急性混合谱系融合基因阳性急性白血病患儿的临床特点

目的分析混合谱系白血病(MLL)融合基因阳性的急性白血病(AL)患儿临床特点,探讨其治疗措施及其预后相关因素。方法选取细胞形态学、分子生物学、免疫分型及巢式反转录聚合酶链反应(RT-PCR)检测MLL融合基因阳性AL患儿51例,对其临床表现、治疗及预后进行回顾性分析。结果51例MLL融合基因阳性AL患儿中急性淋巴细胞白血病(ALL)37例,急性髓细胞白血病(AML)14例。42例涉及11号染色体改变;RT-PCR检测有36例MLL基因重排,15例为串联重复。32例接受正规治疗的AL患儿中24例完全缓解,其中ALL19例,AML5例;缓解时间持续2 a以上者ALL5例,AML仅1例;持续缓解存活者仅16例,ALL12例,AML4例;10例MLL融合基因已转阴,并持续存活。在随访6 a中,32例中复发6例,均为骨髓复发,死亡6例。结论MLL融合基因阳性AL患儿发生率低,化疗效果差,易复发,预后差。少数对化疗敏感的AL患儿MLL融合基因可转阴,并持续存活。     

DEK-NUP214融合基因阳性儿童急性髓系白血病7例分析

目的探讨DEK-NUP214融合基因阳性儿童急性髓系白血病(AML)的临床特征、治疗方案和预后。方法回顾性分析2015年5月至2022年2月中国医学科学院血液病医院儿童血液病诊疗中心收治的7例DEK-NUP214融合基因阳性AML患儿临床特征、遗传和分子学结果、治疗和生存情况。结果 DEK-NUP214融合基因阳性的AML占同期诊断AML的1.02%(7/683)。7例患儿中男4例、女3例, 发病年龄8.2(7.5, 9.5)岁。骨髓原始细胞比例为0.275(0.225, 0.480), 6例FAB分型为M5, 除1例不详外余均伴病态造血。3例携带FLT3-ITD基因突变, 4例携带NRAS基因突变, 2例携带KRAS基因突变。诊断后诱导方案为:4例IAE(伊达比星+阿糖胞苷+依托泊苷), 1例MAE(米托蒽醌+阿糖胞苷+依托泊苷), 1例DAH(柔红霉素+阿糖胞苷+高三尖杉酯碱), 1例DAE(柔红霉素+阿糖胞苷+依托泊苷)。1个疗程诱导达完全缓解者3例。4例患儿未缓解, 分别接受CAG(阿克拉霉素+阿糖胞苷+粒细胞集落刺激因子), IAH(伊达比星+阿糖胞苷+高三尖杉酯碱), CA...     

TEL-AML_1阳性儿童急性淋巴细胞白血病近期疗效分析

目的探讨TEL-AML1融合基因阳性儿童急性淋巴细胞白血病(ALL)的临床和预后特征。方法应用RT-PCR技术,对213例初诊ALL患儿骨髓进行t(12;21)染色体检测和TEL-AML1融合基因检测。结果213例ALL中25例(11.7%)存在t(12;21)染色体改变和TEL-AML1融合基因阳性,25例患儿发病时平均年龄5.8岁(2～10岁),均为非T细胞系免疫表型,以普通型ALL为主,经诱导化疗后全部得到完全缓解。结论t(12;21)/TEL-AML1表达是儿童ALL较为常见的遗传学改变,该类型儿童ALL经化疗预后良好。     

