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Background: Current hemovigilance methods generally rely on survey data or administrative claims data utilizing billing and revenue codes, each of which has limitations. We used electronic health records (EHR) linked to blood bank data to comprehensively characterize red blood cell (RBC) utilization patterns and trends in three healthcare systems participating in the U.S. Food and Drug Administration Center for Biologics Evaluation and Research Biologics Effectiveness and Safety (BEST) initiative. Methods: We used Information Standard for Blood and Transplant (ISBT) 128 codes linked to EHR from three healthcare systems data sources to identify and quantify RBC‐transfused individuals, RBC transfusion episodes, transfused RBC units, and processing methods per year during 2012–2018. Results: There were 577,822 RBC units transfused among 112,705 patients comprising 345,373 transfusion episodes between 2012 and 2018. Utilization in terms of RBC units and patients increased slightly in one and decreased slightly in the other two healthcare facilities. About 90% of RBC‐transfused patients had 1 (~46%) or 2–5 (~42%)transfusion episodes in 2018. Among the small proportion of patients with ≥12 transfusion episodes per year, approximately 60% of episodes included only one RBC unit. All facilities used leukocyte‐reduced RBCs during the study period whereas irradiated RBC utilization patterns differed across facilities. Discussion: ISBT 128 codes and EHRs were used to observe patterns of RBC transfusion and modification methods at the unit level and patient level in three healthcare systems participating in the BEST initiative. This study shows that the ISBT 128 coding system in an EHR environment provides a feasible source for hemovigilance activities. [ABSTRACT FROM AUTHOR]

Background: Longitudinal patterns of immune globulins (IG) use have not been described in large populations. Understanding IG usage is important given potential supply limitations impacting individuals for whom IG is the sole life‐saving/health‐preserving therapy. The study describes US IG utilization patterns from 2009 to 2019. Study Design and Methods: Using IBM MarketScan commercial and Medicare claims data, we examined four metrics overall and by condition‐specific categories during 2009–2019: (1) IG administrations per 100,000 person‐years, (2) IG recipients per 100,000 enrollees, (3) average annual administrations per recipient, and (4) average annual dose per recipient. Results: In the commercial and Medicare populations respectively: IG administrations per 100,000 person‐years increased by 120% (213–470) and 144% (692–1693); IG recipients per 100,000 enrollees grew by 71% (24–42) and 102% (89–179); average annual administrations per recipient rose by 28% (8–10) and 19% (8–9); and average annual dose (grams) per recipient increased by 29% (384–497) and 34% (317–426). IG administrations associated with immunodeficiency (per 100,000 person‐years) increased by 154% (from 127 to 321) and 176% (from 365 to 1007). Autoimmune and neurologic conditions were associated with higher annual average administrations and dose than other conditions. Discussion: IG use increased, coinciding with a growth in the IG recipient population in the United States. Several conditions contributed to the trend, with the largest increase observed among immunodeficient individuals. Future investigations should assess changes in the demand for IVIG by disease state or indication and consider treatment effectiveness. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Summary: Data on cause‐specific mortality after lymphoplasmacytic lymphoma (LPL) and Waldenström macroglobulinaemia (WM) are lacking. We identified causes of death amongst 7289 adults diagnosed with incident first primary LPL (n = 3108) or WM (n = 4181) during 2000–2016 in 17 USA population‐based cancer registries. Based on 3132 deaths, 16‐year cumulative mortality was 23·2% for lymphomas, 8·4% for non‐lymphoma cancers and 14·7% for non‐cancer causes for patients aged <65 years at diagnosis of LPL/WM, versus 33·4%, 11·2% and 48·7%, respectively, for those aged ≥75 years. Compared with the general population, patients with LPL/WM had a 20% higher risk of death due to non‐cancer causes (n = 1341 deaths, standardised mortality ratio [SMR] 1·2, 95% confidence interval [CI] 1·1–1·2), most commonly from infectious (n = 188; SMR 1·8, 95% CI 1·6–2·1), respiratory (n = 143; SMR 1·2, 95% CI 1·0–1·4), and digestive (n = 80; SMR 1·8, 95% CI 1·4–2·2) diseases, but no excess mortality from cardiovascular diseases (n = 477, SMR 1·1, 95% CI 1·0–1·1). Risks were highest for non‐cancer causes within 1 year of diagnosis (n = 239; SMR<1year 1·3, 95% CI 1·2–1·5), declining thereafter (n = 522; SMR≥5years 1·1, 95% CI 1·1–1·2). Myelodysplastic syndrome/acute myeloid leukaemia deaths were notably increased (n = 46; SMR 4·4, 95% CI 3·2–5·9), whereas solid neoplasm deaths were only elevated among ≥5‐year survivors (n = 145; SMR≥5years 1·3, 95% CI 1·1–1·5). This work identifies new areas for optimising care and reducing mortality for patients with LPL/WM. [ABSTRACT FROM AUTHOR]

