Prepubertal growth and growth hormone secretion in children after treatment for hematological malignancies, including autologous bone marrow transplantation

Prepubertal growth standards were used to assess growth in 20 children who had undergone autologous bone marrow transplantation (ABMT) as part of their treatment for hematological malignancy. Most of the patients (16 of 20) were transplanted after a relapse of their disease. A negative change in height standard deviation score (H-SDS) was seen only in the group of patients (n=7) who had received both cranial irradiation therapy (CRT) and 7.5-Gy single-fraction total body irradiation (TBI). Height changes in this group were observed from the time of diagnosis. In contrast, the groups of patients conditioned with chemotherapy only (n=3) or both chemotherapy and TBI, without preceding CRT (n=10), did not demonstrate a significant loss in H-SDS. Weight related to height demonstrated large individual differences over time. Spontaneous growth hormone (GH) secretion, as measured by a four-point sleep curve, was followed longitudinally and an increasing proportion of patients with low peak levels was seen in all patient groups. In summary, prepubertal growth was suppressed only in patients who received cranial irradiation before ABMT. Despite low GH peak levels, normal prepubertal growth was found in patients with no CRT before ABMT.     

儿童急性白血病完全缓解后骨髓幼稚细胞低比例增高的临床意义

目的　了解急性白血病患儿完全缓解 (CR)后骨髓幼稚细胞比例出现 0 0 5～ 0 2 5时对预后的影响 ,为临床治疗策略的调整提供依据。方法　对 1998～ 2 0 0 1年上海儿童医学中心收治急性白血病患儿CR后按骨髓幼稚细胞比例分为A组 (<0 0 5 )和B组 (0 0 5～ 0 2 5 ) ;B组又分为B1(0 0 5～ 0 10 )、B2 (～ 0 15 )、B3(～ 0 2 5 ) 3个亚组 ,分析各组与急性白血病复发的关系。结果　急性淋巴细胞白血病 (ALL)患儿CR后骨髓幼稚细胞≥ 0 10时 ,复发率与阴性对照组差异有显著性 ;急性非淋巴细胞白血病 (ANLL)患儿CR后骨髓幼稚细胞≥ 0 15时 ,复发率与阴性对照组差异有显著性。结论　ALL患儿CR后骨髓中原始淋巴细胞 幼淋巴细胞≥ 0 10及ANLL患儿CR后骨髓中原始粒细胞 早幼粒细胞或原始单核细胞 幼单核细胞≥ 0 15时应考虑及时调整治疗方案。     

Performing bone marrow aspiration and biopsy in children: Recommended guidelines

Bone marrow aspiration (BMA) and bone marrow trephine biopsy are important procedures for the diagnosis of hematological malignancies and nonmalignant diseases in children. During BMA, bone marrow particles are obtained for analysis including microscopic morphologic evaluations and differential counts. During a trephine biopsy, a core of bone marrow is obtained and processed for the evaluation of marrow cellularity and to rule out marrow involvement by solid tumours, lymphomas or other processes. These invasive procedures should only be performed by a trained individual following a standard operating technique. There are no clear published guidelines in the paediatric literature. Hence, the purpose of the present article is to provide guidelines for the performance of BMAs and bone marrow trephine biopsies in children that will be useful for both general paediatricians and paediatric hematologists and oncologists.     

