Higher risk for acute childhood lymphoblastic leukaemia in Swedish population centres 1973-94. Swedish Child Leukaemia Group.

A population-based sample of acute childhood leukaemia cases in Sweden 1973-94 was analysed by a geographical information system (GIS) for spatial leukaemia distribution in relation to population density. The annual incidence rate for acute lymphoblastic leukaemia (ALL) was 3.6, and for acute non-lymphoblastic leukaemia (ANLL) 0.7, cases per 100,000 children. Incidence rates in population centres, constituting 1.3% of Sweden's land area and approximately 80% of the population, compared with the rest of Sweden showed a statistically significant excess of ALL [odds ratio (OR) 1.68; 95% confidence interval (CI) 1.44-1.95], but not ANLL (OR 1.13; 95% CI 0.98-1.32). An increasing trend, however not statistically significant, was found for ALL incidence with both increasing population density in parishes and increasing degree of urbanity in municipalities. These findings support the theories that some environmental factors associated with high population density, such as infectious agents, may be of aetiological importance for childhood acute lymphoblastic leukaemia.     

Childhood leukaemia in The Netherlands, 1973-1986: temporary variation of the incidence of acute lymphocytic leukaemia in young children

The incidence of childhood leukaemia in The Netherlands in the period 1973-1986 was studied by means of the DCLSG nationwide register, which lists all patients according to bone marrow slides classified in the DCLSG central laboratory. Acute lymphocytic leukaemia (ALL) accounted for 81% of cases, acute non-lymphocytic leukaemia (ANLL) for 13%, chronic myelocytic leukaemia (CML) for 2.5%, and acute unclassifiable leukaemia (AUL) for 3%. The peak incidence of ALL was at age 3, common-ALL and pre B-ALL comprising about 95% of the immunophenotypes at this age. Incidence rates for ALL remained stable between 1973 and 1978 at 2.85 cases per 10(5) children per year, exhibited a temporary increase between 1979 and 1984 to 3.60 and dropped back to the lower, previous level in 1985 and 1986. This rise was seen mainly among children in the 1-4 year age group, especially at age 3, and those with common-ALL and an initial WBC less than 5.0 x 10(9) l-1. Cumulative incidence rates per year of birth were fairly homogeneous up to age 6, except for the 1978 birth cohort which exhibited higher rates. Incidence rates for ANLL, CML and AUL remained stable over time. Changes in ascertainment, declining birth rates and a 50% decrease in childhood mortality, e.g. from infectious diseases, could not explain this temporary variation. Moreover, incidence rates in this survey appeared to be similar to those reported in various developed countries for the same period. As far as the aetiology of childhood common-ALL is concerned, therefore, the Dutch data appear to support the hypothesis of 'random mutation' as well as that of a limited role of environmental factors.     

Epidemiological and immunological characteristics of childhood leukaemia in The Netherlands: population-based data from a nationwide co-operative group of paediatricians

In this review results are presented from several population-based epidemiological and immunological studies of children with leukaemia in The Netherlands, who were diagnosed between 1973 and 1982 through a nationwide co-operative group of paediatricians. From 1973 till 1980 annual incidence rates appeared to be 3.1 per 10(5) person-yr. No significant trend was observed in this period. However a preliminary analysis of patients in the 1980-1982 period showed an increase. Mortality rates are decreasing since 1973, as expected. Incidence rates and proportions of different morphological and immunological subtypes reflect the pattern of occurrence in populations with a high standard of living. A relatively high incidence rate of acute lymphocytic leukaemia (ALL) is observed with a peak at the age of 3-5. The proportion of patients with T-cell phenotype among ALL-patients, immunologically typed between 1979 and 1982, appeared to increase with age, while the proportion of common ALL decreased. Statistical analysis of the data of patients with ALL in the Western part of the country including areas with nuclear plants, gave no indication for the presence of clustering. Subclassification of childhood leukaemia (CL), notably ALL, may be necessary for obtaining more specific etiologic clues. In view of the incidence of CL and ALL large scale, immunological and epidemiological investigations of CL, and the related non-Hodgkin's lymphomas, preferably population-based, are necessary.     

