblastic leukemia following treatment for acute myeloid leukemia in children with Down syndrome: A case report and retrospective review of Children's Oncology Group acute myeloid leukemia trials

Children with Down syndrome have a 150‐fold increased risk of developing acute myeloid leukemia (AML) and 20‐fold increased risk of developing acute lymphoblastic leukemia (ALL). Although the risk of developing AML and ALL is significantly increased in children with Down syndrome, the development of both malignancies in the same patient is very rare. We describe a patient with Down syndrome who developed ALL 6 years after being diagnosed with AML. We performed a literature review and Children's Oncology Group query and discovered eight published cases and five cases of ALL following AML in pediatric patients with Down syndrome, as well as six cases of ALL following AML in non‐Down syndrome patients. There was a similar cumulative incidence of ALL after treatment for AML in the Down syndrome and non‐Down syndrome populations. Overall survival in patients with Down syndrome who developed ALL after treatment for AML was comparable to overall survival for patients with Down syndrome with de novo ALL with an average follow‐up of 7 years after ALL diagnosis. Clinical data collected were used to discuss whether this phenomenon represents a secondary leukemia, second primary cancer, or mixed‐lineage leukemia.     

160例儿童急性白血病免疫表型分析

目的　免疫表型可以确定细胞的来源和分化阶段 ,是急性白血病的重要生物学特征。该文了解儿童急性白血病 (AL)抗原表达规律、分布情况并探讨其临床意义。方法　采用流式细胞术直接或间接免疫荧光法检测 1 6 0例儿童AL的免疫表型。结果　 1 6 0例AL中 ,急性淋巴细胞白血病 (ALL) 1 1 2例 ,急性髓细胞白血病(AML) 4 8例。 1 1 2例ALL中 ,T系ALL 1 2例 (1 0 .7% ) ;B系ALL(不包括成熟B ALL) 93例 (83.0 % )。ALL中 ,1 3.8%有髓系抗原表达 ,以CD33阳性最常见 ;AML中 ,4 0 %有淋系抗原表达 ,以CD7阳性率最高。儿童AML淋系抗原表达阳性率高于儿童ALL髓系抗原表达 (P <0 .0 1 )。CD1 4在儿童M 4和M 5的表达频率为 77.8%。B系ALL中CD34阳性率 5 8.5 %。AML中 ,CD34的表达频率为 5 5 .3% ,其中M1和M 2的CD34阳性率为 76 .5 % ,高于其它AML病人的CD34阳性率 (4 3.3% ) ,P <0 .0 5。HLA DR抗原在M 3的表达频率为 1 1 .1 % ,低于其它类型AML病人的HLA DR阳性率 (76 .3% ) ,P <0 .0 1。B系ALL中 ,CD34表达与FAB分型、起病时白细胞数、髓外侵润情况均无关 (P >0 .0 5 ) ;CD34-组婴幼白血病发生率 (1 7.6 % )高于CD34+ 组 (4 .2 % ) ,P <0 .0 5。结论　HLA DR阴性对于M3的诊断具有一定参考价值。     

多色流式细胞术在222例儿童急性白血病免疫分型中的应用

目的　探讨多色流式细胞术在儿童急性白血病 (AL)免疫分型中的应用价值 ,了解儿童AL抗原表达规律和免疫亚型的分布情况。方法　采用CD45/侧散射 (SSC)双参数散点图设门方法进行三色或四色流式细胞术细胞表面及浆内分化抗原的分析。结果　 2 2 2例儿童白血病免疫分型可分为 4类 :未分化型占 0 9% ,急性髓细胞性白血病 (AML)占 35 1% ,急性淋巴细胞白血病 (ALL)占5 5 9% ,混合型急性白血病占 8 1%。 12 4例儿童ALL中 ,B淋巴细胞白血病 (B ALL)占 75 8% ,T淋巴细胞白血病 (T ALL)占 2 4 2 %。AML伴淋巴系抗原表达为 2 4 4 % ,主要表达CD7(12 8% ) ,其次为CD19(6 4 % )和CD2 (5 1% )。B ALL及T ALL伴髓系抗原表达分别为 36 2 %及 30 0 % ,主要表达CD13(18 5 % ) ,其次为CD15(11 3% )、CD11b(6 5 % )和CD3 3 (4 3% )。CD117和CD56主要在AML中表达 ,分别为 73 3%和 38 6 % ,而在ALL中表达率极低 ,仅为 2 0 % (P <0 0 1)。胞浆内抗原CD2 2 、CD3 及髓过氧化物酶 (MPO)分别特异地表达在B ALL、T ALL及AML ,并比胞膜抗原检测更为敏感。结论　应用多色流式细胞术几乎能对所有儿童急性白血病进行准确分型 ,对儿童白血病患者的治疗方案选择及预后判断等均有重要价值。     

