Use of dipyridamole is associated with lower risk of lymphoid neoplasms: a propensity score-matched cohort study.

The anti-cancer potential of dipyridamole has been suggested from experiments, but evidence from population-based studies is still lacking. We aimed to explore if dipyridamole use was related to a lower risk of lymphoid neoplasms. We identified individuals with prescription of aspirin after diagnosis of ischaemic cerebrovascular disease since 2006 by linking several Swedish registers. In these aspirin users, those with dipyridamole prescription were further identified as the study group and patients without dipyridamole were randomly selected as reference group with 1:1 ratio using a propensity score-matching approach. After a median of 6·67 years of follow-up, a total of 46 patients with dipyridamole use developed lymphoid neoplasms with an incidence rate of 0·49 per 1 000 person-years, while the rate in the matched group was 0·74 per 1 000 person-years. As compared to non-users, dipyridamole users were associated with a significantly decreased risk of lymphoid neoplasms [hazard ratio (HR) = 0·65; 95% confidence interval (CI) = 0·43-0·98]. Specifically, the reduced risk was observed for non-Hodgkin lymphomas (HR = 0·64; 95% CI = 0·42-0·94), especially B-cell lymphomas (HR = 0·56; 95% CI = 0·35-0·88). Dipyridamole use was related to a lower risk of lymphoid neoplasms, indicating a clinical potential of dipyridamole to be an adjunct anti-tumour agent against lymphoid neoplasms.

28-year incidence and time trends of childhood leukaemia in former East Germany compared to West Germany after German reunification: A study from the German Childhood Cancer Registry.

BACKGROUND: The aetiology of childhood leukaemia is largely unknown. Analyses of geographical differences may enhance aetiologic insights. The reunification of Germany in 1990 provides a unique opportunity to evaluate incidence patterns and time trends in two merging countries with substantial lifestyle, social and socioeconomic differences. With this study we provide an extensive assessment of 28-year incidence patterns and temporal trends after the German reunification. METHODS: We identified all children diagnosed with a lymphoid leukaemia (LL) or acute myeloid leukaemia (AML) before the age of 15 years between 1991 and 2018 using the German Childhood Cancer Registry (N = 14,922), and evaluated the incidence pattern and temporal trends in former East Germany compared to West Germany by subtype, age at diagnosis and sex. RESULTS: Incidence rates of LL were substantially lower (around 20 %) in Eastern Germany compared to Western Germany at the time of reunification. This was followed by a remarkable increase in Eastern Germany across both sexes and age groups until around 2000, when incidence rates reached the same levels as those in Western German federal states. Thereafter, incidence rates remained rather stable with some indications of a slightly decreasing tendency in both Eastern and Western Germany (estimated annual percentage changes (EAPC) 2005-2018: East Germany = -0.8 %; West Germany = -0.4 %), driven by the 0- to 4-year olds. Overall, AML incidence rates were stable over time in Western Germany, while EAPC for Eastern Germany indicated an increasing tendency (EAPC 1991-2018 = 1.3 %) driven by the older children, mostly during the early 2000s and in most recent years. CONCLUSION: The underlying mechanisms driving the childhood leukaemia rates remain inconclusive. Linkage studies including individual and clinical data would be valuable in evaluating the impact of a population's social, socioeconomic and lifestyle changes on the risk of childhood leukaemia and disease aetiology overall.

Benzene exposure-response and risk of lymphoid neoplasms in Chinese workers: A multicenter case-cohort study.

