重组人生长激素治疗特发性矮小儿童12例

目的　观察重组人生长激素 (rhGH)治疗特发性矮小儿童促生长作用。方法　对 12例特发性矮小儿童使用rhGH治疗 0 .5 7± 0 .18年 ,比较治疗前后年生长速率和预测成年身高结果。结果　经治疗后特发性矮小儿童的年生长速率和预测成年身高有显著提高 ,身高年龄增长明显快于生活年龄和骨龄的增长。结论　rhGH对特发性矮小儿童具有促生长作用     

改善矮小儿童成年身高的药物研究进展

儿童的身高问题越来越被社会、家长及广大儿科医生关注,该文重点介绍改善矮小儿童成年身高的药物研究进展。生长和最终身高与遗传、宫内发育、出生后的营养、环境和内分泌激素等均有关。重组人生长激素、长效人重组生长激素对已批准的适应证改善儿童成年终身高的疗效是确定的,目前主要进行长效人重组生长激素品种的研发上市以及扩大适应证的临床试验。重组人类胰岛素生长因子-1（IGF-1）是治疗IGF-1缺乏的主要药物,使用中要注意低血糖和肿瘤的风险。促性腺激素释放激素类似物（GnRHa）、第三代非甾体类芳香化酶抑制剂等可有效延缓骨骺融合,联合长效人重组生长激素（rhGH）治疗对改善终身高有一定益处,但其疗效与病因、年龄、遗传身高、治疗疗程等因素有关,临床应综合考虑药物远期安全性、疗效以及经济等因素,谨慎评估、选择。修饰后的重组C型利钠肽已完成Ⅲ期临床试验,对改善软骨发育不全儿童的身高有一定获益。期望能继续开发出安全、有效、优质、稳定的新药用于改善儿童矮身材,促进矮小儿童的身心健康。     

重组生长激素治疗原发性肾病综合征患儿生长障碍

目的研究原发性肾病综合征(PNS)患儿血清生长激素(GH)水平,探讨重组GH对PNS患儿生长障碍的治疗作用。方法6例PNS患儿经皮质激素治疗12～18个月后,身高低于同性别同年龄第3百分位,年龄7～12岁,平均9.1岁,男5例,女1例,所有病例均为频繁复发,予重组GH0.1IU/(kg·d),1次/d,采用三角肌或脐周皮下注射,疗程9～18个月。对照组9例为同期住院PNS患儿,年龄6～10岁,平均7.5岁,男6例,女3例,所有患儿均接受皮质激素治疗。结果治疗组经重组GH治疗1个月后,血清GH逐渐恢复正常水平,治疗9～18个月后身高与骨龄接近同年龄的身高与骨龄,平均每月长高(0.88±0.12)cm,治疗中未出现复发,也未见药物不良反应。与对照组比较差异有显著性(P<0.01)。结论对PNS生长发育障碍患儿需早期采取GH治疗,可有效防治其生长障碍。     

儿童急性髓系白血病治疗进展

急性髓系白血病(AML)是由于造血干细胞分化障碍及增殖过度所致异常骨髓造血前体细胞聚集的恶性克隆性疾病。近年来随着危险度分层的合理应用、靶向药物的不断研发、支持治疗的进步、造血干细胞移植技术的日渐成熟,儿童AML的生存率已经较前有明显提高。文章综述儿童AML的治疗进展。     

内分泌系统疾病

071372重组人生长激素治疗生长激素缺乏症患儿影响生长速度疗效的因素/潘思年…∥中华儿科杂志.-2006,44(7).-544~54594例生长激素缺乏症(GHD)患儿治疗前年生长速度(GV)(4.4±1.6)cm,用重组人生长激素(rhGH)后,生长速度明显加快(P<0.01),以头6个月的GV最快,第2~5年GV渐降,但无统计学意义。相关分析提示:头6个月生长速度(GV1)与骨龄(BA0)、类胰岛素样生长因子(IGF-1)SDS、身高Z分值(HtSDS)和激发试验GH峰(SPGH)呈负相关。逐步回归分析显示:BA0和SPGH是影响GV1的独立因素。认为用rhGH治疗至少在头4年内能使GHD患儿呈现有效…     

