联合免疫抑制治疗儿童再生障碍性贫血疗效分析

目的通过对应用联合免疫抑制疗法(IST)的儿童获得性再生障碍性贫血(AA)临床资料分析,总结IST对儿童AA的疗效及预后相关因素,以及阵发性睡眠性血红蛋白尿(PNH)克隆的转化情况。方法回顾性分析安徽医科大学第二附属医院2009年6月—2019年8月应用ATG联合CSA治疗的59例AA患儿的临床资料以及AA患儿不同病程阶段T细胞亚群的变化,总结分析IST对AA患儿的疗效。采用SPSS 16. 0统计软件进行数据分析。结果 59例初诊AA患儿,中位随访时间24个月。(1) IST后1个月、3个月、6个月、9个月、12个月的有效率分别为22%、39%、57%、61%、71%。截止2019年6月随访18例AA患儿的5年无事件生存率达66%。(2)治疗后CD3+T、CD4+T细胞升高,CD8+T细胞下降,CD4+T/CD8+T比值升高,差异有显著性(P 0. 05)。(3)对38例AA患儿进行PNH克隆的随访,发现初诊AA患儿中有11例PNH克隆阳性,IST后3个月PNH克隆均转阴。初诊有无PNH克隆与疗效无相关性。结论 IST治疗儿童AA疗效确切,可以有效地改善AA患儿的细胞免疫功能。初诊时有部分AA患儿存在PNH克隆,IST前后伴PNH克隆不影响疗效。     

探讨儿童再生障碍性贫血患儿初诊时检测血清促血小板生成素的临床意义

目的探讨儿童再生障碍性贫血(AA)初诊时检测血清促血小板生成素(TPO)的临床意义。方法采集45例AA患儿(AA组)和32例健康儿童(对照组)的血清样本,应用酶联免疫吸附试验(ELISA)方法检测其TPO水平,比较重型AA(SAA)与非重型AA(NSAA)患儿在初诊时的TPO水平,并分析AA患儿初诊时TPO水平与血小板、巨核细胞数目的关系。结果 AA患儿血清TPO水平明显高于健康对照儿童,两组比较差异有显著性(P0.05);SAA患儿血清TPO水平明显高于NSAA患儿,两组比较差异有显著性(P0.05);初诊时TPO水平与血小板数(P0.05,r=-0.63)、巨核细胞数(P0.05,r=-0.69)呈负相关。结论 AA患儿初诊时血清TPO水平明显增高,SAA患儿血清TPO水平明显高于NSAA患儿,TPO与血小板、巨核细胞减少程度有明确相关性,检测TPO水平有助于临床早期诊断儿童AA。     

细胞因子网络在再生障碍性贫血发病中的作用

目的检测细胞因子网络在再生障碍性贫血(AA)患儿中的表达,以探讨AA的免疫发病机制及探索新的治疗途径。方法采用双抗体夹心酶联免疫吸附法(ELISA)检测35例AA患儿及30例正常儿童外周血白细胞介素-18(IL-18)、IL-12I、L-3及肿瘤坏死因子-α(TNF-α)水平。结果与正常对照组比较,AA患儿外周血IL-18I、L-12、TNF-α水平升高,而IL-3水平降低,差异均有显著性(P<0.01)。结论细胞因子网络失衡可能在小儿AA发病中起重要作用。     

儿童再生障碍性贫血的治疗策略

儿童再生障碍性贫血(AA)是儿科常见的骨髓衰竭综合征,临床上表现为贫血、感染、出血以及相关症候群,儿童AA正确识别及其严重程度的精准判断对适宜治疗的选择至关重要.     

网织红细胞正常儿童再生障碍性贫血6例诊治分析

目的 探讨网织红细胞正常儿童再生障碍性贫血(AA)的临床诊治方法.方法 回顾性分析2006年4月到2008年12月收治的网织红细胞正常的6例儿童AA的临床资料,检测患儿外周血血常规和网织红细胞参数变化.包括网织红细胞百分率(Ret%)、绝对数(Ret#),并计算网织红细胞生成指数(RPI).观察加用小剂量糖皮质激素治疗后的疗效.结果 试用小剂量糖皮质激素后.4例慢性再生障碍性贫血(CAA)患儿明显好转,2例莺型再生障碍性贫血(SAA)患儿无效.结论 部分AA患儿网织红细胞在正常范围,包括SAA及CAA,诊断再障需全面参考诊断标准;小剂量糖皮质激素治疗网织红细胞正常AA的疗效尚需进一步观察.     

