Infectious diseases in the first year of life, perinatal characteristics and childhood acute leukaemia

The objective of the present study was to investigate the role of early common infections and perinatal characteristics in the aetiology of childhood common leukaemia. A case-control study was conducted from 1995 to 1998 in France, and included 473 incident cases of acute leukaemia (AL) (408 acute lymphoblastic leukaemia (ALL), 65 acute myeloid leukaemia (AML) age-, sex- and region-matched with 567 population-based controls. Data on the medical history of the child and his/her environment were collected using self-administered questionnaires. Analyses were conducted using nonconditional logistic regression. A slight negative association with early infections was observed (OR=0.8; 95% CI (0.6-1.0)). The association was stronger for early gastrointestinal infections. Early day-care was found to be associated with a decreased risk of AL (OR=0.6; 95% CI (0.4-0.8) and OR=0.8; 95% CI (0.5-1.2) for day-care starting before age 3 months and between 3 and 6 months, respectively). No association with breast-feeding was observed, irrespective of its duration. A birth order of 4 or more was associated with a significantly increased risk of AL (OR=2.0; 95% CI (1.1-3.7) with ALL). A history of asthma was associated with a decreased risk of ALL (OR 0.5; 95% CI (0.3-0.90). Although the results regarding birth order and breast-feeding do not fit with Greaves' hypothesis, the study supports the hypothesis that early common infections may play a protective role in the aetiology of childhood leukaemia, although this effect was not more marked for common ALL.     

Childhood and maternal infections and risk of acute leukaemia in children with Down syndrome: a report from the Children's Oncology Group

Children with Down syndrome (DS) are highly susceptible to acute leukaemia. Given the potential role of infections in the aetiology of leukaemia in children without DS, we investigated whether there was an association between early-life infections and acute leukaemia in children with DS. Maternal infections during pregnancy were also examined. We enrolled 158 incident cases of acute leukaemia in children with DS (97 acute lymphoblastic leukaemia (ALL) and 61 acute myeloid leukaemia (AML)) diagnosed at Children's Oncology Group institutions between 1997 and 2002. DS controls (N=173) were selected from the cases' primary care clinics and frequency matched on age at leukaemia diagnosis. Data were collected on demographics, child's medical history, mother's medical history, and other factors by maternal interview. Analyses were conducted using unconditional logistic regression adjusted for potential confounders. A significant negative association was observed between acute leukaemia and any infection in the first 2 years of life (adjusted odds ratio (OR)=0.55, 95% confidence interval (CI) (0.33-0.92); OR=0.53, 95% CI (0.29-0.97); and OR=0.59, 95% CI (0.28-1.25) for acute leukaemia combined, ALL, and AML respectively). The association between acute leukaemia and maternal infections during pregnancy was in the same direction but not significant. This study offers support for the hypothesis that early-life infections may play a protective role in the aetiology of acute leukaemia in children with DS.     

Quantifying the effect of population mixing on childhood leukaemia risk: the Seascale cluster.

A statistical model was developed based on Poisson regression of incidence of childhood leukaemia and non-Hodgkin's lymphoma (NHL) in relation to population mixing among all 119 539 children born 1969-1989 to mothers living in Cumbria, north-west England, (excluding Seascale). This model was used to predict the number of cases in Seascale (the village adjacent to the Sellafield nuclear installation) children, born 1950-1989 and diagnosed before 1993. After allowing for age, the incidence of acute lymphoblastic leukaemia (ALL) and NHL was significantly higher among children born in areas with the highest levels of population mixing, relative risk (RR) = 11.7 (95% confidence interval (CI) 3.2-43) and was highest among children of incomers. The model predicted up to 3.0 (95% CI 1.3-6.0) cases of ALL/NHL in children born in Seascale compared to six observed and 2.0 (95% CI 1.0-3.4) cases in children resident, but not born, in Seascale compared to two observed. Population mixing is a significant risk factor for ALL/NHL, especially in young children, accounting for over 50% of cases in Cumbria and most cases in Seascale.     