多重RT-PCR检测儿童急性髓细胞性白血病融合基因的临床与实验研究

目的研究儿童急性髓细胞性白血病(AML)染色体畸变所形成融合基因的临床和实验关系。方法采用多重巢式RT_PCR方法对38例儿童AML的融合基因联合染色体核型分析、免疫表型、临床资料进行研究。结果38例儿童AML中有23例(60.53%)具有4种融合基因:MLLex7/AF9、TLS/ERG、AML1/ETO、PML1RARα。8例患儿有HOX11原癌基因活化,7例为单纯表达HOX11原癌基因活化,1例同时伴有其他融合基因表达。伴AML1-ETO、PML-RARα的20例患儿中接受化疗的11例全部达CR,且无复发。结论基因分型是儿童AL最精确的分型方法,为临床化疗提供方向:AML表达HOX11者预后不良;伴MLL基因重排者预后极差。采用多重RT-PCR方法可快速同时检测儿童急性白血病29种染色体畸变所形成的融合基因,完善白血病的MICM分型、指导临床个体化治疗。     

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。     

混合谱系白血病基因重排与急性白血病

混合谱系白血病(Mixed Lineage Leukemia,MLL)基因位于11q23,该基因重排是造血系统恶性肿瘤中常见的改变.MLL基因重排阳性的急性白血病(Acute Leukemia,AL)从出生至成人期均可发生,表现为急性淋巴细胞白血病(Acute Lymphoblastic Leukemia,ALL)或急性髓细胞白血病(Acute Myeloid Leukemia,AML).在儿童ALL中发生率大约为6%,其中80%为婴儿ALL.在儿童AML中发生率大约为14%,其中65%为婴儿AML[1].此类白血病具有独特的临床和生物学特征,通常表现为高白细胞计数,对常规化疗不敏感,完全缓解率(Complete Remission,CR)低,生存期短,其中年龄小于1岁的患者预后更差[2].目前WHO已将其单独列为11q23/MLL白血病.现就MLL基因的结构、功能及其异常在引发白血病中的作用方面做一综述,以期为今后开展新的临床治疗提供帮助.     

血管内皮生长因子及其受体在儿童急性白血病中的表达以及临床意义

目的探讨血管内皮生长因子(vascular endothelial growth factor,VEGF)及其受体(vas-cular endothelial growth factor,VEGF)在儿童急性白血病骨髓中的表达,以及化疗前后的变化。方法53例儿童急性白血病患儿,其中急性淋巴细胞白血病(acute lymphocytic leukem ia,ALL)33例,急性髓系细胞白血病(acute myeloid leukem ia,AML)20例,对照组21例为骨髓象正常的非恶性血液病患儿。采用免疫组化方法检测53例急性白血病患儿治疗前后以及对照组骨髓中VEGF/VEGFR(包括Flt-1和KDR两种)的表达。结果VEGR、Flt-1、KDR在急性白血病患儿骨髓中表达水平高于对照组,在AML组中的表达高于ALL组。化疗后获得完全缓解(CR)的40例患儿,其VEGF、Flt-1、KDR的表达在化疗前后差异有显著性(P<0.05);化疗后未获得CR患儿VEGF、Flt-1、KDR的表达在化疗前后无显著性(P>0.05)。同时VEGF、KDR在儿童ALL中化疗后有明显的降低,但Flt-1无明显改变;VEGF、Flt-1、KDR在儿童AML中化疗后均有明显的降低。结论①VEGF、Flt-1、KDR在儿童急性白血病中表达增高。提示VEGF、Flt-1、KDR在儿童急性白血病的发生过程中起着重要作用。②VEGF、Flt-1、KDR在儿童AML中表达比ALL高。VEGF可以作为评价儿童急性白血病化疗反应的指标,同时说明ALL与AML可能具有不同的血管新生机制。     