Clustering of childhood leukaemia in Hong Kong: association with the childhood peak and common acute lymphoblastic leukaemia and with population mixing.

Incidence data of childhood leukaemia (CL) in Hong Kong (1984-90) have been analysed for evidence of variation between small areas. All cases (n=261) were classified by morphological cell type, with the majority (n=205) being acute lymphoblastic leukaemia (ALL), and haematological review has permitted immunophenotypic classification for 73% of these. The data have been examined for evidence of spatial clustering within small census areas (TPUs) and for association with population mixing, with attention focused on those subgroups (especially the childhood peak of ALL--taken here to be diagnoses in children from 24 months up to the seventh birthday--and common ALL) which, it has been hypothesized, may be caused by unusual patterns of exposure and response to common infections. For the whole of Hong Kong, there was evidence of spatial clustering of ALL at ages 0-4 years (P = 0.09) and in the childhood peak (P<0.05). When these analyses were restricted to TPUs where extreme population mixing may have occurred, overall incidence was elevated and significant evidence of clustering was found for ALL (P<0.007) at these ages and for the common ALL in the childhood peak (P = 0.032). Replication of the analyses for subsets of leukaemia that were not dominated by the childhood peak of ALL found no evidence of clustering. This is the first investigation of an association between population mixing and childhood leukaemia in Asia and the first to include clustering and to consider particular subsets. The results are supportive of the ''infectious'' aetiology hypothesis for subsets of childhood leukaemia, specifically common ALL in the childhood peak.     

Childhood leukaemias and CNS tumours: correlation of international incidence rates

Childhood leukaemia has a potential infectious aetiology whilst infections may also be linked to paediatric central nervous system (CNS) tumours. Using data from 29 countries we investigated the correlation between international incidence rates of childhood leukaemia and CNS tumours, focusing on acute lymphoblastic leukaemia (ALL), astrocytoma and ependymoma-subtypes that are hypothesised to have an infectious aetiology. Relationships between incidence rates and national demographic factors were also examined using Pearson's correlation coefficient to quantify associations. Comparing two diagnostic categories of leukaemia with four groups of CNS tumours, a highly significant positive correlation was found between ALL and astrocytoma (r = 0.57, P = 0.002). Higher rates of ALL and CNS tumours were associated with increased affluence, with the strongest correlation for Gross Domestic Product per capita and CNS tumours (r = 0.70, P < 0.001). National incidence rates of childhood ALL and astrocytomas were highly correlated and this may reflect a common environmental cause whose origin may be infectious in nature. International incidence of ALL and CNS tumours were also correlated with economic related factors. Variation in levels of ascertainment may partially explain this, although childhood environmental exposures related to infections will also be affected by levels of affluence.     

Urbanisation and incidence of acute lymphocytic leukaemia among United States children aged 0-4

Acute lymphocytic leukaemia (ALL) incidence among children under 5 years of age was examined, utilising data from 24 United States cancer registries. County-based incidence rates among white children were compared across four levels of urbanisation: large and small metropolitan counties, and adjacent and nonadjacent rural counties. In metropolitan areas, the incidence of ALL was lower among blacks (rate ratio (RR)=0.38, confidence interval (CI)=0.33-0.44) and among Asians/Pacific Islanders (RR=0.78, CI=0.63-0.97) than among whites. Among white children, the incidence of ALL decreased across the four strata of urbanisation, from 67 to 62 to 65 to 54 cases per million person-years at-risk (two-sided trend P=0.009), such that rates were significantly lower in the most remote rural counties than in the most populous metropolitan counties (RR=0.80, 95% CI=0.70-0.91).     

