Добірка наукової літератури з теми "Child leukaemia"

Abstract Leukaemias with MLL gene rearrangement are usually considered prognostically unfavourable and the clinical symptoms typically follow the translocation formation rapidly. MLL rearrangement is thus thought to be a major hit in leukaemogenesis that is either sufficient to cause the disease or it is a very strong and rapid inducer of the subsequent hit(s) required for the malignant transformation. We report an unusual presentation of secondary acute lymphoblastic leukaemia (sALL) with MLL rearrangement. Our patient was diagnosed originally with acute myeloid leukaemia (AML-M3) characterised by PML/RARα fusion and an internal tandem duplication of FLT3 (FLT3/ITD). After 30 months of complete remission of AML, she developed sALL with MLL/FOXO3A fusion gene. Bone marrow (BM) samples taken during AML therapy were analysed for the presence of these aberrations. Both the PML/RARα fusion and FLT3/ITD disappeared shortly after AML onset and did not reappear. However, FISH and quantitative RT-PCR showed the presence of the MLL/FOXO3A fusion 20 months before the diagnosis of sALL, present in 10–90% of BM cells. Morphological examination showed no blast infiltration of the BM at this time. Experiments combining FISH and morphology confirmed the presence of an MLL rearrangement in myeloid as well as lymphoid cells, indicating that the fusion arose in a multipotent progenitor. In order to identify potential secondary genetic events precipitating sALL in this patient, we used Affymetrix 50K single nucleotide polymorphism (SNP) array analysis on DNA from the diagnostic sALL sample versus the "preleukaemic" (remission AML) sample taken 16 months before. This analysis revealed a 10 Mb amplification on 19q13.32 in the sALL sample, not present in the preleukaemic sample: this was confirmed by FISH with a BAC from the amplified region. A difference between the pre-leukaemic and leukaemic cells is also demonstrated by the incomplete rearrangement of IgH gene (DH1/JH) present only at the diagnosis of sALL. There are about 450 genes in the amplified region on 19q and several of them might be involved in deregulation of the preleukaemic cell if overrepresented (e.g. FLT3 ligand, interleukin 11, Ras interacting protein 1, Stem cell growth factor, Aurora C). The long latency period prior to the onset of the secondary leukaemia in our case resembles the mouse model of MLL/FOXO3A. However, in contrast to the animal model and also to the previous reports of MLL/FOXO3A patients (2 cases described so far, both secondary AMLs after Hodgkin’s disease), our child developed leukaemia from the lymphoid lineage. Taken together, these results indicate that the MLL/FOXO3A fusion alone is not sufficient to cause leukaemia and that second hit is required to the onset of the disease. A responsible gene is possibly located on the telomeric part of the 19q.

Acute lymphoblastic leukaemia (ALL) is the most frequent childhood cancer. Children usually present with signs of bone marrow failure like recurrent or prolonged fever, pallor, lethargy, bleeding tendencies, bone pain and others. Occasionally they may present with sign of infiltration of leukaemic cells into other organs such as testicular and central nervous system, rarely to the periorbital or orbital region. Similarly in relapse cases, they typically presented either in bone marrow, central nervous system relapse or testicular but rarely orbital involvement. Here we report the clinical case of a five-year-old boy who developed relapsed B-ALL, presented to us with unilateral right eye swelling without other clinical findings and absence of blast cells in the peripheral blood film as well as bone marrow aspirate specimen.

Acute leukaemia is the most common childhood cancer. The clinical presentation of acute leukaemia includes fever, pallor, bleeding tendencies, hepatosplenomegaly, lymphadenopathy and bone pains. This case is about a 7-year-old boy who presented with 2 months of progressive low back pain after jumping into the sea. Radiologic workup showed compression fractures in the T6–L5 regions of the spine. Trauma and osteogenesis imperfecta were considered initially until the patient developed the classic features of leukaemia. Analysis of the bone marrow aspirate, 2 months after the sea incident, revealed B cell acute lymphoblastic leukaemia (ALL). The low back pain subsided after a week of chemotherapy. A symptom that involves bone pain in a child needs thorough evaluation because a delay in diagnosis affects the outcome of treatment. ALL has been lingering at the time of his accident and this has caused weakening of his spine that resulted in much more severe injury than would have occurred in the absence of the ALL.

