Incidence Of Hematologic Malignancies Research Articles

Incidence of haematological malignancies in adults in Szabolcs-Szatmár-Bereg county between 1983 and 2012. The figures of a thirty-year period – an analysis

In their previous work the authors reported 25 years' findings on the incidence of haematological malignancies in Szabolcs-Szatmár-Bereg county, Hungary. However, there are no other studies on this topic available in Hungary. The aim of the authors was to analyze the incidence of malignant haematological disorders between 1983 and 2012 using data obtained from the leukaemia/lymphoma registry of the Szabolcs-Szatmár-Bereg county. Between January 1, 1983 and December 31, 2012, 3964 adult patients with newly diagnosed haematological malignancy were recorded in the registry. Patients with myelodysplastic syndrome or monoclonal gammopathy were not registered. The annual number of newly diagnosed patients indicated an increasing tendency of malignant haematological disorders. The increase was primarily due to the increasing number of patients with non-Hodgkin's lymphoma, chronic lymphocytic leukaemia, and essential thrombocythaemia. These observations are in line with data reported in the international literature. The incidence rate of haematological malignancies in this region of Hungary was similar to data published in populations from Western European countries and the United States.

Incidence of haematological malignancies by ethnic group in England, 2001–7

The aetiology of most haematological malignancies is largely unknown. Studies of migrant populations can provide insights into the relative importance of genetic and environmental risk factors for these diseases. This study compares incidence rates in British Indians, Pakistanis, Bangladeshis, Black Africans, Black Caribbeans, Chinese and Whites in England from 2001 to 2007. We analysed 134,302 haematological cancer registrations with ethnicity obtained by linkage to the Hospital Episodes Statistics database. Mid-year population estimates from 2001 to 2007 were used. Incidence rate ratios adjusted for age, sex and income were calculated, comparing the six ethnic groups to Whites and to each other. Whites had the highest rates for most subtypes. However, Blacks experienced more than double the incidence of plasma cell and mature T-cell neoplasms compared to other ethnic groups. There were also significant differences in incidence between Indians, Pakistanis and Bangladeshis for Hodgkin lymphoma and mature B-cell neoplasms and between Black African and Black Caribbeans for mature B-cell and other lymphoid neoplasms (all P < 0.001). Our results show that the risk of haematological cancers varies greatly by ethnic group, including within those groups that have traditionally been grouped together (South Asians and Blacks) with many of these differences not explicable by known risk factors.

Time Trend of Multiple Myeloma and Associated Secondary Primary Malignancies in Asian Patients: A Taiwan Population–Based Study

Studies involving second malignancies in patients with multiple myeloma are limited for the Asian population. Using data from population-based insurance claims, we assessed the risk of developing secondary malignancies after multiple myeloma, in particular hematologic malignancies. A retrospective cohort study was conducted in 3970 patients with newly diagnosed multiple myeloma from the registry of catastrophic illnesses between 1997 and 2009. A total of 15880 subjects without multiple myeloma were randomly selected as comparisons from the insured population, frequency-matched based on gender, age, and the date of diagnosis. The incidence of secondary malignancies was ascertained through cross-referencing with the National Cancer Registry System. The Cox proportional hazards model was used for analyses. The incidence of multiple myeloma in the insured population increased annually. The overall incidence of secondary malignancy was lower in the multiple myeloma cohort than in the comparison cohort (93.6 vs. 104.5 per 10,000 person-years, IRR = 0.90, 95% CI = 0.78–1.04). The incidence of hematologic malignancies was 11-fold greater for multiple myeloma patients (47.2 vs. 4.09 per 10,000 person-years) with an adjusted HR of 13.0 (95% CI = 7.79–21.6) compared with the comparison cohort. The relative risk of secondary malignancy was also strong for myeloid leukemia (21.2 vs. 1.36 per 10,000 person-years). Gender- and age-specific analysis for secondary hematologic malignancies showed that males and patients with multiple myeloma <60 years of age had a higher risk of secondary malignancy than females and patients with multiple myeloma >60 years of age. In conclusion, patients with multiple myeloma, especially younger patients, are at a high risk of hematologic malignancies.

Regular recreational physical activity and risk of hematologic malignancies: results from the prospective VITamins And lifestyle (VITAL) study

BackgroundConflicting evidence exists on the relationship between physical activity (PA) and incident hematologic malignancies. Herein, we used a large cohort study to examine this association. Patients and methodsSixty-five thousand three hundred twenty-two volunteers aged 50–76 years were recruited from 2000 to 2002. Incident hematologic malignancies (n = 666) were identified through 2009 by linkage to the Surveillance, Epidemiology, and End Results cancer registry. Hazard ratios (HRs) for hematologic malignancies associated with PA averaged over 10 years before baseline were estimated with Cox proportional hazards models, adjusting for factors associated with hematologic cancers or PA. ResultsThere was a decreased risk of hematologic malignancies associated with PA (HR = 0.66 [95% confidence interval, 95% CI 0.51–0.86] for the highest tertile of all PA, P-trend = 0.005, and HR = 0.60 [95% CI 0.44–0.82] for the highest tertile of moderate/high-intensity PA, P-trend = 0.002). These associations were strongest for myeloid neoplasms (HR = 0.48 [95% CI 0.29–0.79] for the highest tertile of all PA, P-trend = 0.013, and HR = 0.40 [95% CI 0.21–0.77] for the highest tertile of moderate/high-intensity PA, P-trend = 0.016). There were also significant associations between PA and chronic lymphocytic leukemia/small lymphocytic lymphoma or other mature B-cell lymphomas except plasma cell disorders. ConclusionsOur study offers the strongest epidemiological evidence, to date, to suggest an association between regular PA and dose-dependent risk reduction for most hematologic malignancies, particularly myeloid neoplasms.