Background: Sebaceous tumors of the skin occurring in association with an internal malignancy characterize Muir-Torre syndrome (MTS), a variant of hereditary nonpolyposis colon cancer (Lynch syndrome). To the authors' knowledge, only limited information exists regarding incidence patterns of sebaceous carcinoma (SC), and no prior study has quantified risks of associated cancers.Methods: The authors calculated cutaneous SC incidence rates (IRs) and IR ratios in 9 US Surveillance, Epidemiology, and End Results program registries (1973-2003). Indirectly standardized incidence ratios and 95% confidence intervals (95% CIs) were calculated for subsequent cancers among 2-month survivors of SC and for subsequent SC after other primary cancers.Results: Among 664 cases of cutaneous SC, nearly 90% were diagnosed among whites (IR, 0.11 per 100,000 person-years), with significantly lower IR noted among blacks (IR, 0.04). Whereas eyelid SC IRs demonstrated no sex differences and stabilized in recent years, IRs of noneyelid SC predominated in men and rose steadily over time. Survivors of SC had a 43% (95% CI, 15%-76%) increased risk of subsequent cancer, and risk of SC was elevated by 52% (95% CI, 24%-84%) among survivors of other cancers. Whether before or after SC, the significant excesses of other primary cancers were limited to noneyelid SC. Patterns suggestive of genetic predisposition included >20-fold risks for early-onset (diagnosed in patients aged <50 years) SC associated with colon, pancreatic, ovarian, or uterine corpus cancers, whereas late-onset SC (diagnosed in patients aged > or =50 years) predisposed to ureter cancer.Conclusions: This population-based study of cutaneous SC revealed an association with a spectrum of early-onset cancers consistent with MTS. Etiologic heterogeneity was suggested by differences between eyelid and noneyelid SC in incidence patterns and associated cancer risks. [ABSTRACT FROM AUTHOR]

Background: Radiotherapy for Hodgkin lymphoma (HL) increases the risk of salivary gland carcinomas (SGC). To the authors' knowledge, however, the magnitude of the risk has not been assessed to date.Methods: The risks of SGC among 20,928 1-year survivors of HL who were diagnosed between 1973 and 2003 were evaluated in 11 population-based cancer registry areas of the Surveillance, Epidemiology, and End Results (SEER) program. Observed-to-expected ratios (O/E) were assessed by radiation treatment, sex, age at the time of HL diagnosis, calendar year of diagnosis, attained age, time since HL diagnosis, histologic type of SGC, and site of occurrence in the major salivary glands.Results: Among 11,047 HL patients who received radiotherapy as part of their initial treatment for HL, 21 developed subsequent invasive SGC (O/E = 16.9; 95% confidence interval [95% CI], 10.4-25.8). The risk of radiation-related SGC was highest for younger HL patients (age <20 years) (O/E = 45.5; 95% CI, 12.4-116.5) and among 10-year survivors (O/E = 23.9; 95% CI, 13.1-40.1), with risks remaining elevated for at least 2 decades after irradiation. Significant differences in risk by histologic type were observed, with a particularly high risk of developing mucoepidermoid carcinomas (O = 14; O/E = 44.2 [95% CI, 24.2-74.2]) and adenocarcinomas (O = 4; O/E = 30.6 [95% CI, 8.3-78.2]) noted.Conclusions: HL patients treated with radiotherapy experienced a significantly increased risk of SGC, particularly when exposed at young ages or for at least 2 decades after exposure. Although the results of the current study reflect the late effects of former HL treatment approaches, they point to the importance of long-term follow-up and a heightened awareness of SGC risk in this population. [ABSTRACT FROM AUTHOR]

