Association of steroid therapy with vaccine-associated rashes in children with acute lymphocytic leukaemia who received Oka/Merck varicella vaccine

Oka strain varicella vaccine generally has been well tolerated by children with acute lymphocytic leukaemia (ALL) in remission and has induced protection against disease caused by wild-type varicella virus. At the end of 1985, four extensive vaccine-associated rashes were reported among children on maintenance chemotherapy. Steroid therapy in the week before vaccination or in the week following vaccination was significantly associated with rash in a retrospective analysis (odds ratio = 3.84, P = 0.0006). These findings were confirmed prospectively (OR = 2.38, p < 0.05, one-sided) in a second smaller group of children with ALL on maintenance therapy who received varicella vaccination after the end of the data collection for the initial study but before the relationship between rash and steroids was discovered. As a result of these studies, investigators have been asked to withhold steroids for 1 week before vaccination and to delay resumption of steroid therapy for at least 2 weeks after vaccination. These results should serve as a caution that vaccination of these children should be undertaken only with full knowledge of their therapeutic regimen and a thorough clinical understanding of the competing risks of varicella, vaccination and modification of the child's chemotherapy.     

Refuelling of vehicles, the use of wood burners and the risk of acute lymphoblastic leukaemia in childhood

It is plausible that exposure of the parents before birth or of the child to sources of benzene increases the risk of childhood acute lymphoblastic leukaemia (ALL). The aim of this analysis was to investigate whether refuelling a vehicle with petrol before birth or burning wood to heat the home before or after the child's birth increased the risk of childhood ALL. Data from 389 cases and 876 frequency-matched controls were analysed using unconditional logistic regression, adjusting for study matching factors and potential confounders. The odds ratio (OR) for the mother ever refuelling a vehicle with petrol for non-occupational purposes before or during the pregnancy was 0.97 [95% confidence interval (CI) 0.69, 1.38]. The OR for the father for this exposure in the year before conception was 0.88 [95% CI 0.52, 1.48]. The OR for use of a closed wood burner to heat the home in the year before or during pregnancy was 1.41 [95% CI 1.02, 1.94] and 1.25 [95% CI 0.92, 1.70] after birth. We found no evidence that non-occupational refuelling a vehicle with petrol in the year before or during pregnancy increased the risk of ALL in the offspring. There was weak evidence that burning wood in a closed burner to heat the home increased the risk, but there was no dose-response relationship and chance could explain the finding.     

'Building a new normality': mothers' experiences of caring for a child with acute lymphoblastic leukaemia

BACKGROUND: Treatment of childhood cancer occurs over a 2- to 3-year period, with initial intense phases of chemotherapy followed by less severe treatment periods. From first diagnosis, families are encouraged by healthcare professionals (following government guidelines) to try to maintain a normal life. The aim of this paper is to contribute to our understanding of how 'normal' family life is compromised from the perspective of the families themselves during this period of extreme stress and concern for the health and well-being of their child. METHODS: This study was longitudinal and involved a cross section of 32 mothers of children recently diagnosed with acute lymphoblastic leukaemia (ALL) currently participating in the Medical Research Council ALL-97 randomized control trial. Mothers were interviewed at three time points (3-4 months post diagnosis, 15 and 27 months) using a semi-structured format with open-ended questions. A qualitative methodology was employed to analyse interview data using Thematic analysis. RESULTS: Mothers reported understanding the importance of achieving normal life, but described how this was difficult to realize. At first interview, mothers were optimistic that they could achieve the 'normal life' as advised by healthcare workers. At 12 and 24 months, although all mothers reported that life was not back to normal, there were differences in how they perceived this lack of normality. Whereas some families experienced frustration and disappointment, others had adjusted and managed to accept the new order. CONCLUSIONS: Families felt encouraged on diagnosis to be told that despite the severity of the disease and treatment regime, a normal life was possible and should be pursued. Our findings indicate that over time, more concrete information is needed to guide parents through the treatment process in order to help them achieve this.     