Abstract 2535: The difference in the incidence and the trend of hematologic malignancies in Japan and the United States.

Abstract Background: The hematologic malignancies are a collection of heterogeneous diseases with diverse epidemiologic features for which a detailed classification of disease subtypes has evolved dramatically. The incidence of a malignant disease reflects the genetics and cumulative exposure to the environment of a population. Therefore, evaluation of the incidence and trend of a disease in different populations may provide insights into the etiology and pathogenesis of that disease. However, no detailed data based on population-based cancer registry in Asia to see each disease entities are available. Aims: The aim of this study is to assess the incidence and the trend of each hematologic malignancy and to evaluate the difference between Japan and US. The diseases evaluated in this study were acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), multiple myeloma (MM), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). Methods: To evaluate the incidence of hematologic malignancies, we used population-based registry data in Japan and the United States (US). The population-based cancer registry of Japan included 100,637 cases and the data in the US, SEER included 172,925 cases. The period covered in this analysis is 1993-2006 in Japan and 1993-2008 in the US. Rates of sex-specific, age-standardized incidence with 95% confidence intervals were estimated and standardized by age-adjustment according to the world standard population. We also estimated the annual percent change using joinpoint regression analysis and evaluated the significance of the trend. Results: The overall age-standardized incidence rate of all hematologic malignancies per 100,000 in 2006 was 14.9 for males and 10.0 for females in Japan, 33.4 for males and 24.3 for females in the US. The difference in the incidence between Japan and US is impressive for HL, NHL and MM (approximately 3-10 fold), whereas AML, ALL, and CML have a similar incidence. The total number of hematologic malignancies was found to be increasing significantly in Japan whereas no obvious change was seen in the US {annual percent change (95%CI) Japan; +1.5% (0.9 to 2.1), US; +0.1% (-0.1 to 0.2)}. As for details, AML and the lymphoid malignancies (HL and NHL) are increasing significantly in Japan whereas there has been a marginal change in the US. Interestingly, the incidence of CML has been decreasing during this period in both Japan and the US, whereas no obvious change was seen in MM in their country. Conclusion: In conclusion, we showed the difference in the incidence of hematologic malignancies between Japan and the US. The incidence of hematologic malignancies is lower in Japan than the US, but is increasing significantly. The improvement in the quality of cancer registry systems and the organization of these registries between countries enables us to unite the data worldwide that will bring us new insights. Citation Format: Dai Chihara, Lidsay Morton, Hidemi Ito, Tomohiro Matsuda, Akiko Shibata, Tomotaka Sobue, Denis D. Weisenburger, Keitaro Matsuo. The difference in the incidence and the trend of hematologic malignancies in Japan and the United States. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2535. doi:10.1158/1538-7445.AM2013-2535

Regular Recreational Physical Activity and Risk of Hematologic Malignancies: Results From the Prospective Vitamins and Lifestyle (VITAL) Study

AbstractAbstract ▪887▪This icon denotes a clinically relevant abstract Background:Recreational physical activity (PA) provides numerous health benefits, including a reduction in cardiovascular and metabolic diseases and promotion of mental health. Increasing evidence from epidemiological studies also links PA to a reduced risk of major human cancers, particularly those of the colon and breast. On the other hand, previous case-control and cohort studies examining the relationship of PA and incident hematologic malignancies yielded inconsistent results. Given these conflicting findings, we used a large prospective cohort study to examine this association. Patients and Methods:65,322 men and women aged 50–76 years were recruited from 2000–2002 to the VITamins And Lifestyle (VITAL) study. The PA questionnaire at baseline asked about walking by intensity and two broader categories of activities (mild and moderate/strenuous exercise) by type over the past 10 years. For each activity, a corresponding metabolic equivalent (MET) intensity was assigned. Incident hematologic malignancies (n=666) after study enrollment were identified through December 2009 by linkage to the SEER cancer registry. Hazards ratios (HRs) for total incident hematologic malignancies and cancer subcategories associated with PA averaged over the previous 10 years before baseline were estimated by Cox proportional hazards models. Models were adjusted for age, sex, race/ethnicity, education, smoking, self-rated health, daily fruit and vegetable consumption, body mass index, fatigue, self-reported anemia, and family history of leukemia/lymphoma. Results:After adjustment, there was a decreased risk of hematologic malignancies associated with any PA (HR=0.75 [95% CI: 0.61–0.94]) as well as any moderate/high-intensity activity (HR=0.72 [95% CI: 0.57–0.92]). The reduction in risk was greatest among the physically most active participants, both with regard to number of weekly episodes of activity (>4.8 episodes of all activities per week: HR=0.66 [95% CI: 0.51–0.86], P=0.005 for trend; >3.5 episodes of moderate/high-intensity activities per week: HR=0.60 [95% CI: 0.44–0.82], P=0.002 for trend) and metabolic activity (>13.625 MET of all activities per week: HR=0.71 [95% CI: 0.54–0.92], P=0.029 for trend; >11.2972 MET of moderate/high-intensity activities per week: HR=0.65 [95% CI: 0.48–0.89], P=0.005 for trend), respectively. To address the possibility of reverse causation, i.e. the possibility that study participants were physically less active as a result of a yet undiagnosed hematologic malignancy, we repeated these analyses after exclusion of the 146 incident cases that occurred within 2 years of baseline: the reduction in risk of incident hematologic malignancies among the physically most active participants in this study subset was relatively similar to that of the entire study cohort. When we stratified malignancies by WHO disease classification, we found that the association between PA and incident hematologic malignancy was strongest for myeloid neoplasms (HR=0.48 [95% CI: 0.29–0.79] for highest tertile of all PA, P=0.013 for trend; HR=0.40 [0.21-0.77] for highest tertile of moderate/high-intensity PA, P=0.016 for trend). There were also significant associations between episodes of moderate/high intensity PA and incident mature B-cell lymphomas other than chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or plasma cell disorders (>3.5 episodes per week: HR=0.59 [95% CI: 0.36–0.97], P=0.035 for trend) and between episodes of all activities and incident CLL/SLL (>4.8 episodes per week: HR=0.52 [95% CI: 0.26–1.03], P=0.023 for trend). No associations were found with incident plasma cell disorders. Conclusion:Our study offers the strongest epidemiological evidence to date to suggest that regular recreational PA is associated with a dose-dependently reduced incidence of certain hematologic malignancies, with a greater than 50% reduction of risk for the development of neoplasms of myeloid origin for individuals within the top tertile of all or moderate/high-intensity activities. Our data also suggest a trend toward reduced risk for CLL/SLL and other mature B-cell NHLs except plasma cell disorders, although further studies in larger cohorts of participants will be required to assess these associations further. Together, our findings may thus suggest additional important health benefits attributable to regular PA. Disclosures:No relevant conflicts of interest to declare.