In chapter 1, bone structure, bone growth and development, osteoporosis in children and skeletal morbidities in children with acute lymphoblastic leukaemia (ALL) are discussed. After that, the mechanostat and the effect of whole body vibration (WBV) on bone health are considered. Finally, I examine diagnostic approaches to assess the musculoskeletal system. In chapter 2, the incidence and risk factors for skeletal morbidity in ALL children are determined. The medical records of all (n,186, male,110) children presenting with ALL between 1997 and 2007 and treated on UKALL97, UKALL97/01 or UKALL2003 were studied. Skeletal morbidity included musculoskeletal pain (MSP), fractures and osteonecrosis (ON). MSP was classified as any event of limb pain, muscle pain, joint symptoms or back pain that required radiological examination. Fractures and ON were confirmed by X-rays and MRI respectively. We found that skeletal morbidity, presenting as MSP, fractures or ON were reported in 88(47%) children of whom 56(63%) were boys. Of 88 children, 49(55%), 27(30%) and 18(20%) had MSP, fracture(s) or ON, respectively. Six (7%) had both fractures and ON. The median(10th,90thcentiles) age at diagnosis of ALL children without skeletal morbidity was 3.9years(1.4,12), which was lower than in those with skeletal morbidity at 8.2years(2.2,14.3) (p<0.00001,95%CI:1.7,4.4). Children with ALL diagnosed over 8years of age were at increased risk of developing fracture(s) (p=0.01,odds ratio(OR)=2.9,95%CI:1.3,6.5), whereas the risk of ON was higher in those who were diagnosed after 9years of age (p<0.0001,OR=15,95%CI:4.1,54.4). There was no gender-difference in the incidence of skeletal morbidity. Children who received dexamethasone had a higher incidence of skeletal morbidity than those who were treated with prednisolone (p=0.027,OR=2.6,95%CI:1.1,5.9). We concluded that the occurrence of skeletal morbidity in ALL children may be influenced by age and the type of glucocorticoids (GCs). These findings may facilitate the development of effective bone protective intervention. In chapter 3, the aim is to investigate the influence of physical activity, age and mineral homeostasis over the first 12months of chemotherapy on subsequent skeletal morbidity. We reviewed 56 children who presented with ALL between 2003 and 2007 and treated only on iv UKALL2003. The number of in-patient days over the first 12months of chemotherapy was collected and used as a surrogate marker of inactivity and lack of well-being. Data for serum calcium (Ca), phosphate (Pho), magnesium (Mg) and albumin were also collected over this period. Skeletal morbidity was defined as any episode MSP or fractures. We found that the median duration of in-patient days over the first 12months of treatment in children with no skeletal morbidity was 58days(40,100), whereas the median number of in-patient days during the first 12months in those children with any skeletal morbidity, MSP only or fractures only was 83days(54,131), 81days(52,119) and 91days(59,158), respectively (p=0.003). Children with skeletal morbidity and fractures particularly had lower levels of serum Ca, Mg and Pho compared with those without skeletal morbidity over the first 12 months of chemotherapy. There was a higher risk of skeletal morbidity in those who were diagnosed after the age of 8years (p=0.001,OR=16,CI:3,80). Multiple regression analysis showed that the incidence of skeletal morbidity only had a significant independent association with age at diagnosis (p=0.001) and the number of inpatient days (p=0.03) over the first 12months (r=23). All children who were diagnosed after the age of 8years with an inpatient stay of greater than 75 days in the first 12 months of the chemotherapy (n,14) had some form of skeletal morbidity (OR=64). The conclusion was that the incidence of skeletal morbidity in children receiving chemotherapy for UKALL2003 is associated with a higher likelihood of being older and having longer periods of inpatient stay. The close link between age and changes in bone mineral status may be one explanation for the increased bone morbidity in ALL children In chapter 4, the effects of two WBV regimens on endocrine status, muscle function and markers of bone turnover are compared. We recruited 10adult men with a median age of 33years(29,49), who were randomly assigned to stand on the Galileo platform (GP) (frequency (f)=18-22Hz, peak to peak displacement (D)=4mm, peak acceleration (apeak) =2.6-3.8g) or Juvent1000 (f=32-37Hz, 0.085mm,0.3g) platform (JP) three times/week for a period of eight weeks. The measurements were performed at five time points (T0, T1, T2, T3, T4) and performed in a four week period of run-in (No WBV), eight weeks of WBV and a four-week period of washout (No WBV). The measurements included anthropometries, body composition measured by Tanita, muscle function measured by Leonardo mechanography and biochemical markers of endocrine status and bone turnover. The immediate term effect of WBV at 22Hz was associated with an increase in serum growth hormone (GH), increasing v from 0.07μg/l(0.04,0.69) to 0.52μg/l(0.06,2.4) (p=0.06),0.63μg/l(0.1,1.18)(p=0.03) ,0.21μg/l (0.07,0.65) (p=0.2) at 5minutes, 20minutes and 60minutes after WBV, respectively in the GP group. The immediate term effect of GP at 18Hz was associated with a reduction in serum cortisol from 316nmol/l (247,442) at 60minutes pre-WBV to 173nmol/l(123,245)(p=0.01), 165nmol/l(139,276)(p=0.02) and 198nmol/l(106,294)(p=0.04) at 5minutes, 20minutes and 60minutes post-WBV, respectively. At 22 Hz, GP was associated with a reduction in serum cortisol from 269nmol/l(115,323) at 60minutes before WBV to 214nmol/l(139,394)(p=0.5), 200nmol/l(125,337)(p=0.08) and 181nmol/l(104,306)(p=0.04) at 5minutes, 20minutes and 60minutes post-WBV, respectively. Median serum cortisol decreased after eight weeks of WBV from 333nmol/l(242,445) to 270nmol/l(115,323)(p=0.04). Median serum of the carboxy-terminal telopeptide (CTX, bore resorption marker) reduced significantly after eight weeks of WBV from 0.42ng/ml(0.29,0.90) to 0.29ng/ml(0.18,0.44)(p=0.03). None of these changes were observed in the JP group. Therefore, WBV at a certain magnitude can stimulate GH secretion, reduce circulating cortisol and reduce bone resorption. These effects are independent of clear changes in muscle function and depend on the type of WBV that is administered. In chapter 5, the effect of WBV using GP on the bone health of children receiving chemotherapy for ALL was assessed. We recruited 16children with ALL with a median age of 7.8years(5-13.8; 9males), who were randomized either to receive side-alternating WBV (f=16-20Hz,D=2mm, apeak =1-1.6g)(n,9) or to stand on a still platform as a control group (n,7) for 9minutes, once/week for four months. Measurements were performed at baseline, two-month and four-month assessing bone health (DXA and p.QCT), body composition and muscle function by imaging and biochemical assessment. DXA BMC data were corrected for bone area and presented as BMC z-score. We found that the median compliance rate measured as a ratio of actual completed minutes and expected minutes of WBV was 55%(17,100). The median percentage change of total body BMC z score in the WBV group from baseline to four months dropped by 10%(-25,10)(p=0.1), whereas it was 87%(-203,4)(p=0.07) in the control group. The median lumbar spine BMC z-score (L2-L4) in the WBV group was -0.4(-1.3,0.3) and -0.3(-1.4,1.5) at baseline and four months, whereas the respective data in the control group were 0.04(-0.6,2.4) and -0.1(-1.1,1), respectively. The median percentage change in LS-BMC z-score declined from baseline to four-month by19%(-349,365)(p=0.1) vi and 75%(-1016,178)(p=0.1) in the WBV and control groups, respectively. We concluded that WBV is tolerated by children receiving chemotherapy.