Descriptive epidemiology of childhood leukaemia

Internationally there is a 4-fold variation in age-adjusted incidence rates for childhood leukaemia (all types combined), with only slightly greater worldwide differences specifically for acute lymphocytic leukaemia (ALL) and for acute nonlymphocytic leukaemia (ANLL). Total leukaemia rates are highest among Hispanic populations in Costa Rica and Los Angeles (males), due primarily to elevated ALL incidence, while low rates occur among US blacks, Kuwaitis, Israeli non-Jews, and Bombay Indians. In most populations the patterns for ALL are similar to those for total leukaema, with peak incidence at ages 1-4 and a decline thereafter. Lower and more uniform rates are generally observed at all ages for ANLL. Age-adjusted rates for ANLL appear to vary substantially among some populations with uniform ALL incidence rates (e.g., among Asians) and yet appear to be similar in other populations with variation in ALL rates (e.g., whites and blacks in the US). Possible variation among registries in completeness of childhood leukaemia ascertainment and accuracy of diagnosis by cell type should be assessed, while case-control investigations among populations with very high and very low rates may provide useful information about the cell-type specific determinants of childhood leukaemia.     

The relationship of incidence of childhood lymphoblastic leukaemia to social class.

A study has been made of the relationship between socio-economic factors and the incidence of acute lymphoblastic leukaemia (ALL) of childhood. It was found that the incidence of childhood ALL in 12 areas of Queensland. Australia, correlated well with some indicators of above-average socio-economic status for these areas. A similar result was found when Brisbane City was studied separately. Social class was determined from the fathers'' occupations at the time of diagnosis. There was found to be a higher than expected number of ALL cases in each of the upper 5 social classes and a lower than expected number in the remaining 2 lower classes. Factors associated with differences in lifestyle amongst the various social classes may increase or decrease the risk of development of ALL.     

Childhood leukaemia in North West England 1954-1977: epidemiology, incidence and survival.

The annual incidence of leukaemia among children aged up to 14 years as estimated by the Manchester Children''s Tumour Registry has been analysed for the 24 years 1954-1977. A significant increase in acute lymphoid leukaemia (ALL) was found, while the incidence of acute myeloid leukaemia (AML) remained constant. Other types of leukaemia were too rare to be analysed separately. The increase in ALL was concentrated among boys in the 1--5-year age group. Analysis with respect to initial white-cell count showed the increase to be more pronounced in children with initial white cell counts of 1-5 x 10(4)/microliters. The proportion of cases presenting in Lancashire compared with Greater Manchester did not change during the study period. The distribution of cases with respect to social class and socio-economic group of the parents also remained constant. Due to advances in the treatment of childhood ALL survival improved considerably during the study period and no increase in mortality was seen.     

A systematic literature review of the clinical and epidemiological burden of acute lymphoblastic leukaemia (ALL)

Our goal was to identify and summarize the published literature pertaining to the incidence, prevalence, mortality, aetiology, clinical diagnosis, and management of acute lymphoblastic leukaemia (ALL). Acute lymphoblastic leukaemia represents 12% of all leukaemia cases, with a worldwide incidence projected to be 1-4.75 per 100,000 people. Italy, the United States (US), Switzerland, and Costa Rica are the countries with the highest incidence of ALL. Hereditary link, genetic defects, and possibly radiation or chemical exposures are listed amongst the most significant risk factors. Acute lymphoblastic leukaemia is predominantly a disease of childhood, but it affects adults as well. It accounts for 80% of all leukaemia cases in children. The incidence is slightly higher in men than in women and greater in white people than in black people. In 2003 in the US, there were an estimated 5800 deaths from ALL. Presenting signs and symptoms of ALL are fairly non-specific and include fever, anaemia, petechiae, and bone and joint pain. Staging of the disease and patient risk profile are routinely performed to define ALL subtypes and guide management. Chemotherapy, cranial radiation in patients with high-risk disease, and stem cell transplantation for selected patients are the prevalent therapies. Complete remission rates are high, especially amongst children (even 100%); however, long-term survival at 10 years (event-free survival) is in the range of 63% for children and 25-35% for adults. This implies that there is still a strong need for new therapies to maintain remission and prolong survival. Future treatment strategies may be driven by the patient's minimal residual disease status, a measure that more precisely defines remission, prognosis, responsiveness to therapy, and expected long-term survival.     