Retrospective Exploratory Study of HIV+ Patients with and without Paraproteinemia for Association with HIV Status, Comorbidities and Development of Hematological Malignancies

AbstractAbstract 1827 BACKGROUND:Prior studies suggest that HIV+ patients have a higher prevalence of paraproteinemia. Paraproteinemia is a known risk factor for development of hematological malignancy (HM) in non HIV patients. However the pathogenesis of paraproteinemia and the additional risk conferred by it to development of HM in HIV remains unclear. We describe our findings from a large database of HIV+ patients in Montefiore Medical Center with and without paraprotein for differences in HIV status, comorbidities and incidence of HM. METHODS:Our de-identified patient database, Clinical Looking Glass, was used to identify all documented HIV+ patients who underwent at least one serum protein electrophoresis test (SPEP) after the HIV test between January 1st 2001 and December 31st 2011. Patients were classified into SPEP+ and SPEP-, and SPEP+ patients further stratified into distinct (D-SPEP) or faint/multiple/oligoclonal (F-SPEP) cases by visual assessment of gel electrophoresis. Laboratory data was reviewed for comorbidities and HIV status. Results of all biopsies undergone by each patient were reviewed to identify HM diagnoses. RESULTS:A total of 17,961 HIV+ patients were identified of which 2,095 patients had at least one SPEP test. Of those tested, 21.2% were SPEP+ (D-SPEP: 4%; F- SPEP:17.2%). 3.3% had a missing result. IgG was the commonest subtype on immunofixation (85.4%). All 3 groups (SPEP-, D-SPEP and F-SPEP) had a similar median duration of HIV before testing for SPEP. Mean CD4+ value measured around the time of the SPEP test (3 months before or after) was significantly higher in the F-SPEP group compare to both other groups. Patients in the D-SPEP and F-SPEP groups were more likely to be seropositive for Hepatitis C and Rheumatoid Factor (RF) than those who were SPEP-.A significantly higher proportion of patients were biopsied in the D-SPEP and F-SPEP groups than the SPEP-. Overall the incidence of HM in D-SPEP was significantly higher but when adjusted for patients who were biopsied, the higher incidence in D-SPEP did not reach statistical significance. 50–60% of HM were diagnosed within 6 months of the index SPEP; the D-SPEP group had the shortest time to diagnosis of HM after SPEP. The pattern of HM was different among the three groups with the D-SPEP patients mostly developing plasma cell dyscrasias, while the F-SPEP and SPEP- groups had a higher proportion of high grade B and T cell neoplasms. (Table 1). CONCLUSIONS:To our knowledge this is the largest published sample of HIV+ patients tested for paraproteinemia. The higher prevalence of Hepatitis C in SPEP+ patients suggests its role in pathogenesis of paraproteinemia. The higher incidence of HM, especially plasma cell dyscrasias diagnosed close to the index SPEP in the D-SPEP group suggests that D-SPEP may reflect malignant clonal proliferation. In contrast, the F-SPEP group had a similar HM incidence to SPEP- and a higher CD4+ count than the other groups. These suggest that faint/oligoclonal paraproteins may require T cell mediated B cell activation to develop and maybe directed against viral antigens rather than reflect premalignant or malignant proliferation. Understanding antigen specificity of paraproteins may shed light on the risk of HM in HIV+ SPEP+ patients.Table 1Differences between HIV+ SPEP-, HIV+D-SPEP and HIV+F-SPEPCharacteristicHIV+SPEP- (n=1596)HIV+DSPEP+ (n=82)HIV+FSPEP+ (n=348)pAge (yrs)49.4 (SE:0.29)50.5 (SE:1.35)49.9 (SE:0.58)0.604Male (%)53.2%47.6%47.1%0.088Median HIV duration before SPEP (days)8908117600.554Mean CD4 for patients tested (/uL)264 (SE:7.41)295 (SE:32.41)329 (SE:17.88)0.001*Mean HIV viral load for patients tested (copies/ml)127310 (SE:15094)118218 (SE:31448)98378 (SE:27968)0.691Median follow up after SPEP test (days)65410477340.362Hepatitis C+ of total tested patients494 (36.3%)33 (50.8%)125 (41.8%)0.018*Hepatitis B+ of total patients tested96 (9.9%)7 (13.2%)29 (12.4%)0.441ANA +of total patients tested89 (13.7%)5 (18.5%)17 (11.3%)0.531RF + of total patients tested88 (22.7%)11 (45.8%)43 (39.8%)0.000*Patients with HM (% of total N)66 (4.1%)10 (12.2%)21 (6%)0.004*Number of patients s/p biopsy268 (16.8%)22 (26.8%)90 (25.9%)0.000*Number of patients with HM of those biopsied66 (24.8%)10 (45.5%)21 (23.3%)0.087Number of total HM diagnosed after index SPEP37 (56.1%)6 (60%)11 (52.4%)0.918Median time from SPEP test to HM diagnosis (d)56363290.016* Disclosures:No relevant conflicts of interest to declare.