Background: This thesis sits within the arena of weight status during and after childhood acute lymphoblastic leukaemia (ALL), with a particular focus on the prevalence of unhealthy weight status amongst (ALL), Saudi and UK populations. Each chapter in the thesis explores different aspects of unhealthy weight status in ALL which had been highlighted as gaps in the literature at a conference in Puebla, Mexico, at the end of 2006. A summary of each study is given below. Study 1: Background: This study estimated prevalence of unhealthy weight status and metabolic syndrome (MS) amongst Saudi survivors of standard risk ALL. Methods: We recruited 56 survivors, mean age 13.4 years (SD 4.1), a mean of 9.1 years (SD 4.1) post-diagnosis. The BMI for age was used to define weight status relative to national (Saudi) and international (Cole et al., International Obesity Task Force (IOTF), World Health Organisation (WHO), and Centre for Disease Control and Prevention (CDC)) reference data. We measured body composition by dual energy X-ray absorptiometry (DXA), waist circumference, blood pressure, lipid profile (HDL-C, Triglycerides), fasting glucose and insulin. Results: According to international definitions based on BMI for age, around half of the sample had unhealthy weight status. All of the approaches based on BMI for age underestimated over-fatness, present in 27/51 (53%) of the sample according to DXA. Prevalence of MS was 7.1% (3/42 of those over 9-years old) and 5.4% (3/56) by applying the International Diabetes Federation (IDF) definition and National Cholesterol Education Program Third Adult Treatment panel Guidelines (NCEP III), respectively. However, MS by the NCEP III definition was present in 19% of the overweight and obese survivors and 7.1% of the sample had at least two of the components of MS. Conclusions: Unhealthy body weight and over-fatness may be common amongst adolescent Saudi survivors of standard risk ALL, though overweight and obesity may be no more common than in the general Saudi adolescent population. Defining weight status using BMI underestimates over-fatness in this population, as in other populations. Study 2: Background: Underweight, overweight, and obesity at diagnosis may all worsen prognosis in childhood ALL, but no studies have estimated prevalence of unhealthy weight status at diagnosis in large representative samples using contemporary definitions of weight status based on BMI for age. Methods: Retrospective study which aimed to estimate prevalence of underweight, overweight, and obesity at diagnosis for patients with childhood ALL on three successive UK treatment trials: UKALL X (1985-1990, n 1033), UKALL XI (1990- 1997, n 2031), UKALL 97/97-99 (1997-2002, n 898) .The BMI for age was used to define weight status with both UK 1990 BMI for age reference data and the IOTF definitions. Results: Prevalence of underweight was 6% in the most recent trial for which data were available. Prevalence of overweight and obesity was 35% in the most recent trial when expressed using IOTF definitions; 41% when expressed relative to UK 1990 reference data. Conclusions: Even with highly conservative estimates >40% of all UK patients with ALL were underweight, overweight, or obese at diagnosis in the most recent trial for which UK data are available (UKALL 97/99, 1997-2002). Study 3: Background: This study tested the hypothesis that overweight/obesity at diagnosis of childhood ALL was related to risk of relapse. Methods and results: In a national cohort of 1033 patients from the UK there was no evidence that weight status at diagnosis was related significantly to risk of relapse: log ranks test (p value= 0.90) with overweight and obesity as the exposure (n 917); individual (p value= 0.42) and stepwise (p value= 0.96) proportional hazards models, with BMI z score as the exposure (n 1033). Conclusion: The study does not support the hypothesis that overweight/obesity at diagnosis impairs prognosis in childhood ALL in the UK. Study 4: Background: In the sample of Saudi patients recruited to study 1 we compared DXA whole body and lumbar spine bone mineral density (BMD) using manufacturers software with a body size correction which derived bone mineral content (BMC) for bone area and Apparent bone mineral density of lumbar spine (BMADLS). Methods and results: The survivors of ALL were from Saudi Arabia (n 51, mean age 13.5 years). With no corrections, 29 patients (57%) had lumbar spine BMD z score < -1.0 and 21 (41%) had whole body BMD z score < -2. After correction, by using BMC for bone area method only 6 (12%) had lumbar spine BMC z score <-1.0 and 4 (8%) had whole body BMC z score <-2. By using BMADLS method, 18 (35%) had BMC <-1.0 and 6 (11%) had BMC Z score <-2. Conclusions: Correction for body size seems essential to accurate interpretation of DXA bone health data in adolescent survivors of ALL. The three correction methods provided different conclusions, but bone health remains a concern after treatment for ALL.

