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We have collected, by an active retrospective survey, all the cases of hematologic malignancies (HM) newly diagnosed during the time period 1974-1993 in the resident population of Sardinia. Diagnosis was deemed valid, after consultation of clinical records, in more than 90% of the 7264 collected cases. The number of newly diagnosed cases by year more than doubled during the 20-year period investigated. This striking increase can be only partially accounted for by ageing of population. Indeed, age-specific and age-adjusted rates of most of HM increased during this period, although Hodgkin Disease (HD), Chronic Myeloid Leukemia (CML) and Acute Lymphoblastic Leukemia (ALL) were notable exceptions. The observed increase in rates is likely, in a large part, to be fictitious, due to easier access to a health care system, which in the meantime, improved its diagnostic efficiency. This was particularly evident for Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM) and some others myelo- and lympho-proliferative disorders, but its relevance declined after 1984-1989. A likely true increase in occurrence was evidenced for Non-Hodgkin Lymphomas (NHL) and similarly, although to a lesser extent and more doubtful, for Myelodysplasias (MDS) and Acute Myeloid Leukemia (AML). At the end of the studied period each type of HM presented age and sex distributions and age-adjusted rates that show only minor differences from those reported for other western countries. No argument emerged to suggest that any genetic peculiarities of the Sardinian population might have affected the occurrence of HM. The confounding effects of improved diagnostic efficiency have prevented a reliable assessment of influence on incidences of environmental and socio-economic changes that, in relatively recent times, have occurred in Sardinia. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In all, 134 elderly patients (median age 66 years, range 60-75 years) with newly diagnosed acute promyelocytic leukemia (APL) were enrolled in two successive protocols of the Italian multicenter group GIMEMA. All patients received an identical induction with all-trans retinoic acid and idarubicin; 116 (86%) entered complete remission (CR), two (2%) were resistant and 16 (12%) died during induction. After CR, 106 patients received further therapy whereas 10 did not, because of refusal (n = 5) or toxicity (n = 5). Consolidation consisted of three chemotherapy courses in the AIDA protocol (AIDA, 67 patients) or, since 1997, of an amended protocol including only the first cycle (amended AIDA, aAIDA, 39 patients). In the AIDA group, 43 patients (64%) completed consolidation, while seven (11%) and 17 (25%) patients were withdrawn after first and second courses, respectively; nine patients (13%) died in CR and 12 (18%) relapsed. In the aAIDA group, all patients received the assigned treatment; two patients (5%) died in CR and six (15%) relapsed. In the AIDA and aAIDA series, the 3-year overall and discase-free survival rates were 81 and 83% (P = NS), 73 and 72% (P = NS), respectively. We highlight here the frequency and severity of complications linked to intensive chemotherapy in this clinical setting and suggest that, in APL of the elderly, less intensive postremission therapy allows significant reduction of severe treatment-related toxicity and may be equally effective. [ABSTRACT FROM AUTHOR]

Looks at the definition of acquired severe aplastic anemia. Effect of disease on blood cell production; Use of bone marrow transplant in early treatment.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Conflict of Interest Disclosure The authors do not have any conflicts of interest to declare about this work., (Copyright © 2023 ISEH -- Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (© 2022. The Author(s).)

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., Competing Interests: The authors have declared that no competing interests exist.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.

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.