The Difference in the Incidence and the Trend of Malignant Lymphomas in Japan and the United States.

AbstractAbstract 2695 Background:Malignant lymphomas (ML) are heterogeneous groups that the detailed classification is evolving dramatically. An incidence of malignant disease in certain population reflects cumulative exposure to environment, genetics and their combination overtime. Therefore, a comparison of incidences in various population and their secular trends is very helpful to understand etiology of disease. The aim of this study is to assess the incidence and the trend of each ML subtypes and to evaluate the difference between Japan and US. Materials and Methods:We used the data from a population-based cancer registry in Japan and from the Surveillance Epidemiology and End Results (SEER) program 9. Registry data of the US, SEER 9 included 95,155 cases and the data of Japan included 48,658 cases. The period covered in this analyses was 1993 to 2006 in Japan and 1993 to 2008 in the US. Rates of sex-specific, age-standardized incidence with 95% confidence intervals were estimated and standardized by age-adjustment according to the world standard population. We also estimated the annual percent change using joinpoint regression analysis and evaluated the significance of the trend. Results:The overall age-standardized incidence rate of all malignant lymphomas per 100,000 in 2006 was 22.4 for males and 16.0 for females in the US, 7.4 for males and 4.9 for females in Japan. The incidence is higher in the US than Japan with most of the subtypes especially for the nodular sclerosis HL, CLL/SLL and FL. In general, B-cell lymphomas showed large difference in incidence while T-cell lymphomas (TCL) showed similar incidence between Japan and the US. The total numbers of ML are constantly increasing in Japan but not in the US as shown in the figure {annual percent change (95%CI), Japan; +2.6% (2.1, 3.1), US; +0.2% (−0.0, 0.4)}. As for details, follicular lymphoma, mantle cell lymphoma, Burkitt lymphoma and the total numbers of TCL are constantly increasing in both countries. Conclusion:In conclusion, we showed the marked difference in the incidence and the trend of hematologic malignancies between Japan and the US. The incidence of hematologic malignancies is lower in Japan than the US, but is increasing significantly. The most remarkable difference in the incidence was seen with nodular sclerosis HL, CLL/SLL and FL which was consistent with previous reports. Even with the TCL, the incidence seems to be similar to higher in the US except for the ATLL. The improvement in the quality of cancer registry systems and the organization of these registries between countries enables us to unite the data worldwide that will bring us new insights. [Display omitted] Solid line and circle are the data of the US. Dashed line and hollow circle are the data of Japan. Disclosures:No relevant conflicts of interest to declare.

Associations between allergies and risk of hematologic malignancies: Results from the Vitamins and Lifestyle (VITAL) cohort study.

1527 Background: Several case-control studies have suggested a reduced risk of hematologic malignancies (HMs) for individuals with allergies, but results have been inconsistent, and prospective cohort studies have not confirmed this association. Herein, we used the large prospective VITAL study to examine this association. Methods: 64,847 men and women, aged 50-76, completed a baseline questionnaire in 2000-2002 and reported on their current allergies and history of physician-diagnosed asthma. Individuals with prior cancer other than non-melanoma skin cancer were excluded from this analysis. Incident HMs were identified through December 2009 by linkage to the SEER registry; those with a diagnosis of a non-HM during follow-up were censored at the time of that diagnosis. Multivariable Cox proportional hazards models were built with adjustment for sex, race/ethnicity, education, smoking, self-rated health, physical activity, history of anemia in the year before baseline, vegetable use and family history of leukemia or lymphoma. Results: Our analysis included 64,839 participants, among whom 681 (1.03%) incident HMs were found (MDS [69], AML (41], myeloproliferative disorders [60], mature B-cell neoplasms [262], chronic lymphocytic leukemia [107], plasma cell disorders [83], Hodgkin lymphoma [23], T-cell/NK-cell neoplasms [22], and others [14]). In multivariable analyses, a history of any allergy was associated with increased risk of HM (HR=1.21; 95% CI 1.02-1.43, p=0.02). This association was seen for current allergies to plants/grass/trees (HR 1.27 [1.06-1.52], p&lt;0.001) but not for allergies to mold/dust, animals, insects, food, or medications. We did not find an association between a history of asthma and incident HMs (HR=0.95 [0.72-1.26]). Conclusions: Our study indicates a moderately increased risk of HMs inindividuals with a history of allergy, especially to plant, grass or trees. While no causality can be inferred, this may suggest a possible carcinogenic role for chronic stimulation of the immune system. However, further mechanistic investigations focusing on the biochemical markers of immune system as well as on possible gene effect modifiers are needed.