Simple fitting of subject-specific curves for longitudinal data

We present a simple semiparametric model for fitting subject-specific curves for longitudinal data. Individual curves are modelled as penalized splines with random coefficients. This model has a mixed model representation, and it is easily implemented in standard statistical software. We conduct an analysis of the long-term effect of radiation therapy on the height of children suffering from acute lymphoblastic leukaemia using penalized splines in the framework of semiparametric mixed effects models. The analysis revealed significant differences between therapies and showed that the growth rate of girls in the study cannot be fully explained by the group-average curve and that individual curves are necessary to reflect the individual response to treatment. We also show how to implement these models in S-PLUS and R in the appendix.     

Estimation of dynamic treatment strategies for maintenance therapy of children with acute lymphoblastic leukaemia: an application of history-adjusted marginal structural models

Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment is therefore highly dynamic. In 1992-1996, the Nordic Society of Paediatric Haematology and Oncology (NOPHO) conducted a randomised study (NOPHO-ALL-92) to investigate the effect of a new and more sophisticated dynamic treatment strategy. Unexpectedly, the new strategy worsened the outcome for the girls, whereas there were no treatment differences for the boys. There are as yet no general guidelines for optimising the treatment. On basis of the data from this study, our goal is to formulate an alternative dosing strategy. We use recently developed methods proposed by van der Laan et al. to obtain statistical models that may be used in the guidance of how the physicians should assign the doses to the patients to obtain the target of the treatment. We present a possible strategy and discuss the reliability of this strategy. The implementation is complicated, and we touch upon the limitations of the methods in relation to the formulation of alternative dosing strategies for the maintenance therapy.     

福建东部沿海地区人类嗜T淋巴细胞白血病病毒Ⅰ/Ⅱ感染的血清流行病学研究

目的 调查福建东部沿海地区人群人类嗜T淋巴细胞白血病病毒Ⅰ/Ⅱ(HTLV-Ⅰ/Ⅱ)的感染状况。方法 用酶联免疫吸附试验方法筛查1999～2002年福州、宁德两地的吸毒人群、性病就诊者、暗娼及健康献血者、健康体检人群血清标本3259份。阳性者用免疫印迹进行确认。使用EpiInfo6.0软件进行X~2和Fisher’s exact test分析。结果 健康人群HTLV-Ⅰ抗体阳性率为0.06％,吸毒人群为0.32％,性病就诊者及暗娼为0.58％,未检出HTLV-Ⅱ抗体。性病就诊者及暗娼HTLV-Ⅰ抗体阳性率显著高于健康人群(P<0.05),吸毒者HTLV-Ⅰ抗体阳性率与健康人群比较差异无显著性(P>0.05)。HTLV-Ⅰ抗体阳性率在各年龄组间差异均未见有显著性(P>0.05)。HTLV-Ⅰ抗体阳性率在福州、宁德两地差异也未见有显著性(P>0.05)。结论 提示福建东部沿海地区人群以HTLV-Ⅰ的流行为主,且HTLV-Ⅰ的流行水平很低,未发现HTLV-Ⅱ的流行。年龄、性别因素在闽东沿海地区不是HTLV-Ⅰ流行的危险因子,性暴露次数的增加可能是影响HTLV-Ⅰ流行水平的因素。     

The incidence of childhood leukaemia around the La Hague nuclear waste reprocessing plant (France): a survey for the years 1978-1998

BACKGROUND: A previous study has suggested an increased incidence rate of leukaemia from 1978 to 1992 in people aged 0 to 24 years and living in the vicinity of the La Hague nuclear waste reprocessing plant without considering age and cytological type. SETTING: The Nord Cotentin region (France) and the island of Alderney (United Kingdom). STUDY OBJECTIVE: To describe the occurrence of leukaemia for each age group and cytological type from 1978 to 1998 in the same area, using accurate reference incidence rates and adequate estimation of the at risk population. DESIGN: A geographical study of incidence using three zones defined according to their distance from the site (0 to 10 km: Beaumont-Hague electoral ward, 10 to 20 km and 20 to 35 km) has been conducted. The risk of leukaemia was estimated from the standardised incidence ratio (SIR) of the number of cases observed to the number expected. Exact 95% confidence intervals (CI) have been computed. PARTICIPANTS: All people under the age of 25 years living in the study region between 1978 and 1998. MAIN RESULTS: The observed number of cases of leukaemia in the study region as a whole was consistent with the expected value (SIR=1.03; 95%CI: 0.73, 1.41). No cases were observed on Alderney. The SIR in the Beaumont-Hague electoral ward was 2.17 (95%CI: 0.71, 5.07). The highest SIR was observed in the 5 to 9 years age group (SIR=6.38; 95%CI: 1.32, 18.65). This consists in acute lymphoblastic leukaemia cases. CONCLUSION: This study indicates an increased incidence of leukaemia in the area situated at less than 10 km from the plant. Monitoring and further investigations should be targeted at acute lymphoblastic leukaemia occurring during the childhood incidence peak (before 10 years) in children living near the La Hague site and may be other nuclear reprocessing plants.     

