Epidemiology of acute lymphoblastic leukaemia in Sardinia, Italy: Age, sex, and environmental correlates.

Using a database of 1974-2003 incident cases of haematological malignancies, we explored the time trend, geographic spread and socio-economic and environmental correlates of ALL incidence in Sardinia, Italy, by sex and age. The age- and sex-standardized (World population) ALL incidence rate was 2.0 per 100,000 (95% CI 1.8 - 2.1) and showed variable trend patterns by sex and age. In the total population, ALL incidence showed an annual per cent change of -1.4% (95% CI -0.59 - -3.34) over the study period, with a knot separating a downward slope in 1974-1996 from an increase in 1996-2003. ALL incidence replicated such pattern in women but not men, whose incidence did not substantially vary over the study period (APC = -2.57%, 95% CI -5.45 - 0.26). Among women, the spatial analysis suggested a clustering of ALL in the southwestern part of the region, whilst only a commune had a high posterior probability of a high ALL incidence among men. Three unrelated communes showed a high posterior probability of ALL at age ≤ 24; only the most populated urban centre showed excess cases at age ≥ 25 years. There was no correlation between the geographic spread of ALL at ages ≤ 24 and ≥ 25 years (p = 0.082). Urban residence was a risk factor for the younger age group. Residences near industrial settlements and in the most populated urban centre were risk factors for subjects aged ≥ 25 years. Our findings suggest age-related differences in ALL aetiology.

Incidence and Bayesian Mapping of Myeloid Hematologic Malignancies in Sardinia, Italy.

BACKGROUND: The epidemiology of myeloid hematologic malignancies in Italy has been poorly investigated. METHODS: We used a validated database of 1974-2003 incident cases of hematologic malignancies among the resident population (all ages) of Sardinia, Italy, to describe the incidence of myeloid malignancies overall (N = 4389 cases) and by subtype. We investigated the time trend of acute myeloid leukemia (N = 1227 cases), chronic myeloid leukemia (N = 613 cases), and myelodysplastic syndrome (N = 1296 cases), and used Bayesian methods to explore their geographic spread, and Poisson regression analysis to estimate their association with environmental and socio-economic factors. RESULTS: The annual standardized (world population) incidence rate (IR) of myeloid malignancies over the study period was 6.5 per 100,000 (95% CI 6.2-6.7). Myelodysplastic syndromes were the most prevalent subgroup (IR = 1.7, 95% CI 1.5-1.8). Incidence of all myeloid malignancies combined increased sharply during the study period with an annual percent change (APC) of 10.06% (95% CI 9.51-10.61), 19.77% for myelodysplastic syndromes (95% CI 19.63-19.91), and 3.18% (95% CI 2.99-3.37) for acute myeloid leukemia. Chronic myeloid leukemia did not show an upward trend. Apart from sporadic excesses in small rural communities and the major urban area, there was no evidence of spatial clustering. The risk of myeloid malignancies increased with increasing prevalence of sheep breeding. CONCLUSIONS: Our results might prompt further research on the local genetic and environmental determinants of myeloid hematologic malignancies.

Epidemiology of Chronic Lymphocytic Leukemia in Sardinia, Italy (1974-2003).

Several reports have described a worldwide increasing incidence of chronic lymphocytic leukemia (CLL) dating back seven to eight decades. Although genetic susceptibility would be an implausible explanation, the determinants of this upward trend and its spatial coordinates are poorly understood. We explored CLL incidence in Sardinia, Italy, using a validated database including the 1700 CLL cases diagnosed during 1974-2003. We applied Bayesian methods to map the CLL probability by administrative unit and Poisson regression analysis to investigate socioeconomic and environmental determinants adjusting by possible confounders. The standardized (Standard European population) incidence rate for the Sardinian population over the study period was 5.1 per 100,000 (95% confidence interval [CI] 4.9-5.3), increased annually by 5.8% (95% CI 5.7-6.0) consistently by sex and age, and was more noticeable in urban areas. Five administrative units exceeded the 95% posterior probability of an elevated CLL incidence: these were rural areas spread over the regional territory, not suggestive of spatial clustering. The Poisson regression analysis showed that the risk was elevated in urban areas (RR = 1.11, 95% CI 1.05-1.17), among residents ≥ 30 km from the nearest hospital (RR = 1.09, 95% CI 1.06-1.12), and with the local prevalence of cork harvesting (RR = 1.62, 95% CI 1.12-2.34). Our results suggest that better access to health care facilities and improvements in diagnostic efficacy might have generated the observed upward trend in CLL incidence, along with contributing environmental factors.