Trends in childhood leukemia incidence over two decades from 1992 to 2013

Incidence rates of childhood leukemia in the United States have steadily increased over the last several decades, but only recently have disparities in the increase in incidence been recognized. In the current analysis, Surveillance, Epidemiology and End Results (SEER) data were used to evaluate recent trends in the incidence of childhood leukemia diagnosed at age 0–19 years from 1992 to 2013, overall and by age, race/ethnicity, gender and histologic subtype. Hispanic White children were more likely than non‐Hispanic White, non‐Hispanic Black or non‐Hispanic Asian children to be diagnosed with acute lymphocytic leukemia (ALL) from 2009 to 2013. From 1992 to 2013, a significant increase in ALL incidence was observed for Hispanic White children [annual percent change (APC)_Hispanic = 1.08, 95% CI: 0.59, 1.58]; no significant increase was observed for non‐Hispanic White, Black or Asian children. ALL incidence increased by about 3% per year from 1992 to 2013 for Hispanic White children diagnosed from 15 to 19 years (APC = 2.67; 95% CI: 0.88, 4.49) and by 2% for those 10–14 years (APC = 2.09; 95% CI: 0.57, 3.63), while no significant increases in incidence were observed in non‐Hispanic White, Black, or Asian children of the same age. Acute myeloid leukemia (AML) incidence increased among non‐Hispanic White children under 1 year at diagnosis, and among Hispanic White children diagnosed at age 1–4. The increase in incidence rates of childhood ALL appears to be driven by rising rates in older Hispanic children (10–14, and 15–19 years). Future studies are needed to evaluate reasons for the increase in ALL among older Hispanic children.     

Population mixing,childhood leukaemia,CNS tumours and other childhood cancers in Yorkshire

We tested the hypothesis that variation in population mixing attributable to the diversity of migrants moving to an area is associated with the incidence of childhood leukaemia and other childhood cancers. An ecological analysis was performed on 954 children (<15 years) diagnosed with a malignancy between 1986 and 1996 in 532 electoral wards in Yorkshire, UK. Incidence rate ratios (IRR) were calculated for all childhood leukaemias (n=325), acute lymphoblastic leukaemia (ALL) (n=248), central nervous system (CNS) tumours (n=236) and other solid tumours (n=393) Incidence of all childhood leukaemias was significantly lower in areas of high (top decile) population mixing (IRR 0.72, 95% Confidence Interval (CI) 0.54-0.97) and higher in areas of low (bottom decile) population mixing (IRR 1.56, 95% CI 0.73-3.34), but similar patterns of incidence were not observed for central nervous system or other solid tumours. Population mixing may be a proxy for the range of infections circulating in a community and these results are consistent with the hypothesis that greater exposure to infections reduces the risk of developing childhood leukaemia by conferring efficient modulation of the immune system.     

Childhood leukaemias in New Zealand: time trends and ethnic differences.

Registrations from the New Zealand Cancer Registry were used to examine time trends in the incidence of leukaemias among children aged 0-14. There was a statistically significant increase in the incidence of leukaemia among children aged 0-4 during 1953-57 to 1988-90. In this age group, the recorded incidence rate increased from 4.89 per 100,000 person-years in 1953-57 to 7.92 in 1988-90. During 1973-77 to 1988-90 (and probably in earlier years), the increase was due to an increase in acute lymphoblastic leukaemia (ALL). The trends were unlikely to be due to changes in diagnosis or case ascertainment. The childhood leukaemia trends might be related to trends in family size, maternal age, socioeconomic level or exposure to infections. However, there are uncertainties about the importance of these factors or about their trends. The incidence of acute non-lymphoblastic leukaemia (ANLL) decreased between 1968-72 and 1988-90. The time trends highlight the likely importance of environmental factors in the aetiology of childhood leukaemias in New Zealand. The risk of ALL was lower in the Maori than in the non-Maori population (relative risk Maori/non-Maori 0.74). The risk of ANLL was higher among Maori (relative risk 1.84).     

High-contact paternal occupations, infection and childhood leukaemia: five studies of unusual population-mixing of adults.