Descriptive epidemiological information on myeloproliferative neoplasms ( MPNs) and myelodysplastic ( MDS)/ MPNs is largely derived from single institution and European population-based studies. Data obtained following adoption of the World Health Organization classification of haematopoietic neoplasms and JAK2 V617F mutation testing are sparse. Using population-based data, we comprehensively assessed subtype-specific MPN and MDS/ MPN incidence rates ( IRs), IR ratios ( IRRs) and relative survival ( RS) in the United States (2001-12). IRs were highest for polycythaemia vera ( PV) ( IR = 10·9) and essential thrombocythaemia ( ET) ( IR = 9·6). Except for ET and mastocytosis, overall IRs were significantly higher among males ( IRRs = 1·4-2·3). All evaluable MPNs were associated with lower IRs among Hispanic whites than non-Hispanic whites ( NHWs), with the exception of BCR-ABL1-positive chronic myeloid leukaemia ( CML), chronic eosinophilic leukaemia ( CEL) and juvenile myelomonocytic leukaemia. Except for CEL, Asians/Pacific Islanders had significantly lower MPN IRs than NHWs. ET, MPN-unclassifiable and CEL IRs were 18%, 19% and 60% higher, respectively, among blacks than NHWs. Five-year RS was more favourable for younger (<60 years) than older individuals and for women compared with men, except for PV at older ages. RS was highest (>90%) for younger PV and ET patients and lowest (<20%) for older chronic myelomonocytic leukaemia and atypical BCR-ABL1-negative CML patients. Varying MPN and MDS/ MPN incidence patterns by subtype support distinct aetiologies and/or susceptible populations. Decreased survival rates as compared to that expected in the general population were associated with every MPN subtype, highlighting the need for new treatments, particularly among older individuals. [ABSTRACT FROM AUTHOR]

Benzene exposure has been causally linked with acute myeloid leukemia (AML), but inconsistently associated with other hematopoietic, lymphoproliferative and related disorders (HLD) or solid tumors in humans. Many neoplasms have been described in experimental animals exposed to benzene. We used Poisson regression to estimate adjusted relative risks (RR) and the likelihood ratio statistic to derive confidence intervals for cause-specific mortality and HLD incidence in 73,789 benzene-exposed compared with 34,504 unexposed workers in a retrospective cohort study in 12 cities in China. Follow-up and outcome assessment was based on factory, medical and other records. Benzene-exposed workers experienced increased risks for all-cause mortality (RR = 1.1, 95% CI = 1.1, 1.2) due to excesses of all neoplasms (RR = 1.3, 95% CI = 1.2, 1.4), respiratory diseases (RR = 1.7, 95% CI = 1.2, 2.3) and diseases of blood forming organs (RR = ∞, 95% CI = 3.4, ∞). Lung cancer mortality was significantly elevated (RR = 1.5, 95% CI = 1.2, 1.9) with similar RRs for males and females, based on three-fold more cases than in our previous follow-up. Significantly elevated incidence of all myeloid disorders reflected excesses of myelodysplastic syndrome/acute myeloid leukemia (RR = 2.7, 95% CI = 1.2, 6.6) and chronic myeloid leukemia (RR = 2.5, 95% CI = 0.8, 11), and increases of all lymphoid disorders included excesses of non-Hodgkin lymphoma (RR = 3.9, 95%CI = 1.5, 13) and all lymphoid leukemia (RR = 5.4, 95%CI = 1.0, 99). The 28-year follow-up of Chinese benzene-exposed workers demonstrated increased risks of a broad range of myeloid and lymphoid neoplasms, lung cancer, and respiratory diseases and suggested possible associations with other malignant and non-malignant disorders. [ABSTRACT FROM AUTHOR]