Fas/FasL在再生障碍性贫血患儿中的表达及意义

目的研究凋亡基因Fas及其配体(FasL)在儿童再生障碍性贫血(AA)中的表达及意义,探讨AA的发病机制。方法30例AA患儿分为重型再生障碍性贫血(SAA)组12例,慢性型再生障碍性贫血(CAA)组18例,对照组为健康体检儿童10例。采用流式细胞术结合单克隆抗体荧光染色的方法测定AA患儿Fas/FasL表达水平及CD34 细胞数量。比较各组间表达差别。结果AA患儿Fas表达水平显著高于健康对照组(P<0.05),但SAA与CAA组Fas表达水平无差别(P>0.05);FasL表达水平在AA和健康对照组比较无差异(P>0.05)。CD34 细胞数量AA组明显低于健康对照组(P<0.05)。结论Fas/FasL系统参与诱导AACD34 细胞凋亡过程,导致造血干细胞减少,骨髓造血衰竭。     

儿童再生障碍性贫血-阵发性睡眠性血红蛋白尿综合征临床分析

为探讨儿童再生障碍性贫血 -阵发性睡眠性血红蛋白尿 (AA PNH)综合征的临床及实验室检查特点 ,特总结近年我科收治的 5例AA PNH综合征患儿的病历资料 ,从临床、血象、骨髓象、溶血方面的检查、CD5 9+细胞等方面分析其特点。结果显示儿童AA PNH综合征以学龄儿童为多见 ,本文报导 1例发病年龄 1岁半 ,为目前文献报导中年龄最小者 ;儿童AA PNH以AA伴PNH特征多见 ;临床上有严重贫血、肝脾稍大等特点 ;实验室检查可见全血细胞减少、Ret大多不低或升高、血片中可见有核红细胞 ;骨髓红系增生 ,粒红比例倒置、巨核系统大多增生低下 ;Hams试验、蔗糖水溶血试验、尿Rous试验、蛇毒因子 (Cof)溶血试验可阳性 ;血细胞膜CD5 9-细胞增多 ,粒细胞膜CD5 9-细胞比红细胞膜出现早。因此 ,可以结论　儿童AA PNH综合征多见于学龄期 ,以AA伴PNH特征多见。临床上对于全血细胞减少、骨髓红系增生、血Ret升高、血片中可见有核红细胞的患儿 ,应进一步做与PNH有关的检查 ,并综合分析 ,CD5 9-粒细胞增多具有早期诊断价值     

293 例再生障碍性贫血患者髓系肿瘤基因变异分析

目的分析25种髓系肿瘤基因变异与获得性再生障碍性贫血(AA)的相关性。方法收集293例儿童及成人AA患者的临床资料,运用二代测序技术靶向检测25种髓系肿瘤基因,分析AA患者的基因变异情况。结果 293例AA患者中,男性155例、女性138例,儿童青少年142例、成人151例,非重型AA178例、重型或极重型115例。共有19例(6.48%)患者检测出髓系肿瘤基因变异,ASXL1 2例、KRAS 1例、PIGA 2例、TP53 2例、BCOR 2例、TET2 5例、SF3B1 1例、DNMT3A 2例、SH2B3 2例和MPL 1例。男性变异6例(3.87%)、女性变异13例(9.42%),差异无统计学意义(P0.05);儿童青少年变异4例(2.82%)、成人变异15例(9.93%),差异有统计学意义(P0.05);非重型AA患者变异14例(7.78%);重型或极重型AA组变异5例(4.35%),差异无统计学意义(P0.05)。有变异组及无变异组经过6个月免疫抑制治疗,有效率分别为73.68%(14/19)和63.18%(151/239),差异无统计学意义(P0.05)。结论 AA患者中25种髓系肿瘤基因变异率为6.48%,儿童患者变异较成人患者少,有无基因变异对联合免疫抑制治疗效果无影响。     

儿童系统性红斑狼疮相关再生障碍性贫血2例报告并文献复习

目的 总结系统性红斑狼疮(SLE)相关的再生障碍性贫血(AA)的临床特点,以提高对该病的认识.方法 对收治的2例及文献报道的19例儿童SLE相关AA患者进行回顾性分析,并与单纯SLE及普通AA进行比较.结果 21例患者SLE和AA常不能同时诊断(占90.4%),SLE与AA的诊断相隔时间为-1～9年.实验室检查中抗ds-DNA抗体(42.8%)及补体降低(38.9%)的阳性率低于单纯SLE,外周血淋巴细胞比例升高(23.5%)及网织红细胞降低(17.6%)的发生率均低干普通AA,骨髓像、骨髓病理(100%)示骨髓造血不良,T细胞亚群中CD4+降低,CD8+升高,CD4/CD8倒置.治疗的有效率达85.7%,病死率约9.5%.结论 SLE相关AA临床表现无特异性;表现为外周血三系持续减少的患者应尽早作骨髓检查及免疫指标检测,以减少漏诊;其骨髓像、骨髓病理及T细胞亚群的特点与普通AA相似,但预后明显好于普通AA.     