儿童混合表型急性白血病15例临床特征分析北大核心CSCD

目的分析儿童混合表型急性白血病(MPAL)的临床特点、治疗及预后, 为临床优化诊疗方案及提高缓解率提供参考。方法基于2016年世界卫生组织(WHO)的诊断标准, 回顾性分析2012年1月至2020年12月苏州大学附属儿童医院收治的15例MPAL患儿的骨髓细胞形态、免疫分型、细胞遗传学、分子生物学特征以及治疗方案、预后等病例资料。计数数据组间比较采用χ^(2)检验, 符合正态分布的计量资料组间比较采用t检验, 非正态分布的计量资料组间比较采用秩和检验。采用Kaplan-Meier(K-M)法估计生存率, 比较应用Log-rank法。结果苏州大学附属儿童医院8年共收治15例MPAL患儿, 男8例, 女7例, 中位年龄为6.8岁;9例患儿表达B淋系+髓系表型, 5例表达T淋系+髓系表型, 1例表达B淋系+T淋系表型;11例患儿进行了染色体核型检查, 2例为正常核型, 2例为复杂核型, 6例为假二倍体, 1例为亚二倍体;5例患儿检测到融合基因, 其中3例AML-ETO阳性, 1例BCR-ABL阳性, 1例MLL阳性;13例患儿在化疗后完全缓解, 总完全缓解率为86.6%, 2年总生存率为(68.2±13.4)%。15例患儿中14例授受了诱导化疗, 1例因个人原因放弃了治疗。首选急性淋巴细胞白血病(ALL)化疗方案10例, 第1个疗程完全缓解1例, 总完全缓解率10%;首选急性髓系白血病(AML)化疗方案4例, 第1个疗程完全缓解3例, 总完全缓解率75%, 未缓解的1例更换ALL方案后缓解;8例行造血干细胞移植(HSCT)和6例未行HSCT组2年总生存率分别为(70.0±18.2)%、(66.7±19.2)%, 差异无统计学意义(χ^(2)=0.318, P=0.573)。结论儿童MPAL是一种罕见的恶性肿瘤, 以淋系和髓系抗原共表达为主, 单纯化疗或HSCT在短期内均可获得较好的预后, 但长期疗效还有待进一步观察。     

21例伴有AML1/ETO融合基因表达的儿童急性非淋巴细胞白血病的分析

目的 对急性髓细胞性白血病1(AML1)／ETO(eight twenty one)融合基因阳性及阴性的两组病例的主要临床指标进行比较分析,并探讨AML1／ETO融合基因检测在儿童急性非淋巴细胞白血病(ANLL)的临床诊断及预后判断中的意义。方法 采用巢式逆转录聚合酶链反应(RT-PCR))检测白血病患儿AML1／ETO融合基因,并进行法-美-英(FAB)及形态学-免疫学-细胞遗传学(MIC)分型。诱导治疗主要采用柔红霉素、阿糖胞苷(DA)、DA 依托泊甙(足叶乙甙,DAE)、柏林-法兰克福-慕尼黑(BFM)方案。结果 在21例AML1／ETO融合基因表达的ANLL中,经FAB及MIC分型,17例为急性粒细胞白血病部分分化型(M2),占81％,另外4例分别是骨髓异常增生综合征-转化中的原始细胞增多的难治性贫血(MDS—RAEB—T)后转为M2型1例,急性粒单细胞白血病伴嗜酸细胞增多(M4EO)1例,急性单核白血病(M5)1例和嗜酸性粒细胞白血病1例。可评定疗效的20例中,18例达到完全缓解(CR),CR率达90％。8例同期收治的ANLL无融合基因和基因异常的病例,CR率达87．5％。结论 AML1／ETO融合基因阳性及阴性的两组病例,在各主要临床指标方面差异没有显著性。采用RT—PCR检测白血病患儿AML1／ETO融合基因是一种快速、简便、灵敏的辅助诊断方法,对ANLL的诊断及预后判断有重要的临床价值。     