COVID-19 and non-Hodgkin's lymphoma: A common susceptibility pattern?

OBJECTIVE: To explore the link between COVID-19 incidence, socio-economic covariates, and NHL incidence. DESIGN: Ecological study design. SETTING: Sardinia, Italy. PARTICIPANTS: We used official reports on the total cases of COVID-19 in 2020, published data on NHL incidence, and socio-economic indicators by administrative unit, covering the whole regional population. MAIN OUTCOMES AND MEASURES: We used multivariable regression analysis to explore the association between the natural logarithm (ln) of the 2020 cumulative incidence of COVID-19 and the ln-transformed NHL incidence in 1974-2003, weighing by population size and adjusting by socioeconomic deprivation and other covariates. RESULTS: The cumulative incidence of COVID-19 increased in relation to past incidence of NHL (p < 0.001), socioeconomic deprivation (p = 0.006), and proportion of elderly residents (p < 0.001) and decreased with urban residency (p = 0.001). Several sensitivity analyses confirmed the finding of an association between COVID-19 and NHL. CONCLUSION: This ecological study found an ecological association between NHL and COVID-19. If further investigation would confirm our findings, shared susceptibility factors should be investigated among the plausible underlying mechanisms.

Incidence of non-Hodgkin's lymphoma among adults in Sardinia, Italy.

The causes of the peculiar time trend in the incidence of non-Hodgkin's lymphoma (NHL) in most parts of the world and of its geographic distribution are still unknown. We used the data base of 1974-2003 incident cases of hematological malignancies to explore the time trend of NHL incidence in the region of Sardinia, Italy, and we used Bayesian methods to plot the probability of NHL incidence by residential unit on the regional map. In 1974-2003, 4109 NHL cases were diagnosed among resident adults in Sardinia, with an incidence rate of 13.38 x 10-5 (95% CI 12.97-13.80). NHL incidence showed an upward trend along the study period with an average annual percent change (APC) of 4.94 (95% CI -5.39-16.4), which did not vary by gender or by age-group. Cancer registry data, covering part of the region starting from 1993, suggest that the increasing trend did not persist in the subsequent years. Areas with the highest probability of an excess incidence tended to cluster in the north-eastern part of the region and in two major urban centers, with the low incidence areas located in the south, confirming previous observations. Prevalence of viral infections, environmental and occupational exposures, or socio-economic deprivation would not explain the peculiar geographic distribution we observed. These findings provide convincing arguments for extending the coverage of routine cancer registration over the whole Sardinian population, while prompting further research on the genetic and environmental determinants of NHL in the risk areas.

Time trend and Bayesian mapping of multiple myeloma incidence in Sardinia, Italy.

A few reports have described increasing trends and spatial distribution of multiple myeloma (MM). We used a validated database including the 1606 cases of MM diagnosed in Sardinia in 1974-2003 to explore its time trend, and we applied Bayesian methods to plot MM probability by administrative unit on the regional map. Over the 30 years of observation, the MM standardized incidence rate (standard world population, all ages) was 2.17 × 10-5 (95% CI 2.01-2.34), 2.29 (95% CI 2.06-2.52) among men, and 2.06 (95% CI 1.83-2.28) among women. MM incidence increased by 3.3%/year in 1974-2003, in both males and females, particularly among the elderly and in the high incidence areas. Areas at risk tended to cluster in the north-eastern part of the region. A higher proportion of elderly in the resident population, but not socioeconomic factors, nor livestock farming, was associated with higher incidence rates. The steep upward time trend and the spatial clustering of MM suggest interactions between genetic and environmental determinants that might be more efficiently investigated in the areas at risk.