BACKGROUND: While international agreement supports a causal relationship of benzene exposure with acute myeloid leukemia, there is debate about benzene and lymphoid neoplasm risks. METHODS: In a case-cohort study with follow-up of 110 631 Chinese workers during 1972-1999, we evaluated benzene exposure-response for non-Hodgkin lymphoma (NHL), lymphoid leukemias (LL), acute lymphocytic leukemia (ALL), and total lymphoid neoplasms (LN). We estimated benzene exposures using state-of-the-art hierarchical modeling of occupational factors calibrated with historical routine measurements and evaluated cumulative exposure-response using Cox regression. RESULTS: NHL and other specified LN were increased in exposed vs unexposed workers. However, there was no evidence of exposure-response for NHL or other specified LN. Based on a linear exposure-response, relative risks at 100 parts per million-years (RR at 100 ppm-years) for cumulative benzene exposure using a 2-year lag (exposure at least 2 years before the time at risk) were 1.05 for NHL (95 percent confidence interval (CI) = 0.97, 1.27; 32 cases), 1.11 for LL (95% CI < 0, 1.66; 12 cases), 1.21 for ALL (95% CI < 0, 3.53; 10 cases), and 1.02 for total LN (95% CI < 0, 1.16; 49 cases). No statistically significant exposure-response trends were apparent for these LN for 2 to <10-year or ≥10-year lags. NHL risks were not significantly modified by sex, age, or year at first exposure, attained age, or time since exposure. CONCLUSION: Given the study strengths and limitations, we found little evidence of exposure-response for benzene and NHL, LL, ALL, or total LN, although NHL and other specified LN were increased in exposed vs unexposed individuals.

Changes in long term survival after diagnosis with common hematologic malignancies in the early 21st century.

Five-year survival has increased for many hematologic malignancies in the 21st century. However, whether this has translated into greater long-term survival is unknown. Here, we examine 10- and 20-year survival for patients with multiple myeloma (MM), acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphoid leukemia (CLL), chronic myeloid leukemia (CML), non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL). Data were extracted from the Surveillance, Epidemiology, and End Results-9 database. Patients age 15+ with the above malignancies were included. The newly developed boomerang method was used to examine 10- and 20-year relative survival (RS) for patients in 2002-2006 and 2012-16. Ten and 20-year RS increased for each malignancy examined, with increases ranging from +4.4% units for 20-year RS for AML to +23.1% units for 10-year RS for CML. Ten year RS was >50% in 2012-16 for patients with CLL, CML, HL, NHL, and DLBCL, at 77.1%, 62.1%, 63.9%, 64.5%, and 63.0%, respectively. Survival dropped between 10 and 20 years after diagnosis for most malignancies. Long-term survival is increasing for common hematologic malignancies, but late mortality is an ongoing issue. Further study of long-term outcomes in curable malignancies to determine the reason for these later decreases in survival is indicated.

Increased risk of lymphoid malignancy in patients with herpes zoster: a longitudinal follow-up study using a national cohort.

BACKGROUND: The association between herpes zoster and the risk of lymphoid neoplasms in Asian populations has not yet been established. We performed a longitudinal follow-up study using a nationwide cohort to assess the risk of lymphoid neoplasms arising after herpes zoster infection in the adult Korean population. METHODS: Data from participants ≥20 years of age who were registered in the Korean National Health Insurance Service-National Sample Cohort database between 2002 and 2013 were collected. We extracted the data of participants with herpes zoster (n = 59,495) as well as those of matched references at a ratio of 1:4 (n = 237,980) and investigated the subsequent occurrence of lymphoid neoplasms. A stratified Cox proportional hazards model was used to calculate unadjusted hazard ratios (HRs) as well as those adjusted for the Charlson comorbidity index score. RESULTS: The rate of lymphoid neoplasms was higher in the herpes zoster group (0.15% [90/59,495]) than in the reference group (0.08% [212/237,980], P < 0.001). The unadjusted and adjusted HRs of herpes zoster in patients with lymphoid neoplasms were 1.68 (95% confidence interval [CI] = 1.31-2.15) and 1.58 (95% CI = 1.23-2.02), respectively (P < 0.001 for both). On subgroup analyses according to age and sex, herpes zoster was associated with an increased risk of lymphoid neoplasms in all subgroups; the adjusted HRs were 1.53 (95% CI = 1.05-2.24) for patients < 60 years old, 1.58 (95% CI = 1.14-2.20) for patients ≥60 years old, 1.64 (95% CI = 1.16-2.31) for men, and 1.51 (95% CI = 1.06-2.16) for women (P < 0.05 for all). On subgroup analysis of lymphoid neoplasm subtypes, herpes zoster was associated with the risk of Hodgkin's disease (adjusted HR: 3.23 [95% CI = 1.17-8.93]) and multiple myeloma/malignant plasma cell neoplasms (adjusted HR: 2.17 [95% CI = 1.33-3.54]) (P < 0.05 for both). CONCLUSION: Herpes zoster is associated with lymphoid neoplasm development in the Korean population irrespective of age and sex. The risks of Hodgkin's disease and plasma cell neoplasms are significantly elevated in patients with herpes zoster.