多重RT-PCR检测儿童急性淋巴细胞白血病融合基因的临床研究

目的研究急性淋巴细胞白血病（ALL）患儿染色体畸变所致融合基因与临床危险度分层及治疗的关系。方法采用多重RT-PCR方法检测儿童ALL的常见融合基因,结合染色体核型分析、免疫表型及临床资料对152例ALL患儿进行临床研究。结果152例ALL患儿中有43例（29．5％）具有9种常见融合基因表达,包括 TEL/AML1、BCR/ABL（P190）、BCR/ABL（P210）、E2A/PBX1、MLL/ENL、MLL/AF9、TLS/ERG、CBF/MYH11、Hox11。TEL/AML1融合基因阳性23例,其中1例放弃治疗,1例因早期治疗反应不良,评估为高危,其他21例均早期治疗反应良好,目前停药10例（停药时间4～30个月）,11例仍为完全缓解（CR）,1例停药18个月后骨髓复发。E2A/PBX1融合基因阳性4例,其中3例评估为中危,目前均CR中,1例因早期治疗反应不良,评估为高危,化疗过程中复发死亡;BCR/ABL（P190）阳性5例,BCR/ABL（P210）阳性3例,其中5例行骨髓移植治疗（4例移植后数月骨髓复发,1例CR中）,1例选择高危方案化疗后骨髓复发,另外2例临床未缓解,放弃治疗;MLL基因阳性2例,均评估为中危,1例MLL/AF9,经强化疗后目前已停药18个月,1例MLL/ENL,在化疗过程中复发,放弃治疗;TLS/ERG融合基因1例,早期治疗反应不良,经强化疗后达CR,目前已停药20个月;Hox11融合基因阳性4例,均评估为中危,化疗后3例CR中,1例因复发放弃治疗。结论 TEL/AML1表达者化疗效果良好;BCR/ABL、MLL基因重排等化疗效果差,需骨髓移植或强烈化疗。采用多重RT-PCR方法可快速同时检测儿童急性白血病29种常见融合基因,完善白血病的MICM分型、指导临床个体化治疗。     

Down syndrome and leukemia: unusual clinical aspects and unexpected methotrexate sensitivity

Twenty-four patients with Down syndrome and leukemia were studied. A strong male predominace (79%) was found. Age ranged between 18 months and 15 years (mean: 5 6/12); 54% of the patients were less than 4 years of age at the time of diagnosis. A preleukemic phase was noted in 6/24 patients. This phase, characterized essentially by thrombocytopenia, lasted from 2–8 months. Patients with preleukemia had unusual blast cell morphology and involvement of more than one cell line (dyserythropoiesis, hypolobulated megakaryocytes) and were probably M₇ leukemias. All patients demon-strated severe methotrexate toxicity at standard methotrexate doses. Toxicity, manifesting as mouth ulcerations and bone marrow depression was seen regardless of the route of administration (oral, intrathecal or intravenous). A 30%–50% reduction of the standard dose was tolerated. Methotrexate absorption and clearance were studied in two patients and were found to be normal. We postulate that the observed toxicity of methotrexate may be due to a gene dosage effect for enzymes known to be on chromosome 21 and intervening in purine metabolism. Increased purine synthesis implies greater tetrahydrofolic acid demands and therefore greater sensitivity to an antifolate agent.Abbreviations All acute lymphoblastic leukemia - AML acute myelogenous leukemia - MTX methotrexate - 6-MP 6-mercaptopurine - ITP idiopathic thrombocytopenic purpura - IV intravenous - po oral administration     

Clinico-Hematological profile of congenital leukemia

Congenital leukemia is a rare disorder that usually presents with extramedullary infiltrates and myeloid phenotype in 80% cases. The authors present 4 cases of congenital leukemia diagnosed over 11 year period, three of which were of acute lymphoid leukemia and one was of biphenotypic leukemia.     

细胞外信号调节激酶-1的表达与儿童急性白血病近期疗效关系的研究

目的 探讨细胞外信号调节激酶-1（extracelluar signal-regulated kinase-1，ERK1）的表达与儿童急性白血病（AL）的关系。方法 50例儿童AL（AL组）和26例完全缓解AL（AL-CR组）患者为病例组，23例非肿瘤性疾病患者为对照组。采用超敏SP免疫组织化学法，检测病例组、对照组骨髓细胞中ERKI的表达情况。结果 ERKI阳性率在AL组为68％，明显高于AL-CR组和对照组（P〈0．01）：在高危AL中阳性率分别为90．91％，明显高于标危AL（P〈0．01）。16例化疗前ERKI阳性率为75％，化疗缓解后阳性率为0（P〈0．01）。结论 AL患者ERKI的过度表达率较高，可作为近期疗效观察的指标。     