Haemolymphatic cancer among children in Sardinia, Italy: 1974-2003 incidence.

OBJECTIVES: To explore the time trend and geographical distribution of childhood leukaemia incidence over the territory of the Italian region of Sardinia. SETTING: All hospitals departments, diagnostic centres and social security agencies in Sardinia were regularly screened in 1974-2003 to identify, register and review the diagnoses of incident cases of haematological malignancies (HM). PARTICIPANTS: The whole child population aged 0-14 resident in Sardinia. PRIMARY AND SECONDARY OUTCOME MEASURES: Incidence and time trend of childhood HM and childhood acute lymphoblastic leukaemia (ALL) over the study period, and use of Bayesian methods to plot the probability of areas with excess incidence on the regional map. RESULTS: Overall, 675 HM cases, including 378 ALL cases, occurred among children aged 0-14 years resident in Sardinia in 1974-2003, with an incidence rate of 6.97×10-5 (95% CI 6.47 to 7.51) and 3.85×10-5 (95% CI 3.48 to 4.26), respectively. Incidence of HM and ALL showed an upward trend along the study period especially among females. Three communes out of the 356 existing in 1974, namely Ittiri, Villa San Pietro and Carbonia, stand out as areas with excess incidence of HM and ALL in particular and another, Carloforte, for ALL only. CONCLUSIONS: Our results might serve as convincing arguments for extending the coverage of routine cancer registration over the whole Sardinian population, while prompting further research on the genetic and environmental determinants in the areas at risk.

Autologous stem cell transplantation after complete remission and first consolidation in acute myeloid leukemia patients aged 61-70 years: results of the prospective EORTC-GIMEMA AML-13 study.

BACKGROUND AND OBJECTIVES: The optimal post-remission treatment for elderly patients with acute myeloid leukemia (AML) is presently unknown. Recent studies have reported the feasibility of autologous peripheral blood stem cell transplantation (PBSCT) in this population. We evaluate the outcome of this post-remission approach after complete remission (CR) and consolidation in elderly patients included in the EORTC-GIMEMA AML-13 trial. DESIGN AND METHODS: PBSCT after induction and consolidation chemotherapy was evaluated in patients aged 61 to 70 years with a WHO performance status 0-1. The induction therapy was mitoxantrone, etoposide and cytarabine (MICE) with or without granulocyte colony-stimulating factor (G-CSF) during and/or after chemotherapy. The consolidation therapy consisted of non-infusion or infusional idarubicin, etposide and cytarabine (mini-ICE). RESULTS: Sixty-one patients were scheduled for stem cell harvest by leukapheresis after s.c. recombinant human G-CSF administration initiated after hematopoietic recovery from consolidation. Stem cells were effectively harvested from 54 patients. A median of two aphereses (range, 1-5) were performed, resulting in a median collection of 11.7 x 10(8) nucleated cells/kg (range, 2.4-99.8) containing 40.2 x 10(4) CFU-GM/kg (range, 0-786.8), and 5 x 10(6) CD34+ cells/kg (range, 0.1-99.8). For the whole group of 61 patients, the median disease-free survival (DFS) was 1.0 years and the 3-year DFS rate was 21%, while the median overall survival (OS) was 1.4 years and the 3-year OS rate was 32%. A total of 26 patients could not be autografed due to inadequate/no harvest (21 patients), early relapse (3 patients), or treatment refusal (2 patients). Autologous transplantation was performed in 35 patients following conditioning with the BAVC regimen. The median time for granulocyte recovery >0.5 109 yen/L was 24 days and for platelets >20 x10(9)/L was 23 days following transplantation. After a median follow-up of 5.0 years from transplantation, the median DFS and OS were 1.1 and 1.6 years respectively, and the 3-year rates were 28% and 39% respectively. Eight autografted patients were still in continuous complete remission, 22 patients had relapsed and five had died in CR. INTERPRETATION AND CONCLUSIONS: Intensification of remission including autologous PBSCT is feasible in about half of harvested patients aged 61 to 70 years old, and did not improve the general outcome. This shows the limitations of autologous PBSCT and other intensive treatment modalities in elderly AML patients. Key words: acute myeloid leukemia, elderly, autologous stem cell transplantation.