Female reproductive factors and risk of lymphoid neoplasm: The Japan Public Health Center-based Prospective Study.

Although a possible role of reproductive factors in lymphomagenesis has been hypothesized, results of epidemiological studies have been inconsistent. Here, we investigated the association between reproductive factors and the risk of lymphoid neoplasm and its subgroups. We used data from a large-scale, population-based prospective study in a Japanese cohort with 42 691 eligible women aged 40-69 years from 1990 to 1994. During a mean follow up of 18.7 years, we identified 176 cases of lymphoid neoplasm and 90 of non-Hodgkin lymphoma (NHL). A multivariable-adjusted Cox proportional hazards regression model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the risk of lymphoid neoplasms and its subgroups according to self-reported reproductive factors. Parous women had an increased risk of lymphoid neoplasm compared with nulliparous women (HR = 2.51, 95% CI, 1.03-6.13). An increased risk of lymphoid neoplasms was found in women with later onset of menarche (≤13 years old; reference: 14-15; HR = 1.75, 95% CI = 1.10-2.79: ≥16; HR = 1.93, 95% CI = 1.17-3.19: P-trend: 0.01) and a shorter menstrual cycle (28-29 days; reference: ≤27; HR = 1.60, 95% CI = 1.05-2.43, P-trend = 0.81). No association was observed between lymphoid neoplasms and other reproductive factors, including age at first birth, breastfeeding, type of menopause, or exogenous hormone use. Our study suggests that ever parity, late age at menarche and a short menstrual cycle length may be associated with the development of lymphoid neoplasms. The inconsistency seen in epidemiological research to date warrants further investigation.

Gestational age and childhood leukemia: A meta-analysis of epidemiologic studies.

OBJECTIVE: An increasing amount of evidence shows that childhood leukemia is initiated in utero. Birth characteristics initiated in utero, such as gestational age, may play a role in leukemogenesis. The purpose of our meta-analysis is to explore the association between gestational age and childhood leukemia. METHODS: Relevant studies up to 21 April 2017 were collected by searching PubMed and EMBASE databases. Subgroup analysis, sensitivity analysis and publication bias assessment were conducted. RESULTS: A total of 13 studies were included. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for preterm birth and postterm birth were 1.06 (0.98, 1.13) and 1.01 (0.90, 1.13) for childhood leukemia, 1.04 (0.97, 1.11) and 1.03 (0.95, 1.12) for acute lymphocytic leukemia (ALL), 1.20 (1.00, 1.44) and 1.20 (1.00, 1.43) for acute myeloid leukemia (AML), compared with full-term birth. Study type and study region were the reasons behind the heterogeneity. In subgroup analyses, the summary ORs with 95% CI for childhood leukemia and ALL were 1.23 (1.07, 1.41) and 1.21 (1.06, 1.39) for postterm birth in cohort studies. No significant changes in sensitivity analyses and no publication bias were observed in our analysis. CONCLUSION: Our results suggest that both preterm and postterm infants have an elevated risk of developing AML. In addition, postterm birth increased the risk of childhood leukemia and ALL in cohort studies. However, more studies are warranted to validate these results and explore the biologic mechanisms underlying these relationships.