DNA Damage in Nijmegen Breakage Syndrome Cells Leads to PARP Hyperactivation and Increased Oxidative Stress

Nijmegen Breakage Syndrome (NBS), an autosomal recessive genetic instability syndrome, is caused by hypomorphic mutation of the NBN gene, which codes for the protein nibrin. Nibrin is an integral member of the MRE11/RAD50/NBN (MRN) complex essential for processing DNA double-strand breaks. Cardinal features of NBS are immunodeficiency and an extremely high incidence of hematological malignancies. Recent studies in conditional null mutant mice have indicated disturbances in redox homeostasis due to impaired DSB processing. Clearly this could contribute to DNA damage, chromosomal instability, and cancer occurrence. Here we show, in the complete absence of nibrin in null mutant mouse cells, high levels of reactive oxygen species several hours after exposure to a mutagen. We show further that NBS patient cells, which unlike mouse null mutant cells have a truncated nibrin protein, also have high levels of reactive oxygen after DNA damage and that this increased oxidative stress is caused by depletion of NAD+ due to hyperactivation of the strand-break sensor, Poly(ADP-ribose) polymerase. Both hyperactivation of Poly(ADP-ribose) polymerase and increased ROS levels were reversed by use of a specific Poly(ADP-ribose) polymerase inhibitor. The extremely high incidence of malignancy among NBS patients is the result of the combination of a primary DSB repair deficiency with secondary oxidative DNA damage.

Risk of second cancers in Waldenström macroglobulinemia

An increased incidence of second cancers has been reported in lymphoproliferative disorders. We assessed the frequency, characteristics and predictive factors of second cancers in 230 patients with Waldenström macroglobulinemia (WM) and compared the incidence of second cancers in WM with that of an age- and sex-matched control population. Twenty-two patients (10%) developed solid cancers and 10 (4%) second hematologic malignancies. In a competing risk model, the cumulative incidence of solid cancers was 12% at 10 years and 17% at 15 years while the incidence of hematologic malignancies was 6% and 8%, respectively. The overall risk of second cancer in WM was 1.69 times higher than expected (P = 0.002). WM patients were at increased risk for diffuse large B-cell lymphoma [standardized incidence ratio (SIR) 9.24, P < 0.0001], myelodisplastic syndrome/acute myeloid leukemia (SIR 8.4, P < 0.0001), brain cancer (SIR 8.05, P = 0.0004). The risk of a second hematologic malignancy was fourfold higher in patients previously treated, though not reaching statistical significance (P = 0.19). WM patients are at higher risk of second cancers as compared with the general population. The sample size does not allow firm conclusions about the effect of therapy on the development of second cancers.

A systematic review of validated methods for identifying lymphoma using administrative data

To systematically review published studies for algorithms that identified lymphoma as a health outcome of interest in administrative or claims data and examined the validity of the algorithm to identify lymphoma cases. A systematic literature search was executed using PubMed and the Iowa Drug Information Service database. Two investigators reviewed search results to identify studies using administrative or claims databases from the USA or Canada that both reported and validated an algorithm to identify lymphoma. The search identified 713 unique citations with 402 eliminated by an initial screen of the article abstract. The remaining 311 resulted in one study that identified and validated an algorithm. Ten other studies reported algorithms but were not validated. The validated study reported four possible algorithms that had a specificity (> 99%), but the algorithm using two diagnostic codes recorded within 2 months had the best positive predictive value (PPV = 62.83%) and a sensitivity (79.81%). The most comprehensive algorithm required multiple diagnostic codes 2 months apart or diagnostic, and procedure codes on the same day had the greatest sensitivity (88.31%) and a PPV = 56.69%. The algorithm that required only a single diagnostic or procedure code had the worst PPV (34.72%). The International Classification of Disease, Ninth Revision diagnostic, clinical procedure, and complication codes for lymphoma can identify incident hematologic malignancies and solid tumors with high specificity but with relatively low to moderate sensitivity and PPVs. When diagnostic and procedure codes were required on the same visit or multiple codes between visits, then PPV was increased. Relying on a single registry to confirm true positive cases is also not sufficient.

P5-18-10: Utilisation of Primary and Secondary G-CSF Prophylaxis Enables Optimal Dose Delivery of Standard Adjuvant Chemotherapy in Early Breast Cancer: Results of 1655 Patients from a Single Institution.

Abstract Background: Chemotherapy for early breast cancer (EBC) confers significant survival advantages. However, myelosuppression is a common cause of chemotherapy dose reduction that may subsequently compromise survival benefits. Primary prophylaxis (PG) with granulocyte-colony stimulating factor (G) is indicated for TAC regimen, but rates of grade 3/4 neutropenia (G3/4N) associated with other adjuvant regimens in a non-trial setting are not well documented. Optimal use of G will likely enable planned dose delivery, leading to optimal BC outcomes. This retrospective study reports dose delivery outcome with judicious use of G in a single institution. Methods: Consecutive patients (pts) with EBC who received chemotherapy at Mount Hospital from January 1999 — December 2010 were included. Data was collected prospectively for pt characteristics, regimen given and neutropenic complications. Only pts who received a minimum of 1 cycle of chemotherapy were included. PG was only available in pts receiving TAC after 1/4/2007; Secondary G prophylaxis (SG) was given for G3/4N in first cycle, febrile neutropenia (FN) or delay in neutrophil recovery (DN). Primary outcome measure was dose delivery defined as relative dose intensity (RDI — fraction of dose per unit of time of standard regimen) and fraction planned dose received (PDR). Secondary endpoints included EBC outcome and incidence of haematological malignancies. Results: Over the 12-yr period, 1655 pts (62% node positive) with mean age of 51yr (24-88yr) were included. Chemotherapy given — n(%): Non-anthracycline(A)/taxane(T) 63(3.8); A 671(40.5); AT 666(40.2); T-only 255(15.4). Overall 64% of pts received G: PG given for TAC in 167(10); SG was given for first cycle G3/4N 677(41), FN 87(5) — 89% during first cycle, DN 109(7). Mean RDI and PDR was 0.97 v 0.95 and 0.98 v 0.97 for pts who received G and did not, respectively. Amongst pts aged &amp;lt; or ≥65yr, rate of G use and &amp;gt;85% PDR were comparable (65% v 66%; and 4% v 6%, respectively). Five cases of myelodysplasia or acute leukaemia were reported (4 pts received G) — 0.37% v 0.17% of pts having G or not, respectively. All cases received an anthracycline with cyclophosphamide. At median follow-up of 44.9 months [Q1: 25.1- Q3: 69.6], DFS was 88.9% and OS 92.6%. PDR &amp;lt;85% occurred in 5% pts, with OS of 78% v 93% if pts received &amp;lt; or ≥85%, respectively. Discussion: Significant rates of myelosuppression occur with regimens commonly used in the community. These regimens are not associated with FN rates &amp;gt;20% and thus PG is not advised. Routine monitoring of first-cycle neutrophil nadir enabled the identification of those pts at high risk of developing further neutropenic complications and consequent need for dose reduction or delay. Utilisation of G in these high risk pts enabled a high RDI to be delivered, comparable to pts who did not experience significant myelosuppression. Further, pts who did not develop significant first cycle myelosuppression were largely spared the need for G. In this manner, concerns regarding haematological toxicity and costs associated with G use are minimised. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-10.