实时荧光定量PCR检测细胞周期蛋白C在小儿急性淋巴细胞白血病中的表达

目的：应用实时荧光定量PCR（RQ-PCR）法检测人细胞周期蛋白C(CCNC)在儿童急性淋巴细胞白血病（ALL）中的表达，以探讨CCNC基因与儿童ALL的关系。方法：提取正常儿童、初治儿童ALL骨髓组织及ALL细胞系6T-CEM的总RNA并逆转录为cDNA，应用RQ-PCR法检测CCNC的表达。结果：在正常儿童、初治儿童ALL骨髓及6T-CEM细胞系的CCNC的阳性表达率均为100%，在正常儿童CCNC基因平均相对表达强度为13.5±0.30，而在初治儿童ALL中为2.35±0.83，两者比较有统计学意义（P＜0.05）。结论： CCNC在初治ALL患儿中低表达，提示其有可能是一个抑癌基因。     

Relapsed acute leukemia in children: Oman experience

Acute leukemia (AL) is the most common malignancy in children in Oman. It accounts for over one-third of all childhood cancers, most of which (∼75%) are acute lymphoblastic leukemia (ALL). Over a decade, a total of 128 cases of childhood acute leukemia have been diagnosed and managed at Paediatric Haematology/Oncology Unit, Sultan Qaboos University Hospital, which is the national referral center of pediatric leukemia cases. A retrospective review of case notes was used to study all children with a diagnosis of acute leukemia from January 1993 to January 2003. All the cases were diagnosed using a bone marrow aspirate with morphological and immunophenotypic classification. Over this period, 24 cases relapsed. They were classified as per BFM group as “very early,” “early,” and “late” according to the time from diagnosis to first relapse and were divided into isolated bone marrow (BM), extramedullary site, and combined relapse. Sixteen percent of ALL cases and 58.6% of acute myeloid leukemia (AML) cases so far relapsed. Most of the AML cases relapsed very early on in treatment. Eleven patients had combined relapse in BM and extramedullary site (9 in the central nervous system, 1 in the testicles, and 1 in the eye). The overall outcome of these patients is very poor, and only 6 patients out of 24 are still alive. In conclusion, the relapse rates of childhood AL are more or less similar to those of other reports but the overall outcome is very poor. A large majority of the patients in this study are either very early or early relapsers. Future studies including genetic and molecular analysis may be able to explain the difference in clinical outcome of these relapsed AL cases.     

同源盒基因HOXA9在儿童急性白血病中的表达及其临床意义

目的：研究同源盒基因HOXA9在儿童急性白血病（AL）患儿骨髓单个核细胞中的表达,并探讨其临床意义。方法：采用RT-PCR方法检测46例不同时期AL患儿HOXA9 mRNA的表达水平,以15例特发性血小板减少性紫癜（ITP）患儿作为对照。结果：46例AL患儿（52份骨髓标本）HOXA9基因阳性表达率为63%,其中急性髓细胞白血病(AML)组阳性表达率（86%）明显高于急性淋巴细胞白血病（ALL）组（35%）及对照组（13%）（P<0.05）; AML组HOXA9 mRNA表达水平明显高于ALL组及对照组（P<0.05）。HOXA9在各型儿童AML中表达不同,mRNA相对表达水平依次为：M5型＞M4型＞M1和（或）M2型,而在M3型中未检测到表达。HOXA9在AML患儿高危组中的阳性表达水平较高。AML患儿初治组HOXA9基因阳性表达率及mRNA水平明显高于缓解组和对照组（P<0.05）,而缓解组与对照组比较差异无统计学意义;未缓解组HOXA9基因表达显著高于缓解组和对照组（P<0.05）。结论：HOXA9基因高表达与AL的发生相关;AML患儿HOXA9基因表达水平明显高于ALL患儿。HOXA9基因高表达者与白血病危险程度有关,且提示预后不良。因此,HOXA9基因有望成为儿童AL诊断、治疗及判断预后的一个靶点。     