Over the past twenty years the incidence of both childhood acute lymphoblastic leukaemia (ALL) and type 1 diabetes have risen in many developed countries, including New Zealand. Although the explanations for this increase and the precise aetiology of both diseases remain unclear, environmental factors are thought to be important. One factor receiving increasing attention is the role of infections introduced through population mixing. However, previous studies on this topic show mixed results and population mixing itself tends to be under-theorised. Furthermore, this issue has not been adequately assessed in New Zealand, a country characterised by high levels of population mobility. In this research, a variety of population mixing measures for small areas in New Zealand were developed. National data on ALL registrations were obtained from the New Zealand Cancer Registry, and regional type 1 diabetes data were obtained from the Canterbury Diabetes Register for the Canterbury Region of the South Island. The analyses were undertaken in three stages. First, standardised incidence ratios of each disease were examined at different geographical and temporal scales, between areas of differing socioeconomic status, and in urban and rural New Zealand. Second, cluster analysis was employed to test for spatial-temporal clustering of the two diseases. Finally, multivariate regression analyses were utilised to investigate the association between each disease and the various measures of population mixing at the area-level. The results reveal similarities in the geographical epidemiology of childhood ALL and type 1 diabetes in New Zealand. The majority of the findings were suggestive of an infectious aetiology for both diseases. In addition, higher incidence of both diseases was observed in areas which increased the most in population mixing over short time periods (6/7 years). Furthermore, raised type 1 diabetes incidence was also associated with high population mixing in early life.

Background and aims: Leukaemia is a cancer of the blood and is the most common type of childhood cancer with almost 500 new cases every year in the UK. There is a vast amount of research exploring the experiences of parents of children with cancer, however, there is less research focussed on parents whose children are in the maintenance phase of Acute Lymphoblastic Leukaemia (ALL) treatment. This treatment phase usually occurs in the first or second year following diagnosis but can start much earlier. The maintenance phase still involves active treatment but with less visits to and stays in hospital. At this stage, parents have been through the most intense segment of the treatment regimen and may have encountered various Khalighyprotocol may therefore have valuable advice to provide to other parents regarding coping and useful supports. This study aimed to explore the coping style and patterns of accessing support in mothers and fathers who have a child diagnosed with ALL and who are in the maintenance phase of treatment. The aim was also to explore whether there were differences between mothers and fathers with regards to coping and support. Methods: Three mothers and two fathers were interviewed separately using a semi structured interview. These interviews were then transcribed and analysed using interpretative phenomenological analysis (IPA). Results: Four main themes were identified through interviews with parents: the parental role; internal coping strategies; external coping strategies; and looking to the future. Conclusions: Parents were found to use a variety of coping strategies and accessed various sources of support to help them to deal with their child’s ALL diagnosis. These coping strategies could be shared with parents who are new to the haematology service. There were however, significant difficulties with recruitment which means it was not possible to compare mothers and fathers in terms of coping style and types of support accessed. This highlights that the recruitment strategy needs revising if further research is to be conducted in this area.

by Tong Sau Lan.
Thesis (M.S.Sc.)--Chinese University of Hong Kong, 1992.
Includes bibliographical references (leaves 68-75).
abstract --- p.ii
statement of originality --- p.iv
acknowledgements --- p.v
table of contents --- p.vi
list op tables --- p.vi i
list of figures --- p.v iii
list of appendices --- p.ix
introduction --- p.1
Chapter chapter i - --- understanding of the illness leukaemia --- p.3
"Leukaemia: its symptoms, treatment and side effects on children" --- p.3
The changing outlook of treatment --- p.7
Chapter chapter ii - --- RESEARCH STUDIES ON LEUKAEMIC PATIENTS --- p.10
Previous and changing research studies emphasis with leukaemic children --- p.10
"Psychological and behavioral relevances: social adaptation, self-esteem, and anxiety" --- p.14
Research studies on Chinese leukaemic children --- p.27
Chapter chapter iii - --- method --- p.30
Chapter chapter iv - --- results --- p.40
Chapter chapter v - --- discussion --- p.56
references --- p.68
appendices --- p.76