Protective vaccination against bovine leukaemia virus infection by means of cell-derived vaccine

Tests were performed to determine whether live mammalian cells producing env gene glycoproteins and main structural protein p24 of bovine leukaemia virus (BLV), heterologous to bovine species, could serve as an immunogen in cattle to prevent induction of bovine leukaemia. Ovine virus-non-producing clonal cells NP-2 were used as the immunogen. The NP-2 cells synthesized only the env gene products — glycoprotein gp51 and gp30 and main structural protein p24 of BLV. The NP-2 cells, inoculated into rats, induced an antibody response directed against envelope glycoproteins of BLV. The antibodies neutralized the infectivity of BLV as determined by the VSV/BLV pseudotype neutralization test. Similar results were obtained by vaccination of cattle with these cells. A dose of 2 × 10⁶ live cells inoculated subcutaneously induced an antibody response in cattle, while a high dose of killed cells was ineffective. The antibodies in cattle were directed against env products of BLV. A group of 92 cows was vaccinated and followed up for 4 years. The antibody levels fluctuated slightly during the 4-year observation period, generally decreasing with time, but revaccination always increased the antibody titre. No transfer of seropositivity was observed to seronegative animals which were kept in contact with vaccinated ones. In a separate experiment a group of young heifers, after repeated vaccination, were challenged with a high dose of infectious virus and/or virus-producing cells. The response to BLV infection was followed by syncytial induction assay after co-cultivation of white blood cells with indicator cells CC81. While the unvaccinated control animals, 2 months after virus challenge, were found to be infected, all vaccinated and challenged animals were protected during a 1-year observation period. From the data obtained it can be concluded that vaccination with live heterologous cells producing env gene products and p24 of BLV can protect cattle against BLV-induced leukaemia.     

Effect of diethylcarbamazine on cats given feline leukaemia virus vaccine

Leukocell (Norden Laboratories, Lincoln, NE, USA), a commercially available retroviral vaccine, is given to protect susceptible cats against feline leukaemia virus. Oral diethylcarbamazine, an immunomodulator used in the treatment of filariasis, when given with 1 ml i.m. Leukocell, increased titres and duration of serum antibodies to feline oncornavirus-associated cell membrane antigen and transient average monocyte counts in treated/vaccinated cats as compared to cats that received vaccine without diethylcarbamazine. These results may have implications for the development of more effective retroviral vaccination techniques for humans as well as for cats.     

Vitamin supplement use among children with Down's syndrome and risk of leukaemia: a Children's Oncology Group (COG) study