儿童自身免疫性溶血性贫血和Evans综合征复发及其相关因素分析

目的研究和探讨儿童自身免疫性溶血性贫血(AIHA)和Evans综合征复发率及其相关因素。方法采用同期病例对照法,比较不同因素与复发的相关性。结果40例患者中有7例复发,复发率为17·5%,Coombs阴性患者复发率为66·66%,Coombs阳性患者复发率为13·51%。复发发生在首次发病的2个月到2年7个月之间,4例在停药后,2例在激素减量中。复发诱因中感染因素占4例(57·14%),主要为呼吸道和消化道感染;无诱因者3例(42·86%)。复发组和未复发组患儿的性别、抗体的类型、是否存在其他自身免疫性疾病、患病时的血红蛋白水平和网织红细胞计数等均与复发无关(P>0·05)。细胞免疫功能的检查结果显示复发组CD3增高、CD8降低,经统计学分析两组存在显著差异(P<0·05)。结论儿童AIHA和Evans综合征的复发率远低于成人,复发患者免疫功能异常较未复发患者显著。     

儿童自身免疫性溶血性贫血和Evans综合征复发及其相关因素分析

目的研究和探讨儿童自身免疫性溶血性贫血（AIHA）和Evans综合征复发率及其相关因素。方法采用同期病例对照法，比较不同因素与复发的相关性。结果40例患者中有7例复发，复发率为17．5％，Coombs阴性患者复发率为66．66％，Coombs阳性患者复发率为13．51％。复发发生在首次发病的2个月到2年7个月之间，4例在停药后，2例在激素减量中。复发诱因中感染因素占4例（57．14％），主要为呼吸道和消化道感染；无诱因者3例（42．86％）。复发组和未复发组患儿的性别、抗体的类型、是否存在其他自身免疫性疾病、患病时的血红蛋白水平和网织红细胞计数等均与复发无关（P 〉 0．05）。细胞免疫功能的检查结果显示复发组CD3增高、CD8降低，经统计学分析两组存在显著差异（P 〈 0．05）。结论儿童AIHA和Evans综合征的复发率远低于成人，复发患者免疫功能异常较未复发患者显著。     

Utility of spinal MRI in children with anorectal malformation

Background  The association between spinal cord anomalies and imperforate anus is well recognized. Until now, the incidence of tethered cord has been assumed to be higher in patients with high-type imperforate anus. However, recent reports suggest that tethered cord is as common in patients with a low lesion as in those with a high lesion. Objective  To review the incidence of spinal cord anomalies in those with a low lesion and those with a high (including intermediate) anorectal malformation (ARM), and to determine the best diagnostic imaging strategy. Materials and methods  A group of 50 consecutive patients with postoperative ARM and in whom spinal MRI had been performed were identified retrospectively. We reviewed and compared the following factors between those with a high lesion and those with a low lesion: (1) clinical symptoms, (2) spinal cord anomalies, and (3) vertebral anomalies. Results  The incidence of spinal cord anomalies was no different between those with a high lesion and those with a low lesion, and spinal cord anomalies were present regardless of the presence of vertebral anomalies or symptoms. Conclusion  Owing to the high incidence of spinal cord anomalies in patients with imperforate anus, MRI is the best imaging tool for detecting such anomalies regardless of the level of the lesion.     

Ureteral obstruction following allogeneic bone marrow transplantation in children

Two patients with Ph + CML underwent URD-BMT after conditioning with Bu-Cy-LPAM. They developed hemorrhagic cystitis with an extremely complicated and painful course, caused by ureteral obstruction, requiring prolonged hospitalization. No virus other than cytomegalovirus was found and in both cases was attributed to Cy use. Treatment is usually conservative, but in the case of severe obstruction, a surgical approach should be considered and performed as early as possible to preserve renal function.     

Outcomes of Burkitt lymphoma with bone marrow involvement or Burkitt leukemia in Chinese children

Importance:Burkitt lymphoma with bone marrow involvement and Burkitt leukemia behave aggressively.Thus far,there are limited data concerning survival and toxici...     