With the current worldwide health problems of an epidemic of obesity identified by the WHO in 1997 as a disease running parallel with other major diseases that are causing untold suffering both amongst the very young with childhood blood cancer leukaemia and an increasing epidemic amongst the elderly with Alzheimer's Dementia disease. The problem for many authorities is both cause and possible solutions. Most explanations as to why obesity occurs remain unsatisfactory. While medical science has improved the survival rates for childhood leukaemia cancer, it so far, has not provided sufficient explanation, as to why, the high incidence of child leukaemia continues to occur despite medical advances. The burden of Alzheimer's disease is also reaching epidemic proportions across the Western world as well as other countries, such that, the spiralling economic cost of care alone is now calculated in the billions, and which, if it continues may possibly cripple the, economy of some countries. The question remains, why, in this modern day and age with all the advances of science and understanding of medical science these three apparently disparate areas of human affliction continue to increase across many populations. Currently there are no plausible answers forthcoming for the proliferation of these diseases. In relation to obesity, many still regard it merely a matter of eating too much and exercising too little. For child leukaemia especially those born leukaemic, it is tenuous to correlate the disease with lifestyle factors. For those who develop Alzheimer’s Disease, lifestyle over a lifetime could certainly have a part to play, but what, when other individuals with similar lifestyles do not develop the disease? The simplest common factor explaining the onset of these three afflictions is diet. The question arises as to what kinds of dietary changes are now in place or what type of food changes are being invoked and consumed, in sufficient quantities, and that are perhaps markedly different from previous generations. The food supply of the majority of humans in the 21st century contains large amounts of industrially processed products. These new, and abundant, dietary components may contain, and have, unexpected consequences and effects contributing to obesity, child leukaemia and Alzheimer's disease. The one foremost food ingredient besides sugar, that seems to dominate the food supply is soybean. Industrially processed soybean products are now ubiquitous in the food supply of many nations. Unlike traditional Asian soy derived foods, western style industrially processed soy products (soybean oil, soy flour, soy milk, soy lecithin, tofu and an extensive array of soy utilizing processed packaged foods), are not subject to fermentation. Fermentation reduces anti-nutrient and phytohormonal contents of soy although not completely. It is well recognized that modern soy products block absorption of essential minerals (e.g. iodine) and that they contain large amounts of (e.g. genistein). Although soy is promoted as a source of cheap protein, that is supposed to improve human diets, its anti-nutrient and xenoestrogen component content, may in actual fact, produce more detrimental effects for the human body, than the so far perceived and commercially promoted “benefits” derived from increased consumption of readily and cheaply available soy protein. The capacity of soy to not only lower iodine intake besides other essential minerals and nutrients, also, introduces into the human body, a number of extraneous estrogen like substances which may slow down metabolism sufficiently and promote female pattern of fat deposition. Hence, their hypothesized link to obesity in the first instance. Genistein is also known to be a topoisomerase type II poison, and could well be a contributing factor to interference of cellular development, causing DNA disruption and creating chromosomal aberrations in the rapidly developing embryo, during the vulnerable prenatal stages, especially, where the mother is ingesting soy products as part of her diet. And similarly therefore, the hypothesis linking soy to childhood leukaemia. Furthermore, genistein, despite some short term studies not only disrupts thyroid function, with its interaction with the hippocampus, pituitary and thyroid axis may also possibly be a slow, contributing factor, to the early stages of memory loss as well as impaired motor coordination as frequently observed in Alzheimer's symptoms. The meta-analysis of soy consumption and these three major diseases with prevalence across all countries for which WHO information is available, presented in this thesis, is the first in the literature tabulating an empirical result supporting the hypothesis that industrially processed soy products may contribute to the worldwide increase of overweight and obesity, childhood leukaemia and Alzheimer's disease. Of special interest are the results showing greater prevalence of obesity and poor, but heavily soybean exposed, Latin American countries than in wealthy, but using little soy, countries of the European Union. The results also show, that the two nations with the highest consumption of soy per capita, are also the two nations with the highest incidence of child leukaemia, and also the highest incidence of Alzheimer's disease (China and USA) besides their problems with an epidemic of obesity. These empirical findings indicate the need for the implementation of public health measures, to counter the increasing obesity and Alzheimer’s epidemics, the continued high incidence of childhood leukaemia despite improved medical survival rates. At policy level it may have to be decided to weigh up the economic-political benefits as opposed to the economic drain due to the escalating high cost and maintenance of medical care for all these diseases. On a broader scale, this thesis also argues that the food industry needs to be more thoroughly scrutinised to prevent its profit seeking business model and/or behaviour from creating worldwide public health problems.
Thesis (M.Med.Sc.) -- University of Adelaide, School of Medicine, 2013