二次移植治疗异基因造血干细胞移植后复发儿童急性白血病的临床疗效分析

目的 探讨二次单倍体移植治疗异基因造血干细胞移植后复发的儿童急性白血病的效果。方法 回顾性分析本中心2014年3月1日—2022年5月30日儿童急性白血病异基因造血干细胞移植术后复发后接受二次单倍体异基因造血干细胞移植的7例病例资料,其中急性髓细胞白血病5例,急性淋巴细胞白血病2例,分析二次移植后总体生存率、无病生存率、移植相关死亡率。结果 7例患儿均完成造血重建,粒细胞植入中位时间11(9-17)天,血小板植入中位时间13(9-18)天,随访至2022年5月30日,1例因原发病未缓解死亡,1例于移植+86天原发病复发,且合并休克、呼吸衰竭,家属放弃治疗死亡。2例合并慢性移植物抗宿主病(cGVHD),为皮肤局限型。1年总生存率(OS)71%(5/7),1年无病生存率(DFS)43%(3/7)。结论 二次单倍体异基因造血干细胞移植治疗儿童白血病疗效较好,是异基因造血干细胞移植后复发的儿童白血病患儿的治疗方法之一。     

儿童造血干细胞移植后巨细胞病毒感染的临床研究

目的了解儿童造血干细胞移植后巨细胞病毒的感染率和防治方法。方法对从2001年8月到2007年3月北京儿童医院血液病中心37例作造血干细胞移植的血液肿瘤及先天遗传性疾病患儿进行回顾性分析。结果31例可研究病例中,5例自体造血干细胞移植及5例同基因造血干细胞移植患儿无人类巨细胞病毒（HCMV）感染,21例异基因造血干细胞移植患儿,发生HCMV感染7例,感染率为33.3%,大剂量阿昔洛韦加丙种球蛋白预防及早期更昔洛韦加大剂量静脉丙种球蛋白治疗,仅1例发生巨细胞病毒相关性间质性肺炎（CMV-IP）,无1例发生巨细胞病毒感染相关死亡。结论巨细胞病毒感染是儿童造血干细胞移植术后的主要并发症,临床上进行定期监测、前瞻性预防、早期诊断和及时合理治疗,对降低移植术后巨细胞病毒感染和提高移植成功率至关重要。     

重组人生长激素注射液治疗儿童生长激素缺乏症的临床评价

目的 生长激素缺乏症(GHD)有赖于生长激素替代治疗.生长激素注射液可简化注射过程,提高依从性.进一步评价中国重组人生长激素注射液治疗儿童GHD的疗效和安全性.方法 采用多中心、前瞻性、随机开放的研究方法 ,对31例[男20例,女11例,年龄(10.5±4.1)岁]确诊为完全件GHD的患儿,给予重组人生长激素注射液,0.25 mg/(kg·周)[0.107 U/(kg·d)],每晚睡前皮下注射1次,治疗3、6、9、12个月后进行随访,疗程12个月.比较治疗前后的身高增长量(△HT)、年生长速率(growth velocity,GV)、身高均值标准差积分(HT SDS)、血胰岛素样生长因子Ⅰ(IGF-1)、胰岛素样生长因子结合蛋白质3(IGFBP-3)、抗生长激素抗体和骨成熟情况的变化,并评估药物治疗的安全性.结果 (1)治疗3、6、9、12个月后△HT(cm)分别为4.0±1.3、7.0±2.0、10.3±2.6和12.9±3.3(P<0.01),显示治疗后呈良好线性生长;GV(cm/年)治疗前为2.7±0.9,治疗后分别升至16.0±5.1、14.1±4.0、13.7±3.5和12.9±3.3,显示治疗后追赶生长明显,治疗前后比较,差异有统计学意义(P<0.01);HT SDS治疗前为-4.62±1.46,治疗后分别为-3.80±1.53、-3.28±1.60、-2.86±1.75和-2.47±1.86,显示治疗后身高与同年龄同性别正常儿童差距逐步缩小,与治疗前相比差异有统计学意义(P<0.01);(2)血IGF-1(ug/L)治疗前为41±64,治疗后分别为179±155、202±141、156±155和159±167;IGFBP-3(mg/L)治疗前为1540±1325,治疗后分别为3891±1815、4051±1308、3408±1435和3533±1413,显示随着身高增长,IGF-1、IGFBP-3被药物激活到较高水平,治疗前后差异均有统计学意义(P<0.01);(3)在治疗6个月、12个月后进行骨龄评估,骨成熟程度(△BA/△CA)分别为1.01±0.57、1.07±0.75,显示骨龄无加速发展;(4)治疗期间未发生严重不良事件,与药物有关的伴随反应主要表现为甲状腺功能减低.结论重组人生长激素注射液足一种安全有效治疗儿童GHD的药物.     

