儿童急性巨核细胞白血病MICM分型诊断

目的分析2例急性巨核细胞白血病(AMKL)患儿的诊断过程,探讨儿童AMKL的MICM分型诊断方法。方法细胞形态学按急性白血病FAB标准诊断分型;免疫表型检测应用流式细胞仪;细胞遗传学检测采用G显带技术分析核型;白血病融合基因采用多重巢式RT-PCR方法。结果 2例AMKL患儿均为男性,婴幼儿期发病,以出血、发热和贫血为主要表现,血小板和血红蛋白减少,骨髓原始巨核细胞异常增生超过30%;免疫分型表达CD41a、CD42b、CD61;复杂染色体核型;1例融合基因阴性,1例EVI1融合基因阳性。结论儿童AMKL较为少见,完善相关检查明确MICM分型诊断,有利于治疗及改善预后。     

儿童急性巨核细胞白血病9例分析

目的分析儿童急性巨核细胞白血病患者的临床特征、免疫表型、细胞遗传学特征,为临床诊断及进一步治疗提供相关依据。方法对我院确诊的9例急性巨核细胞白血病患者的临床表现、实验室检查进行分析。结果9例发病年龄均小于3岁,男∶女为7∶2,89%患者急性起病,89%患者因出血就诊。肝大患者占78%,所有患者均出现重度血小板减少,中度贫血患者占89%。骨髓幼稚巨核细胞均大于20%。所有患者肿瘤细胞均表达CD41抗原。3例患者伴有染色体复杂核型异常。本组患者均失访。结论1.本病临床是以出血、肝脏肿大为主要表现,其发病年龄小,急性起病、男性较多见。2.常伴血小板重度减少,免疫标记CD41细胞是急性巨核细胞白血病快捷的诊断方法,本病可伴有复杂核型。3.预后差。     

儿童骨髓增生异常/骨髓增殖性疾病临床及生物学特征分析

目的探讨儿童骨髓增生异常/骨髓增殖性疾病(MDS/MPD)的临床及生物学特征。方法对我科收治的28例MDS/NPD临床资料进行分析总结。结果临床主要以贫血、出血为首发症状,部分可见肝脾肿大;血常规示两系以上血细胞减少,骨髓中可见病态造血,幼稚细胞比例增高;染色体异常多见,可见毒-7、+8等特异性染色体核型异常。结论儿童MDS/MPD非常少见,占儿童血液系统恶性肿瘤的2%,具有与成人MDS不同的临床表现和生物学特征。     

CD20阳性儿童B系急性淋巴细胞白血病临床特点及生存分析

目的探讨儿童B系急性淋巴细胞白血病(B precursor acute lymphoblastic leukemia,B-ALL)CD20抗原表达情况与临床特点及预后的关系。方法回顾性分析广西医科大学第一附属医院儿科血液病房2005年1月-2012年8月收治的200例初诊B-ALL患儿临床特点和生存情况。结果 CD20阳性54例(27%),阴性146例(73%),两组患儿在性别、年龄、外周血白细胞计数、血红蛋白水平、血小板计数、骨髓幼稚细胞数、FAB分型、细胞遗传学改变、初诊时中枢神经系统白血病发生、临床危险度分型及诱导缓解治疗第19 d骨髓状态的差异无显著性;Kaplan-Meier曲线生存率分析显示,CD20阳性和CD20阴性组B-ALL患儿的预计3年EFS分别为(65.5±10.1)%和(70.3±5.7)%,两组差异无显著性(P=0.677)。结论 CD20在儿童B-ALL中的表达与一般临床特点及预后无关,尚不能作为B-ALL危险度的预测因素。     