急性白血病免疫分型与临床研究

目的了解儿童急性白血病(AL)免疫表型的分布情况和抗原表达规律,并与临床特征及预后相结合,为临床个体化用药提供指导。方法对85例新近诊断为AL患儿,采用CD45/SSC双参数散点设门方法进行三色流式细胞术免疫表型分析。其中胞膜抗原采用单克隆抗体三色直接免疫荧光标记法,胞浆内抗原采用双色直标法。结果1.AL 85例免疫分型:未分化型(AUL)1例,占1.2%;杂合型7例,占8.2%;急性髓性白血病(AML)18例,占21.2%;急性淋巴细胞白血病(ALL)59例,占69.4%。其中B-ALL 50例,占84.7%;T-ALL 6例,占10.2%;T/B-ALL 3例,占5.1%。2.ALL 59例中髓系抗原表达31例,占52.5%。髓系抗原表达阳性组和阴性组临床特征、治疗反应及预后方面无明显差异。3.AML患儿中有淋系抗原表达5例,占27.8%,低于ALL有髓系表达。其中以CD7阳性率最高,为60%;CD14在M4、M5表达率为75%;CD13、CD33在AM中表达率分别为83.3%、94.4%。4.混合型白血病7例。其中B/M 6例,TB/M 1例;2例在FAB分型中疑为混合型,余5例为ALL。结论应用多色流式细胞术可较好地分析每例白血病患儿,尤其是对于混合型白血病及抗原交叉表达者更有意义。     

CD56阳性伴特异髓系抗原表达的白血病5例临床和预后分析

目的 CD56阳性并伴特异髓系抗原表达的白血病在儿童罕见,但有独特的临床特点及预后,有人认为可能来源于非成熟自然杀伤(NK)细胞,但备受争议,分析其临床过程有助于加深认识。方法白血病患儿有以下特征者纳入分析:骨髓幼稚细胞细胞化学染色过氧化酶阴性(MPO-)伴免疫表型CD56+CD3-CD7+CD34+和髓系抗原+,或细胞化学MPO+伴CD56+CD3-HLA-DR-和髓系抗原+。根据文献前者被认为可能是髓系/NK前体细胞急性白血病(MNKPL),后者可能是髓系/NK细胞急性白血病(MNKL)。治疗采用高危急性淋巴细胞白血病方案,含阿糖胞苷、米托蒽醌、依托泊苷、门冬酰胺酶和甲氨蝶呤等。结果 2005-2008年,5例1～8岁男性患儿具有上述特征,4例符合MNKPL,1例符合MNKL。符合MNKPL的4例并无成人患者常见的明显髓外浸润,但有骨髓活检的2例见明显骨髓纤维化。该4例对治疗反应极其缓慢,至今3例已持续缓解20～57个月,1例死于缓解期肺炎。结论有CD56+并伴特异髓系抗原表达的儿童白血病其临床特征可能异于成人患者,用含有用于髓系和淋系白血病化疗药物的治疗方案,可能有助于改善MNKPL的预后。     

Acute and chronic kidney injury during therapy for pediatric acute leukemia: A report from the Leukemia Electronic Abstraction of Records Network (LEARN)

Children with acute leukemia are at increased risk of kidney injury. Using electronic health record data from three centers between 2010 and 2018, this study retrospectively described acute kidney injury (AKI) and chronic kidney disease (CKD) prevalence in children with acute lymphoblastic or myeloid leukemia (ALL, AML) using Common Terminology Criteria for Adverse Events (CTCAE) and Kidney Disease Improving Global Outcomes (KDIGO) definitions. AKI during therapy was 25% (ALL) and 32% (AML) using CTCAE, versus 84% (ALL) and 74% (AML) using KDIGO. CKD prevalence was low and Grade 1/Stage 2. Further investigation is needed to optimally define kidney injury in acute leukemia.     

Osteoarticular manifestations as initial presentation of acute leukemias in children and adolescents in Bahia, Brazil

OBJECTIVE: This study was to determine the prevalence and characteristics of the osteoarticular manifestations on initial clinical presentation of acute leukemias (ALs) on childhood in the state of Bahia, Brazil. MATERIALS AND METHODS: This retrospective study assessed the medical records of 406 patients with AL from January 1995 to December 2004. RESULTS: Acute lymphocytic leukemia (ALL) was diagnosed in 313 (77.1%) patients and acute myeloid leukemia (AML), in 93 (22.9%) patients, including 241 males (59.4%) and 165 females (40.6%). Age ranged from 9 months to 15 years (average: 6.18 y). The most common presenting features were fever (18.5%), musculoskeletal diffuse tenderness (15.0%), pallor (11.4%), and leg tenderness (5.7%). Prior referral to our center, the most frequent initial diagnosis was anemia (15.8%), leukemia (15.0%), amygdalitis (3.7%), and rheumatic fever (2.7%). Osteoarticular manifestations were found on 54.7% of the patients with AL, with a higher frequency among patients between 1 and 9 years of age (58.7%, P=0.0007). The presence of joint tenderness (16.2% in ALLx5.4% in AML), arthritis (26.6% in ALLx9.7 in AML), bone tenderness (26.1% in ALLx16.1% in AML), limb tenderness (49.5% in ALLx25.8% in AML), and antalgic gait (32.8% in ALLx9.7% in AML) had higher prevalence on ALL. The large joints, chiefly the knees (10.6%), ankles (9.4%), elbows (4.4%), and shoulders (3.6%) were more often affected. CONCLUSIONS: AL should be considered on the differential diagnosis of osteoarticular symptoms of unknown etiology in children.     