Background and Objectives: The reasons for the worldwide increase in non-Hodgkin's lymphoma (NHL) are not clearly understood. We investigated whether an increasing trend over time has also occurred in the Italian region of Sardinia, the population of which exhibits peculiar genetic features, due to millenary isolation and pressure from 2,500 years of malarial endemism. We also investigated the geographic variation in NHL risk within the region., Design and Methods: We designed a descriptive epidemiology study of NHL among the Sardinian population by following up the incidence of this disease in the period 1974-1993. We calculated the standardized incidence rate (SIR) of NHL by year for the total population and by gender. The time trend of Hodgkin's disease (HD) was also evaluated as a comparison term and for validation purposes. We also mapped NHL risk in the 361 administrative units (communes) of the region., Results: NHL incidence in the Sardinian population over the whole study period was 7.5 x 10(-5) year(-1) (men: 8.2; women: 6.7), and increased from 4.1 in 1974 to 9.1 in 1993. The increasing trend was consistent by gender, and mostly affected subjects aged 55 years or older. Nodal and extra-nodal forms of NHL shared the same pattern of increasing incidence. Excluding the few NHL cases related to AIDS did not change the results. No such pattern was observed for HD incidence. The NHL incidence rate (age > or = 25 years) ranged from 0.0-60.0 x 10(-5) year-1 across communes. Areas at risk were located mainly in the northern part of the region, but risk among men was also elevated in the major urban area in southern Sardinia., Interpretation and Conclusions: Our study shows that NHL incidence increased 2.2-fold in Sardinia from 1974 to 1993, a finding which is consistent with other world-wide report. The risk has risen in a few areas, mainly in central and northern Sardinia and in the major urban areas. Analytic studies are under way to investigate a broad range of risk factors, including viral, occupational, and environmental factors, that might account for our results.

Two hundred fifty-three patients with newly diagnosed acute promyelocytic leukemia (APL) were eligible to enter the multicentric GIMEMA-AIEOP "AIDA" trial during the period July 1993 to February 1996. As a mandatory prerequisite for eligibility, all patients had genetic evidence of the specific t(15;17) lesion in their leukemic cells confirmed by karyotyping or by reverse transcription-polymerase chain reaction (RT-PCR) of the PML/RAR alpha fusion gene (the latter available in 247 cases). Median age was 37.8 years (range, 2.2 to 73.9). Induction treatment consisted of oral all-trans retinoic acid (ATRA), 45 mg/m2/d until complete remission (CR), given with intravenous Idarubicin, 12 mg/m2/d on days 2, 4, 6, and 8. Three polychemotherapy cycles were given as consolidation. Hematologic and molecular response by RT-PCR was assessed after induction and after consolidation. At the time of analysis, 240 of the 253 eligible patients were evaluable for induction. Of these, 11 (5%) died of early complications and 229 (95%) achieved hematologic remission. No cases of resistant leukemia were observed. Of 139 cases studied by RT-PCR after induction, 84 (60.5%) were PCR-negative and 55 (39.5%) PCR-positive. One hundred sixty-two patients were evaluable by RT-PCR at the end of consolidation. Of these, 159 (98%) tested PCR-negative and 3 (2%), PCR-positive. After a median follow up of 12 months (range, 0 to 33), the estimated actuarial event-free survival for the whole series of 253 eligible patients was 83% +/- 2.6% and 79% +/- 3.2% at 1 and 2 years, respectively. This study indicates that the AIDA protocol is a well-tolerated regimen that induces molecular remission in almost all patients with PML/RAR alpha-positive APL. Preliminary survival data suggest that a remarkable cure rate can be obtained with this treatment.

We report the case of a young female patient, a Jehovah's witness, affected by peroxidase-positive acute leukemia. The patient, completely aware of the risks both of the disease and of the usual treatment for acute myeloid leukemia, refused any transfusional support. An atypical treatment plan with low hematological toxicity but also with reduced probability of positive results was therefore proposed and accepted. Initial treatment with vincristine and prednisone induced remission; therapy was then continued for 32 months with monthly cycles of aracytin and 6-thioguanine, at accurately tailored dosages to avoid excessive hematological toxicity. The patient never needed blood support and never suffered infectious or hemorrhagic events. She is still in remission, 11 years off-therapy. The ethical and legal aspects of treatment decisions in such situations are discussed. In the author's opinion, neither withholding all treatment nor insisting on standard measures is correct: on the contrary, as always, treatment in such cases must be tailored on the patient's needs, which include not only his physical condition but his religious beliefs as well.

CML was diagnosed by chance in a 24-year-old woman at the 15th week of pregnancy which, on being informed of her disease she decided to continue. No treatment was given until the 24th week, when WBC reached 140,000/mm3 and it was believed necessary to begin treatment. A program of leukapheresis was started, with the sole aim of reducing the expanding leukemic pool. With 8 leukapheresis, performed at intervals of 2-8 days, WBC were reduced and kept at about 100,000/mm3; after the 8th procedure there was a progressive reduction of WBC to 40,000/mm3, which level was maintained without further treatment for about 4 weeks. Pregnancy and fetal development continued normally. Labor was induced at the 37th week of gestation, and a normal male infant was delivered whose development to date (20 months of age) is normal.