The aetiology of marginal zone lymphoma ( MZL) is purported to differ by anatomic site. While this is supported by clinical series of single MZL sites, no population-based study has comprehensively assessed incidence patterns across sites. To gain insight into disease aetiology, we assessed MZL incidence by site using data from 18 U.S. Surveillance, Epidemiology and End Results ( SEER) Program population-based registries. We calculated age-adjusted incidence rates ( IRs) by sex, race, and calendar year. During 2001-2009, 4,081 ( IR = 5·7/1,000,000 person-years) and 8,821 ( IR = 12·3) individuals were diagnosed with nodal MZL and extranodal MZL, respectively. The most common extranodal sites were stomach ( IR = 3·8), spleen ( IR = 1·6), eye/adnexa ( IR = 1·4), and lung, skin, and salivary glands ( IRs = 0·9-1·0). We observed distinct age-specific patterns by MZL site, with IRs increasing steeply at younger ages and less prominently after mid-life at several sites, except skin. Gender and racial/ethnic disparities were also apparent across sites. Between 2001-2005 and 2006-2009, MZL IRs decreased significantly for gastric (−15%) and soft tissue (−28%) sites, whereas IRs increased significantly for lung (18%), skin (43%), and kidney/renal pelvis (116%). In combination, our findings support the contention that MZL is characterized by aetiological heterogeneity across sites and susceptibility is probably influenced by intrinsic characteristics and environmental exposures. [ABSTRACT FROM AUTHOR]

BACKGROUND Population-based studies comprehensively describing incidence patterns of human papillomavirus (HPV)-related preinvasive and invasive neoplasms prior to widespread HPV vaccination are sparse. METHODS Age-adjusted incidence rates (IRs), IR ratios (IRRs), and annual percent changes (APCs) in IRs were calculated for potentially HPV-related tumors diagnosed in the Surveillance, Epidemiology and End Results (SEER) Program during 1978 through 2007. RESULTS Overall IRs for preinvasive tumors were significantly higher than for invasive squamous cell tumors of cervix (IRR = 3.42), vulva (IRR = 1.87), and vagina (IRR = 1.19) and significantly lower for adenomatous cervical tumors (IRR = 0.43), and squamous cell tumors of penis (IRR = 0.64), anus (males, IRR = 0.53; females, IRR = 0.14), and head and neck (H&N) (males, IRR = 0.01; females, IRR = 0.02). Incidence of preinvasive squamous tumors of cervix, vagina, and penis rose rapidly over time and decreased for invasive neoplasms. The most rapid increases occurred for preinvasive (males, APC = 16.0; females, APC = 7.3) and invasive anal tumors (males, APC = 3.6; females, APC = 2.3). IR patterns were generally similar among evaluable racial/ethnic groups, with the exception of H&N invasive tumor IRs which increased exclusively among white males. CONCLUSIONS Contrary to the opposing trends of preinvasive and invasive squamous tumors of cervix, vagina, and penis, preinvasive and invasive anal tumor IRs increased significantly over time by sex, age, and racial/ethnic groups. Successful HPV vaccination programs are needed to measurably reduce incidence of HPV-related neoplasms in the future, particularly for cancer sites with rising incidence rates for which effective screening modalities are limited. Cancer 2013;119:2291-2299. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

Population-based plasmacytoma incidence and survival data are sparse. We analyzed incidence rates (IRs), IR ratios (IRRs), and 5-year relative survival for plasmacytoma overall and by site – bone (P-bone) and extramedullary (P-extramedullary) – in the Surveillance, Epidemiology and End Results (SEER) Program (1992–2004). For comparison, we included cases of multiple myeloma (MM) diagnosed over the same time period in SEER. Incidence of MM ( n = 23 544; IR 5·35/100 000 person-years) was 16-times higher than plasmacytoma overall ( n = 1543; IR = 0·34), and incidence of P-bone was 40% higher than P-extramedullary ( P < 0·0001). The male-to-female IRRs for P-bone, P-extramedullary, and MM were 2·0, 2·6, and 1·5, respectively. For plasmacytoma and MM, IRs were highest in Blacks, intermediate in Whites, and lowest in Asian/Pacific Islanders. Compared with Whites, the Black IR was ∼30% higher for P-extramedullary and P-bone and 120% higher for MM. IRs for all neoplasms increased exponentially with advancing age, less prominently at older ages for plasmacytoma than MM. Distinct age, gender, and race incidence patterns of plasma cell disorders suggest underlying differences in clinical detection, susceptibility, disease biology and/or aetiological heterogeneity. Five-year relative survival for P-bone, P-extramedullary, and MM varied significantly by age (<60/60+ years), supporting age-related differences in disease burden at presentation, disease biology, and/or treatment approaches. [ABSTRACT FROM AUTHOR]