Vitamin supplements have been proposed for children with Down's syndrome (DS) with claims of improving cognitive abilities, or immune or thyroid function. Several studies have shown decreased levels of zinc in this population. Because children with DS have a 50-fold increased risk of developing acute leukaemia during the first 5 years of life, we explored the relation between child vitamin and herbal supplement use and the risk of leukaemia in a case-control study. During the period 1997-2002, we enrolled 158 children with DS aged 0-18 years that were diagnosed with acute lymphoblastic leukaemia (ALL) (n = 97) or acute myeloid leukaemia (AML) (n = 61) at participating Children's Oncology Group institutions. We enrolled 173 DS children without leukaemia (controls), selected from the cases' primary care clinic and frequency-matched on age. Data were collected via telephone interviews with mothers of the index child regarding use of multivitamins, zinc, vitamin C, iron and herbal supplements, including age at first use, frequency and duration. Among controls, 57% reported regular multivitamin use (>/=3 times/week for >/=3 months) compared with 48% of ALL cases and 61% of AML cases. We found no evidence of an association between children's regular multivitamin use and ALL or AML (adjusted odds ratios [OR] = 0.94 [95% CI 0.52, 1.70] and 1.90 [0.73, 4.91] respectively). There was a suggestion of an increased risk for AML associated with regular multivitamin use during the first year of life or for an extended duration (ORs = 2.38 [0.94, 5.76] and 2.59 [1.02, 6.59] respectively). Despite being the largest study of DS-leukaemia, our sample size was small, resulting in imprecise effect estimates. Future research should include larger sample sizes as well as a full assessment of diet including vitamin supplementation to adequately examine the relation between nutritional status and childhood leukaemia.     

室内氡对人体健康影响的研究现状

随着人们对居住环境质量要求的不断提高，室内氡（Rn）对人体健康影响也已成为公众关注的公共卫生问题。本文首先简要介绍Rn的特性及其对人体的暴露途经，然后全面综述国内、外关于室内Rn影响人体健康的人群流行病学和分子流行病学的研究结果，并提出今后开展室内Rn暴露控制的研究工作展望。     

Incidence of lymphohaematopoietic malignancies in a petrochemical industry cohort: 1983-94 follow up

OBJECTIVES—In response to a previous finding of increased mortality from lymphohaematopoietic (LH) malignancies, this study examines incidence of LH malignancy in a petrochemical industry cohort. Emphasis is on chronic lymphocytic leukaemia (CLL) and on comparisons by period of first employment.
METHOD—The study cohort consists of 8942 employees who were active in the period 1970-92 and alive on 31 December 1982. Record linkage with the Louisiana tumour registry (LTR) provided information on cancer for cases occurring between 1983 and 1994. Standardised incidence ratios (SIR), with the south Louisiana population as a comparison, were computed for all cancers, all LH malignancies and specific LH subtypes. Analyses were conducted for sex and race categories, and by period of first employment, job type, duration of employment, and latency.
RESULTS—672 Cases of cancer were identified, including 59 LH malignancies. Women (n=1169) had an overall cancer SIR below unity and four LH malignancies versus 2.28 expected. Among the 7773 men, those first employed before 1950 had no overall cancer excess, a significant 1.4-fold increase in overall LH malignancies (43 observed versus 30.78 expected), and four CLL cases versus 3.27 expected. Findings for men first employed after 1950 are based on fewer cases, but there was no indication of excesses of overall cancer or LH malignancy. Numbers were too small in the group first employed after 1950 for meaningful analysis of LH malignancy subtypes such as CLL (one case).
CONCLUSION—These findings do not suggest a continuing excess of CLL but do suggest a small increase in incidence of overall LH malignancy for workers first employed before 1950. This may reflect associations with earlier workplace conditions, although work related patterns are mixed. Interpretation is limited by the diverse group of diseases within LH malignancies, and the lack of control for non-work factors other than sex, age, race, and period of diagnosis. This study has a major advantage of more complete and reliable cancer ascertainment compared with the mortality investigation, and shows the feasibility and benefits of using cancer registry incidence data in an occupational cohort study.


Keywords: petroleum industry; lymphohaematopoietic; chronic lymphocytic leukaemia; incidence     

包钢职工白血病死亡病例对照研究

采用病例对照研究的方法，探索包钢职工白血病死亡与生产过程中的职业有害因素和生活环境因素的关系。白血病20例，病例与对照的比例为1：4。研究的因素包括九种职业有害因素以及受教育程度、经济收入、居信条件等一般社会经济状况，吸烟、饮酒、饮食、疾病史、医疗史和医用诊断X线照射情况等。直接面询收集的资料用IBM微机处理，主要用成组和非成组分析方法计算比数比（OR值）。根据OR值计算结果，仅见白血病死亡与高硅粉尘、煤焦油逸散物和高温作业有显著性关联，未见与生产环境中放射性因素和其他生物环境因素有任何关联。