Prognostic value of day 14 blast percentage and the absolute blast index in bone marrow of children with acute lymphoblastic leukemia

The product of the percentage blasts on the bone marrow aspirate (BMA) and the biopsy cellularity has been termed the "absolute blast index aspirate" (ABI-aspirate) and is used to measure disease response on day 7 of induction therapy. The authors compared the event-free survival (EFS) in high-risk and standard-risk patients as identified by the ABI-aspirate and the BMA percentage blasts on day 14 of induction therapy. Both indices identified high-risk cases. EFS of patients categorized as high-risk by these 2 methods and the high-risk criteria used by the authors' service (WCC of > 20 x 10(9)/L, age < 2 and > 8 years and a peripheral blood blast count of > 1.0 x 10(9)/L on day 8 of induction) did not differ. There was concordance between patients identified as high risk by all 3 methods. The results confirmed the prognostic value of the ABI-aspirate and the BMA percentage blasts on day 14 of induction therapy, but these methods were not superior to the high-risk criteria currently in use.     

Ketamine anesthesia with or without diazepam premedication for bone marrow punctures in children with acute lymphoblastic leukemia

Ketamine is a drug widely used for analgesia and sedation of children for diagnostic and therapeutic procedures. The authors investigated in a randomized controlled clinical trial if diazepam premedication would have a beneficial effect on side effects related to ketamine anesthesia for bone marrow punctures (BMPs) in children with acute lymphoblastic leukemia (ALL). Sixteen children 4 years or older at the time of BMP were eligible. The first 2 BMPs after complete remission was obtained were studied. BMPs were performed under ketamine anesthesia (1.0-1.5 mg/kg iv), as usual. Patients were randomized to receive 1 h before the first BMP blinded, either diazepam or placebo orally and before the second BMP the other way round. Blood pressure, heart rate, and oxygen saturation were monitored, and patients were observed for signs of anxiety, pain, and other side effects. The patients were interviewed after each BMP and asked for their preference 1 week after the second BMP. Ketamine anesthesia appeared as safe and effective after diazepam premedication as after placebo premedication. From the interviews and questionnaires, it was clear that half of the children preferred diazepam premedication because of less awful dreaming and more gradual falling asleep and waking up. Diazepam premedication may be useful for selected children with ALL receiving ketamine anesthesia for BMPs.     

儿童急性白血病併发曲霉菌病的临床诊断和治疗——附7例临床病例报告

目的探讨儿童急性白血病患者曲霉菌感染,尤其是肺曲霉菌病的临床特点及其诊断和治疗。方法对我院血液肿瘤病房7例曲霉菌病进行回顾性分析,观察其发病时间、诱因,临床症状及X线、CT表现及治疗效果。通过血或痰等分泌物培养,X线及CT检查等诊断。所有粒细胞缺乏的发热患者积极抗生素治疗的基础上予大扶康预防或经验治疗,3~7天无效者改用两性霉素B。结果诊断曲霉菌肺炎6例,曲霉菌鼻窦炎2例(1例合并肺炎)。鼻窦炎1例鼻窦冲洗液培养为曲霉菌。另1例口唇坏死组织切片见大量菌丝及孢子。曲霉菌肺炎主要根据肺部CT特征性改变及治疗转归临床诊断。2例原发病未缓解者死亡,其它5例均经两性霉素B治疗好转。两性霉素B副作用主要有:寒战、高热、低钾血症及一过性肾功能损害,均无需停药。结论深部曲霉菌感染临床表现不典型,诊断困难,肺部CT检查对其早期发现、及早治疗有重要意义。曲霉菌肺炎典型CT改变为球形或团块状阴影,伴“晕轮征”或“新月征”。以胸膜为基底的楔形实变影提示发生致命性咯血的可能。两性霉素B疗效肯定,副作用可耐受。原发病的缓解及粒细胞恢复也是真菌感染能否治愈的重要因素。     

