Lamivudine facilitates optimal chemotherapy in hepatitis B virus-infected children with hematological malignancies: a preliminary report

Hepatitis B virus (HBV) reactivation is well documented in infected patients who have hematologic malignancies, precluding appropriate chemotherapy courses and, therefore, increasing the possibility of relapse of malignancies. The objective of this study was to evaluate lamivudine treatment to prevent hepatitis B reactivation in children with cancer who acquired infection with HBV and so allow completion of optimal chemotherapy. Ten children (7:3 M:F; median age: 9.8 years), undergoing chemotherapy for hematological malignancies and suffering from immunosuppressive-induced hepatitis B virus reactivation, were treated concurrently with lamivudine (3 mg/kg bw,od) for up to 18 months. All were HBsAg+ve, HBsAb-ve, HBV-DNA+ve. Serology markers (HBsAg/Ab, HBeAg/Ab, HBV-DNA) and ALT were tested 3 monthly. Histological assessments were performed pre- and 18 months post-lamivudine therapy. During lamivudine therapy chemotherapy courses were completed for all children, and none of the patients suffered reactivation of hepatitis. After a median follow-up of 10 months, remission of malignancy was maintained in 7/10 patients while 3 patients relapsed. HBeAg+ve seroconversion occurred in 4/9 HBeAg+ve children within 3 months. After 9 months of therapy, 8/10 were HBV-DNA-ve. Six out of 7 children with histological evidence of chronic hepatitis showed marked improvement post-therapy. Lamivudine therapy for up to 18 months in children receiving chemotherapy helped prevent recurrence of hepatitis B exacerbations and improved the underlying chronic hepatitis, while facilitating completion of appropriate chemotherapy regimens without compromise.     

Hepatitis B reactivation in allogeneic hemopoietic stem cell transplantation setting: A pediatric experience

Abstract:  Reactivation of HBV is a well known complication in patients undergoing HSCT. Lamivudine treatment appears to prevent hepatitis B virus reactivation and to decrease the mortality in at risk HSCT patients. We describe HBV reactivation occurred in three allogeneic HSCT pediatric patients coming from Eastern Europe, one of whom was successfully treated with lamivudine. Our experience confirms that HBV-DNA may persist as intra-hepatic infection or in extra-hepatic sites and that HBV reactivation may appear during immunodepression. Careful and complete screening for HBV markers is mandatory before HSCT, especially in children coming from countries at risk for HBV. Furthermore, a treatment with lamivudine could also represent an efficacious prophylaxis in pediatric patients to avoid HBV reactivation and to decrease the development of severe hepatic disease.     

以血液系统损害为首发症状的儿童系统性红斑狼疮

目的探讨以血液系统改变为首发或主要表现的儿童SLE的临床特点、治疗方案及预后。方法对2005年6月-2011年6月收治以血液系统改变为主并最终确诊为SLE的38例患儿进行回顾性分析。其血液学改变按白细胞改变、贫血及血小板减少进行分析,并随访6～40个月。结果本组患儿血液系统改变中贫血28例(73.7%)、白细胞改变24例(63.2%)、血小板减少15例(39.5%),距确诊SLE的平均时间为8.5(0～24)个月。针对患儿不同症状选择免疫治疗,本组30例患儿SLE基本无活动,6例轻度活动,2例中度活动,无重度活动。15例PLT减少患儿中10例恢复正常,5例PLT维持在安全水平,8例已停药观察。16例自身免疫性溶血性贫血患儿中13例未再出现溶血发作,死亡1例;另2例患儿间断有轻度溶血发作。2例SLE相关再生障碍性贫血治疗显效。1例SLE相关纯红细胞再生障碍性贫血得到有效控制。结论儿童SLE很隐匿,初期常表现为血液系统损害,值得重视,对治疗效果欠佳患儿或青春期前后女童应警惕SLE,延长随访期限,评估病情以选择治疗方案和疗程。     