儿童造血干细胞移植相关的内分泌并发症及评估

造血干细胞移植技术应用于儿童血液肿瘤及非肿瘤性疾病治疗, 使患儿生存率及预期寿命得到改善。但随着患儿生存时间的延长, 各种内分泌并发症会出现在这些儿童肿瘤幸存者中, 降低患儿的生活质量。儿童造血干细胞移植相关的并发症是由于原发病和(或)移植前后治疗所致, 包括糖脂代谢异常、性腺功能减退、身材矮小等。规律的内分泌评估可帮助临床医生及早发现造血干细胞移植患儿的内分泌功能异常。该文总结了珠蛋白生成障碍性贫血及急性白血病患儿在造血干细胞移植术后常见的内分泌并发症及随访评估指标, 旨在对造血干细胞移植术后患儿的内分泌功能监测提供参考。     

儿童造血干细胞移植后毛霉菌病临床诊疗进展

儿童毛霉菌病是造血干细胞移植后罕见的严重并发症之一。免疫功能抑制、中性细胞减少症、移植物抗宿主病、铁负荷过载、静脉高营养、糖皮质激素及钙调神经磷酸酶抑制剂使用等多种危险因素与儿童造血干细胞移植后毛霉菌病的发生密切相关。由于儿童移植后毛霉菌病侵袭进展迅速，其临床诊疗极具挑战性。文章综述儿童造血干细胞移植后毛霉菌病的流行病学特点、发病机制、诊断及治疗的研究进展，为进一步完善适用于儿童移植后毛霉菌病的诊疗规范提供建议。     

Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation

Growth acceleration and bone maturation were studied for 3 y in 69 children with severe short stature and a history of intrauterine growth retardation (IUGR), to determine the effect of treatment with recombinant human growth hormone (r-hGH). The patients were enrolled in an open, multicentre trial and were randomly allocated to either the treated group (Group 1) or the control group (Group 2). The children in Group 1 were treated daily with 0.2 IU/kg/body weight (0.067 mg/kg) s.c, during 3 y and the children in Group 2 started the study with a 1-y observation period followed by a 3-y treatment period. At birth, their mean weight standard deviation score (SDS) was -2.5 and their mean length SDS -3.5. At baseline, the patients were prepubertal, non-GHdeficient, with no known dysmorphic features. Mean age was 4.5 y, bone age was 3.3 y, height SDS was -3.4, height velocity (HV) SDS was -1.6, and body mass index SDS was -1.4. After 1 y of treatment, linear HV in Group 1 increased in comparison with the pre-treatment period (from 5.7 ± 2.0 to 10.1 ± 1.7cm/y; p < 0:001)and with the firstyear of observation in Group2( p < 0:001). Increased HV was sustained during the second and third year of treatment and was significantly higher than at baseline. A similar growth pattern was seen during the 3y of GH treatment in Group 2. Mean height SDS for chronological age increased by 2.0 ± 0.7 in the two groups after 3 y of treatment. HV after 1 y of treatment was negatively correlated with growth velocity at baseline. Bone age remained retarded but increased with a mean of almost 4 y after 3y of treatment in both groups. Even at a dose that is three times the replacement dose treatment with r-hGH was well tolerated. From these results, we conclude that r-hGH treatment over 3 y can induce sustained catch-up growth in young children with severe short stature and a history of IUGR. Long-term studies are needed to assess ultimate effects on final height.     