Non-AIDS-Defining Hematologic Malignancies in HIV-Infected Patients: A Nationwide Epidemiologic Study in Japan

Abstract 2183 Background.The prevalence of HIV infection is estimated to be less than 0.1% in Japan; however, the number of newly reported HIV-infected persons has gradually increased, and the estimated number of HIV-infected patients now ranges from 6300 to 10000. Since the introduction of highly active antiretroviral therapy (HAART), the morbidity and incidence of AIDS-defining cancers has decreased. However, the incidence of non-AIDS-defining cancers has increased in Japan. To elucidate the incidence and clinical outcome of non-AIDS-defining hematologic malignancies, excluding non-Hodgkin's lymphomas, in HIV-infected patients, we conducted a nationwide epidemiologic study. Methods.We surveyed 429 regional AIDS centers and 497 educational hospitals certified by the Japanese Society of Hematology. Epidemiologic data for HIV was sourced from the Joint United Nations program on HIV/AIDS. Results.We obtained data from 511 institutes (55.4%). From 1991 to 2010, 47 cases of non-AIDS-defining hematologic malignancies were found—19 cases of Hodgkin’s lymphoma (HD), 13 of AML, 7 of ALL, 4 of CML, 2 of multiple myeloma, 1 of CLL, and 1 of MDS-RAEB1. The mean age was 49.3 years (21–70 years), and 93.6% patients were male. The mean CD4-positive cell count was 303.7/μL (1–1371/μL). The mean duration from the diagnosis of HIV infection to hematologic malignancy was 45.0 months (0–204 months). Before diagnosis, 68.1% patients had been treated with HAART and 51.1% patients had AIDS. Sixteen of 19 HD patients were treated with ABVD or radiation therapy. Of these, 80% patients achieved complete remission, with a 2-year overall survival of 62.3%. Twelve of AML and 6 of ALL patients were treated with standard induction chemotherapy. Eight of twelve patients (66.7%) with AML and five of six patients (83.3%) achieved complete remission. The median survival for both AML and ALL patients was 16 months, with 42.8% ALL and 30.8% AML patients alive after 4 years. Comparison of the last 2 decades (1991–2000 and 2001–2010) showed a 4.7-fold increase in the incidence of hematologic malignancies (11.5 vs. 54.6/100000 person-years). Conclusion.A nationwide epidemiologic study revealed that HIV-infected patients are at high risk of hematologic malignancies, and that the incidence of hematologic malignancies has increased in the past decade. The prognosis was equivalent to that of HIV-negative patients, and standard chemotherapy may be a feasible treatment option for HIV-infected patients with hematologic malignancies. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network

Background:Ascertainment of cases and disease classification is an acknowledged problem for epidemiological research into haematological malignancies.Methods:The Haematological Malignancy Research Network comprises an ongoing population-based patient cohort. All diagnoses (paediatric and adult) across two UK Cancer Networks (population 3.6 million, >2000 diagnoses annually, socio-demographically representative of the UK) are made by an integrated haematopathology laboratory. Diagnostics, prognostics, and treatment are recorded to clinical trial standards, and socio-demographic measures are routinely obtained.Results:A total of 10 729 haematological malignancies (myeloid=2706, lymphoid=8023) were diagnosed over the 5 years, that is, from 2004 to 2009. Descriptive data (age, sex, and deprivation), sex-specific age-standardised (European population) rates, and estimated UK frequencies are presented for 24 sub-types. The age of patients ranged from 4 weeks to 99 years (median 70.6 years), and the male rate was more than double the female rate for several myeloid and lymphoid sub-types, this difference being evident in both children and adults. No relationship with deprivation was detected.Conclusion:Accurate population-based data on haematological malignancies can be collected to the standard required to deliver reproducible results that can be extrapolated to national populations. Our analyses emphasise the importance of gender and age as disease determinants, and suggest that aetiological investigations that focus on socio-economic factors are unlikely to be rewarding.