Survival trends in childhood chronic myeloid leukaemia in Southern-Eastern Europe and the United States of America

AimTo assess trends in survival and geographic disparities among children (0–14 years) with chronic myeloid leukaemia (CML) before and after the introduction of molecular therapy, namely tyrosine kinase inhibitors (TKIs) in Southern-Eastern European (SEE) countries and the USA.MethodsWe calculated survival among children with CML, acute lymphoblastic (ALL) and acute myeloid leukaemia (AML) in 14 SEE (1990–2014) cancer registries and the U.S. Surveillance, Epidemiology and End Results Program (SEER, 1990–2012). We used Kaplan–Meier curves and multivariate Cox regression models to calculate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsAmong 369 CML cases, substantial improvements were noted in 2-year survival during the post-TKI (range: 81–89%) compared to pre-TKI period (49–66%; HR: 0.37, 95% CI: 0.23–0.60). Risk of death was three times higher for <5-year-old children versus those aged 10–14 years (HR: 3.03, 95% CI: 1.85–4.94) and 56% higher for those living in SEE versus SEER (HR: 1.56, 95% CI: 1.01–2.42). Regardless of geographic area and period of TKI administration, however, age seems to be a significant determinant of CML prognosis (pre-TKI period, HR_0–4y: 2.71, 95% CI: 1.53–4.79; post-TKI period, HR_0–4y: 3.38, 95% CI: 1.29–8.85). Noticeably, post-TKI survival in CML overall approximates that for ALL, whereas therapeutic advancements for AML remain modest.ConclusionRegistry data show that introduction of molecular therapies coincides with revolutionised therapeutic outcomes in childhood CML entailing dramatically improved survival which is now similar to that in ALL. Given that age disparities in survival remain substantial, offering optimal therapy to entire populations is an urgent priority.     

Longer breast-feeding and protection against childhood leukaemia and lymphomas

The role of breast-feeding in protecting against childhood acute leukaemia and lymphomas is uncertain. We investigated this issue in a case-control study comprising 117 patients, aged 2-14 years, with acute lymphocytic leukaemia (ALL), Hodgkin's (HL) and non-Hodgkin's lymphoma (NHL), as well as 117 controls matched for age, sex and ethnicity. Information was collected via a telephone interview of the mothers. The median duration of breast-feeding among patients was significantly shorter than among controls, 7 (range 0-23) and 10 (range 0-20) months, respectively (P<0.0001). Breast-feeding of 0-6 months' duration, when compared with feeding of longer than 6 months, was associated with increased odds ratios (OR) for ALL (OR=2.47, 95% confidence interval (CI) 1.17-5.25), HL (OR=3.75, 95% CI 0.80-18.69), NHL (OR=4.06, 95% CI 0.82-22.59), and overall (OR=2.79, 95% CI 1.54-5.05). In the patient group, there were a significantly higher number of children and people per family, and patients were of a higher birth order than controls. In multivariate analysis, breast-feeding duration continues to be an independent predictor of lymphoid malignancies (P=0.015). In conclusion, breast-feeding lasting longer than 6 months may protect against childhood acute leukaemia and lymphomas.     

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.     

Childhood acute leukaemia in a tropical population.

The clinical features of acute leukaemia (AL) were documented prospectively among Nigerian children resident in the South-Western rain-forest area of the country, and compared to the features in Caucasians. Twenty-nine of 51 newly diagnosed cases of AL occurred in childhood, including 19 cases of acute lymphoblastic leukaemia (ALL) and 11 of acute myelogenous leukaemia (AML). The incidence of ALL the AML in Ibadan children was the same, estimated as 0.8 X 10(-5). Thus childhood ALL was about one-third as common in Ibadan as in most developed Caucasian countries. ALL and AML occurred most frequently in the age groups 10-14 and 5-9 years respectively. Six cases of AML were associated with chloromas. Only 2 of the ALL patients survived more than one year after standard chemotherapy. The poor result appeared to be attributable to frequent occurrence among the ALL patients of adverse prognostic factors such as hyperleucocytosis, age less than 2 or greater than 7 years, L2 morphology and low PAS reactivity of the lymphoblasts. Unknown environmental factors are believed to be responsible for the unusual features of AL in children in Ibadan.     