重组人生长激素治疗对特发性矮小儿童的糖脂代谢及甲状腺功能的影响

目的 探讨重组人生长激素(r-hGH)对特发性矮小(ISS)儿童的糖、脂代谢及甲状腺功能的影响.方法 选取2009年1月至2013年1月应用r-hGH治疗并定期随访的ISS儿童47例,年龄为10±3岁,治疗期限为3~24个月,随访间隔为每3个月1次,检测治疗后0~1年及治疗后1~2年时的空腹血糖、胰岛素、血脂、甲状腺功能等指标的变化.结果 r-hGH治疗后,患儿空腹血糖、胰岛素水平、胰岛素敏感指数、空腹血糖/胰岛素比值(FGIR)与治疗前比较差异无统计学意义,但FGIR有下降趋势;FGIR结论 r-hGH治疗ISS儿童是安全可靠的,可改善脂代谢,对甲状腺功能、空腹血糖、胰岛素水平无明显影响,但有胰岛素敏感性降低的可能.     

生长激素治疗生长激素缺乏症时心脏结构和功能变化

目的评价用人重组生长激素（r－hGH）治疗原发性生长激素缺乏症患者时心脏结构和功能变化。方法对9例确诊为原发性生长激素缺乏患者用r－hGH治疗前后及对20例年龄、性别相匹配的正常青少年通过一维和二维心超检查。结果治疗后患儿的空间隔厚度、左室后壁厚度及心肌重量指数明显上升,与正常相比,仍有一定差异,但差异比治疗前明显缩小。结论生长激素缺乏患者心脏的结构已经受累,但功能尚未有影响,经r-hGH治疗后,心肌重量指数明显上升,提示r-hGH对改善生长激素缺乏患者心脏结构有一定作用。     

Primary adrenal insufficiency in a child after busulfan and cyclophosphamide-based conditioning for hematopoietic stem cell transplantation

High rates of skeletal complications, growth disturbances, thyroid and gonadal dysfunction have been described in children undergoing stem cell transplantation. Although secondary adrenal insufficiency has been diagnosed, no primary adrenal insufficiency has been reported after busulfan and cyclophosphamide (Bu/Cy)-based conditioning regimens for stem cell transplantation in children. A 9-year-old girl with myelodysplastic syndrome was treated with stem cell transplantation of allogeneic origin. She received myeloablative conditioning chemotherapy, Bu and Cy. Her serum cortisol level was normal before stem cell transplantation. Then, 17 months after stem cell transplantation, chronic graft-versus-host disease developed and was treated with methyl prednisolone for 3 months. The control endocrinological investigation revealed low serum cortisol and high serum adrenocorticotropin (ACTH) levels 6 months after completion of methyl prednisolone treatment. The ACTH stimulation test demonstrated primary adrenal insufficiency, and the other etiologies of primary adrenal insufficiency were excluded. The patient received oral prednisolone replacement therapy. She was followed-up for 44 months and required increases in steroid doses during stress periods. Primary adrenal insufficiency which was observed in our patient after Bu/Cy-based conditioning regimen for stem cell transplantation has not been reported in children and adrenal function should be closely monitored in these patients both before stem cell transplantation and after stem cell transplantation.     