Urinary 6-sulfatoxymelatonin excretion in humans during domestic exposure to 50 hertz electromagnetic fields.

OBJECTIVES: Exposure to extremely low frequency electromagnetic fields (ELF-EMF) has been suggested to suppress melatonin secretion, which might result in higher cancer risks because of its missing oncostatic action. We investigated the effects of residential exposure to ELF-EMF on the excretion of urinary 6-sulfatoxymelatonin (6-OHMS), the major melatonin metabolite, as an indicator of nocturnal melatonin secretion. METHODS: 6-OHMS was measured in two spot urine samples, collected at 22.00 h and 08.00 h, in 29 men and 22 women. Spot ELF-EMF measurements were conducted at the centre and the four angles of the living room, the bedroom, and the kitchen of study subjects at low current configuration (all lights and appliances turned off), and they were repeated immediately at high current configuration (all lights and appliances turned on). RESULTS: Risk of a reduced 6-OMHS nocturnal secretion was elevated for daily alcohol intake (OR = 6.4; 95%C.I. 1.4,33.1), and body mass index (BMI) above the median (OR = 2.2; 95%C.I. 0.5,9.6). Risk of disrupted rhythm of 6-OHMS excretion was moderately elevated for domestic ELF-EMF exposure above the upper tertile at low current configuration (OR = 2.6; 95%C.I. 0.4,15.7). CONCLUSION: Alcohol consumption, BMI, and gender seem to affect nocturnal melatonin secretion, while an effect of residential exposure to ELF-EMF is uncertain. Future studies should properly account for the effect of such variables, when addressing the hypothesis of disturbances in melatonin secretion as a plausible explanation for the reported excess risk of several tumoral diseases associated with low level ELF-EMF exposure.

Newly diagnosed cases of hematologic malignancies in Sardinia in the early 2000: an estimation of their number, age and geographic distribution on the basis of a previous epidemiologic survey.

We estimate the number of cases of hematologic malignancies expected to be newly diagnosed in the resident population of Sardinia during the year 2001, and classify the predicted cases according to disease, age and geographic distribution. The implications of these predictions for the Sardinian health care system are discussed, particularly with respect to the development of policies aimed to ensure the most adequate medical care.

Low-dose thalidomide ameliorates cytopenias and splenomegaly in myelofibrosis with myeloid metaplasia: a phase II trial.

PURPOSE: A phase II dose-escalation trial was conducted to ascertain low-dose thalidomide safety and response in patients with advanced myelofibrosis with myeloid metaplasia (MMM). PATIENTS AND METHODS: Thalidomide was administered together with current therapy to 63 patients, starting at 50 mg daily and increasing to 400 mg as tolerated. RESULTS: Half of the patients sustained daily doses more than 100 mg and the drop-out rate was 51% at 6 months: the drop-out rate was lower in patients with high baseline fatigue score. At efficacy analysis, anemia was ameliorated in 22% of the patients and transfusions were eliminated in 39% of transfusion-dependent patients. Platelet count increased by 50 x 10(9)/L or more in 22% of patients with an initial count lower than 100 x 10(9)/L. Splenomegaly decreased by more than 50% of the initial size in 19% of patients. Reduction of an overall disease severity score occurred in 31% of patients and was associated with a significant reduction of fatigue. Disease severity amelioration was independently predicted by a high baseline myeloproliferative index (ie, large splenomegaly, thrombocytosis, or leukocytosis). CONCLUSION: Low-dose thalidomide displays an acceptable toxicity profile and provides an objective and subjective advantage to a relevant portion of MMM patients.