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1.
目的评估亲缘单倍体造血干细胞移植在儿童高危血液肿瘤治疗中的安全性及疗效。方法回顾性分析22例14岁及以下的高危恶性血液病患儿在接受亲缘单倍体造血干细胞移植后的并发症及疗效。结果全部患儿移植后造血干细胞植入成功。I~Ⅱ度急性移植物抗宿主病(GVHD)发生率为64%(14/22),Ⅲ-Ⅳ度为14%(3/22);慢性广泛型GVHD发生率为23%(5/22);6例无GVHD发生。至随访期末,移植早期(〈100d)相关死亡率为O,总生存率为86%(19/22),多因素分析提示移植后原发病的复发为影响总生存率的高危因素(P〈0.05),移植后未出现复发或者复发倾向、出现复发或者复发倾向的两组患儿总生存率分别为94%和60%(P=0.017)。结论亲缘单倍体因造血干细胞移植在高危儿童血液肿瘤的治疗中是安全有效的,亲缘单倍体供者为合适的供者选择。  相似文献   

2.
目的探讨后置环磷酰胺(PTCY)方案造血干细胞移植(allo-HSCT)治疗WAS的临床疗效。方法回顾性分析9例接受PTCY方案allo-HSCT治疗的WAS患儿的临床资料,包括移植前临床评分、供者情况、移植后粒细胞及血小板植入时间,移植后嵌合度及移植并发症。结果 9例患儿移植时中位年龄为15(4~108)个月,2例为同胞全相合供者,7例为半相合供者,回输移植物的单个核细胞中位数为15. 7(11. 3~27. 4)×10~8/kg,CD34+细胞中位数为9. 5 (4. 4~26. 1)×106/kg。中性粒细胞和血小板植入中位时间分别为14 (12~16) d和15 (11~29) d。中位随访时间为20(3~48)个月,所有病例均存活,仅1例患儿发生3度急性移植物抗宿主病(GVHD),无慢性GVHD,所有患儿移植后2周短串联重复序列结合聚合酶链反应(STR-PCR)检测显示为完全供者型嵌合。4例患儿发生巨细胞病毒血症,1例EB病毒血症,1例发生自身免疫溶血性贫血,3例发生免疫性血小板减少。结论 PTCY方案allo-HSCT可有效治疗WAS,该预处理方案无严重移植相关并发症,且无混合嵌合发生,并有效减少GVHD。  相似文献   

3.
目的探讨造血干细胞移植对重型先天性中性粒细胞缺乏症(SCN)的治疗效果。方法1例2岁7个月SCN患儿,经粒细胞集落刺激因子(G.CSF)治疗7个月无效后行HLA不全相合无关脐血移植,预处理采用BU/CY+Flud方案[马利兰(BU)1.2mg/kg·次,每6h一次,连用4d;环磷酰胺(CY)60mg/(kg·d),连用2d;氟达拉滨(Flud)30mg/(m^2·d),连用4d。输入脐血有核细胞11.24×10^7/kg,CD34+细胞6.41×10^5/kg。移植物抗宿主病(GVHD)的预防采用抗胸腺球蛋白+环胞菌素A+吗替麦考酚酯。移植后应用G.CSF加速造血重建。结果+17d粒细胞植入,+21d血小板植入,+20d取患儿骨髓经STR基因位点检测证实为完全供者型嵌合状态,此后嵌合稳定。+24d出现Ⅱ度GVHD;无肝静脉闭塞病、间质性肺炎、出血性膀胱炎等并发症,未出现慢性GVHD。随访14个月,前囟闭合,身高增加3cm,复查颅骨及膝关节x线片,骨质疏松明显好转,免疫球蛋白及补体正常,T细胞、B细胞亚群及NK细胞基本正常。结论本例为我国首例采用造血干细胞移植治疗SCN成功,为今后SCN的治疗积累了初步的经验。  相似文献   