MRI of the hypothalamic-pituitary axis in children

In childhood, the MR characteristics of the normal pituitary gland are well established. During the first 2 months of life the adenohypophysis demonstrates high signal. Pituitary gland height (PGH) decreases during the 1st year of life and then increases, reaching a plateau after puberty. The magnetization transfer ratio (MTR) increases in both sexes up to the age of 20 years. On dynamic contrast-enhanced studies, the posterior pituitary lobe enhances simultaneously with the straight sinus, and the adenohypophysis later, but within 30 s. In genetically determined dysfunctional states, the adenohypophysis may be normal, hypoplastic, or enlarged. Pituitary enlargement, observed in Prop 1 gene mutations, is characterized by a mass interposed between the anterior and posterior lobes. An ectopic posterior lobe (EPP), associated with a hypoplastic or absent pituitary stalk, may be observed in patients with hypopituitarism. Tumors of the hypothalamic-pituitary (HP) axis may be the origin of adenohypophyseal deficiencies. A small hypointense adenohypophysis is found in iron overload states and is often associated with hypogonadotrophic hypogonadism. Absence of the posterior lobe bright signal, with or without a thick pituitary stalk or a mass at any site from the median eminence to the posterior pituitary lobe, may be found in diabetes insipidus. Hydrocephalus, suprasellar arachnoid cysts, hypothalamic hamartomas and craniopharyngiomas may result in central precocious puberty (CPP). Increased PGH in girls with idiopathic CPP is useful for its differential diagnosis from premature thelarche (PT). Pituitary adenomas, observed mainly in adolescents, present the same MR characteristics as those in adults.     

儿童复发急性淋巴细胞白血病临床特征与疗效分析

目的探讨复发儿童急性淋巴细胞白血病(ALL)的临床特征,总结危险度分层方案治疗复发儿童ALL的中期疗效。方法回顾分析2008年8月-2014年6月初诊为ALL并经治疗后复发的46例患儿临床资料,其中28例根据复发时间、复发部位及免疫分型,分为S1、S2、S3、S4四组,采用ALL-REZ BFM 2002方案接受不同强度治疗。结果 46例患儿中,单独骨髓(BM)、单独中枢神经系统(CNS)、单独睾丸、联合复发(BM+CNS)分别为26例(56.5%)、13例(28.3%)、1例(2.2%)和6例(13.0%)。复发距第一次完全缓解(CR1)的中位时间为1.4(0.1~4.5)年,极早期、早期、晚期复发分别为22(47.8%)、15(32.6%)和9(19.6%)例。B细胞ALL 40例(87.0%),T细胞ALL6例(13.0%)。临床危险度分型S1、S2、S3、S4组分别为1、23、11例和11例。复发后放弃失访18例,坚持治疗28例,采用ALL-REZ BFM 2002方案治疗后CR2为82.8%。S1、S2、S3、S4期患儿的CR2分别为100%(1/1)、94.7%(18/19)、60%(3/5)和33.3%(1/3)。2年无病生存率(DFS)为(49.7±10.8)%。(S1+S2)与(S3+S4)组的2年DFS分别为(59.7±13.4)%和(25.0±15.3)%(χ~2=5.312,P=0.021)。结论在本组病例中,儿童ALL复发最常见于早期及BM复发,预后较差,而单独CNS复发预后良好,S1、S2期患儿采用ALL-REZ BFM 2002方案治疗可获得较好疗效,S3、S4期患儿仍需进一步寻找更为有效的化疗方案或接受造血干细胞移植,以改善最终预后。     