儿童急性阑尾炎手术后粘连性肠梗阻的相关因素分析

目的探讨儿童急性阑尾炎(acute appendicitis,AA)术后发生粘连性肠梗阻(adhesive ileus,AI)的影响因素及相关预防措施。方法收集天津市儿童医院2014年1月至2017年6月行阑尾切除术(acute appendicitis resection,AAR)的168例AA患者为研究对象,按照术后是否发生AI分为梗阻组(n=42)和未梗阻组(n=126),以性别、年龄、病程、阑尾炎类型、是否穿孔、手术方式、手术操作时间、是否留置引流管、术前相关炎症指标(PCT、CRP、白细胞及中性粒细胞)为自变量进行回归分析。结果42例AAR后发生AI的时间与年龄存在相关性(r=0.535,P<0.05),Logistic分析结果显示:病程长(OR=1.071,95%CI:1.040~1.104)、PCT水平升高(OR=1.735,95%CI:1.178~2.555)为AI的危险因素;而年龄较大(OR=0.966,95%CI:0.945~0.987)、男性(OR=0.199,95%CI:0.049~0.802)及采用腹腔镜手术(OR=0.092,95%CI:0.015~0.543)为AI的保护因素。结论AA病程、PCT、年龄、性别及手术方式是AAR后发生粘连性肠梗阻的影响因素,当儿童AA满足手术适应证时,应及早行腹腔镜阑尾切除术;对于年龄较小及术前PCT水平较高的患者,术后应警惕AI发生的可能。     

Glutathione S transferase theta 1 gene (GSTT1) null genotype is associated with an increased risk for acquired aplastic anemia in children

Two main factors have been implicated in the mechanism underlying the pathogenesis of acquired aplastic anemia: environmental factors and genetic susceptibility. Individuals vary in their ability to metabolize several DNA-damaging agents due to polymorphisms of biotransforming enzymes. Genetically determined differences in the expression of these enzymes could explain interindividual risks in developing acquired aplastic anemia. The aim of the study was to characterize the genetic polymorphism of biotransforming phase I (p450-cyp2E1) and phase II [microsomal epoxide hydrolase (mEh), glutathione S-transferase (GST)] enzymes in pediatric patients with acquired aplastic anemia. The GSTT1 null genotype (absence of both alleles) was associated with a significantly increased risk for acquired aplastic anemia (odds ratio, 2.8; 95% confidence interval, 0.15-5.7). In contrast, the GSTM1 null genotype or polymorphisms within the p450-cyp2E1 and mEh genes was not significantly different in patients and controls. Multivariate analysis was performed to assess whether the enzymes together or with other variables as age, gender, or response to therapy may have any significant association with the tested genotypes. In no combinations of the mentioned parameters was an association found with acquired aplastic anemia. GST are mainly involved in metabolizing hematotoxic and mutagenic substrates such as benzene derivatives. The GSTT1 null genotype may modulate the metabolism of exogenous pollutants or toxic intermediates. The absence of the GSTT1 enzyme, leading to genetic susceptibility toward certain pollutants, might determine the individual risk for development of acquired aplastic anemia in children.     