We have evaluated the hypothesis of a negative association between glucose 6-phosphate dehydrogenase (G6PD) deficiency and cancer in a cohort of 481 Sardinian males with hematological malignancies. The frequency of G6PD deficiency in the patients was not different from the incidence in a group of 16,219 controls. The same conclusion resulted from the comparison of the frequency of expression of the GdB gene in 23 heterozygous women having a clonal hematologic disease and a control group of 37 healthy heterozygotes. Therefore at present there is no evidence that G6PD deficiency has a protective effect against development of hematologic neoplasms.

The results obtained with oestrogen treatment of diffuse malignant cancer of the breast are reported. Improvement was obtained in 50% of cases, 23.3% remained stationary and 26.6% worsened. Side effects were confined essentially to liver trouble of colostatic type, a disturbance that was temporary and closely linked with the drug dose employed. Some aspects of high dose antitumour hormone treatment are examined in detail: hormone dose in the induction phase and during maintenance, latency time before the appearance of the first signs of improvement, relationship between age, sexual endocrinal state and therapeutic result, correlation between time of onset of the disease, free interval and result obtained.

For the first time the presence of a consistent number of malignant lymphomas among persons at high risk for AIDS has been documented in Italy. The majority of our cases started to occur in 1983, in line with the trend for a 2-year delay in the spread of the epidemic of AIDS in Europe. The patients with non-Hodgkin's lymphomas had an increased incidence of high grade subtypes, particularly of the Burkitt type, and were in an advanced stage with frequent extranodal involvement. Patients with Hodgkin's disease had a lower incidence of extranodal localization in comparison with the North American series. American patients with malignant lymphomas were reported to be predominantly homosexual; in contrast, the Italian cases were mostly drug addicts. The occurrence of malignant lymphomas was also correlated in Italian patients as well as in American patients with a shorter survival time, when compared with malignant lymphomas occurring in the same age group of the general population.

2-alpha-methyl-17-beta hydroxy-androstan-3-one was given to advanced breast cancer patients whose general condition (preterminal in many cases) or haematological picture precluded other cytostatic management. Rapid progression of the tumour was noted in 65%, improvement in 15% and no change in 20%. It is felt that androgens alone should only be given where other more effective treatments are contraindicated. They can be associated with polychemotherapeutic courses to exploit their anabolising and antianaemic activity.

Philadelphia (Ph) chromosome-positive chronic myelogenous leukaemia (CML) was studied in a subject heterozygous for the X chromosome-linked alloenzyme system of glucose-6-phosphate dehydrogenase (G6PD). Determination of G6PD mosaicism showed homogeneous expression in granulocytes, erythrocytes and platelets. Cytogenetic studies showed the typical Ph translocation in all metaphases from bone marrow and peripheral blood myeloid cells, bcr rearrangement was detected in bone marrow and in granulocytes. B cells were stimulated with Epstein-Barr virus (EBV) in order to evaluate involvement of lymphocytes, EBV-transformed lymphoblastoid cells expressed a single G6PD phenotype and therefore probably derived from the leukaemic stem cell. However they had a normal karyotype and a constitutional bcr restriction pattern. Molecular analysis in this case of CML clarifies the differentiative potential of cells belonging to the leukaemic clone, by demonstrating that clonal Ph-negative B cells maintain normal differentiative capacity and have a bcr gene sequence which is not rearranged.

Three patients with acute lymphoblastic leukemia (ALL) and heterozygous for the Mediterranean variant of glucose-6-phosphate dehydrogenase (G6PD) have been investigated with the 2-deoxyglucose-6-phosphate (2dG6P) method to determine the number and type of progenitor cells in which the disease arose. A monoclonal origin was established for the lymphoblasts, while the other hemopoietic cell lines were not involved in the leukemic process.