儿童急性巨核细胞白血病临床特点及预后分析

目的 研究儿童急性巨核细胞白血病（acute megakaryocytic leukemia,AMKL）的临床特点及急性髓系白血病（acute myeloid leukemia,AML）03方案的疗效及预后。方法 收集2011年5月至2019年12月确诊为AMKL的47例患儿的临床资料,分析其疗效及预后因素。采用Kaplan-Meier法及log-rank检验进行生存分析。结果 47例AMKL患儿中,22例非唐氏综合征AMKL患儿使用AML03方案治疗,中位随访时间为11.4个月。非唐氏综合征AMKL患儿诱导Ⅱ后骨髓细胞学缓解率为85%,微小残留病（minimal resident disease,MRD）阴性率为79%;2年总生存（overall survival,OS）率及无事件生存（event-free survival,EFS）率分别为50%± 13%和40%±12%。单因素分析提示：免疫表型标志物CD56阳性组2年EFS率、OS率均低于CD56阴性组（P < 0.05）;诱导Ⅱ后骨髓细胞学未缓解组2年EFS率及OS率均低于缓解组（P < 0.05）;诱导Ⅱ后MRD阳性组2年EFS率低于MRD阴性组（P < 0.05）;移植与非移植患儿2年OS率与EFS率比较差异无统计学意义（P > 0.05）。结论 儿童AMKL缓解率低,预后较差。免疫表型标志物CD56阳性、早期治疗反应中的骨髓细胞学及MRD结果是影响预后的重要因素。异基因造血干细胞移植对AMKL预后无显著影响。     

伴GATA1变异的非唐氏综合征急性巨核细胞白血病2例并文献复习

目的探讨GATA1基因变异致急性巨核细胞白血病(AMKL)的临床特征。方法分析2例GATA1基因变异致AMKL的非唐氏综合征患儿的临床资料,并复习相关文献。结果例1为2岁女性AMKL患儿,无特殊面容及发育迟缓;病初骨髓染色体核型示50,XX,+8,+10,+21,+21[7]/46,XX[13];基因检测示GATA1基因变异c.52dupT;经诱导化疗骨髓缓解后复查外周血染色体示46,XX;目前无病生存。例2为1岁男性AMKL患儿,无特殊面容;病初骨髓染色体核型示47,XY,+21[10]/46,XY[10];基因检测示GATA1变异;经化疗骨髓缓解后复查染色体示46,XY;目前持续缓解中。结论提示在非唐氏综合征儿童罹患AMKL时需重视GATA1基因变异的检测。     

儿童急性巨核细胞白血病研究进展

急性巨核细胞白血病(AMKL)是一类以原始巨核细胞克隆增殖为特征的异质性血液系统恶性肿瘤.儿童发生AMKL的风险高于成人,占儿童急性髓系白血病的4％～15％.基因组学研究进一步揭示了 AMKL发病机制,为靶向治疗等药物的开发提供了科学基础.本文就儿童AMKL的风险分层、预后分析和治疗相关的最新研究进展进行了综述,为进一...     

小儿再生障碍性贫血的诊断及鉴别诊断

目的提高对小儿再生障碍性贫血(AA)诊断及鉴别诊断的认识。方法对30例CAA、17例骨髓增生异常综合征(MDS)及4例小儿急性淋巴细胞白血病前期(pre-ALL)做血象、骨髓象及骨髓活检分析。结果CAA组与MDS组血象单核细胞及血小板计数间比较(P<0·05),有显著性差异。CAA组骨髓增生低下,原始+早幼粒细胞、原始+早幼红细胞、巨核细胞明显少于MDS,各组间比较(P<0·01),有显著差异性,并见MDS各系病态造血。骨髓活检CAA组96%以上造血组织明显减少、脂肪组织明显增多,巨核细胞缺如或减少(均<2个/片),检出率9·7%,纤维组织增生检出率16·3%。MDS组70%增生良好,近60%检出红系同一阶段发育幼红细胞岛,近90%检出幼稚前体细胞异常定位(ALIP),全部病例见纤维组织增生和小巨核细胞等异常。4例pre-ALL示三系细胞减少,骨髓增生减低,巨核细胞0~6个/片,活检示脂肪组织增多,造血组织明显减少,亦可见病态造血,1~4周内转变为急性淋巴细胞白血病(ALL)。结论CAA患儿外周血细胞减少,骨髓造血功能衰竭,无病态造血。MDS外周血单核细胞增多,骨髓增生良好,具有多系病态造血;ALIP、巨核细胞形态异常及红系同一阶段发育幼红细胞岛伴纤维组织增生是其特征。pre-ALL具有CAA和MDS的临床及实验室特点,但在短期内转变为ALL又与之不同。     