儿童传染性单核细胞增多症与急性淋巴细胞白血病GST基因遗传多态性研究

目的：探讨谷胱甘肽硫转移酶基因GSTT1及GSTM1多态性与儿童传染性单核细胞增多症（IM）、儿童急性淋巴细胞白血病（ALL）易感性的关系。方法：采用多重PCR技术对106例IM患儿、41例ALL患儿和100例非血液系统性疾病、非肿瘤疾病患儿外周血标本进行GSTT1和GSTM1基因多态性检测,分析不同基因型与儿童IM、ALL发病的关系。结果：IM组GSTT1纯合缺失基因型频率明显高于对照组,差异有统计学意义（P<0.05）;携带GSTT1纯合缺失基因型的个体发生IM的风险是携带GSTT1非纯合缺失基因型个体的2.186倍。GSTM1/GSTT1基因联合缺失型个体发生IM的风险是非联合缺失型个体的4.937倍。GSTM1纯合缺失基因型在ALL组的分布频率明显高于对照组,差异有统计学意义(P<0.05)。携带GSTM1纯合缺失基因型的患儿发生ALL的风险是携带GSTM1非纯合缺失基因型个体的2.242倍。GSTM1/GSTT1基因联合缺失型个体发生ALL的风险是非联合缺失型个体的8.552倍。结论：GSTT1或GSTM1纯合缺失基因型的儿童对IM或ALL易感性升高,当同时存在GSTT1和GSTM1纯合缺失时,IM或ALL易感性更高。GSTT1和GSTM1在IM及ALL致病过程中可能都发挥了作用。     

汉族儿童Ⅱ相药物代谢酶基因GSTM1和GSTT1的多态性分布

目的 了解谷胱甘肽-S-转移酶M1(GSTM1)和T1(GSTT1)基因多态性在中国汉族儿童中的分布特点,为临床针对不同基因型个体化药物治疗提供理论基础。方法 选择首都医科大学附属北京儿童医院健康查体汉族儿童的血样,提取DNA。应用PCR法检测GSTM1和GSTT1基因型,并判断代谢表型。检索PubMed等数据库,获得亚洲人群、黑种人和高加索人群GSTM1和GSTT1基因多态性分布的数据,与本研究分析人群数据进行比较,分析基因多态性的种族差异。结果 786份研究样本纳入分析。①中国汉族分析人群GSTM1和GSTT1完全缺失基因型/慢代谢型(*0/*0)的频率分别为59.3%(466/786例)和58.4%(459/786例);单拷贝缺失基因型/中间代谢型(*1/*0)的频率分别为34.0%(267/786例)和35.1%(276/786例);未缺失基因型/快代谢型(*1/*1)的频率分别为6.7%(53/786例)和6.5%(51/786例)。②GSTM1和GSTT1基因多态性分布互相独立,无明显关联。③GSTM1和GSTT1基因多态性无显著性别差异。④本研究汉族分析人群GSTM1和GSTT1基因多态性分布与亚洲人群较为接近,与黑种人和高加索人群有显著差异。结论 GSTM1和GSTT1基因在中国汉族儿童中以完全缺失基因型/慢代谢型(*0/*0)为主,具有种族特异性,为不同基因型个体制定合适的用药方案提供了参考依据。     

Role of GSTM1, GSTP1, and GSTT1 gene polymorphism in ifosfamide metabolism affecting neurotoxicity and nephrotoxicity in children

The aim of this study was to evaluate the impact of GSTM1, GSTT1, and GSTP1 gene polymorphism on urinary excretion of unchanged ifosfamide, 2-dechloroethylifosfamide (2DCIF), and 3-dechloroethylifosfamide (3DCIF) with regard to the incidence of ifosfamide-related nephrotoxicity and neurotoxicity in children. The study comprised 76 children (38 girls, 38 boys) ages 9.84 to 210 months who were being treated for various malignant diseases with ifosfamide. The children were enrolled after identification of genotype coding for three classes of glutathione S-transferases (GSTM1, GSTT1, and GSTP1) at the initial stage of diagnosis. (P) nuclear magnetic resonance spectroscopy was used to analyze the urinary excretion of unchanged ifosfamide, 2DCIF, and 3DCIF metabolites on consecutive days after the end of the 3-hour infusion of ifosfamide. In children with polymorphic locus of the GSTP1 gene compared with children with homozygous wild alleles, increased urinary excretion of 3DCIF (P=0.029) and decreased creatinine clearance was found (Mann-Whitney P=0.03; median 81.1 mL/min/1.73 m vs. 105.0 mL/min/1.73 m, respectively). The authors' multidimensional analysis model revealed that besides the total ifosfamide dose and co-administration of other toxic drugs, polymorphic locus of GSTP1 gene may be one of the factors determining a higher toxicity of the cytostatic agent. The model was construed at P=0.029. Moreover, no correlation was found between the GSTM1 or GSTT1 genotype and ifosfamide toxicity and the urinary excretion of its metabolites. The results of this analysis indicate that individual reactions to ifosfamide can depend on inherited genetic polymorphisms, especially associated with the GSTP1 gene coding detoxifying enzyme.     