by Betty Shuc Han Wills.
Year shown on spine: 1997.
Thesis (M.Phil.)--Chinese University of Hong Kong, 1996.
Includes bibliographical references (leaves 117-128).
ACKNOWLEDGMENT --- p.i
ABSTRACT --- p.ii
TABLE OF CONTENTS --- p.iv
LIST OF APPENDICES --- p.viii
Chapter CHAPTER 1 --- INTRODUCTION --- p.1
Chapter CHAPTER 2 --- LITERATURE REVIEW --- p.6
Parental Responses to the Diagnosis of Acute Lymphocytic Leukaemia (ALL) --- p.7
Disclosure Of the Child's Diagnosis --- p.10
Impact of Cancer Treatment on Parents --- p.14
Sources of Support for Parents --- p.18
Coping Strategies of Parents of Children With ALL --- p.20
Coping With The Uncertainty of the Disease --- p.23
Research Studies Involving Chinese Parents --- p.24
Summary Of Issues From Literature Review --- p.27
Chapter CHAPTER 3 --- METHODOLOGY
Research Design --- p.29
Sampling --- p.31
Data Collection Method --- p.32
Data Collection Procedure --- p.34
Ethical Considerations --- p.38
Pilot Study --- p.40
Data Analysis --- p.42
Issues of Reliability and Validity --- p.45
Validity --- p.45
Reliability --- p.48
Chapter CHAPTER 4 --- RESULTS & DISCUSSION
Introduction --- p.50
Chapter (I). --- Parents' Profile --- p.51
Demographic Characteristics Of The Parents
Chapter (II). --- Major categories Corresponding To Interviewing The Mothers --- p.54
Initial Reactions of the Child's Confirmed Diagnosis --- p.55
Unpreparedness for the child's Diagnosis
Suddenness of the Diagnosis --- p.56
Physical and psychological reactions to the child's Diagnosis --- p.58
Sources of Support for the Mothers --- p.62
The mothers' main source of support
Other sources of support for the mothers --- p.64
Disclosure Of Child's Diagnosis --- p.66
Disclosure of the child's diagnosis to the child
Disclosure of the child's diagnosis to members of the immediate and extended families --- p.68
Disclosure of child's diagnosis to non-family members --- p.70
Uncertainty Brought On By The Illness --- p.71
Waiting for confirmation of diagnosis
Uncertainty about the success of treatment --- p.73
Uncertainty about the child's future --- p.74
Changes In The Family Routine --- p.75
Needed to normalise family life
Chapter (III). --- Major Categories Corresponding to Interviewing The Fathers Initial reactions to the child's confirmed diagnosis of ALL --- p.78
Suddenness of diagnosis --- p.79
Physical and psychological reactions to the diagnosis --- p.80
Disclosure Of The Child's Diagnosis --- p.82
Disclosure of the child's diagnosis to the child
Disclosure of the child's diagnosis to members of the immediate and extended family --- p.85
Disclosure of the child's diagnosis to non-family members --- p.86
Sources Of Support For The Fathers --- p.87
Support from immediate and extended families
Support from medical professionals --- p.89
Support from friends --- p.90
Changes In The Family Routine --- p.91
Coping Strategies Utilised By The Fathers --- p.92
Open communication
Use of religious beliefs and rituals --- p.93
Chapter (IV). --- Comparison Of Categories Found Between The Mothers And The Fathers --- p.95
Initial reactions to the child's confirmed diagnosis of ALL
Disclosure of the child's diagnosis --- p.96
Sources of support for the parents --- p.100
Changes in the family routine --- p.101
Summary of findings --- p.103
Chapter (V). --- Differences between the initial and second interviews --- p.105
Chapter CHAPTER FIVE --- CONCLUSION
Limitations Of The Study --- p.108
Implications For Nursing Practice --- p.112
Recommendations For Future Research --- p.114
Conclusion --- p.115
REFERENCES --- p.117
APPENDIX I - PERSONAL DATA FORM --- p.129
APPENDIX II - INTERVIEW SCHEDULE --- p.130
APPENDIX III - CONSENT FORM --- p.134
APPENDIX IV - SAMPLE SCRIPT OF INTERVIEWS WITH MOTHERS --- p.135
APPENDIX V - MATRICES ON MOTHERS AND FATHERS --- p.140
APPENDIX VI - SAMPLE OF FIELD NOTES FOR MOTHERS AND FATHERS --- p.143

Related physiology 596The child with cancer 598Paediatric brain tumours 600Bone tumours 602Neuroblastoma 604Rhabdomyosarcoma (RMS) 606Acute myeloid leukaemia (AML) 608Acute lymphoblastic leukaemia (ALL) 610Wilms tumour 612T-cell acute lymphoblastic leukaemia 614Lymphoma 616Bone-marrow transplantation 618Related skills...

AbstractFamily as a relationship of cooperation and solidarity refers to responsibility and education between generations. Often, the intermingling of mutual responsibility of all family members and upbringing within a specific parent-child relationship is not at all obvious. But it is set in motion when a child falls ill with leukaemia and the sibling becomes a donor, because care of the sick child changes the family structure, and thus what parents understand by responsible action and the significance that education has. In the first section, I deal with education, responsible parenthood and family issues. The second part discusses family and illness. This is followed by an analysis of the Kirstein family from the Lübeck project on bone marrow donation between siblings, in which a child has been diagnosed with leukaemia. Finally, I work through the different dimensions of responsibility in education and family interaction in the family structure.

AbstractThe families we approached have two exceptional things in common: they all experienced the dramatic event of a life-threatening disease such as leukaemia affecting one of their children; and, in all of these families, that child was treated with a stem cell transplant taken from a sibling’s body. In this last chapter of the book we reflect very briefly on our interview experiences, analysis, and discussions. In the end, we identify open questions and further areas which may invite further research.

Human T-cell leukaemia virus (HTLV)-1 and HTLV-2 belong to the genus Deltaretrovirus of the family Retroviridae. They only infect humans, produce a lifelong infection, and can be transmitted from mother to child, through sexual intercourse, and via cellular blood components and organ transplantation. Both viruses are present in all continents and have a heterogeneous distribution. HTLV-1-endemic foci (general population prevalence >1%) are found in Japan, the Caribbean, South America, Africa, and Australo-Melanesia. There are endemic foci of HTLV-2 among native Amerindians and Central African populations. HTLV-1 and 2 also occur among people who inject drugs. It is unclear why some infected people develop associated diseases while others remain asymptomatic.

This chapter contains clinical images of artefactual/factitious disease noting that abuse may be accidental, perpetrated by others, or self-inflicted (dermatitis artefacta/factitia). A list of cutaneous signs suspicious of possible child abuse followed by pointers in the examination and history is provided. Suspicious bruising and purpura are covered with a list of conditions mimicking or causing bruising, including serious systemic diseases such as leukaemia, infections, and clotting disorders. An explanation is given of how to proceed in cases of suspected sexual abuse and highlights some diseases that might be mistaken for abuse. The different of types of factitious disease, including psychiatric disorders such as obsessive-compulsive disorder and dysmorphophobia, are described. Normal habit disorders are outlined including infant hair pulling, which should be differentiated from hair-pulling disorder (previously known as trichotillomania).

Acute myeloid leukaemia accounts for 15-20% of paediatric leukae-mia. This chapter describes the epidemiology, clinical features, inves-tigation, diagnosis and classification of acute myeloid leukaemia in children. Treatment with intensive chemotherapy and (in some chil-dren) haemopoietic stem cell transplantation, treatment complications and prognosis are described. Acute promyelocytic leukaemia in chil-dren and Down syndrome-acute myeloid leukaemia are also discussed briefly.