The incidence of hematological neoplasms morbidity on radiation-contaminated territories in Cherkasy region. / ZAKhVORIuVANIST' NA GEMATOLOGIChNI NOVOUTVORENNIa V RADIATsIY̆NO ZABRUDNENYKh REGIONAKh ChERKAS'KOÏ OBLASTI.

OBJECTIVE: The main goal was to analyze the incidence of the morbidity in 1980, 1989, 2001, 2014 years and the structures of the absolute number of hematopoietic and lymphoid neoplasms cases during the period 1980-2014 on radiation contaminated and not contaminated territories in Cherkasy region. MATERIALS AND METHODS: The epidemiological indecies of hematological neoplasms were analyzed on radiation con taminated and not contaminated territories in Cherkasy region during the period from 1980 to 2014. Referring the territory in Cherkasy region to radiation contaminated is based on settlements dosimetry certification of Ukraine after the Chornobyl accident. 63 settlements were enrolled to radiation contaminated areas in Cherkasy region and 11 settlements assigned as not contaminated areas. RESULTS: The first positions in the list of the hematological neoplasms structure and frequency among new cases during 1980-2014 on not contaminated territories in Cherkasy region occupied by lymphoid leukemia, Hodgkin's lymphoma and myeloid leukemia and on the radiation contaminated territories - chronic, acute lymphoid and myeloid leukemia and lymphoma, diffuse large cell lymphoma. In the structure of hematological neoplasms record ed on the contaminated territories in Cherkasy region, there is a smaller proportion of Hodgkin's lymphoma cases (C81) than 0.84 fold (RR = 0.84; 95 % CI = 0.75-0.93) and more than 1.15 times (RR = 1.15; 95 % CI = 1.02-1.30) other unspecified malignant lymphoid and hematopoietic neoplasms. In 2001 on the radiation contaminated terri tories in Cherkasy region increase the incidence of acute and chronic myeloid leukemia in 2.46 times (p = 0.024) observed compared to non contaminated areas there (5.30 per 100 000, 95% CI = 3.03-8.33 versus 2.15 per 100,000, 95 % CI = 0.66-3.64). It was calculated that RR of acute and chronic myeloid leukemia (C92) in 2001 on radiation contaminated areas in Cherkasy region is 1.40 (95 % CI = 1.12-1.17) and Hodgkin's lymphoma (C81) on condition ally clean areas Cherkasy region - 1.70 (95 % CI = 1.36-2.12).

Aspectos generales de algunas entidades dentro de los síndromes linfoproliferativos crónicos: La leucemia linfoide crónica / General aspects of some entities within chronic lymphoproliferative syndromes: chronic lymphocytic leukemia

La leucemia linfoide crónica es el tipo de leucemia más común en los países occidentales, afecta con mayor frecuencia al sexo masculino, con una edad promedio al diagnóstico de 65 años. La variedad más frecuente es la de estirpe B; comprenden un grupo de neoplasias biológicamente diferentes, caracterizadas por una proliferación y acúmulo de linfocitos pequeños de apariencia madura en sangre periférica, médula ósea y tejidos linfoides. Es el prototipo de enfermedad maligna que involucra a defectos de la muerte celular programada o apoptosis. Esta enfermedad puede presentar variaciones en sus características inmunofenotípicas, clínicas, citogenéticas y moleculares. Aproximadamente, el 80 por ciento de los pacientes con leucemia linfoide crónica B presentan anormalidades cromosómicas, principalmente: deleciones de los cromosomas 11,13, 6,14 y 17, estas tres últimas de mal pronóstico. Pueden presentar además, disfunciones inmunes responsables de inmunodeficiencia y autoinmunidad. Se desconoce la causa de esta enfermedad aunque los informes iniciales sugieren la implicación de los genes Bcl-1 y Bcl-2, es por eso que la terapia actual está dirigida a la inhibición de Bcl-2 por ser el responsable en la regulación de la apoptosis(AU)