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目的探讨细胞周期蛋白D3、E的表达与儿童急性白血病(AL)的关系。方法采用免疫组织化学法,对广西医科大学第一附属医院儿科2002年1月至2004年5月收治的50例初发或复发儿童AL,其中急性淋巴细胞白血病(ALL)30例(高危ALL12例,标危ALL18例),急性非淋巴细胞白血病(ANLL)20例,和26例完全缓解AL(AL CR)患儿,以及23例同期住院的非恶性疾病患儿(对照组),检测其骨髓细胞中细胞周期蛋白D3、E的表达情况。结果AL组中细胞周期蛋白D3、E阳性率分别为54%和46%,高于AL CR组和对照组(P<0.01);在ALL和ANLL间差异无显著性(P>0.05)。高危ALL细胞周期蛋白D3阳性率明显高于标危ALL(P<0.01)。化疗前细胞周期蛋白D3、E表达阳性率明显高于化疗缓解后(P<0.01)。细胞周期蛋白D3、E在AL组中的表达呈正相关(r=0.5298,P<0.01)。结论细胞周期蛋白D3、E与儿童AL发病有关,它们的表达存在相关性,可作为疗效观察的指标;细胞周期蛋白D3可能与患儿不良预后有关。     

The results of high risk children's acute lyrnphoblastic leukemia total therapy. A report from the Polish children's leukemia/lymphoma study group

The study evaluates the efficacy of seven drug systemic therapy and three drug intrathecal treatment in children with acute lymphoblastic leukemia (ALL). Three hundred and thirty-five children with ALL treated at six hematological centers in Poland were divided into two groups: standard group and high risk group according to the BFM score method. Ninety-two children estimated as high risk patients diagnosed between 1978 and 1981 were treated according to the Polish Children's Leukemia/Lymphoma Study Group (PCLSG) program adopted from LSA₂L₂ regimen. The patients received prednisone, vincristine, adriamycin and cyclophosphamide as remission induction treatment, followed by cytarabin and 6-thioguanine given as consolidation therapy. The central nervous system prophylaxis consisted of cranial irradiation and intrathecal methotrexate, cytarabin and hydrocortisone. In maintenance phase, three different drug combinations were given as intermittent therapy. The total duration of therapy was 2.5 years. The life table analysis showed a 38% disease free survival and 50% complete continuous remission (CCR) for the total group of patients. A relatively high incidence of CNS relapse was observed. These results indicated that the regimen applied was not satisfactorily effective for the increased risk of ALL. Three of seven evaluated prognostic indices—age, mediastinal mass and cytochemical features—were significantly associated with probability of survival of the patients with protocol applied. Some other therapy proposals are discussed.     

The results of high risk children's acute lyrnphoblastic leukemia total therapy. A report from the Polish children's leukemia/lymphoma study group

The study evaluates the efficacy of seven drug systemic therapy and three drug intrathecal treatment in children with acute lymphoblastic leukemia (ALL). Three hundred and thirty-five children with ALL treated at six hematological centers in Poland were divided into two groups: standard group and high risk group according to the BFM score method. Ninety-two children estimated as high risk patients diagnosed between 1978 and 1981 were treated according to the Polish Children's Leukemia/Lymphoma Study Group (PCLSG) program adopted from LSA₂L₂ regimen. The patients received prednisone, vincristine, adriamycin and cyclophosphamide as remission induction treatment, followed by cytarabin and 6-thioguanine given as consolidation therapy. The central nervous system prophylaxis consisted of cranial irradiation and intrathecal methotrexate, cytarabin and hydrocortisone. In maintenance phase, three different drug combinations were given as intermittent therapy. The total duration of therapy was 2.5 years. The life table analysis showed a 38% disease free survival and 50% complete continuous remission (CCR) for the total group of patients. A relatively high incidence of CNS relapse was observed. These results indicated that the regimen applied was not satisfactorily effective for the increased risk of ALL. Three of seven evaluated prognostic indices—age, mediastinal mass and cytochemical features—were significantly associated with probability of survival of the patients with protocol applied. Some other therapy proposals are discussed.     