肿瘤

002921米托慈醒治疗白血病机制的探讨/徐令…//实用儿科临床杂志一19”,14(5).一281,295 实验显示HL一60白血病细胞在米托葱酿的作用下,出现典型的凋亡特征,细胞形态学表现出细胞核裂解,染色质聚集,核碎裂,胞浆浓缩,有空泡形成,DNA琼脂糖电泳出现典型梯形条纹。提示米托葱醒通过诱导白血病细胞凋亡起到治疗白血病的作用。参5(张家栋) 002922小儿急性淋巴细胞白血病骨髓巨核细胞的观察/张惠…//贵阳医学院学报一2000,25(1).一32一33 67例中有16.4%的患儿巨核细胞数量正常和增高,其中幼稚型巨核细胞比例增高,颗粒型阶段明显增高,产板型阶段…     

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。     

Skeletal manifestations of pediatric acute megakaryoblastic leukemia

Once considered rare, acute megakaryoblastic leukemia (AMKL) now accounts for about 12% of all cases of de novo acute myeloid leukemia in children. Most cases of AMKL are difficult to diagnose because of their complex clinical presentation and unusual bone marrow morphologic features. In children, AMKL is often confused with metastatic solid tumors or myelodysplastic syndrome. Between January 1984 and December 1999, 43 patients were diagnosed with childhood AMKL at the authors' institution. Five of these presented with unusual skeletal lesions. These abnormalities (bilaterally symmetrical periostitis and osteolytic lesions) differed markedly from those commonly reported in association with pediatric acute leukemias. The authors present their experience and review the literature to define the spectrum of bony involvement associated with AMKL. This report will contribute to the evolving clinical characterization of this entity and increase clinicians' and radiologists' awareness of the manifestations of AMKL.     

Telomerase and the benign and malignant megakaryoblastic leukemias of Down syndrome

The most common form of leukemia in Down syndrome patients is megakaryoblastic leukemia. There are two forms of the disease. Transient leukemia (TL) is a form of megakaryoblastic leukemia that occurs in newborns with Down syndrome and usually disappears spontaneously within the first 3 months of life. Acute megakaryoblastic leukemia (AMKL) occurs in Down syndrome children within the first 4 years of life and is fatal without treatment. The megakaryoblasts of TL and AMKL are indistinguishable by light and electron microscopy; yet, TL is benign and AMKL is malignant. One of the hallmarks of many malignancies is the expression of telomerase. It is therefore hypothesized that the transient, benign form of megakaryoblastic leukemia (TL) would not contain telomerase activity, whereas telomerase would be demonstrable in the malignant form of the disease. Telomerase activity was determined in the blood and/or bone marrow aspirates in 29 cases of AMKL and 34 cases of TL. The authors found telomerase activity in 15 of 29 (52%) cases, of AMKL and in only 4 of 34 (12%) cases of TL (P < 0.001). Furthermore, three of the four telomerase-positive TL cases were particularly severe, of which two were fatal. Telomerase activity is found frequently in the leukemic cells of the malignant form of megakaryoblastic leukemia but rarely in the benign form of the disease (TL). Observations provide evidence that telomerase may be a critical factor for the malignant conversion of leukemic cells.     