Chronic lymphoid leukemia is the most common type of leukemia in Western countries, which most often affects males and the average age at diagnosis is 65 years. The most common form is the B-cell and is described in this article. LLC comprise a biologically distinct group of neoplasms characterized by proliferation and accumulation of small mature lymphocytes appearance in peripheral blood, bone marrow and tissues linfoides. Is the prototype of malignant disease involving defects programmed cell death or apoptosis. This disease may present variations in their immunophenotypic, clinical, cytogenetic and molecular characteristics. Approximately 80 percent of patients with B-CLL have chromosomal abnormalities, mainly: deletions of chromosomes 11, 13, 6, 14 and 17. These last three are bad prognosis. The patients with CLL may have also immune dysfunctions responsible for immunodeficiency and autoimmunity. It is unknown the cause of CLL although initial reports suggest the involvement of Bcl-1 and Bcl-2 gene is why the current therapy is directed to inhibition of Bcl-2 as this is responsible in regulating apoptosis(AU)

Time and spatial trends in lymphoid leukemia and lymphoma incidence and survival among children and adolescents in Manitoba, Canada: 1984-2013.

OBJECTIVES: To test for time and spatial trends in lymphoid malignancies, including lymphoid leukemia (LL), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL), in children and adolescents in the province of Manitoba, Canada. METHODS: Incident cases diagnosed between 1984 and 2013 were identified from the Manitoba Cancer Registry. We assessed time trends in age-standardized incidence rates using joinpoint regression and in 5-year relative survival using Poisson regression model. Kulldorff's scan method was used to assess spatial variation and clustering. RESULTS: Age-standardized incidence rates (per million person-years) in males and females were 34.0 (95% confidence interval [CI] 28.9-39.1) and 26.2 (95% CI 21.5-30.7) for LL, 10.5 (95% CI 7.7-13.3) and 12.5 (95% CI 9.4-15.7) for HL, 12.5 (95% CI 9.3-15.4) and 7.7 (95% CI 5.2-10.2) for NHL (except for Burkitt lymphomas), and 3.2 (95% CI 1.6-4.7) and 1.5 (95% CI 0.4-2.5) for Burkitt lymphomas. Age- and sex- standardized LL incidence rate increased 1.4% (95% CI 0.3%-2.5%) per year, while the changes for HL and NHL incidence rates were not statistically significant. There were geographic differences in age-standardized incidence rates for LL, HL, and NHL and spatial clusters were detected in southern part of the province. Five-year relative survival has improved over time and there was no difference between rural and urban areas. CONCLUSIONS: Lymphoid leukemia incidence rate increased over time and varied by geographic area. Further research should examine the factors contributing to these trends.

Nonrandom occurrence of lymphoid cancer types in 140 families.

We studied 140 families with two or more lymphoid cancers, including non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), chronic lymphocytic leukemia (CLL), and multiple myeloma (MM), for deviation from the population age of onset and lymphoid cancer co-occurrence patterns. Median familial NHL, HL, CLL and MM ages of onset are substantially earlier than comparable population data. NHL, HL and CLL (but not MM) also show earlier age of onset in later generations, known as anticipation. The co-occurrence of lymphoid cancers is significantly different from that expected based on population frequencies (p < .0001), and the pattern differs more in families with more affected members (p < .0001), suggesting specific lymphoid cancer combinations have a shared genetic basis. These families provide evidence for inherited factors that increase the risk of multiple lymphoid cancers. This study was approved by the BC Cancer Agency - University of British Columbia Clinical Research Ethics Board.