拉米夫定、雷公藤总苷联合蝮蛇抗栓酶治疗乙型肝炎病毒相关性肾炎

目的 探讨拉米夫定、雷公藤总苷联合蝮蛇抗栓酶(LTA方案)治疗儿童乙型肝炎病毒相关性肾炎(HBV-GN)的疗效.方法 对住院的60例确诊为HBV-GN患儿随机分为观察和对照组各30例.观察组以拉米夫定100ms/d,1次/d,口服12个月;雷公藤总苷片0/5 ms/(kg·d),2次/d,口服,12个月;蝮蛇抗栓酶0.01 U/(kg·d)静脉滴注,1次/d,治疗3d.对照组仅予雷公藤总苷0.5 ms/(kg·d)治疗12个月.疗程结束后根据<中药新药治疗慢性肾炎的I临床研究指导原则>和<中药新药治疗病毒性肝炎的临床研究指导原则>中的判定标准判定二组患儿的疗效.采用PEMS 3.1软件进行统计学分析.结果 1.观察组患儿临床控制10例(33.3%),显效9例(30.O%),有效10例(33.3%),无效1例(3.3%),总有效率96.7%;对照组临床控制6例(20.0%),显效4例(13.3%),有效10例(33.3%),无效lO例(33.3%),总有效率66.7%.二组总有效率比较差异有统计学意义(P<0.05).2.观察组尿蛋白总有效率93.3%,尿红细胞总有效率96.6%;而对照组分别为76.6%和80.0%,二组比较有统计学差异(P<0,05).3.二组患者治疗前后比较,肝-肾功能指标均有明显改善,但观察组更明显,二组均未发现严重不良反应.结论 拉米夫定、雷公藤总苷联合蝮蛇抗栓酶治疗儿童HBV-GN安全有效.     

儿童血液病化疗并发脓毒症60例临床分析

目的 分析总结血液病患儿化疗后并发脓毒症的病原菌种类、药敏特点和临床特征,以指导临床合理用药.方法 以65例次化疗后合并脓毒症患儿为病例组,回顾分析其血培养病原菌的分布和药敏特点,以同期55例化疗后发热但未合并脓毒症患儿为对照组,分析2组患儿发热时中性粒细胞计数(ANC),中性粒细胞缺乏期持续时间及其预后.结果 血液病化疗后合并脓毒症患儿的主要致病菌是革兰阴性杆菌(52例次),分别为铜绿假单胞菌(20例次)、肺炎克雷伯杆菌(12例次)、大肠埃希菌(11例次)、嗜麦芽窄食单胞菌(4例次)、肠杆菌(3例次)和沙门菌(2例次).革兰阴性杆菌对美罗培南最敏感,对复方磺胺甲唑最易耐药.培养出革兰阳性球菌13例次,分别为凝固酶阴性葡萄球菌(7例次)、金黄色葡萄球菌(3例次)和肠球菌(3例次).革兰阳性菌对万古霉素最敏感,对青霉素和红霉素最易耐药.ANC＜0.5×109 L-1或中性粒细胞缺乏持续时间＞7 d的患儿更易合并脓毒症.脓毒症组患儿有7例合并感染性休克,预后差.对照组患儿治疗后体温正常.结论 革兰阴性杆菌为儿童血液病化疗后脓毒症的主要致病菌,脓毒症的发生与ANC及中性粒细胞缺乏持续的时间有关.     

Serum Tumor Necrosis Factor Does Not Correlate with Changes in Muscle Volume in Children with Malignancies

This study examined the connection between serum tumor necrosis factor (TNF) concentration and the development of cachexia in 12 children with acute lymphoblastic leukemia (ALL). The changes in muscle thickness were used as criteria for malnutrition, estimated by an ultrasound method during the 16 weeks of chemotherapy subsequent to diagnosis. Serum TNF concentrations were elevated at diagnosis and gradually decreased toward the reference limits by week 16. There was no correlation between TNF and muscle thickness. The results were also compared to those obtained from 8 children with other malignancies in whom the mean relative weight remained below normal whereas in those with ALL it gradually increased to + 15%. Thus, we found no evidence of the association between elevated serum TNF concentrations and cachexia in man.     

Hepatitis B in children: complexities in management

Chronic hepatitis B virus (HBV) infection by definition is persistence of hepatitis B surface antigen (HBsAg) in the serum for > or =6 months. The risk of developing chronic HBV infection ranges from 90% in neonates to <5% in immunocompetent adults. HBV acquired by perinatal infection has a prolonged immune-tolerant phase, characterized by the presence of hepatitis Be antigen (HBeAg), high HBV-DNA and normal alanine aminotransferase (ALT) levels. Efficient and multi-specific helper and cytotoxic T-cell response is essential for controlling HBV infection. Chronic HBV infection is characterized by a state of HBV-specific T-cell hyporesponsiveness. The goal of therapy in chronic HBV infection is to eliminate or significantly suppress HBV replication and prevent the progression of liver disease to cirrhosis with the potential development of liver failure or hepatocellular carcinoma (HCC). In adults, drugs currently licensed for treatment of HBV infection: are interferon-alpha (IFN-alpha), lamivudine (LMV) and adefovir dipivoxil (ADV), the first two are also licensed to use in children. IFN-alpha has the advantage of having a more durable response, fixed duration of treatment and lack of resistant mutants. The disadvantages of IFN-alpha include need for thrice-weekly injections, higher cost and more side-effects compared with the nucleoside analogues. Nucleoside analogues can be given orally and used in decompensated cirrhosis and transplant recipients. ADV and newer drugs like tenefovir can successfully treat mutants produced after prolonged LMV therapy. Current protocols exclude children with immunotolerant HBV. Periodic screening with liver ultrasound scan and alpha-fetoprotein (AFP) in all children with chronic HBV infection is recommended. The severe shortage of cadaveric donor organs has led to the use of marginal (including anti-HBc-positive) cadaveric donor livers in selected transplant candidates with high medical urgency; 5-10% of all liver transplants are because of HBV. Using hepatitis B immunoglobulin and nucleoside analogues has made the outcome following liver transplantation for hepatitis B, comparable with, if not slightly better, than that in patients with other diagnoses. Future treatments should be based on the restoration of HBV-specific T-cell responses to levels similar to that seen in subjects controlling HBV.     