Polymorphism within the glutathione S-transferase P1 gene is associated with increased susceptibility to childhood malignant diseases

BACKGROUND: Glutathione S-transferases (GSTs) are involved in the metabolism of carcinogens and anticancer drugs. Functional polymorphisms exist in at least three genes that code for the GSTs, such as the GSTM1 and GSTT1 gene deletions or the A-G transition within the GSTP1 gene, which represents distinct GSTP1a and GSTP1b alleles. In the present case-control study, we aimed at estimation of the relationship between the GSTM1, GSTT1, and GSTP1 genotypes and the susceptibility to various types of childhood malignancies and the early relapses of diseases. PROCEDURE: Using the polymerase chain reaction on the DNA extracted from peripheral blood leukocytes, we identified the GSTM1, GSTT1, and GSTP1 genotypes in 234 children at the initial stage of a childhood malignancy as well as in 460 age-and sex-matched healthy subjects who served as controls. The follow-up period for the effects of the anticancer therapy ranged from 11 to 43 months. RESULTS: Compared to the controls, a significant increase in the frequency of the GSTP1b/GSTP1b genotype (odds ratio (OR) 5.7; 95% confidence limit (CL) from 2.4 to 13.8; Pearsons Chi-square P = 0.0001) was detected in the children with neoplasms. The GSTM1 and GSTT1 genotypes did not show any correlation with the risk of the de novo diagnosed neoplasms. During the observation, 62 children (26%) were found to be present with a local or disseminated recurrence of the diseases. The analysis indicated a trend in increasing risk of relapse for carriers of the GSTP1a allele (OR = 3.29; 95% CL from 0.73 to 14.67 P = 0.03). CONCLUSIONS: Our results support the hypothesis that GST genotype affects etiology and outcome of a variety of childhood malignancies.     

Are glutathione S-transferase gene polymorphisms linked to neonatal jaundice?

Glutathione S-transferases (GSTs) are a major group of phase II detoxification enzymes involved in the metabolism of both endogenous and xenobiotic compounds. In addition to their catalytic function in detoxification, GSTs participate in binding to nonsubstrate ligands such as bilirubin. Ligandin, which is one of the principal hepatic-binding proteins, is also a member of the GST family. The aim of the present study was to investigate the possible relationship between neonatal jaundice and the GST gene polymorphisms. The study cohort consisted of a patient group of 116 newborns (plasma bilirubin levels ≥15 mg/dl) and a control group of 54 newborns (plasma bilirubin levels <13 mg/dl). In the patient group, the null genotype frequencies in GSTM1 and GSTT1 were 52.6 and 19%, respectively; in the control group, these were 63 and 27.8%, respectively. The frequencies of GSTM1 and GSTT1 were similar in the patient and control groups (p > 0.05). Total bilirubin levels were found to be significantly higher in patients with the GSTM1 null genotype than in patients with the GSTM1 wild genotype (p = 0.042). There was no statistically significant difference in total bilirubin levels between patients with the null GSTT1 genotype and those with the wild GSTT1 genotype. It is conceivable that there is a relation between GSTM1 gene polymorphism and total bilirubin levels in neonatal jaundice. We suggest that GSTM1 gene polymorphisms may affect ligandin functions in hepatocytes, which are important in bilirubin transportation. Consequently, patients with the GSTM1 null genotype may have higher total levels of bilirubin.     

Gene dose effects of GSTM1, GSTT1 and GSTP1 polymorphisms on outcome in childhood acute lymphoblastic leukemia

Children with acute lymphoblastic leukemia (ALL) react very differently to chemotherapy. One explanation for this is inherited genetic variation. The glutathione S-transferase (GST) enzymes inactivate a number of chemotherapeutic drugs administered in childhood ALL therapy. Two multiplexing methods were applied for genotyping the GSTM1 and GSTT1 genes (distinguishing between 0, 1, or 2 gene copies) and the GSTP1 313 A>G polymorphism, simultaneously. A total of 263 childhood ALL patients were genotyped. No gene dose effect on outcome was demonstrated with either GST polymorphisms. Grouping of GSTM1 and GSTT1 into poor (0 or 1 gene copy)-and good metabolizers (at least 2 gene copies)-showed that the poor metabolizers had a trend toward a better outcome (event-free survival =91.8%) compared with the good metabolizers (event-free survival =83.2%). Similarly, in the adjusted analysis the good metabolizers demonstrated a 2.2-fold higher risk trend of experiencing an event (resistant disease or relapse) compared with the poor metabolizers (P=0.066; hazard ratio =2.248; 95% confidence interval, 0.948-5.327). In conclusion, our results suggest that the combined gene dose of GSTM1 and GSTT1 may influence outcome in childhood ALL.     