Examination of temporal trends in the incidence of childhood leukaemias and lymphomas provides aetiological clues.

The age-sex distributions and temporal trends in incidence of leukaemia and lymphoma from the Manchester Children's Tumour Registry (MCTR), 1954-1998, are reported. This 45-year study includes 1795 children, all of whom had a histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses all the children were under 15 years of age and were resident in a geographically defined area of northwest England covered by the MCTR. Log-linear modelling identified significant linear increases in acute lymphoblastic leukaemia (ALL) (average annual increase 0.7%; P= 0.005) and in Hodgkin's disease (HD) (1.2%, P=0.04), but not in acute myeloid leukaemia (AML), nor in non-Hodgkin's lymphoma (NHL). The increase in ALL was most pronounced amongst males, aged 1-4 years, and is likely to be due to precursor B-cell leukaemias. The increases in ALL and HD are discussed in relation to current hypotheses suggesting a role for infection. Additionally, a non-linear cohort effect was identified for NHL (P= 0.008), which may indicate the involvement of environmental factors other than infection.     

Clinical features, cytogenetics and outcome in acute lymphoblastic and myeloid leukaemia of infancy: report from the MRC Childhood Leukaemia working party.

The clinical features, cytogenetics and response to treatment have been examined in 180 infants (aged <1 year) with acute leukaemia; 118 with acute lymphoblastic leukaemia (ALL) and 62 with acute myeloid leukaemia (AML). Comparison of clinical features showed no difference in age or sex distribution between infants with ALL and AML but infants with ALL tended to have higher leucocyte counts at presentation. Cytogenetic abnormalities involving 11q23 were found in 66% of ALL and 35% of AML cases, the commonest, t(4;11) being found only in ALL. The other recognised 11q23 translocations were found in both types of leukaemia. Few patients had the common cytogenetic abnormalities associated with ALL in older children and few with AML had good risk abnormalities. Four year event-free survival 60% cf 30% (P = 0.001) and survival 65% cf 41% (P = 0.007) were significantly better in AML than ALL. These results were due to a lower risk of relapse 27% cf 62% at four years. Superior event-free survival was also seen in the subgroup of patients with 11q23 abnormalities and AML (55% cf 23%). The reasons for superior response in AML are unknown but may be related to the intensity of treatment, lineage of the leukaemia or other as yet unidentified factors.     

Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study.

There is a well-known raised risk of leukaemia in children with neurofibromatosis type 1 (NF-1). We carried out the first detailed population-based study of leukaemia and non-Hodgkin lymphoma (NHL) associated with NF-1 in order to estimate the risk and elucidate the relationship between these conditions. Over the 17 year study period there were five cases of chronic myelomonocytic leukaemia (CMML) in patients with NF-1 (relative risk 221; 95% CI 71-514), 12 cases of acute lymphoblastic leukaemia (ALL) (relative risk 5.4; 95% CI 2.8-9.4) and five cases of NHL (relative risk 10.0; 95% CI 3.3-23.4). Marrow cytogenetics could be reviewed for seven patients. Specific abnormalities found were monosomy 21 in a child with CMML and 7p+, 17p- in a child with ALL. No abnormalities were reported of 17q, which includes the NF1 gene. CMML occurred predominantly in boys, who also had a family history of NF-1. ALL and NHL were more often found in children with no previous family history.     