Granulocytic sarcoma

Granulocytic sarcoma (GS) is an extramedullary tumor mostly associated with acute or chronic myelogenous leukemia (AML). GS can virtually involve any structure in body. Rarely the tumor may be seen before the diagnosis of underlying hematological malignancies. We present two cases where GS was sole presentations, months before the diagnosis of AML.     

Current management of childhood acute lymphocytic leukemia

Despite major advances in the treatment of childhood leukmia, there remain controversies in classification, prognostic importance of clinical and laboratory investigations, intensity of induction chemotherapy, presymptomatic CNS therapy, type and duration of maintenance chemotherapy and the role of bone marrow transplantation. In this review, some of these problems are highlighted and differences between long-term results of treatment from group studies, and those reported from Melbourne are discussed.     

Lack of mitogenic effects of growth hormone on human leukemic lymphoblasts

To determine whether human growth hormone (HGH) can cause proliferation of human leukemic lymphoblasts, we studied colony formation in semi-solid medium of MOLT 4, a cell line derived from an adolescent with acute lymphoblastic leukemia (ALL). Although exposure to single doses of HGH in supraphysiologic concentrations resulted in almost two-fold increases in number of colonies compared with control samples, physiologic concentrations had no effect. Similarly, physiologic concentrations of HGH had no effect on thymidine incorporation in short-term cultures of fresh lymphoblasts from children with ALL. In addition, total white blood cell and differential counts in 14 children with isolated growth hormone deficiency were reviewed pre- and post-treatment with HGH. In no case was there evidence of in vivo lymphocytosis or blastogenesis.Abbreviations HGH human growth hormone - ALL acute lymphoblastic leukemia - LCM leukocyte conditioned medium - PHA phytohemagglutinin - WBC white blood cell     

ADEP方案双诱导加HAD方案治疗儿童急性粒细胞和急性粒单核细胞性白血病临床疗效分析

目的　分析初治急性粒细胞性白血病 (急粒 )和急性粒单核细胞性白血病 (M4)患儿用ADEP(阿糖胞苷、柔红霉素和依托泊苷 )方案双诱导加HAD(大剂量阿糖胞苷和柔红霉素 )方案的疗效。方法　总结 1991年 7月至 1999年 12月北京大学人民医院 2 6例急粒和 10例M4其中男 2 1例 ,女 15例 ,EFS(长期无病生存 ) 3年以上 ,停药 2年以上 ,中位EFS 7年 ,随访时间至 2 0 0 2年 12月。结果　 (1)用ADEP诱导治疗一个疗程完全缓解率 (CR)91% ,粒细胞白血病EFS率 5 0 % ,M4EFS率 5 7% ,中位生存时间 7年。 10例复发患儿 83%在 6～ 10个月内复发。(2 )大剂量阿糖胞苷 1g/m2 每日 2次持续 3d或 4d加蒽环类方案两者EFS率和复发率无差别 ,但在疗程中 16例用Idr(去甲氧柔红霉素 )的患儿长期存活 11例 (6 8 75 % ) ,6例不用Idr的患儿长期存活 1例 (16 7% ) ,差异有显著性。结论　 (1)用ADEP双诱导方案加HAD方案 ,在疗程中用Idr,有高的CR率和较高的EFS率。 (2 )对 10例复发病例分析 ,9例有高危因素存在 ,复发时间 80 %在CR后 6～ 10个月内 ,因此有高危因素的患儿 ,最好在CR 4～ 6个月期间行造血干细胞移植治疗