四种化疗药物诱导正常骨髓及白血病细胞株凋亡作用的比较

目的探讨化疗药物诱导正常骨髓及白血病细胞凋亡作用的差异。方法检测了临床常用４种药物作用后凋亡细胞出现的比例（形态学指标为ＡＰＯ％、流式细胞仪指标为ｓｕｂ－Ｇ１％）和细胞ＤＮＡ断裂（ｌａｄｄｅｒ）的变化。结果足叶乙甙、阿糖胞苷、长春新碱、柔红霉素作用４８小时，正常骨髓细胞ＡＰＯ％分别为１７．９％±４．６％、３０．５％±６．５％、１６．７％±４．２％、１２．３％±０．７％；ｓｕｂ－Ｇ１％分别为１０．５％±３．１％、２７．９％±４．７％、６．５％±１．５％、４．５％±１．５％、仅阿糖胞苷组有ｌａｄｄｅｒ出现。白血病细胞株ＡＰＯ％分别为８０．９％±８．４％、３８．１％±７．７％、５２．６％±９．３％、２４．２％±６．１％；ｓｕｂ－Ｇ１％分别为７３．４％±１２．７％、５９．８％±１０．１％、４７．６％±９．３％、２６．７％±６．８％，且都有ｌａｄｄｅｒ出现。结论化疗药物也能诱导正常骨髓细胞凋亡，但明显低于诱导白血病细胞凋亡的作用     

抗凋亡基因Bcl-2在儿童急淋白血病中表达与早期治疗反应关系的初步研究

目的探讨骨髓细胞抗凋亡基因Bcl-2表达蛋白在儿童急性淋巴细胞白血病(ALL)患者中的表达状况与临床相关危险因素及其早期治疗反应的关系。方法采用S-P免疫组织化学方法,检测32例ALL患者治疗前后骨髓细胞Bcl-2的表达。选择同期住院的非白血病患者15例正常骨髓作为对照。结果Bcl-2蛋白在ALL中表达明显高于对照组(t=3·2558、P<0·01);治疗前后高危组、中危组、低危组间比较均有显著性差异(F分别为3·4317、4·1132,P均<0·05,早期治疗反应差与早期治疗反应好组间比较均有显著性差异(t分别为2·9462、2·3747,P<0·01、<0·05);治疗反应好组,一个疗程后Bcl-2蛋白表达水平显著下降(t=1·7309;P<0·05),治疗反应差组,一个疗程后Bcl-2蛋白表达水平下降,但较化疗前无显著性差异(t=1·1875;P>0·05),仍显著高于对照组病例(t=2·4164;P<0·05)。结论抗凋亡基因Bcl-2蛋白在儿童急淋白血病患者中存在高表达,与临床危险因素有关,可以作为一个影响儿童ALL疗效、预后,评定危险程度的新的生物学指标。     

Methotrexate infusions as central nervous system prophylaxis in children with acute lymphocytic leukemia: the Norwegian experience

This study included all 690 children in Norway diagnosed as having acute lymphocytic leukemia (ALL) from July 1975 till the end of 1997. Relapses and deaths were monitored until the end of 2000. Neuroleukemia prophylaxis was intravenous methotrexate (MTX) infusions as intermediate-dose methotrexate (IDM) or high-dose methotrexate (HDM) combined with intrathecal MTX. From 1992, systemic therapy was considerably intensified, and, in addition, patients in a subgroup of the high-risk and very high-risk groups were given prophylactic cranial irradiation. The overall findings showed that MTX significantly reduced central nervous system (CNS)-related relapses, and, in general, reinforced systemic therapy reduced significantly non-CNS relapses and deaths. The overall crude survival was 75%. During the study period, the crude survival improved for patients on standard protocols from initially 65 to 90%. Forty patients (6%) developed isolated CNS relapse, 27 (4%) had combined CNS relapse, whereas 180 (26%) had non-CNS relapse. When IDM and HDM were compared, the cumulative risk for isolated CNS relapse was significantly lower with HDM, 12 and 5%, respectively. For any relapses that involved the CNS, the risk remained significantly lower for HDM, 8 versus 18%. Of the 40 patients with isolated CNS relapse, 23 survived (58%).     

Combination chemotherapy for bone marrow relapse in childhood lymphoblastic leukaemia (ALL).