CD147和基质金属蛋白酶9在非霍奇金淋巴瘤中的表达及其与预后的关系

目的 探讨CD147和基质金属蛋白酶9(MMP-9)在非霍奇金淋巴瘤(NHL)中的表达,分析表达水平与临床分期、肿块大小、血清乳酸脱氢酶(LDH)水平及与预后的关系.方法采用免疫组化方法研究病理标本中CD147、MMP-9的表达及其与临床指标之间的关系,探讨两者的相关性及其与NHL预后的关系.结果 ①免疫组化结果 :73%病例(45/62)CD147表达阳性,其中(+)11例,(++)13例,(+++)21例,阴性表达17例;81%病例(50/62)MMP-9表达阳性,其中(+)13例,(++)18例,(+++)19例,阴性表达12例;CD147与MMP-9的表达有明显相关性.②CD147的表达与临床骨髓浸润、肿块大小、LDH值以及临床分期有关;MMP-9的表达与骨髓浸润和临床分期有关.③CD147(-)～(+)组5年生存率明显高于(++)～(+++)组,同样MMP-9(-)～(+)组5年存活率显著高于(++)～(+++)组.Cox多因素风险分析提示CD147和MMP-9都是影响预后的重要因素.结论 CD147和MMP-9的表达与NHL的预后相关,高表达者预后不良.     

Acute megakaryoblastic leukemia after transient myeloproliferative disorder with clonal karyotype evolution in a phenotypically normal neonate

We report a case of transient myeloproliferative disorder (TMD) in a neonate without features of Down syndrome (DS) with clonal karyotype evolution, after apparent spontaneous resolution of TMD, but eventually progressing to acute megakaryoblastic leukemia (AMKL). The patient had petechiae, thrombocytopenia, and blastemia. Trisomy 21 with a satellited Y chromosome (Yqs) was found in proliferating blasts. A stimulated peripheral blood culture confirmed the constitutional origin of the Yqs, but did not reveal the presence of any trisomic 21 cell. By the age of 3 months, clonal chromosome evolution in the form of an interstitial deletion of the long-arm of chromosome 13 [del(13)(q13q31)] was detected along with trisomy 21 in unstimulated bone marrow cultures. However, remission was achieved without treatment at the age of 4 months. Trisomy 21 and del(13)(q13q31) were not identified in either cytogenetics or fluorescence in situ hybridization studies at that time. The child was asymptomatic until the age of 20 months when anemia and thrombocytopenia prompted a bone marrow biopsy, revealing changes consistent with AMKL. The remission proceeded by clonal karyotype evolution in a neonate with TMD demonstrates that clonal karyotype evolution does not indicate an immediately progressive disease. However, the development of AMKL after TMD in this case illustrates the increased risk for leukemia in TMD cases, even without DS. The gradual clonal evolution of the blasts in our patient suggests that "multiple hits" oncogenesis applies to TMD progression to acute leukemia.     

High-signal T2 changes of the bone marrow of the foot and ankle in children: red marrow or traumatic changes?

Background High-signal T2-weighted bone marrow changes can be found in both bone marrow edema and hematopoietic marrow and are often seen on pediatric MR images of the feet and ankle.Objective To evaluate whether high-signal T2 changes of the bone marrow seen on pediatric MRI of feet and ankles represent residual hematopoietic marrow.Materials and methods A total of 402 bones in 41 pediatric MRI studies of feet and ankles (34 children, 1–18 years) were reviewed by two observers who were blinded to the patients’ ages. The studies were reviewed for the presence of high-signal changes of the bone marrow on sagittal fluid-sensitive images. The frequency and location of these foci were correlated with the patients’ ages.Results High-signal T2 changes of the bone marrow were seen in 45/402 bones (11%) and in 24/41 patients younger than 16 years (59%). The changes were most commonly located in the calcaneus (54%), followed by the talus (35%) and navicular bone (35%), invariably at the endosteal surface. In 16 ankles, such foci were seen in the feet but not in the distal tibia/fibula. Symmetric presence (two ankles) or absence (four ankles) of high-signal marrow were seen in six of seven patients with bilateral ankles.Conclusion High-signal T2 changes of the bone marrow in pediatric feet and ankle MRIs have a symmetric, fairly consistent pattern and disappear after the age of 15 years. We believe that these high-signal areas are normal and represent residual hematopoietic marrow.