Wachstum und Entwicklung nach konventioneller onkologischer Therapie und nach Stammzelltransplantation im Kindesalter

Owing to improved survival of children with cancer and after stem cell transplantation (SCT), interest in late effects is increasing. Disturbances of growth and puberty are a particular focus of study.After conventional cancer therapy outlook for growth and pubertal development is favorable.Patients with ALL frequently develop pronounced chronic obesity unrelated to cranial irradiation. This phenomenon is not present in children with other cancer types.After stem cell transplantation disturbances of growth and puberty are particulary related to total body irradiation (TBI).Growth seems unaffected after chemoconditioning, but disturbed puberty and fertility is observed in females predominantly with high dose busulfan. We report our observations with 111 children after conventional cancer treatment and 40 patients after SCT followed up for at least 6 years.There was no significant growth retardation and no deficit in final height in patients after conventional therapy. Children with ALL/NHL frequently developed obesity. After SCT with TBI growth retardation and impaired puberty are common.Long term follow up and efficient cooperation between paediatric oncologists and endocrinologists are essential for diagnosis and management of disturbed growth and puberty in children with cancer.     

Improvement of growth after growth hormone treatment in children who undergo liver transplantation

BACKGROUND: Chronic liver insufficiency in children is frequently associated with growth retardation. Growth resumes after successful orthotopic liver transplantation in the majority of children with previous chronic liver failure. However, a subgroup of children demonstrates stunted growth even after orthotopic liver transplantation. The current study was conducted to determine whether administration of recombinant human growth hormone might benefit these patients. METHODS: Ten children were identified who met the criteria of growth failure despite normal transplant function in a cohort of 60 transplantation patients: height standard deviation score (hSDS) for chronological age less than -2, and growth velocity SDS (gvSDS) for chronological age equaling 0. Seven of these patients were treated with subcutaneous injections of recombinant human growth hormone at 4.0 U/m2 body surface area per day for at least 1 year. Two patients in this group showed insufficient growth hormone response to stimulation (arginine, clonidine) before therapy. Treatment was begun after a median time of 4.6 years after liver transplantation (2.55-8.4 years). Five children were treated with cyclosporin A and prednisolone and two with tacrolimus and prednisolone for maintenance immunosuppression. RESULTS: Within 3 months of treatment, median serum levels of insulin-like growth factor (IGF)-I increased from 0.05 to 0.71 (P < 0.02). Within 1 year, median hSDS improved from -2.7 (range, -5.6 to -2.3) to -2.1 (-4.5 to -1.4; P < 0.03). Median annual growth rate increased from 3.9 cm/year (range, 3-6) in the year before treatment to 8.2 cm/year (range, 6.1-10.4; P < 0.02) after the beginning of recombinant human growth hormone therapy. All patients tolerated treatment without side effects. During the cumulative treatment time of 14 years no rejection episode was observed. CONCLUSIONS: Short-statured prepubertal liver transplant recipients who do not show sufficient compensatory growth after transplantation benefit from treatment with recombinant human growth hormone. Treatment with the hormone was safe without any side effects.     

重组人生长激素替代治疗对生长激素缺乏症患儿糖代谢的影响

目的观察国产重组人生长激素(r-hGH)替代治疗对生长激素缺乏症(GHD)患儿糖代谢的影响。方法用国产r-hGH对GHD 15例患儿治疗3个月。治疗前后行口服葡萄糖耐量试验(OGTT)及胰岛素(INS)释放试验(IRT)。分别于0、30 mun,1、2 h采静脉血行血浆葡萄糖(PG)及胰岛素(INS)测定。结果治疗前患儿糖耐量均正常,治疗3个月后OGTT空腹PG 无明显增加,但PG 30min(P<0.01)、1 h(P<0.05)、2 h(P<0.05)、血糖曲线下面积(AUCglu)(P<0.01)均明显增加;虽葡萄糖耐量曲线上移,但均未出现糖耐量损伤(IGT)或糖尿病(DM)。IRT空腹INS(P<0.05)、30 min(P<0.05)、1 h(P<0.01)、2 h(P<0.01)、INS曲线下面积(AUCins)(P<0.01)均显著增加,稳态模型胰岛素抵抗指数(Homa IR)明显上升(P<0.05)。结论GHD患儿r-hGH替代治疗3个月后INS敏感性下降,糖耐量降低,提示应用r-hGH替代治疗患儿应监测PG、INS水平     

Growth-chart-based qualitative evaluation of height growth after hematopoietic stem cell transplantation