The US National Cancer Institute’s Surveillance, Epidemiology and End Results program was used to develop aetiological clues for hairy cell leukaemia (HCL). Descriptive techniques (age-adjusted incidence trends, age-specific incidence rates (IR), and age distributions-at-diagnosis) were supplemented with mathematical models (two-component mixture, generalized linear regression, and age-period-cohort). There were 2856 cases of HCL diagnosed during 1978–2004 (IR 0·32/100 000 person-years). IRs were nearly 4-fold greater among men than women and more than 3-fold higher for Whites than Blacks. Temporal trends were stable over time. Age-specific IRs increased rapidly until approximately 40 years then rose at a slower pace. The age-specific IR curves reflected bimodal early- and late-onset age distributions-at-diagnosis (or density plots), with some variation by gender. Among both men and women, a two-component mixture model fitted the data better than a single density or cancer population. Age-period-cohort models confirmed statistically significant age-related effects after full adjustment for temporal trends (calendar-period and birth-cohort effects). In summary, age incidence patterns (rates and bimodal densities) suggested that HCL is a heterogeneous disease, consisting of at least two underlying subgroups and/or cancer populations by age-at-onset. Distinct early- and late-onset HCL populations may reflect different age-related causal pathways, risk factor profiles, and/or stem cells of origin. [ABSTRACT FROM AUTHOR]

The 2001 World Health Organization classification scheme considers B-cell chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) in an aggregate category (CLL/SLL) because of shared clinicopathological features. We have estimated age-adjusted incidence rates (IRs) of CLL and SLL in the population-based Surveillance, Epidemiology and End Results Program in the United States to analyse patterns of CLL and SLL separately and jointly. Age-standardized to the 2000 US population, overall IRs were 3·83 per 100 000 person-years for CLL ( n = 15 676) and 1·31 for SLL ( n = 5382) during 1993–2004. Incidence of the combined entity, CLL/SLL, was 90% higher among males compared to females, and the male:female IR ratio was significantly higher for CLL (1·98) than for SLL (1·67). CLL/SLL IRs were 25% and 77% lower among Blacks and Asian/Pacific Islanders, respectively, compared to Whites. A significant reporting delay was evident for CLL but not for SLL, so that CLL/SLL temporal trends must be interpreted cautiously. CLL and SLL IRs increased exponentially with age among all gender/race groups, with CLL IRs increasing more steeply with advancing age than SLL. Avenues of future research include assessment of delayed- and under-reporting to cancer registries and exploration of race, gender, and age effects in epidemiological studies. [ABSTRACT FROM AUTHOR]

This overview of the epidemiology of chronic lymphocytic leukaemia (CLL) summarizes the evolution of classification and coding systems and describes the intersection of pathogenesis and aetiology. The role of the putative precursor to CLL, monoclonal B-cell lymphocytosis (MBL), is considered, and ideas for future investigations of the MBL-CLL relationship are outlined. We discuss the epidemiology of CLL, focusing on descriptive patterns and methodological considerations. Postulated risk factors are reviewed including the role of ionizing and non-ionizing radiation, occupational and environmental chemical exposures, medical conditions and treatments, and lifestyle and genetic factors. We conclude by raising key questions that need to be addressed to advance our understanding of CLL aetiology. Recommendations for future epidemiological studies are given, including the standardization of reporting of CLL across cancer registries, the clarification of the natural history of MBL, and the circumvention of the methodological shortcomings of prior epidemiological investigations in relation to radiation, chemical exposures and infectious agents. [ABSTRACT FROM AUTHOR]

We read with interest the article by Higano et al, which reported the results of the PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED).[1] The authors reported a cerebrovascular event (CVE) rate of 2.8%; a prior pooled analysis of phase 3 trials[[2], [4]] reported a CVE rate of 3.5% among patients treated with sipuleucel-T.[6] We would like to request clarification of the PROCEED methodology and analysis to help the reader interpret the results. The adjudication process may have used more stringent diagnostic criteria for CVE than the PROCEED study protocol, thereby resulting in fewer outcomes being identified and a potential underestimation of CVE rates. Third, comparison of CVE rates in PROCEED with those in the preceding phase 3 clinical trials was limited by potential differences in the CVE case definition. [Extracted from the article]