Congenital abnormalities and acute leukemia among children with Down syndrome: a Children's Oncology Group study

Children with Down syndrome, due to their heightened risk of leukemia and increased prevalence of congenital abnormalities, comprise a valuable population in which to study etiology. A Children's Oncology Group study investigated the causes of childhood leukemia in children with Down syndrome diagnosed at ages 0 to 19 years during the period 1997-2002. Telephone interviews were completed with mothers of 158 cases [n=97 acute lymphoblastic leukemia (ALL) and n=61 acute myeloid leukemia (AML)] and 173 controls. Odds ratios (OR) and 95% confidence intervals (95% CI) were computed via unconditional logistic regression to evaluate the association between congenital abnormalities and acute leukemia overall, and ALL and AML analyzed separately. The results do not provide evidence for an association among the index children (OR(Combined), 0.74; 95% CI, 0.45-1.23; OR(ALL), 0.67; 95% CI, 0.38-1.20; OR(AML),1.03; 95% CI, 0.49-2.16) or their siblings (OR(Combined), 1.23; 95% CI, 0.71-2.13; OR(ALL), 1.12; 95% CI, 0.60-2.09; OR(AML), 1.60; 95% CI, 0.66-3.86), suggesting congenital malformations do not confer additional risk of leukemia beyond the risk attributable to trisomy 21 in this population.     

Ecological association between indoor radon concentration and childhood leukaemia incidence in France, 1990-1998.

The objective of this study was to evaluate the ecological association between indoor radon concentration and acute leukaemia incidence among children under 15 years of age in the 348 geographical units (zones d'emploi, ZE) of France between 1990 and 1998. During that period, 4015 cases were registered by the French National Registry of Childhood Leukaemia and Lymphoma. Exposure assessment was based on a campaign of 13 240 measurements covering the whole country. The arithmetic mean radon concentration was 85 Bq/m (range, 15-387 Bq/m) and the geometric mean, 59 Bq/m (range: 13-228 Bq/m). A positive ecological association, on the borderline of statistical significance (P=0.053), was observed between indoor radon concentration and childhood leukaemia incidence. The association was highly significant for acute myeloid leukaemia (AML) (P=0.004) but not for acute lymphocytic leukaemia (ALL) (P=0.49). The standardized incidence ratio (SIR) increased by 7, 3 and 24% for all acute leukaemia, ALL and AML, respectively, when radon concentration increased by 100 Bq/m. In conclusion, the present ecological study supports the hypothesis of a moderate association between indoor radon concentration and childhood acute myeloid leukaemia. It is consistent with most previous ecological studies. Since the association is moderate, this result does not appear inconsistent with the five published case-control studies, most of which found no significant association.     

Inclusion of patients with acute leukemia in clinical trials: a prospective multicenter survey of 1066 cases

Background: To estimate the prevalence of adults and children with acute leukemia (AL) included in clinical trials and to determine factors associated with noninclusion.Patients and methods: All patients with AL admitted to the 17 departments managing AL in Paris area from 2005 to 2007 were prospectively included. Clinical data, therapeutic decisions, and enrollment in trials were recorded. Reasons that prevented accrual were identified.Results: A total of 1066 admissions with AL (85% of adults) were recorded, and 34 trials were open. In adults, the rate of inclusion in a trial was 25% [95% confidence interval (CI) 21% to 28%] for acute myeloid leukemia (AML) and 23% (95% CI 17% to 29%) for acute lymphoid leukemia (ALL). In children, the rate of inclusion was 58% (95% CI 41% to 73%) for AML and 64% (95% CI 55% to 72%) for ALL. The rate of inclusion varied across centers, with a significant increase when they were involved in clinical research. Patients included in trials differed significantly from those not included according to age, primary/secondary AL, leukemia type, results of cytogenetic analyses, and stage of disease.Conclusions: The rate of inclusion is higher than in oncology. This difference may be explained by management in specialized centers often involved in clinical research.     