This chapter discusses paediatrics. It includes history and examination, common infant symptoms, neonatal life support (NLS), the neonatal intensive care unit (nicu), ventilatory support for neonates, examination of the neonate, neonatal jaundice, rhesus haemolytic disease, respiratory distress syndrome (RDS) and other neonatal problems, minor neonatal problems, enteral and parenteral nutrition, breastfeeding and bottle feeding, preterm and small-for-dates babies, genitourinary diseases, disorders of sex development, congenital heart disease, murmurs and heart sounds in children, orofacial clefts (cleft lip and palate), neural tube defects (NTDS), measles, rubella, mumps, and erythroviruses, varicella (herpes) zoster virus (VZV), vertical HIV infection, non-accidental injury, sudden unexplained infant death (SUID/SIDS), screening and child health promotion, genetic disease and prevention, genetic counselling, childhood obesity, hypertension in children, upper and lower respiratory infection, cystic fibrosis, asthma in children, infective endocarditis (IE), rheumatic fever, diarrhoea, malnutrition, abdominal pain, abdominal distension, coeliac disease, urinary tract infection (UTI), renal failure and disease, acute glomerulonephritis and nephrotic syndrome, failure to thrive, growth charts, endocrine and metabolic diseases, precocious puberty, diabetes mellitus (DM), diabetic ketoacidosis (DKA), poisoning (iron, salicylate, paracetamol), acute lymphoblastic leukaemia (ALL), anaemia, primary antibody deficiencies, raised intercranial pressure, migraine, encephalitis, meningitis, epilepsy and febrile convulsions, behavioural problems, delays in talking and walking, impairment and disability, developmental screening tests, paediatric reference intervals and charts.

Under 2% of all cancers in industrialized countries occur in childhood and adolescence, but they account for a much larger proportion of total population life years potentially lost to cancer. Total incidence is about 160 per million in children and 200 per million in adolescents. In children, leukaemias account for one third of all malignancies and CNS tumours for one quarter. In adolescents, lymphomas account for one quarter of cases and leukaemias, CNS tumours, and carcinomas each for about 15%. Five-year survival exceeds 80% for many childhood and some adolescent cancers. Although survival of adolescents is high overall, survival for several types of cancer is markedly lower than in children. Infants under a year of age also tend to have lower survival. Excess mortality continues beyond 25 years from diagnosis of childhood cancer. The risk of developing a second primary cancer is about six times that in the general population. The causes of most childhood cancers remain unknown. The principal established exogenous causes are ionizing radiation, ultraviolet radiation from sunlight, and certain viruses. Up to 10% of children and adolescents with cancer may have germline mutations in cancer predisposition genes. If one child in a family has cancer, then that child’s siblings have approximately double the risk of the general population for developing childhood cancer, but this could well be entirely accounted for by familial syndromes. Significantly raised or reduced risks of childhood cancers have been linked to polymorphic variants of certain genes, though many of these associations remain to be replicated.