Iron Deficiency Anemia in Children Presenting with Lymphoreticular Malignancies and the Effect of Induction Therapy

There is scant information regarding iron deficiency in children with malignant disorders. Serum iron status of children with lymphoreticular malignancies (LRMs) at onset and at the end of induction therapy, compared to the normal population, was evaluated. Prospective cohort study conducted between July 2002 and March 2004. Previously untreated children recently diagnosed with LRM were studied. Age-matched controls were enrolled from follow-up and growth monitoring clinics. Hematological (complete blood counts and red cell indices) parameters and markers of iron status (serum iron, serum ferritin, total iron binding capacity) were estimated at presentation and at the end of remission induction therapy, that is, 5 weeks after initial evaluation. Bone marrow iron store were only assessed in cases. Thirty-five children (31 with acute lymphoid leukemia, 2 with acute myeloid leukemia, and 2 with non-Hodgkin lymphoma; 27 boys and 8 girls; 2 to 12 years of age) were evaluated in the study cohort. Anemia was documented in 80% of children with LRM. Iron deficiency was an important etiological factor. In the majority of cases therapy resulted in significant improvement towards normalization of deranged hematological parameters. This phenomenon could be attributed to enhanced quantity and quality of erythropoietic activity and red cell transfusions. The observation suggests that therapeutic iron supplements are not indicated in the majority of children on therapy for malignant disorders. Various hematological and body iron status parameters should be assessed on a case-by-case basis.     

Hepatitis B Vaccination in Children with Cancer

Between September 1991 and April 1993 the hepatitis B vaccination with recombinant hepatitis B vaccine was administered in 41 cancer patients following first diagnosis. All patients were under 16 year of age, with negative hepatitis B virus (HBV) serology and normal hepatic function. They received 40 μg of vaccine by injection into the deltoid muscle at 0, 1, and 2, months, with a fourth dose planned at the 4th month for nonresponders. At 1 year a booster dose was given. All the patients began vaccination within 1 month following diagnosis, and periodic serologic follow-up was performed immediately after each vaccination and also in the 6th, 9th, and 12th months after vaccination. Patients with production of anti-HBs at a titer equal to or greater than 10 mIU/L were considered seropositive. The seroconversion rates were 12.4%, 21.9%, 41.0%, and 48.7% after the first, second, third, and fourth monthly doses, respectively. Seroconversion rates were 56.0% at 6 months, 67.5% at 9 months, and 70.5% at 12 months. Geometric mean antibody titers were 212 and 373 mIU/L at 9 and 12 months, respectively. No serious side effects were observed. HBV vaccination is recommended for pediatric cancer patients.     

Blastic transformation in chronic myelogenous leukemia: Experience with 50 patients

Fifty consecutive patients with blastic chronic myelogenous leukemia were evaluated clinically, morphologically, biochemically, and therapeutically. Forty-five patients had a preceding stable phase (38 Ph +, 7 Ph -); five patients presented with de novo Ph+ blast crisis. The most frequent clinical signs of impending blast crisis were weakness, fatigue, increasing splenomegaly, anemia, thrombocytopenia, marrow fibrosis, and a rising neutrophil alkaline phosphatase. Fever (unrelated to infection), skin infiltration, lymphadenopathy, hepatomegaly, thrombocytosis, and basophilia were much less common. The development of aneuploidy occurred in less than one-half of the total group. Myeloblastic morphology at blastic transformation was most frequent with occasional lymphoblastic, promyelocytic, and undifferentiated cases seen. Terminal deoxynucleotidyl transferase was present in one-third of the patients, but had no clear-cut relationship to the morphology. Response to treatment was generally disappointing (two complete and 15 partial remissions in 45 treated patients).     