4.
目的探讨儿童异基因造血干细胞移植(allo-HSCT)后淋巴细胞增殖性疾病(PTLD)的诊治及预后。方法回顾性分析4例allo-HSCT后EBV相关性PTLD(EBV.PTLD)患儿的临床资料。其中,急性淋巴细胞白血病(高危)(ALL—HR)2例,重型再生障碍性贫血(SAA)2例。异基因外周血造血干细胞移植(allo-PBSCT)3例,异基因脐血造血干细胞移植(allo-UCBSCT)1例。结果4例患儿分别于allo.HSCT后第53、101、22、42d发生PTLD。临床表现为发热、鼻塞、扁桃体肿大、淋巴结肿大和肝脾肿大,移植前均EBNA-1-IgG(+)、VCA.IgG(+);移植后EBV.DNA1.69×10^4~8.62×10^8 copies/mL。经淋巴结病理活检确诊为EBV-PTLD,其中1例为T细胞来源,3例为B细胞来源。例1予减停免疫抑制剂、使用利妥昔单抗、联合COP方案化疗及供者淋巴细胞输注(DU)治疗,PTLD反复且发生严重皮肤GVHD、肺部感染,移植后第193d死亡。余3例予减停免疫抑制剂及利妥昔单抗治疗,临床表现消失且EBV.DNA转阴,分别随访17、12、7个月均无病存活。结论动态监测EBV—DNA对PTLD早期发现具有重要意义。减停免疫抑制剂联合利妥昔单抗治疗EBV-PTLD疗效明显。化疗可导致严重感染,DLI治疗存在严重GVHD危险,不宜作为一线治疗。  相似文献   

5.
Chen HR  Ji SQ  Yan HM  Wang HX  Liu J  Xue M  Zhu L 《中华儿科杂志》2004,42(4):294-298
目的 探讨CD2 5抗体用于预防儿童白血病半匹配未去除T细胞骨髓移植重度移植物抗宿主病 (GVHD)的疗效。方法  10例儿童白血病患者接受人类白细胞抗原 (HLA) 2~ 3个位点不合半匹配骨髓移植 ,移植方法除了供者用粒细胞集落刺激因子 (G CSF)及受者应用环孢素A(CSA)、氨甲蝶呤 (MTX)、抗胸腺细胞球蛋白 (ATG ,FreseniusHemocare ,Germany)和霉酚酸酯 (MMF)预防GVHD的综合措施外 ,加用抗CD2 5单克隆抗体 (舒莱 ,novartispharmaswitzerland)预防GVHD ,剂量各为 2 0mg ,在移植前 2h和移植后第 4天应用 ,观察移植后的疗效 ,移植结果与前期未用CD2 5抗体移植组作回顾性比较。结果  10例移植后均获造血重建 ,粒细胞 >0 5× 10 9/L的中位天数是 19d ,血小板大于 2 0× 10 9/L的中位天数是 2 2d ,骨髓植活直接证据检测证实为完全供者造血。无一例发生急性Ⅱ~Ⅳ度GVHD ,未用CD2 5抗体对照组 8例中发生急性Ⅱ~Ⅳ度GVHD有 4例 ,差异有显著性(P =0 0 14 7)。可评价慢性GVHD的 8例均发生慢性GVHD ,为局限性慢性GVHD。中位随访 12个月 (范围 9~ 2 4个月 ) ,2例为移植相关死亡 ,1例移植后 14个月因复发死亡 ,实际无病生存率是70 %。结论 儿童半匹配未去除T细胞骨髓移植中应用舒莱 ,明显降低急性重症GVHD发生 ,临床  相似文献   

6.
自体外周血干细胞移植治疗难治性学龄前儿童风湿病   总被引:2,自引:0,他引:2  
Wu FQ  Luan Z  Lai JM  Tang XF  Lu J  Liu ZW  Wang TY 《中华儿科杂志》2007,45(11):809-813
目的探讨自体外周血干细胞移植(auto-PBHSCT)治疗难治性学龄前儿童风湿病的可行性、安全性和有效性。方法幼年皮肌炎(JDM)、幼年系统性红斑狼疮(JSLE)、幼年类风湿关节炎(JRA)各1例,均为男性患儿,年龄分别为3、6,6岁,病程分别为14、3.6、22个月,常规治疗中病情进展,库欣征明显,患病后患儿身高均无增长。JDM患儿肌力Ⅱ级,吞咽肌和呼吸肌受损,明显Gottron’s征和向阳性皮疹;JSLE患儿表现为蝶形红斑、蛋白尿、贫血,脑MRI显示脱髓鞘病变,系统性红斑狼疮疾病活动性指数(SLEDAI)≥12分;JRA患儿双膝、踝、腕、肘严重多关节炎。以环磷酰胺(CTX)+粒细胞集落刺激因子(G-CSF)进行外周造血干细胞动员,经CliniMACS细胞分选仪分选CD34‘细胞。预处理方案:JSLE和JRA为卡氮芥(BCNU)+足叶乙甙(VP16)+阿糖胞苷(Ara-C)+马法兰(MEL)及抗胸腺球蛋白(ATG);JDM为CTX+Mel及ATG。回输CD34^+细胞数分别为9.45×10^6/kg、5.46×10^6/kg和9.60×10^6/kg。观察移植治疗前后风湿病状态和免疫学指标的变化。结果3例患儿移植后分别于+9d、+13d、+11d粒细胞≥0.5×10^9/L,+14d、+18d和+13d血小板≥20×10^9/L。CIM处于低水平,CD4/CD8倒置。JDM移植后1个月皮疹消失,肌力Ⅴ级,移植后2个月血清肌酶、肌电图恢复正常。JSLE移植后3个月皮疹消退,无蛋白尿,脑MRI病变吸收,移植后8个月自身抗体转阴性,SLEDAI为2~3分。JRA移植后3周关节炎好转,移植后3个月无关节肿胀及活动受限。均停用激素和免疫抑制药物,库欣征消退,18个月身高增长10~15cm,均已上小学或学前班,随访25~27个月无复发。结论auto-PBHSCT治疗难治性学龄前儿童风湿病近期疗效显著,安全性及远期疗效有待进一步观察。  相似文献   