Breast-feeding and risk of childhood acute leukemia.

BACKGROUND: Breast-feeding is well known to have a protective effect against infection in infants. Although the long-term effects of breast-feeding on childhood cancer have not been studied extensively, a protective effect against childhood Hodgkin's disease and lymphoma has been suggested previously from small investigations. In this study, we tested the hypothesis that breast-feeding decreases the risk of childhood acute leukemia. METHODS: A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were included in the analysis. Information regarding breast-feeding was obtained through telephone interviews with mothers. All leukemias combined, histologic type of leukemia (ALL versus AML), immunophenotype of ALL (early pre-B cell, pre-B cell, or T cell), and morphology of AML were assessed separately in the data analysis. RESULTS: Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias (odds ratio [OR] for all types combined = 0.79; 95% confidence interval [CI] = 0.70-0.91). A reduction in risk was seen separately for AML (OR = 0.77; 95% CI = 0.57-1.03) and ALL (OR = 0.80; 95% CI = 0.69-0.93). The inverse associations were stronger with longer duration of breast-feeding for total ALL and AML; for M0, M1, and M2 morphologic subtypes of AML; and for early pre-B-cell ALL. CONCLUSION: In this study, breast-feeding was associated with a reduced risk of childhood acute leukemia. If confirmed in additional epidemiologic studies, our findings suggest that future epidemiologic and experimental efforts should be directed at investigating the anti-infective and/or immune-stimulatory or immune-modulating effects of breast-feeding on leukemogenesis in children.     

Busulfan, cyclophosphamide, and melphalan conditioning for autologous bone marrow transplantation in hematologic malignancy

Sixteen patients with poor-prognosis acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and non-Hodgkin's lymphoma (NHL) underwent conditioning with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (BUCY-2) plus melphalan (90 or 135 mg/m2) and autologous bone marrow transplantation (AuBMT) in a phase I study. At the melphalan dose of 90 mg/m2, grade greater than or equal to 3 regimen-related toxicity (RRT) was observed in five patients (31%; 95% confidence interval [CI], 11% to 59%), with hepatic (venoocclusive disease [VOD]) and urinary (hemorrhagic cystitis) RRT being the most frequent complications. Further escalation of the melphalan dose to 135 mg/m2 was deemed excessively toxic, as three of five patients had grade greater than or equal to 3 RRT. Following this experience, 21 patients with multiple myeloma (MM) and chronic myelogenous leukemia (CML) were treated with BUCY-2 plus melphalan 90 mg/m2 and AuBMT in separate studies. Three of these patients--all with extensively pretreated MM--had grade greater than or equal to 3 RRT (14%; 95% CI, 3% to 36%); no others had grade greater than or equal to 3 RRT. Therefore, a total of eight of the 37 patients (22%; 95% CI, 10% to 38%) who received BUCY-2 plus melphalan 90 mg/m2 conditioning developed grade greater than or equal to 3 RRT; three of these patients (8%; 95% CI, 3% to 25%) died of RRT. Although limited by the relatively small number of patients, our analysis of the patients receiving this regimen showed that the presence of parameters denoting the lymphoid diagnostic group (ie, ALL, NHL, and MM), more extensive pretreatment, and/or more advanced disease status were associated with a higher incidence of grade greater than or equal to 3 RRT. Response data on the AML, ALL, and NHL patients who received BUCY-2 plus melphalan 90 mg/m2 were analyzed: three patients (all with AML in first or second remission) are leukemia-free at 3.0, 2.8, and 1.4 years after AuBMT. The actuarial 2-year event-free survival in this group is 17% (95% CI, 5% to 54%). Response data on the MM and CML patients will be reported subsequently. BUCY-2 plus melphalan at a dose of 90 mg/m2 before AuBMT produces acceptable toxicity in patients who are not heavily pretreated. A full evaluation of the antineoplastic effects of this regimen requires further study.     