The hypothesis has been tested that, among excesses of childhood leukaemia associated with extreme population-mixing, the incidence is higher for the children of men in occupations involving contact with many individuals (particularly children), as noted in certain childhood infections. Data on childhood leukaemia were examined from five previous studies of the author in which significant excesses had been found associated with population-mixing involving adults. Occupational titles were categorized according to the estimated level of work contacts as medium, high, very high or indeterminate. Occupations involving frequent contact with children were categorized as having a very high contact level given the high frequency of exposure to the infection postulated as underlying childhood leukaemia. There was a significant positive trend (P < 0.001) in childhood leukaemia risk at ages 0-14 years across the occupational contact categories from the reference group (comprising the medium and low plus indeterminate categories) through high to very high (i.e. high-child) contact categories in the combined data from the author''s five studies of adult population-mixing; this significant trend also applied at ages 0-4 (P < 0.001) and 5-14 (P < 0.01) years. The excess in the high category was mainly because of paternal occupations connected with the construction industry and transport, suggesting a broader definition of the ''very high'' contact category. No sign of these excesses was found in a limited examination of the question outside areas of population-mixing using mortality data for childhood leukaemia in the general population of England and Wales. The findings represent the first individual-based support for infection underlying childhood leukaemia that is promoted by population-mixing, as well as further support for the role of adults in transmission of the infection.     

The Northern region Children's malignant disease registry 1968-82: incidence and survival

All cases of childhood cancer diagnosed before the 15th birthday in the years 1968-1982 and resident in the Northern Health Authority region have been registered. There were 1171 registrations and only two have been completely lost to follow up. The overall annual incidence of cancer was 107.1 per million children, similar to previously reported figures. There was no significant change in the rate over the 15 year period either for all cancers or individual cancer types. Eighty six percent of registrations had central review of pathological material. There has been a significant move towards centralisation of care over the 15 years and a significant improvement in survival over the three quinquennia for all cases and for most individual types. High white blood cell count at presentation was confirmed as a bad prognostic feature in children with acute lymphoblastic leukaemia (ALL). Children treated for ALL in a peripheral hospital had a significantly worse survival than those referred to a specialist centre. Survival rates were calculated for all of the major types of malignancy. The registry includes four sibling pairs with cancer and one family with three siblings affected. Ten children developed secondary primary tumours.     

Community lifestyle characteristics and lymphoid malignancies in young people in the UK

Data from a specialist registry of haematopoietic malignancies in England and Wales (1984–1988) have been analysed to investigate variations of incidence by age and diagnostic subtype of lymphoid malignancies in young people (aged 0–24 years). Attention has been focussed on the role of community lifestyle indicators for small areas, derived from routine sources, in an ecological analysis. The predominant conditions were acute lymphoblastic leukaemia (ALL)—42.4%, and Hodgkin's disease (HD)—37.5%. Lowest overall incidence at approximately 8 years of age corresponded to the termination of the childhood peak for ALL. Opposite trends of incidence rates with distance from urban centres (urban distance) were observed for the two age groups: odds ratios (OR) for areas > 20 km from towns and cities were 1.46 (95% confidence interval 1.01–2.12) for ages 0–7 and 0.75 (95% confidence interval 0.56-0.99) for ages 8–24. For the younger group this was entirely attributable to ALL. HD, which was dominant in the older group, had highest incidence in connurbations but the gradient of risk for older onset ALL followed the overall pattern for this age group. A positive relationship with socioeconomic status was evident for both age groups but this was considerably stronger for the older cases (OR = 1.16, 95% confidence interval 1.01-1.33) than for the younger for whom it was not independent of urban distance. These results display an association between expression of lymphoid malignancies in young people and urban distance which is not attributable to socioeconomic status; for urban distances the distribution is shifted towards ALL and towards younger age at onset.     

Acute Lymphoblastic Leukaemia in the Elderly

Acute lymphoblastic leukaemia (ALL) is rare in adults over the age of 60 years, with an incidence of 1 per 100,000 per year. We review the current (sparse) literature and our Regional experience of 62 consecutive cases of ALL in this age group collected over a ten year period.