7.
目的观察脐血移植(CBT)治疗儿童血液系统恶性疾病的植入率、移植相关并发症和生存情况。方法血液系统恶性疾病患儿19例,其中无关供者16例,同胞供者3例。脐血与患儿HLA6个位点全相合6例,1个位点错配10例,2个位点错配3例。移植时疾病状态,高危10例,标危9例。预处理主要采用Bu/Cy或Cy/TBI方案,同时应用抗胸腺球蛋白(ATG)。GVHD预防主要采用环孢菌素A(CsA)、骁悉(MMF)及甲基泼尼松龙(MP)三联方案,3例同胞供者移植则单用CsA预防GVHD。移植脐血的细胞数量是,有核细胞(TNC)5.96×107/kg(2.57~12.20),CD34+细胞2.20×105/kg(0.31~5.80)。结果18例成功重建粒系造血,中位重建时间17(11~35)天;15例血小板植入,中位重建时间38(25~112)天。发生急性GVHD9例,其中Ⅰ度~Ⅱ度7例,Ⅲ度~Ⅳ度aGVHD2例;慢性GVHD3例。移植后随访4~86个月,复发3例,死亡8例,其中移植相关死亡6例,移植相关死亡率(TRM)31.6%。因CMV感染导致间质性肺炎死亡4例,占移植相关死亡的66.7%(4/6)。2年总生存率(OS)和无事件生存率(EFS)分别为62.54%(±11.24%)、44.53%(±12.22%);标危移植组与高危移植组病人2年OS分别为88.89%(±10.48%)、40.00%(±15.49%)。结论本组儿童血液系统恶性疾病脐血移植的植入率、移植相关并发症和生存情况与国外文献报道相似,移植时疾病状态为标危时治疗效果较好,CMV感染所致间质性肺炎是移植相关死亡的主要原因。  相似文献   

8.
非血缘相关脐血移植治疗儿童高危白血病的临床观察   总被引:1,自引:0,他引:1  
目的:非血缘脐血具有快速寻求、容易得到和HLA配型不严格的特点,该文进行了非血缘相关脐血移植(UD-UCBT)治疗儿童恶性白血病的研究并探讨其疗效问题。方法:对6例难治性白血病患儿,包括3例急性淋巴细胞白血病(2例高危CR1,1例标危CR2),2例幼年慢性粒单细胞白血病(1例缓解期,1例加速期)和1例急性髓系白血病(AML- M5,CR1)进行了非血缘相关脐血移植,HLA高分辨1例全相合,1例5个位点相合,1例4个位点相合,3例3个位点相合。预处理选用白消安/环磷酰胺/ATG或全身放疗/环磷酰胺/ATG为主方案。于 0 d 回输脐血,有核细胞中位数为8.51×107/kg,CD34+细胞中位数为1.81×105/kg。预防移植物抗宿主病(GVHD)采用环孢霉素A、甲基泼尼松龙和骁悉或CD25单抗。结果:中性粒细胞绝对值(ANC)≥0.5×109/L和PLT≥20×109/L的中位天数分别是+13 d、+30 d,移植证据均为供者型。4例出现Ⅰ~Ⅲ度GVHD,均控制。随访中位时间12个月,未发生慢性GVHD,现存活4例血型均转为供者型,无复发。结论:脐血提供快速有效的造血干细胞,为治疗儿童白血病提供良好时机,非血缘相关脐血移植能耐受HLA多个位点不相合。急性GVHD发生率也较高,存在移植物抗白血病作用。  相似文献   