Growth failure is one of the most common late complications in children undergoing hematopoietic stem cell transplantation (SCT). The present report describes a qualitative method of evaluating height growth after SCT, using a growth chart. The patients were divided into three groups according to the shape of their growth chart: the normal growth chart group, the early-onset growth retardation group (E-group), in which a decreased growth rate was seen during the first year after SCT, and the late-onset growth retardation group (L-group), in which a decreased growth rate was seen more than 1 yr after the SCT. In the E-group, total body irradiation and prolonged steroid therapy were thought to contribute to the growth failure, whereas in the L-group, impaired pubertal development was thought to be responsible. The growth pattern in the L-group may, therefore, be of particular clinical importance, because the final stature of the subjects in this group can be improved by pharmacological adjustment of pubertal onset. Although limited by the small size and heterogeneous nature of the sample, our results suggest that growth-chart-based evaluation may provide important information to stratify subjects showing inadequate growth after SCT into two groups whose follow-up and treatment should be individualized.     

异基因造血干细胞移植治疗粘多糖病I型1例报告

目的：粘多糖病I型是一种进行性多器官受累的遗传代谢性疾病,Hurler综合征是粘多糖病I型的最严重类型,常导致进行性的中枢神经系统受损和早期死亡。该研究进行了异基因造血干细胞移植治疗该病的初步尝试,探讨异基因干细胞移植治疗粘多糖病的疗效。方法：1例男性粘多糖病I型Hurler综合征患者,2岁1个月,供者为其胞姐,HLA配型一个HLA-B位点不合。预处理方案为减低预处理剂量的BuCy方案马利兰(BU)每日3.7mg/kg,-9~-6d;环磷酰胺(Cy)每日42.8mg/kg,-5~-2d;抗胸腺细胞球蛋白每日3.5mg/kg,-7,-5,-3,-1d。输入重组人粒细胞集落刺激因子动员的供者CD34+细胞(12.8×106/kg),以环孢素A、骁悉、赛呢哌、抗胸腺细胞球蛋白和氨甲喋呤预防移植物抗宿主病(GVHD)。结果：移植后14d,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,中性粒细胞和血小板植活时间分别为+11d和+19d。仅出现肝、胃肠Ⅰ级预处理相关毒性,无严重预处理相关并发症。未发生急、慢性移植物抗宿主病和移植物衰竭,移植后临床症状明显改善,认知能力持续增加。结论：异基因造血干细胞移植治疗粘多糖病I型疗效肯定,减低剂量的预处理方案有利于降低预处理相关毒性;移植前后加强免疫抑制治疗,适当增加供者造血干细胞输注数量,有利于促进植入,减少移植物衰竭以及GVHD的发生。     

Authentic recombinant human growth hormone. Results of a multicenter clinical trial in patients with growth hormone deficiency

197 patients with growth hormone deficiency (144 boys, 53 girls, age 1.5-19.5 [mean 11 +/- 3.6], bone age 0.3-15 [mean 8.9 +/- 3.5] years) were treated for one year with authentic recombinant human growth hormone (r-hGH, Norditropin] in several European paediatric centers. 107 patients were newly treated (group A), and 90 transferred from pituitary or methionine hGH (groups B and C). In 19 of the latter, treatment was interrupted for 6 months (group B), in the others, it was changed without interruption (group C). The dosage was 0.45 +/- 0.2 IU/kg/week given s.c. 6-7 times a week. Height velocity increased from 4.1 +/- 2.4 to 8.3 +/- 2.5 (group A), 2.6 +/- 1.8 to 8.3 +/- 2.3 (group B), and 6.2 +/- 2.7 to 6.8 +/- 2.2 cm/year (group C). Few patients complained of local discomfort at the injection site, but this disappeared after changing metacresol in the solvent to 0.9% benzyl alcohol. Only 3 patients developed antibodies to hGH in low titers, which did not interfere with growth. No changes in E. coli protein antibodies were observed. It is concluded that r-hGH is an efficient and safe treatment for children with growth hormone deficiency.