Acute Hepatitis B in Children with Papular Acrodermatitis

Thirteen children who had repeated liver biopsies over a period of 2-16 years after the onset of papular acrodermatitis (PAC) were studied retrospectively. Six patients, rebiopsied within 36 months after the onset of PAC, had histologic evidence of chronic periportal hepatitis. However, repeated biopsies in 3 of the patients revealed a normal liver or chronic portal hepatitis. Whereas all patients had at the end of the observation markers of hepatitis B virus infection, 8 of the 10 patients studied had HBs antigenemia. These data indicate that severe active liver disease may regress without treatment in patients who have had PAC. However, the high frequency of a chronic HBsAg-carrier state among these patients suggests either an inefficient clearance of the virus or an altered immune reaction.     

Hepatitis B Virus Infection in the Infants Born to HBe Antigen Negative Carrier Mothers: A Preliminary Report

One hundred infants born to hepatitis-Be antigen (HBeAg)-negative carrier mothers were followed with or without the administration of hepatitis-B vaccine (HB vaccine) and/or hepatitis-B hyperimmune globulin (HBIG). Among the infants without treatment, 7.6% of the infants born to the antibody-to HBeAg (anti-HBe)-positive carrier mothers and 14% of those born to the carrier mothers without HBeAg and anti-HBe developed HBs-antigenemia, whereas none of the infants treated became positive for HBsAg. The results indicate the necessity for preventive measures for the babies born to HBsAg-carrier mothers, regardless of their HBeAg state.     

A Simplified Master's Two-Step Test for Preschool Children: A Preliminary Report

To investigate a simplified Master's two-step test (MTT) for preschool children aged 4 to 6 years exercise tests with new stairs, with risers 18 cm and 20 cm high, were employed. The subjects were 162 preschool children who were divided into four groups according to the height of the riser and the number of steps taken (60 and 72 steps per 3 minutes). In these tests, the 4-year-old children obtained similar mean heart rates immediately after exercise (156.9 to 161.6 BPM) in spite of different exercise tests, and the 5- and 6-year-old children obtained significantly higher mean heart rates (166.0 and 162.1 BPM, respectively) in the test with a 20 cm riser taking 72 steps. If a single protocol is to be used for children aged 4 to 6, the test with a 20 cm riser and taking 72 steps seems to be the best with reference to the achieved heart rates and performance ratios.     

Parenteral Acetylsalicylic Acid Treatment in Children with Sickle Cell Pain Crisis: A Preliminary Report

Bone vasocclusive crisis (VOC) is a frequent reason for hospitalization of children with sickle cell disease. In spite of significant efforts, no effective antisickling agent has been found, and hydration and analgesia are the recommended modes of treatment.Oral aspirin, acetaminophen, or codeine is recommended for mild pain, as is a parenteral narcotic for moderate or severe crises.     

Significant Morbidity and Mortality Attributable to Rothia Mucilaginosa Infections in Children with Hematological Malignancies or Following Hematopoietic Stem Cell Transplantation

Rothia mucilaginosa is a gram-positive coccus that poses a diagnostic challenge and often requires DNA pyrosequencing for diagnosis as it can be easily mistaken for coagulase-negative staphylococci on initial culture results. While it is often times normal human oral and upper respiratory tract microbiota, it can be a virulent pathogen in immunocompromised patients. Most commonly, it causes bacteremia (catheter and non-catheter related) and meningitis in these patients. Our objective was to report the incidence of R. mucilaginosa infections in neutropenic children with hematological malignancies or following hematopoietic stem cell transplantation at a major children's hospital. We report 11 patients in this cohort who developed clinically significant R. mucilaginosa infections, including three deaths directly attributable to this microorganism. Three patients developed significant neurological involvement, accounting for two of the deaths, and one patient died of disseminated infection. Except for one, all patients had severe neutropenia, central line catheters, and mucosal breakdown at the time of infection. Patients who succumbed never achieved neutrophil recovery. In conclusion, R. mucilaginosa can lead to life-threatening infections in immunocompromised hosts, especially in profoundly neutropenic patients.     

Six Years' Experience of Total Parenteral Nutrition in Children with Hematological Malignancies at a Single Center: Management, Efficacy, and Complications

Total parenteral nutrition (TPN) is an important issue in supportive care of children with leukemia. We studied 131 consecutive children (87 male, 44 female) with hematological malignancies who received TPN at our center from July 1984 to July 1990 with the aim of evaluating the efficacy and complications of TPN. The use of TPN was associated with lack of any alteration of the anthropometric indexes used in this study. The complications were prevalently metabolic, generally mild, and easily controlled. Laboratory monitoring of nutritional status during TPN is probably of little value in this setting. The feasibility of in-ward preparation of TPN by nurses makes TPN possible at low cost provided that patients are selected carefully.