A cohort study is one in which the outcome (usually disease status) is ascertained for groups of individuals defined on the basis of their exposure. At the time exposure status is determined, all must be free of the disease. All eligible participants are then followed up over time. Since exposure status is determined before the occurrence of the outcome, a cohort study can clarify the temporal sequence between exposure and outcome, with minimal information bias. The historical and the population cohort study (Box 9.1) are efficient variants of the classical cohort study described above, which nevertheless retain the essential components of the cohort study design. The exposure can be dichotomous [i.e. exposed (to obstetric complications at birth) vs. not exposed], or graded as degrees of exposure (e.g. no recent life events, one to two life events, three or more life events). The use of grades of exposure strengthens the results of a cohort study by supporting or refuting the hypothesis that the incidence of the disease increases with increasing exposure to the risk factor; a so-called dose–response relationship. The essential features of a cohort study are: ♦ participants are defined by their exposure status rather than by outcome (as in case–control design); ♦ it is a longitudinal design: exposure status must be ascertained before outcome is known. The classical cohort study In a classical cohort study participants are selected for study on the basis of a single exposure of interest. This might be exposure to a relatively rare occupational exposure, such as ionizing radiation (through working in the nuclear power industry). Care must be taken in selecting the unexposed cohort; perhaps those working in similar industries, but without any exposure to radiation. The outcome in this case might be leukaemia. All those in the exposed and unexposed cohorts would need to be free of leukaemia (hence ‘at risk’) on recruitment into the study. The two cohorts would then be followed up for (say) 10 years and rates at which they develop leukaemia compared directly. Classical cohort studies are rare in psychiatric epidemiology. This may be in part because this type of study is especially suited to occupational exposures, which have previously been relatively little studied as causes of mental illness. However, this may change as the high prevalence of mental disorders in the workplace and their negative impact upon productivity are increasingly recognized. The UK Gulf War Study could be taken as one rather unusual example of the genre (Unwin et al. 1999). Health outcomes, including mental health status, were compared between those who were deployed in the Persian Gulf War in 1990–91, those who were later deployed in Bosnia, and an ‘era control group’ who were serving at the time of the Gulf war but were not deployed. There are two main variations on this classical cohort study design: they are popular as they can, depending on circumstances, be more efficient than the classical cohort design. The population cohort study In the classical cohort study, participants are selected on the basis of exposure, and the hypothesis relates to the effect of this single exposure on a health outcome. However, a large cohort or panel of subjects are sometimes recruited and followed up, often over many years, to study multiple exposures and outcomes. No separate comparison group is required as the comparison group is generally an unexposed sub-group of the panel. Examples include the British Doctor's Study in which over 30,000 British doctors were followed up for over 20 years to study the effects of smoking and other exposures on health (Doll et al. 1994), and the Framingham Heart Study, in which residents of a town in Massachusetts, USA have been followed up for 50 years to study risk factors for coronary heart disease (Wolf et al. 1988). The Whitehall and Whitehall II studies in the UK (Fuhrer et al. 1999; Stansfeld et al. 2002) were based again on an occupationally defined cohort, and have led to important findings concerning workplace conditions and both physical and psychiatric morbidity. Birth cohort studies, in which everyone born within a certain chronological interval are recruited, are another example of this type of study. In birth cohorts, participants are commonly followed up at intervals of 5–10 years. Many recent panel studies in the UK and elsewhere have been funded on condition that investigators archive the data for public access, in order that the dataset might be more fully exploited by the wider academic community. Population cohort studies can test multiple hypotheses, and are far more common than any other type of cohort study. The scope of the study can readily be extended to include mental health outcomes. Thus, both the British Doctor's Study (Doll et al. 2000) and the Framingham Heart Study (Seshadri et al. 2002) have gone on to report on aetiological factors for dementia and Alzheimer's Disease as the cohorts passed into the age groups most at risk for these disorders. A variant of the population cohort study is one in which those who are prevalent cases of the outcome of interest at baseline are also followed up effectively as a separate cohort in order (a) to study the natural history of the disorder by estimating its maintenance (or recovery) rate, and (b) studying risk factors for maintenance (non-recovery) over the follow-up period (Prince et al. 1998). Historical cohort studies In the classical cohort study outcome is ascertained prospectively. Thus, new cases are ascertained over a follow-up period, after the exposure status has been determined. However, it is possible to ascertain both outcome and exposure retrospectively. This variant is referred to as a historical cohort study (Fig. 9.1). A good example is the work of David Barker in testing his low birth weight hypothesis (Barker et al. 1990; Hales et al. 1991). Barker hypothesized that risk for midlife vascular and endocrine disorders would be determined to some extent by the ‘programming’ of the hypothalamo-pituitary axis through foetal growth in utero. Thus ‘small for dates’ babies would have higher blood pressure levels in adult life, and greater risk for type II diabetes (through insulin resistance). A prospective cohort study would have recruited participants at birth, when exposure (birth weight) would be recorded. They would then be followed up over four or five decades to examine the effect of birth weight on the development of hypertension and type II diabetes. Barker took the more elegant (and feasible) approach of identifying hospitals in the UK where several decades previously birth records were meticulously recorded. He then traced the babies as adults (where they still lived in the same area) and measured directly their status with respect to outcome. The ‘prospective’ element of such studies is that exposure was recorded well before outcome even though both were ascertained retrospectively with respect to the timing of the study. The historical cohort study has also proved useful in psychiatric epidemiology where it has been used in particular to test the neurodevelopmental hypothesis for schizophrenia (Jones et al. 1994; Isohanni et al. 2001). Jones et al. studied associations between adult-onset schizophrenia and childhood sociodemographic, neurodevelopmental, cognitive, and behavioural factors in the UK 1946 birth cohort; 5362 people born in the week 3–9 March 1946, and followed up intermittently since then. Subsequent onsets of schizophrenia were identified in three ways: (a) routine data: cohort members were linked to the register of the Mental Health Enquiry for England in which mental health service contacts between 1974 and 1986 were recorded; (b) cohort data: hospital and GP contacts (and the reasons for these contacts) were routinely reported at the intermittent resurveys of the cohort; (c) all cohort participants identified as possible cases of schizophrenia were given a detailed clinical interview (Present State examination) at age 36. Milestones of motor development were reached later in cases than in non-cases, particularly walking. Cases also had more speech problems than had noncases. Low educational test scores at ages 8,11, and 15 years were a risk factor. A preference for solitary play at ages 4 and 6 years predicted schizophrenia. A health visitor's rating of the mother as having below average mothering skills and understanding of her child at age 4 years was a predictor of schizophrenia in that child. Jones concluded ‘differences between children destined to develop schizophrenia as adults and the general population were found across a range of developmental domains. As with some other adult illnesses, the origins of schizophrenia may be found in early life’. Jones' findings were largely confirmed in a very similar historical cohort study in Finland (Isohanni et al. 2001); a 31 year follow-up of the 1966 North Finland birth cohort (n = 12,058). Onsets of schizophrenia were ascertained from a national hospital discharge register. The ages at learning to stand, walk and become potty-trained were each related to subsequent incidence of schizophrenia and other psychoses. Earlier milestones reduced, and later milestones increased, the risk in a linear manner. These developmental effects were not seen for non-psychotic outcomes. The findings support hypotheses regarding psychosis as having a developmental dimension with precursors apparent in early life. There are many conveniences to this approach for the contemporary investigator. ♦ The exposure data has already been collected for you. ♦ The follow-up period has already elapsed. ♦ The design maintains the essential feature of the cohort study, namely that information bias with respect to the assessment of the exposure should not be a problem. ♦ As with the Barker hypothesis example, historical cohort studies are particularly useful for investigating associations across the life course, when there is a long latency between hypothesized exposure and outcome. Despite these important advantages, such retrospective studies are often limited by reliance on historical data that was collected routinely for other purposes; often these data will be inaccurate or incomplete. Also information about possible confounders, such as smoking or diet, may be inadequate.