SERUM metabolomics of acute lymphoblastic leukaemia and acute myeloid leukaemia for probing biomarker molecules

Acute leukaemia (AL) is a critical neoplasm of white blood cells. Diagnosing AL requires bone marrow puncture procedure, which many patients do not consent to for it is invasive. Hence sensitive and specific early diagnostic biomarkers are essential for non‐invasive diagnosis, new therapeutics and improving the disease prognosis. To differentiate the metabolic alterations associated with acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), we investigated serum of ALL and AML patients in comparison with two controls using gas chromatography coupled with triple quadrupole tandem mass spectrometry and multivariate statistical analysis. Twenty seven out of 1425 metabolites were found differentiative among ALL, AML, aplastic anaemia (APA) patients and healthy control using p‐value ≤ 0.001. ALL is the most dissimilar group from other three groups as in hierarchical clustering showed 72.1% dissimilarity. Model generation using PLSDA gave an overall accuracy of 91.9%. This study helps in metabolic fingerprinting of control and disease serum at high significance levels and could be used for early diagnosing of AL. Based on pathways analysis, fatty acid metabolism is deregulated in patients with AL and may represent an underlying metabolic pathway associated with disease progression. Copyright © 2016 John Wiley & Sons, Ltd.     

Body size and obesity during adulthood,and risk of lympho-haematopoietic cancers: an update of the WCRF-AICR systematic review of published prospective studies

BackgroundTo summarise the evidence on the associations between body mass index (BMI) and BMI in early adulthood, height, waist circumference (WC) and waist-to-hip ratio (WHR), and risk of lympho-haematopoietic cancers.MethodWe conducted a meta-analysis of prospective studies and identified relevant studies published up to December 2017 by searching PubMed. A random-effects model was used to calculate dose–response summary relative risks (RRs).ResultsOur findings showed BMI, and BMI in early adulthood (aged 18–21 years) is associated with the risk of Hodgkin’s and non-Hodgkin’s lymphoma (HL and NHL), diffuse large beta-cell lymphoma (DLBCL), Leukaemia including acute and chronic myeloid lymphoma (AML and CML), and chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). The summary RR per 5 kg/m² increase in BMI were 1.12 [95% confidence interval (CI): 1.05–1.20] for HL, 1.05 (95% CI: 1.03–1.08) for NHL, 1.11 (95% CI: 1.05–1.16) for DLBCL, 1.06 (95% CI: 1.03–1.09) for ML, 1.09 (95% CI: 1.03–1.15) for leukaemia, 1.13 (95% CI: 1.04–1.24) for AML, 1.13 (95% CI: 1.05–1.22) for CML and 1.04 (95% CI: 1.00–1.09) for CLL, and were1.12 (95% CI: 1.05–1.19) for NHL, 1.22 (95% CI: 1.09–1.37) for DLBCL, and 1.19 (95% CI: 1.03–1.38) for FL for BMI in early adulthood analysis. Results on mortality showed a 15%, 16% and 17% increased risk of NHL, MM and leukaemia, respectively. Greater height increased the risk of NHL by 7%, DLBCL by 10%, FL by 9%, MM by 5% and Leukaemia by 7%. WHR was associated with increased risk of DLBCL by 12%. No association was found between higher WC and risk of MM.ConclusionOur results revealed that general adiposity in adulthood and early adulthood, and greater height may increase the risk of almost all types of lympho-haematopoietic cancers and this adds to a growing body of evidence linking body fatness to several types of cancers.     