The patterns of cytogenetic abnormalities and immunophenotypes differs from those seen in ALL in childhood and young adults, but are similar to those reported in previous studies. B-ALL was found at twice the rate observed in younger adults (9/51 versus 6/99) and T-ALL was rare (2/51). In our patients we had few cytogenetic results but in the literature up to 50% of patients have been found to be Philadelphia positive, supporting the hypothesis that ALL in this group is often a stem cell disorder. In our patients treatment results were disappointing, with only 30% of those given 'curative' treatment achieving a complete remission, and a relapse rate of 92%, mirroring other published series. The overall four year survival was 4%. We conclude that ALL in the elderly is a rare condition with an extremely poor prognosis. Aggressive treatment may prolong life but it seldom cures.     

Patterns of care and survival for adolescents and young adults with acute leukaemia--a population-based study

We report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15-29 years during 1984-94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984-88 and 1989-94 for those aged 15-19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984-88 and 1989-94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group.     

Incidence of Childhood Leukemia in Iraq, 2000-2019

Background: Leukemia is a major concern for children worldwide. Around 30% of malignancies in children (ages 0–14) are caused by leukemia. Objective: This study aims to explore the time trends in the incidence of childhood leukemia (aged 0-14 years) in Iraq between 2000 and 2019. Methods: Poisson regression with a log link function was used to analyze the long-term trends of incidence related to childhood leukemia cancer based on published data from the Iraqi cancer registry between 2000 and 2019. Annual estimates of the population, by 5-year age groups and by gender obtained from the United Nations, population Division. Results: A total of 8,570 cases of leukemia children in Iraq between 2000 and 2019 were recorded, the boys to girl ratio were 1.32 to 1. The most diagnosed type of leukemia was Acute lymphoblastic leukemia, accounting for about 33.56%, followed by Leukemia Not specify (NOS) (17.3%) with a relatively equal proportion of stated instances between boys and girls in these subsets. The age-standardized incidence rates, aged 0-14 years, from 2000-2019 were 3.45/100,000 for both genders. The Joinpoint regression ASRs analysis of childhood leukemia from 2000-2019 among 0 –14 age group for both genders indicate that there was an overall significant increasing trend at 1.23% per year, while no one joinpoint was identified during the entire study period. Among boys, there was an overall insignificant increasing trend at 0.77% per year. Among girls, there was an overall significant increasing trend at 1.93% per year, while one joinpoint was identified during the entire study period.  Conclusions: The overall (both genders) incidence rate of childhood leukemia has been increasing significantly in Iraq. The test for trends was insignificant among boys, while it was significant among girls. The increasing trend of leukemia requires further epidemiological studies to describe incidence by geography in Iraq.     

Socioeconomic status and childhood acute lymphocytic leukemia incidence in São Paulo, Brazil

To investigate the association of childhood ALL and SES, we collected data on 507 children aged 0–14 years diagnosed with ALL between 1997 and 2002 from the population‐based Cancer Registry of São Paulo, Brazil, covering 96 districts. Each child was assigned to an SES category based on the district of residence at diagnosis. Four SES categories were created from high to low, based on the Social Exclusion Index (SEI) that includes the following indicators: poverty, employment, inequality, education and violence. Using Census data, cases were also classified into quintiles according to the percentage of households with more than 7 persons. Age‐specific and age‐standardized incidence rates were calculated using the 1960 world standard population. Age‐adjusted incidence rate was 3.68/100,000 for males and 2.87/100,000 for females. Children living in areas with lowest SES presented a significant lower risk of ALL compared with those living in the wealthiest districts (Rate Ratio [RR] = 0.34; 95% Confidence Interval [CI] = 0.28–0.44). Lower incidence rates of childhood ALL were also found in areas with high percentages of households with more than 7 persons (≥5.7%) compared with areas where there were ≤2.2% (RR = 0.32, 95% CI 0.25–0.43). There was a strong correlation between SEI and crowding (rho = ?0.95, p < 0.001). Population‐based attributes for SES and household size may be useful surrogate markers of early exposure to childhood infections, which has been found to decrease the risk of ALL. © 2008 Wiley‐Liss, Inc.