Thirty-four children with acute lymphoblastic leukaemia (ALL) in relapse or resistant to initial induction received combination chemotherapy with prednisolone, vincristine, l-asparaginase, and daunorubicin. L-asparaginase was given subcutaneously on alternate days for four weeks and was well tolerated. A complete remission was achieved in 96% of children in relapse and in five out of six children resistant to induction. Remission was achieved without hospitalisation in over 60% of patients. The median duration of subsequent remission was only 13 weeks, but six out of eight children receiving a second course of the drug combination achieved a further remission. We conclude that prolonged l-asparaginase therapy in combination with an anthracycline might well be used in initial or consolidation therapy for childhood ALL.     

非亲缘异基因骨髓移植治疗儿童白血病

目的　评价非亲缘异基因骨髓移植 (URD BMT)治疗儿童急性和慢性白血病的临床疗效。方法　 6例白血病患儿 ,其中慢性髓系白血病 2例 ,急性淋巴细胞白血病 3例 (第 1次完全缓解 ) ,急性早幼粒细胞白血病 1例 (第 2次完全缓解 ) ,由台湾慈济骨髓捐赠中心提供无关供者骨髓。预处理方案为马利兰 环磷酰胺 (Bu/Cy2 )方案 ,急性移植物抗宿主病 (aGVHD)预防为霉酚酸酯(MMF)、环孢菌素A(CsA)加氨甲喋呤 (MTX)联合方案 ;以前列素E1预防肝静脉闭塞病 (VOD) ,以巨细胞病毒 (CMV)抗原血症监测和更昔洛韦预防CMV病。供、受者间HLA基因位点型全相合 3例 ,1个基因位点型不合 2例 ,2个基因位点型不合 1例。结果　 6例患儿经DNA短串联重复序列多态性分析证明为供髓植入 ,中性粒细胞 >0 5× 10 9/L的中位天数为 14 5 (13～ 18)d ,血小板 >2 0×10 9/L的中位天数为 16 (11～ 2 3)d。发生Ⅱ～Ⅳ度aGVHD 2例 (33% ) ,局限性慢性移植物抗宿主病(cGVHD) 3例 ,未发生广泛性cGVHD。中位随访时间 4 12 (187～ 1338)d ,全部患儿均无病生存。结论非亲缘异基因骨髓移植是治疗儿童急性和慢性白血病的有效方法。     

Pelvic MRI in children with Crohn disease and suspected perianal involvement

MRI is an important imaging tool in evaluation of adult and pediatric patients with Crohn disease. Pelvic MRI, in particular, has become the method of choice to evaluate for perianal fistulas and associated complications of Crohn disease. MRI can define the extent and location of perianal fistulas and abscesses, as well as provide critical information for operative management. In this pictorial essay, we describe useful MRI techniques for evaluation of perianal complications in pediatric patients with Crohn disease. We review pertinent anatomy and illustrate typical examples of perianal fistulas with and without abscess. We show one case of clinically suspected perianal fistula that was actually a pilonidal sinus.     

Altered bone metabolism in children infected with human immunodeficiency virus

Aim: Data on bone homoeostasis of children infected with human immunodeficiency virus (HIV), at the time of the gain in bone mass, are very rare. To determine possible alterations in bone metabolism, 13 prepubertal vertically HIV-infected children were studied. Methods: Viral load, CD4 count, interleukin-6 (IL-6), growth hormone, insulin-like growth factor-I (IGF-I), IGF binding protein-3 (IGFBP-3), acid-labile subunit (ALS), IGFBP-3 proteolysis, osteocalcin in blood and N-terminal telopeptide of type I collagen in urine were determined. Lumbar spine bone mineral density was examined by dual-energy X-ray absorptiometry. Results: Low osteocalcin levels were found in all patients. Low IGF-I was found in only six children, who had low CD4 count and high IL-6 levels, with normal levels of IGFBP-3 and ALS, absent IGFBP-3 proteolysis and decreased bone mineral density, irrespective of viral load or growth. Conclusion: Low serum osteocalcin levels appear to be an initial warning sign of possible altered bone metabolism in HIV-infected children. However, only when the immune system becomes more seriously compromised is bone loss measurable by bone densitometry.