9.
1 一般资料及诊断标准本组患儿男5例,女3例.~5天3例,~12天5侧。新生儿硬肿症Ⅱ度2例,Ⅲ度2例.新生儿重度窒息并发心力衰竭1例,新生儿肺炎并发心衰、呼衰2例,新生儿肺炎并发败血症1例.此8例患儿均系临终状态肺出血,表现为口鼻涌出大量鲜血或鲜红色泡沫样液体,3例死亡尸解后见肺出血均超过2个肺叶。在抢救时该组患儿呼吸停止3例次,心跳停止2例次。4例新生儿硬肿症肺出血均发生在复温治  相似文献   

10.
目的 探讨脐血造血干细胞移植(UCBT)治疗儿童恶性血液病的疗效。方法 回顾性分析接受UCBT 的37 例恶性血液病患儿的临床资料,包括急性淋巴细胞性白血病14 例,急性髓细胞性白血病9 例,幼年粒单细胞白血病5 例,慢性粒细胞白血病和骨髓增生异常综合征各3 例,急性混合型白血病2 例,淋巴肉瘤性白血病1 例。其中34 例非血缘相关,3 例血缘相关。HLA 配型6/6 相合5 例,5/6 相合12 例,4/6 相合11 例,3/6 相合9 例。移植中位年龄5.7 岁,中位体重20 kg。结果 中性粒细胞和血小板植入中位天数分别是12 d 和25 d,植入率分别为95% 和78%。中性粒细胞植入率与CD34+ 细胞数呈正相关(P=0.011)。血小板植入率与CD34+ 细胞数和有核细胞数均有关(分别P=0.001、0.014)。急性移植物抗宿主病(GVHD)的发生率为49%,慢性GVHD 为11%。随访中位时间54 个月,5 年移植相关病死率、总生存率和无病生存率分别为27%、57%和41%。结论 脐血移植是快速获得的造血干细胞来源之一,为恶性疾病患儿争取了治疗时间。  相似文献   

11.
There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.  相似文献   

12.
Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica , has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance.

Conclusion: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.  相似文献   

13.
孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%~5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相  相似文献   

14.
A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.  相似文献   

15.
Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.  相似文献   

16.
During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.  相似文献   

17.
18.
The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.  相似文献   

19.
We investigated the intra-acinar pulmonary vascular muscularization in the developing human fetal lung between the 17th and 24th gestational weeks, that is, during the canalicular phase of lung development. Fifteen hypoplastic and 25 normal developed lungs were included in this study using monoclonal alpha -smooth muscle (sm) actin antibodies for smooth muscle detection. Computer-aided image analysis was performed for morphometrical measurements and statistical evaluation. Alphasm-actin-immunoreactive intra-acinar vessels down to a luminal diameter of less than 10 mu m were detected in hypoplastic as well as in normally developed lungs. Crucial differences presented as follows: significantly higher density of intra-acinar vessels, especially due to alpha -sm-actin-negative vessels less than 30 mu m in luminal diameter, in the control group; significantly higher alpha -sm-actin immunoreactivity per section unit as well as per vessel in the hypoplastic lung group. As suggested by others, alpha-sm-actin-positive cells of the intra-acinar vessel wall in the developing human lung were demonstrated to be smooth muscle cells, their immediate precursors, and pericytes. We conclude that the increased alpha -sm-actin immunoreactivity represents muscularization of the vessel wall in functional terms and may be regarded as one structural cause among others for the establishment of persistent fetal circulation in hypoplastic lungs.  相似文献   

20.
The World Health organisation recommends breast feeding infants for the first six months of life. When this breast feeding does not occur either through parental choice or medical need, infant formulas will be required. There is a bewildering array of formulas on the UK market for many different requirements. When faced with an unsettled infant many parents (and healthcare professionals) will experiment with the infant formula available and then attend the paediatric clinic looking for help and advice. It is therefore essential that paediatricians understand what milks are available and what the key differences between different products are. This review attempts to provide a simple guide through many of the formulations currently available in the UK; and offers advice for the dietary management of the child with extra calorie requirements, infants with cow's milk protein allergy, gastro oesophageal reflux disease, apparent unresolved hunger and infantile colic. Whatever the underlying condition, there is likely to be an infant formula that is suitable in this generation of ever expanding formulations.  相似文献   

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