Survival of childhood leukemia in Singapore

The objective of this study was to evaluate the treatment outcome of children with acute leukemias at a university hospital in Singapore. Between January 1988 and January 1994, 66 children were treated, comprising 13 cases of acute myeloid leukemia (AML) and 53 of acute lymphoblastic leukemia (ALL). The 2-year disease-free survival (DFS) was computed according to the Kaplan-Meier method. The results showed that the survival for AML was poor, with a 2-year DFS of only 30%. The major cause of death for AML was leukemia and leukemia-related complications, such as hemorrhage and severe infections. In contrast, a 62% 2-year DFS was achieved for ALL. It was found that marked hepatosplenomegaly (enlarged liver and/or spleen ≥10 cm below the costal margin) at presentation correlated with a significantly shortened survival in our patients with ALL. The major cause for treatment failure in ALL was recurrence of disease. We conclude that the DFS for our patients with ALL at 2 years was fair. The treatment results for AML were poor, but the numbers are too small to make any definite conclusions. © 1996 Wiley-Liss, Inc.     

不同诊断标准下儿童急性不明谱系白血病的临床特点和预后分析

目的 探索不同诊断标准下儿童急性不明谱系白血病（acute leukemias of ambiguous lineage,ALAL）的临床特点和预后。 方法 回顾性收集2015年12月至2019年12月诊治的39例儿童ALAL的临床资料,其中34例接受治疗。根据世界卫生组织和欧洲白血病免疫学分型协作组ALAL的诊断标准,将患儿分为ALAL组（28例）和伴髓系表达组（11例）。分析比较两组患儿临床特点、治疗及预后的差异。 结果 34例接受治疗的患儿3年无事件生存（event-free survival,EFS）率和总生存率分别为75%±9%和88%±6%。采用髓系方案、淋系方案、髓系方案诱导未缓解转淋系方案患儿的3年EFS率分别为33%±27%、78%±10%和100%±0%（P<0.05）。诱导治疗后微小残留病阴性的患儿3年EFS率高于阳性患儿（96%±4% vs 38%±28%,P<0.05）。ETV6-RUNX1阳性均在伴髓系表达组,BCR-ABL1阳性、MLL-r阳性、高白细胞（白细胞≥50×10⁹/L）均在ALAL组。伴髓系表达组和ALAL组的3年EFS率差异无统计学意义（100%±0% vs 66%±11%,P>0.05）。 结论 淋系方案治疗ALAL患儿的疗效优于髓系方案,诱导治疗后微小残留病阳性提示不良预后。伴髓系表达的患儿未合并高白细胞和不良遗传学改变,预后好,提示将其按ALAL诊断和治疗时需尤为谨慎。     

Molecular findings in childhood leukemia in Brazil: high frequency of MLL-ENL Fusion/t(11;19) in infant leukemia

Translocations involving chromosome 11q23 are frequently found in pediatric leukemia, especially in infants. The mixed lineage leukemia (MLL)-AF4 fusion/t(4;11) is mostly found in acute lymphoblastic leukemia (ALL) and MLL-AF9 fusion/t(9;11) in acute myeloid leukemia (AML). We study 441 consecutive new cases of childhood leukemia diagnosed in Brazil. Chromosomal translocation was determined solely by conventional polymerase chain reaction (PCR) in 72 out of 265 ALL and in 43 out of 103 AML. MLL-AF4 fusion/t(4;11) was detected in 3 out of 265 ALL and MLL-AF9 fusion/t(9;11) in 4 out of 103 of AML. MLL-rearrangements were presented in 7 out of 23 infant leukemia, whose 5 were MLL-ENL fusion/t(11;19). No fusion MLL-AF4 fusion/t(4;11) was found. Other translocation frequencies differed from that reported for an American population suggesting interethnic differences on chromosomal translocations frequencies in acute leukemia.