A population-based study of the epidemiology and clinical features of adults with acute myeloid leukemia in Algeria: report on behalf of the Algerian Acute Leukemia Study Group

In Algeria, the incidence of hematologic malignancies has been difficult to estimate for many years. Today, many hematological centers, including 14 university hospitals, have been developed in the entire north and have useful epidemiological data pertinent to acute myeloid leukemia (AML). We studied the incidence of AML and its subtypes, age distribution, geographic distribution and trends in the rate of diagnosis over the last 5 years in Algeria. Secondary goals were to study trends of referral of AML cases from various regions to specific centers to assess the needs for health infrastructure and change of current practices. Retrospective analysis of nationwide survey of all adult cases of AML (>16 years) diagnosed between 1 January 2006 and 31 December 2010. A survey form was distributed to all departments of hematology at the 15 participating centers. The 1426 cases of AML diagnosed during the study period represented an annual incidence of 0.91/100000 persons with a male to female (M/F) ratio of 1:16 and a median age of 45 years (range, 16-82 years). Nationally, 20% of cases AML were diagnosed in the whole western region of the country, 47% in the central and 33% in the east. There was a trend of continuous increase in the rate with age and in the rate of diagnosis over the last 5 years. The most common subtype was M2, followed by M4 and M5. An overall increase in the number of AML patients diagnosed nationwide over the last five years indicates a need for additional health care resources including curative and therapy-intense strategies, such as stem cell transplant facilities to optimize outcome. The relatively younger age of patients compared to the Western countries may be due to the demographic composition of our population.

Vitamin, mineral, and specialty supplements and risk of hematologic malignancies in the prospective VITamins And Lifestyle (VITAL) study.

Increasing evidence suggests that nutrients from fruits and vegetables have chemoprotective effects on various cancers including hematologic malignancies, but the effects of nutritional supplements are poorly examined. Herein, we prospectively evaluated the association of vitamin, mineral, and specialty supplements with incident hematologic malignancies in 66,227 men and women aged 50 to 76 years from Washington State recruited from year 2000 to 2002 to the VITamins And Lifestyle (VITAL) cohort study. Hematologic malignancies cases (n = 588) were identified through December 2008 by linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry. HRs and 95% CIs associated with supplement use were estimated with Cox proportional hazards models. After adjustment, high use of garlic supplements [≥4 days per week for ≥3 years; HR = 0.55 (95% CI = 0.34-0.87); P(trend) = 0.028] and ever use of grape seed supplements [HR = 0.57 (95% CI = 0.37-0.88)] were inversely associated with hematologic malignancies in our models. In addition, high use (8-10 pill-years) of multivitamins was suggestive of an inverse association [HR = 0.80 (95% CI = 0.64-1.01)]. In contrast, no associations were observed for the remaining supplements. These data indicate that the use of garlic and grape seed may be associated with reduced risk of hematologic malignancies. This is the first cohort study to suggest a possible role of these supplements in the chemoprevention of hematologic malignancies.

Long-Term Use of Acetaminophen, Aspirin, and Other Nonsteroidal Anti-Inflammatory Drugs and Risk of Hematologic Malignancies: Results From the Prospective Vitamins and Lifestyle (VITAL) Study

Among previous studies examining the associations of over-the-counter analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs) and incident hematologic malignancies, results were inconsistent for NSAIDs but suggested an increased risk with acetaminophen (paracetamol). Herein, we used a large prospective cohort study to examine these associations. In total, 64,839 men and women age 50 to 76 years were recruited from 2000 to 2002 to the Vitamins and Lifestyle (VITAL) study. Incident hematologic malignancies (n = 577) were identified through December 2008 by linkage to the Surveillance, Epidemiology and End Results cancer registry. Hazard ratios (HRs) associated with use of analgesics for total incident hematologic malignancies and cancer subcategories were estimated by Cox proportional hazards models. Models were adjusted for age, sex, race/ethnicity, education, smoking, self-rated health, arthritis, chronic musculoskeletal pain, migraines, headaches, fatigue, and family history of leukemia/lymphoma. After adjustment, there was an increased risk of incident hematologic malignancies associated with high use (≥ 4 days/week for ≥ 4 years) of acetaminophen (HR, 1.84; 95% CI, 1.35 to 2.50 for high use; P trend = .004). This association was seen for myeloid neoplasms (HR, 2.26; 95% CI, 1.24 to 4.12), non-Hodgkin's lymphomas (HR, 1.81; 95% CI, 1.12 to 2.93), and plasma cell disorders (HR, 2.42; 95% CI, 1.08 to 5.41), but not chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; HR, 0.84; 95% CI, 0.31 to 2.28). By comparison, there was no association with risk of incident hematologic malignancies for increasing use of aspirin, nonaspirin NSAIDs, or ibuprofen. High use of acetaminophen was associated with an almost two-fold increased risk of incident hematologic malignancies other than CLL/SLL. Neither aspirin nor nonaspirin NSAIDs are likely useful for prevention of hematologic malignancies.

Safety and Risk of Allogeneic Peripheral Blood Stem Cell Donation: The Comprehensive Report of Nation-Wide Consecutively Pre-Registered 3,264 Family Donor Survey In 10years Project by Japan Society for Hematopoietic Cell Transplantation.