上海地区汉族人谷胱甘肽S转移酶基因多态性分析(英文)

目的：测定GST基因在上海地区健康汉族人中的遗传多态性,筛选出汉族人的GST候选单核苷酸多态性(SNP)位点,为开展GST基因多态性与汉族人群肿瘤易感性及治疗相关性研究作一初步探索。方法：采用荧光标记自动测序法,筛选GSTT1,GSTM1基因在20名上海地区的汉族健康志愿者中的候选SNP位点。结果：4例受检者在GSTT1外显子4和3之间的第86 057位点发生点突变,由腺嘌呤A取代鸟嘌呤G,经与Genebank中SNP数据库比对,可能为一新的GSTT1基因候选SNP位点;在外显子5的第793位点和921位点,所有受检者均为G&A的杂合子。GSTM1在8个外显子中均发现有候选SNP位点,但多为单核苷酸的杂合子。约40%受检者的外显子2出现腺嘌呤A缺失,所有受检者在第1 383位点和1 385位点分别是A&G受C&G杂合子;在第101位点60%个体为A&T杂合,40%个体为腺嘌呤A的纯合子。我们还初步发现在外显子2的190 bp以后可能存在多个碱基或小片段缺失。结论：上海地区健康汉族人的GST基因具有丰富的遗传多态性。这些多态性是否为汉族人所特有、与肿瘤易感性的关系,以及这些可能的候选SNP位点是否会造成其编码氨基酸的改变并引起产物蛋白一级结构的变化、进而导致GST酶活性发生改变而表现为具有不同的表型及基因型,尚需深入探讨。     

Genetic polymorphisms of glutathione-S-transferase and microsomal epoxide hydrolase in egyptian acquired aplastic anemia patients

Exposure to various environmental toxins with a reduced ability to metabolize them may lead to acquired aplastic anemia (AA). Genetic polymorphism of the detoxifying enzymes, the glutathione-S-transferase (GST) and microsomal epoxide hydrolase (mEh), with alteration in their activities could explain the genetic interindividual risks for AA. We aimed to characterize the genetic polymorphisms of the GST and mEh and to test their impact on the susceptibility, disease severity, and prognosis in Egyptian patients with AA. The GST and mEh genotypes were determined by multiplex-polymerase chain reaction and polymerase chain reaction-restriction fragment length polymorphism analysis, respectively, in 21 patients with AA and 20 healthy control subjects. The mEh functional phenotypes were assessed. The frequency of GST θ1-null genotype was found significantly higher in AA patients compared with the controls (odds ratio=2.8, 95% confidence interval = 1.1-7.8; P = 0.001). The frequency of heterozygous 139A--G of the mEh gene was significantly higher in AA patients compared with the controls (odds ratio=3.07, 95% confidence interval = 1.23-7.7; P = 0.018). Moreover, the patients with normal functional phenotype of the mEh had significantly favorable prognosis than those with abnormal enzyme activity (P = 0.027). Thus, the GST θ1-null genotype and the 139A--G mEh gene polymorphism may enhance the susceptibility to AA and provide an evidence of gene-environmental interaction.     

Prognostic factors and evolution of acquired aplastic anemia in childhood. A prospective analysis of 48 androgen-treated cases

Forty-eight cases of acquired aplastic anemia in children were analyzed in comparison to 26 cases of genetic aplastic anemia and 483 cases of aplastic anemia in adults. All were gathered from similar institutions and all were similarly followed and treated with androgens. The following conclusions were drawn: 1) Initial severity is greater in children than in adults, and is greater in acquired than in genetic aplastic anemia; 2) even in cases of similar initial severity, the early death rate is higher in children than in adults; 3) a multiparametric index allows the correct prediction of short-term evolution in 70% of the cases and thus aids in providing an indication for bone marrow graft; its sensitivity is similar to that of the classical parameters proposed by Camitta, et al., but its specificity significantly higher; 4) most deaths occurred during the first 3-4 months and the chance for long-term improvement appears similar in the more severe than in the less severe cases if they survive this delay; 5) some data (relapse after androgen withdrawal and androgen-dependence and failure of corticoid therapy alone) suggest that androgen therapy in children is useful, as it is in adults, and that corticosteroids do not modify the course of the disease at its usual dosage (1 mg/kg/day); and 6) very few side effects, particularly concerning height, of androgens were noted in the survivors at adult age after long-term androgen therapy prescribed before puberty.