Incidence and survival time trends for Spanish children and adolescents with leukaemia from 1983 to 2007

Objective. We have analysed incidence and survival trends of children and adolescents with leukaemia registered in Spanish population-based cancer registries during the period 1983-2007. Methods. Childhood and adolescent leukaemia cases were drawn from the 11 Spanish population-based cancer registries. For survival, registries with data for the period 1991-2005 and follow-up until 31-12-2010 were included. Overall incidence trends were evaluated using joinpoint analysis. Observed survival rates were estimated using Kaplan-Meier, and trends were tested using the log-rank test. Results. Based on 2606 cases (2274 children and 332 adolescents), the overall age-adjusted incidence rate (ASRw) of leukaemia was 47.9 cases per million child-years in children and 23.8 in adolescents. The ASRw of leukaemia increased with an annual percentage change of 9.6 % (95 % CI: 2.2-17.6) until 1990 followed by a stabilisation of rates. In adolescents, incidence did not increase. Five-year survival increased from 66 % in 1991-1995 to 76 % in 2001-2005. By age, survival was dramatically lower in infants (0) and adolescents (15−19) than in the other age groups and no improvement was observed. In both children and adolescents, differences in 5-year survival rates among major subgroups of leukaemias were significant. Conclusions. The increasing incidence trends observed in childhood leukaemias during the study period were confined to the beginning of the period. Remarkable improvements in survival have been observed in Spanish children with leukaemias. However, this improvement was not observed in infants and adolescents (AU)

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Pneumonia diagnosis in childhood and incidence of leukaemia, lymphoma and brain cancer: a Danish nationwide cohort study.

OBJECTIVES: There is an ongoing debate on the possible association between infections in early childhood and subsequent cancer risk, but it remains unclear if a hospital admission for infection is associated with risk of childhood cancer diagnosis. We examined if a hospital-based diagnosis of pneumonia was a clinical marker of the three most common childhood cancers. DESIGN: Population-based cohort study. SETTING: Denmark, hospital diagnoses, 1994-2013. METHODS: Using national health registries, we compared the observed incidence of leukaemia, lymphoma and brain cancer among 83 935 children with a hospital-based pneumonia diagnosis with that expected among children in the general population. We calculated absolute cancer risks and standardised incidence ratios (SIRs) as a measure of relative risk. RESULTS: The cancer SIRs were substantially increased during the first 6 months of follow-up; lymphoid leukaemia: 6.2 (95% CI 3.5 to 10.3); myeloid leukaemia: 14.8 (95% CI 6.0 to 30.6); Hodgkin's lymphoma: 60.8 (95% CI 26.2 to 120), non-Hodgkin's lymphoma: 15.9 (95% CI 5.2 to 37.2) and brain cancer: 4.4 (95% CI 1.9 to 8.7). The 6-month absolute risks of leukaemia, lymphoma and brain cancer were all low, reaching 0.05% when combined. An increased risk persisted beyond 5 years for non-Hodgkin's lymphoma and brain cancer. However, the 5-year absolute cancer risk was 0.14%. CONCLUSIONS: The short-term incidence of leukaemia, lymphoma and brain cancer was higher than expected and persisted beyond 5 years for non-Hodgkin's lymphoma and brain cancer. However, the absolute cancer risk was low.

[Leukemia cutis: clinical features of 27 mexican patients and a review of the literature]. / Leucemia cutis (LC): características clínicas de 27 pacientes mexicanos y una breve revisión de la literatura.

BACKGROUND: Leukemia Cutis (LC) consists in neoplastic leukocytic infiltration of the skin and is strongly associated with the presence of extramedullary disease and poor prognosis. However, there are few studies in the literature regarding this entity. We perform a retrospective study of 27 mexican patients in order to analyze the clinical features and prognosis of LC in Mexico, and a brief review of the literature. METHODS: Cases diagnosed as LC by skin biopsy were selected from the database of the Department of Dermatology of National Institute of Medical Science and Nutrition Salvador Zubirán. Cases were searched between the dates of January 1993 and December 2013. RESULTS: Twenty-seven cases which were histologically confirmed with cutaneous leukemic infiltrate were included. Of these patients 60% were male and the mean age at diagnosis was 42 yr (19 to 80 yr). The predominant tipe of LC was acute myeloid leukemia (AML) with 48% of the cases. Nodular neoformations were the main clinical manifestation with 63% of the cases. The mean interval between the diagnosis of LC and death was 10 months (CI 95%). CONCLUSIONS: The presence of LC is a marker of poor prognosis and can precede the relapse of systemic leukemia. Cutaneous infiltration may be the first or the only sign of progression, so doctors should be familiar with the clinical manifestations of this disease.