AbstractAbstract 1180 Background:Although peripheral blood stem cell (PBSC) donation has been considered safe and less stressful, certain fetal or life-threatening acute (within 30 days of post donation) adverse events as well as late occurrence of hematological malignancies have been reported among donors. Since the Japan Marrow Donor Program requires the confirmation of safety and risk of PBSC donation at family donors prior to applying this technique for volunteer donors, the Japan Society for Hematopoietic Cell Transplantation (JSHCT) performed nation-wide consecutive pre-registration and follow up for PBSC family donors from 2000 to 2010. This time, we report the comprehensive outcome of this project. Methods:The JSHCT mandated the registration of every PBSC family donor at the donor registration center then, issued donor identification number to each donor. The society required every harvest center to observe the JSHCT standards for donor eligibility, stem cell mobilization and harvest. The society also required to notify it of any severe adverse events, the results of the day30 clinical and laboratory check and of the annual health check for five years. Findings:Among 3,264 pre-registered donors, 47 emergency reports were submitted for 5 years and it was revealed that acute unexpectedly severe adverse events such as interstitial pneumonitis or anginal attack occurred at 0.58 % of donors although no mortality cases within 30 days of post donation were found. The relationship between donors' basic information such as age or gender and clinical and laboratory abnormalities obtained from 2,882 day 30 reports was studied and it revealed the followings; the risk factor for fatigue, headache, insomunia, anorexia and nausea was female, the risk factors for prolongation of hospitalized period were older age, low body weight, high total dose of granulocyte colony stimulating factor (G-CSF), the presence of past or current health problems and the episode of past stem cell donation, the risk factors for thrombocytopenia were older age and high total dose of G-CSF, the risk factors for splenomegary were older age and high total dose of G-CSF, the risk factors for poor CD34+ cell mobilization were older age, female and the episode of past stem cell donation, the risk factor for over CD34+ stem cell mobilization was younger age. The information from 6,233 annual health checks from 1,708 donors for 5 years showed the followings; the incidence of non-malignant but significant health problems was 1.5%, the incidence of non hematological malignancies was 0.7%, the incidence of hematological malignancy was 0.06%. It was also confirmed that the incidence of hematological malignancies among PBSC donors was not high compared with that among retrospectively surveyed bone marrow family donors. Interpretation:The consecutive donor pre-registration and annual follow up system that sets strict standards for donor eligibility, cell mobilization and harvest is effective in preventing real life-threatening acute adverse events and also is useful to know the real figures on PBSC donors and to assure donor safety. Such a system should be applied to all hematopoietic stem cell (family and volunteer, bone marrow and peripheral blood) donors. Disclosures:No relevant conflicts of interest to declare.

Long-Term Use of Acetaminophen, Aspirin, and Other Non-Steroidal Anti-Inflammatory Drugs and Risk of Hematologic Malignancies: Results From the Large, Prospective VITamins and Lifestyle (VITAL) Cohort Study

AbstractAbstract 2153 Background:Several epidemiological studies have examined the association of aspirin use and other over-the-counter analgesics or anti-inflammatory drugs and the incidence of hematologic malignancies. Although previous results have been inconsistent, some studies have suggested a reduced risk of leukemia or lymphoma with regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs). On the other hand, some but not all studies have reported an increased risk of leukemia or lymphoma with regular use of acetaminophen. Methods:We evaluated the association of analgesic use to hematologic malignancies in a prospective cohort of 64,839 men and women aged 50 to 76 years from Washington State recruited in 2000 to 2002 to the VITamins And Lifestyle (VITAL) study. Eligible participants completed a 24-page baseline questionnaire, including detailed questions about medication use during the previous 10 years. Incident cases of hematologic malignancies (n=577, including MDS [n=54], AML [n=36], myeloproliferative disorders [n=46], CLL/SLL [n=88] and other non-Hodgkin lymphomas [n=235], Hodgkin lymphomas [n=22], plasma cell disorders [n=66], mature NK/T cell neoplasms [n=17], and other entities [n=13]) were identified through December 2008 by linkage to the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry. The censored date was the date of withdrawal from the study, death, move out of the SEER catchment area, or last date of linkage to SEER for diagnosis of hematologic malignancy. In addition, participants were excluded if they had any cancer prior to baseline other than non-melanoma skin cancer and were censored at the time of diagnosis of a non-hematologic malignancy during follow-up to remove treatment for a prior cancer as a cause of any subsequent hematologic cancer. Medication use was categorized as “no use”, “low use” (use for either less than 4 days/week or less than 4 years), and “high use” (use for at least 4 days/week and at least 4 years). Hazards ratios (HRs) and 95% confidence intervals (95% CI) associated with use of acetaminophen, aspirin, and non-aspirin NSAIDs for total incident hematologic malignancies and cancer subcategories were estimated by Cox proportional hazards models. Multivariable-adjusted models were fit by adjusting for age, sex, race/ethnicity, education, smoking, self-rated health, history of fatigue/lack of energy, and family history of leukemia or lymphoma. All models except low-dose aspirin were further adjusted for history of rheumatoid arthritis, history or non-rheumatoid arthritis or chronic neck/back/joint pain, and history of migraines or frequent headaches. The model for low-dose aspirin was further adjusted for history of coronary artery disease, stroke, diabetes, or use of antihypertensive or lipid-lowering medications. Results:After adjustment, there was an increased risk of incident hematologic malignancies associated with increasing use of acetaminophen (HR=1.81 [95% CI: 1.33–2.46] for high use; p=0.009 for trend). The association with high use of acetaminophen was seen for MDS/AML (HR=2.23 [1.09-4.56]), non-Hodgkin lymphomas (HR=1.82 [1.14-2.92]), and plasma cell disorders (HR=2.32 [0.98-5.50]) but not CLL/SLL (HR=0.83 [0.30-2.35]). By comparison, there was no association with risk of incident hematologic malignancies for increasing use of low-dose aspirin (HR=1.04 [0.81-1.33] for high use; p=0.856 for trend), regular-dose aspirin (HR=0.86 [0.67-1.11] for high use; p=0.329 for trend), non-aspirin NSAIDs (HR=1.04 [0.75-1.43] for high use; p=0.820 for trend), or ibuprofen (HR=0.98 [0.67-1.44] for high use; p=0.956 for trend). Conclusion:Use of acetaminophen increased the risk of incident hematologic malignancies other than CLL/SLL in a usage-dependent manner, with an almost 100% increased risk for use least 4 days/week for of at least 4 years. Neither aspirin nor non-aspirin NSAIDs decreased risk and are unlikely to be useful for chemoprevention. Disclosures:No relevant conflicts of interest to declare.