Pegfilgrastim primary prophylaxis in patients with non-Hodgkin lymphoma: results from an integrated analysis

Severe neutropenia and febrile neutropenia (FN) are serious, dose‐limiting side effects of chemotherapy for aggressive non‐Hodgkin lymphoma (NHL). Observational data suggest that with current practice neutropenia management up to 23% of patients receiving CHOP‐like regimens experience FN, and around half of patients do not receive the planned relative dose intensity (RDI). In this integrated analysis we assessed the efficacy of pegfilgrastim for preventing FN and related outcomes in patients with NHL. A literature search was used to identify chemotherapy regimens with an FN risk ≥15% that are used to treat lymphoma. Search results were then used to identify clinical trials in which these regimens were administered with pegfilgrastim primary prophylaxis. Individual patient data were available for three trials meeting the inclusion criteria, and these were combined in an integrated analysis. The primary outcome measure was the incidence of FN in any cycle. A total of 282 patients were included in the analysis [mean age 65 years (SD ± 12.5 years); 172 (61%) aged ≥ 65 years]. All patients had NHL and 244 (87%) received RCHOP‐21. The incidence of FN in any cycle was 16% (95% CI 12–20%) (13% in patients aged <65 years; 18% in patients aged ≥65 years). Chemotherapy dose delays >3 days occurred in 26% (95% CI 20–31%) of patients, and was relatively consistent across age groups. Chemotherapy dose reductions ≥10% were seen in 43% (95% CI 37–49%) of patients and were more frequent in the elderly. Overall, 83% (95% CI 78–87%) of patients received ≥90% RDI (89% of patients aged <65 years; 78% of patients aged ≥65 years). In this integrated analysis of NHL patients at higher risk of FN receiving pegfilgrastim primary prophylaxis, the overall incidence of FN was 16% and a high proportion of both younger and elderly patients achieved RDI ≥90%. Copyright © 2011 John Wiley & Sons, Ltd.     

Human herpes virus-6 seroprevalence and leukaemias: a case-control study. GIMEMA (Gruppo Italiano Malattie Ematologiche dell' Adulto).

The relationships between acute myeloid leukaemia (AML), acute lymphocytic leukaemia (ALL), chronic myeloid leukaemia (CML) and refractory anaemia with excess of blasts (RAEB) and human herpes virus (HHV)-6 antibody level were investigated in a multicentre case-control study. An association between increased HHV-6 seropositivity and geometric mean titre ratio with AML was shown: P for trend = 0.022, adjusted odds ratio 1.20, 95% confidence interval 1.07-1.33 respectively. No association was found between HHV-6 and ALL, CML or RAEB.     

Cell proliferation is related to in vitro drug resistance in childhood acute leukaemia

Bone marrow and peripheral blood samples from 362 patients with acute lymphoblastic leukaemia (ALL) proliferating cell and 90 patients with acute myeloid leukaemia (AML) were analysed for S-phase fractions, Ki67 antigen, and proliferating cell nuclear antigen expression. The S-phase fractions were correlated with in vitro drug resistance to 15 different anticancer agents. Leukaemia cells isolated from bone marrow had higher S-phase fractions than leukaemia cells isolated from peripheral blood (in initial ALL, median values resp. 6.9 and 2.7%, in initial AML resp. 5.3 and 1.3%; both P<0.01). Relapse ALL samples derived from bone marrow showed increased S-phase fractions (median 9.9%) compared with initial ALL samples (median 6.9%; P<0.01). ALL samples obtained at initial diagnosis showed higher S-phase fractions (median 6.9%) and higher Ki67 expression (median 30%) than initial AML samples (median resp. 5.3 and 14%; both P<0.05). The S-phase fractions were not related to white blood cell count, age, or gender. Within initial ALL, the S-phase fraction correlated significantly but modestly strong (rho=0.3-0.5; P<0.05) with sensitivity to antimetabolites (cytarabine, mercaptopurine, thioguanine), L-asparaginase, teniposide, and vincristine. Similar results were found within subgroups of initial ALL (nonhyperdiploid and common/precursor-B-lineage ALL). In relapsed ALL and AML such correlations were not found. In conclusion, cell proliferation differs between leukaemia subgroups and increased proliferation is associated with increased in vitro sensitivity to several anticancer agents in initial ALL.