Occupational exposure to polycyclic aromatic hydrocarbons and lymphatic and hematopoietic neoplasms: a systematic review and meta-analysis of cohort studies.

Data on the risk of lymphatic and hematopoietic neoplasms among workers whose jobs entail high exposure to polycyclic aromatic hydrocarbons (PAH) are sparse, and mainly based on small-size studies. We carried out a systematic review of occupational cohort studies that reported results on incidence or mortality from Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), leukemia or multiple myeloma (MM) among workers exposed to PAH. We computed meta-analytic estimates using a random effect model. Meta-relative risk (meta-RR) was computed separately by each type of neoplasm, job or industry. We identified 41 studies (12 in iron and steel foundries, 11 in aluminum plant, 6 in cokeries, 6 in carbon electrode manufacturing, 2 on asphalt workers, 2 on creosote-exposed workers, 1 on tar distillery workers and 1 evaluating both tar distillery workers and roofers). No significant excess risk of any lymphatic and hematopoietic neoplasms was found among workers employed in jobs or industries entailing high PAH exposure. Among 18 meta-analytic estimates by job or industry and type of neoplasm, 16 were close to unit, i.e., between 0.72 and 1.27, whereas the meta-RR was 1.38 [95 % confidence interval (CI) 0.95-2.01] for HL in foundry workers and 2.01 (95 % CI 0.96-4.22) for NHL in workers exposed to creosote. There was no association between occupation entailing high PAH exposure and risk of MM or leukemia.

Moderate-dose cyclophosphamide in the treatment of relapsed/refractory T-cell large granular lymphocytic leukemia-associated pure red cell aplasia.

BACKGROUND: T-cell large granular lymphocyte leukemia (T-LGLL) is a rare disorder characterized by clonal proliferation of large granular lymphocytes (commonly CD3+/CD8+/CD57+). However, the available data regarding the optimal treatment for relapsed/refractory T-LGLL patients are limited. METHODS: We retrospectively reviewed 10 patients treated with immunosuppressive therapy consisting of intravenous moderate-dose cyclophosphamide (MD-CTX) together with oral cyclosporine A for relapsed/refractory T-LGLL in our hospital between July 2006 and March 2013. RESULTS: The overall response rate to MD-CTX was 60% (6/10; hematologic complete remission rate, 50%; hematologic partial remission rate, 10%). The median time to response was 28.5 days (range, 20-118 days). The relapse rate of MD-CTX was 50% (3/6); two of these three patients achieved hematologic complete remission after receiving a second course of MD-CTX. Neutropenia was the major adverse event of the MD-CTX regimen. The median time to neutropenia was 5.5 days (range, 1-10 days) and the median neutropenia duration was 5 days (range, 3-15 days). None of the patients developed severe infection. CONCLUSIONS: The MD-CTX regimen appears efficacious and safe in the treatment of relapsed/refractory T-LGLL patients.

Increased incidence of bladder cancer, lymphoid leukaemia, and myeloma in a cohort of Queensland melanoma families.

Familial cancer risk has been proposed as a shared feature of many cancers, and overall susceptibility is influenced by combinations of low to moderate risk polymorphisms, rare high penetrance germline mutations, and modulation of risk by environmental and genetic factors. Clustering of melanoma occurs in approximately 10 % of families, and an over-representation of additional cancers has been noticed in some 'melanoma' families. The degree to which other cancers aggregate in families affected by melanoma has not been well defined. Therefore, this study aimed to assess the risk of cancers other than melanoma in a cohort of 178 'intermediate risk' melanoma families, not selected for specific genetic mutations. Families designated as 'intermediate risk' had two first degree relatives (FDRs) affected by melanoma when ascertained between 1982 and 1990, and were followed up over a 33 year period to assess new occurrences of cancer. We included 414 melanoma cases and 529 FDRs, comprising 25,264 person years of observation. Standardised incidence ratios and their 95 % confidence intervals were calculated for all invasive cancers, comparing observed to expected cases of cancer based on age and sex specific incidence rates for the Queensland population. Statistically significant increases were found for bladder cancer in females (observed, 7; expected, 1.99; SIR, 3.52; 95 % CI 1.41-7.25), lymphoid leukaemia in females (observed, 6; expected, 1.75; SIR, 3.43; 95 % CI 1.26-7.46), and myeloma in female melanoma cases (observed, 4; expected, 0.82; SIR, 4.89; 95 % CI 1.33-12.52). Over-representation of bladder cancer, lymphoid leukaemia, and myeloma in females of the cohort may suggest sex-dependent co-modifiers, and it is possible that specific combinations of polymorphisms predispose to certain cancer types.

Body size in early life and risk of lymphoid malignancies and histological subtypes in adulthood.

Risk of adult lymphoid malignancy is associated with recent adiposity. Some have reported apparent associations with adiposity in childhood or early adulthood, but whether these associations are independent of recent adiposity is unknown. Birth weight, body size at age 10 years, clothes size at age 20 years, and recent body mass index (BMI) were recorded in 745,273 UK women, mean age 60.1 (SD 4.9) at baseline, without prior cancer. They were followed for 11 years, during which time 5,765 lymphoid malignancies occurred. Using Cox regression, a higher risk of lymphoid malignancy was strongly associated with higher recent BMI (RR=1.33, 95%CI 1.17-1.51, for BMI 35+ vs <22.5 kg/m(2)), and this association remained essentially unchanged after adjustment for birth weight and body size at 10. Higher lymphoid malignancy risk was also associated with large size at birth, at age 10, and at age 20 years, but after adjustment for recent BMI, the significance of the associations with large size at birth and at age 10 years was sufficiently reduced that residual confounding by adult BMI could not be excluded; a weak association with large size at 20 years remained (adjusted RR =1.17, 95%CI 1.10-1.24 for large size at age 20 vs. medium or small size). We found no strong evidence of histological specificity in any of these associations. In conclusion, our findings suggest a possible role of adiposity throughout adulthood in the risk of lymphoid malignancy, but the independent contribution of body size at birth and during childhood appears to be small.

Clinical course and therapeutic implications for lymphoid malignancies in Nijmegen breakage syndrome.

Nijmegen breakage syndrome (NBS, MIM #251260) is an autosomal recessive chromosomal instability disorder. Majority of patients affected are of Slavic origin and share the same founder mutation of 657del5 within the NBN gene encoding protein involved in DNA double-strand breaks repair. Clinically, this is characterized by a microcephaly, immunodeficiency and a high incidence of pediatric malignancies, mostly lymphomas and leukemias. Anticancer treatment among patients with NBS is challenging because of a high risk of life threatening therapy-related toxicity including severe infections, bone marrow failure, cardio- and nephrotoxicity and occurrence of secondary cancer. Based on systemic review of available literature and the Polish acute lymphoblastic leukemia database we concluded that among patients with NBS, these who suffered from clinically proven severe immunodeficiency are at risk of the complications associated with oncological treatment. Thus, in this group it reasonable to reduce chemotherapy up to 50% especially concerning anthracyclines methotrexate, alkylating agents and epipodophyllotoxines, bleomycin and radiotherapy should be omitted. Moreover, infection prophylaxis using intravenous immunoglobulin supplementation together with antifungal and antibacterial agent is recommended. To replace radiotherapy or some toxic anticancer agents targeted therapy using monoclonal antibodies and kinase inhibitors or bone marrow transplantation with reduced-intensity conditioning should be considered in some cases, however, this statement needs further studies.