Multiple Myeloma Mortality Research Articles

Association of BMI, Smoking, and Alcohol with Multiple Myeloma Mortality in Asians: A Pooled Analysis of More than 800,000 Participants in the Asia Cohort Consortium.

To date, few epidemiologic studies have been conducted to elucidate lifestyle-related risk factors for multiple myeloma in Asia. We investigated the association of body mass index (BMI), smoking, and alcohol intake with the risk of multiple myeloma mortality through a pooled analysis of more than 800,000 participants in the Asia Cohort Consortium. The analysis included 805,309 participants contributing 10,221,623 person-years of accumulated follow-up across Asia Cohort Consortium cohorts. HRs and 95% confidence intervals (95% CI) for the association between BMI, smoking, and alcohol at baseline and the risk of multiple myeloma mortality were assessed using a Cox proportional hazards model with shared frailty. We observed a statistically significant dose-dependent association between BMI categories and the risk of multiple myeloma mortality (<18.5 kg/m2: HR = 0.80, 95% CI: 0.52-1.24; 18.5-24.9 kg/m2: reference; 25.0-29.9 kg/m2: HR = 1.17, 95% CI: 0.94-1.47; ≥30 kg/m2: HR = 1.61, 95% CI: 0.99-2.64, P trend = 0.014). By sex, this association was more apparent in women than in men (P for heterogeneity between sexes = 0.150). We observed no significant associations between smoking or alcohol consumption and risk of multiple myeloma mortality. This study showed that excess body mass is associated with an increased risk of multiple myeloma mortality among Asian populations. In contrast, our results do not support an association between smoking or alcohol consumption and the risk of multiple myeloma mortality in Asian populations. This study provides important evidence on the association of BMI, smoking, and alcohol with the risk of multiple myeloma mortality in Asian populations.

Severe obesity does not worsen transplantation outcome in multiple myeloma

Obesity and severe obesity are increasingly prevalent in the United States. Epidemiological studies have shown an association between obesity and mortality in multiple myeloma (MM) (Br J Haematol 2014;166:667-676). Autologous peripheral blood stem cell transplantation (autoPBSCT) remains a crucial element in the treatment of MM. There is limited data analyzing the relationship between severe obesity and transplant outcomes in MM patients in the era of modern therapy, routine post-transplant maintenance, and genetic-based risk stratification.

Incidence and Mortality of Multiple Myeloma in China, 2006-2016: An Analysis of the Global Burden of Disease Study 2016

Background: The accurate information about burden of multiple myeloma (MM) at national and provincial level remain unknown in China. Methods: We used data from the Global Burden of Disease Study 2016 (GBD 2016) to calculate the burden of MM and to describe the temporal trend in China. Findings: It was estimated that there were 16 500 new cases and 10 300 deaths of multiple myeloma in China. The age-standardized incidence rates (ASIR) and mortality rates (ASMR) per 100 000 population were 1.03 (95%UI, 0.88-1.17) and 0.67 (95%UI, 0.59-0.77). Males had higher incidence and mortality rates than females in all age groups. An upward trend with age in incidence and mortality were observed. Furthermore, higher incidence and mortality rates clustered in those developed provinces. The incidence of MM in China increased significantly from 2006 to 2016, while the mortality increased from 2006 to 2014, and then remained stable from 2014 to 2016. Interpretation: The burden of MM had a heterogeneous pattern in China, which highlighted the need of differentiated disease prevention and control strategies in both national and provincial levels. Funding Statement: China Special Program for Basic Research 2014 from Ministry of Science and Technology (Grant number: 2014FY121100). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: Not required.

Understanding mortality in multiple myeloma: Findings of a European retrospective chart review.

ObjectivesThis study aimed to provide real‐world data on the characteristics and treatment of patients with multiple myeloma (MM) at the time of death.MethodsThe study was a retrospective patient chart review across France, Germany, Italy, Spain and the UK during 2016, and included patients who had died in the 3 months before the index date.ResultsData from 786 patients were reviewed. At the time of death, 37% of patients were receiving active treatment, 12% were in a treatment‐free interval and 51% were receiving only supportive care. Death before and during active first‐line treatment was not uncommon (6% and 24% of patients, respectively) but these deaths were often not solely due to disease progression; factors such as renal failure and infection frequently played a role (in 30% and 20% of patients at first‐line, respectively). Most deaths at later lines were due to progressive disease. Cox model results suggested that early deaths were associated with advanced disease stage, high‐risk cytogenetics and poor response and relapse profiles.ConclusionsThese real‐world data could be used to help develop strategies for improving survival in patients with MM and to support management tailored to the stage of disease.

PB2156 RISK FACTORS ASSOCIATED WITH EARLY MORTALITY IN PATIENTS WITH MULTIPLE MYELOMA

Background:Early mortality (EM) in multiple myeloma (MM) ranges from 4% to 25% mostly depending on the patients included and on treatment options. EM tends to be lower in clinical trials including younger, transplant‐eligible patients or in bortezomib‐ and lenalidomide‐based regimens in comparison with elderly patients and conventional chemotherapy treatment.Aims:To estimate risk factors associated with EM in patients with newly diagnosed MM.MethodsPatients with newly diagnosed MM were included into the study (from Jan 2013 to Feb 2019). EM was defined if it occurred within 1 year of entry into the study. Adverse cytogenetic abnormalities were specified as gain(1q), t(4;14), t(14;16), t(14;20) or del(17p).Results:A total of 174 patients with newly diagnosed MM (82 male, 92 female; median age 61 years) were involved in the study. Follow‐up period was 1‐71.4 months (median 8 months). The majority of patients developed an advanced stage of disease (Duriе‐Salmon stage 3–141 (81.1%), ISS stage 3–99 (56.9%)). All patients received chemotherapy regimens containing proteasome inhibitors as first‐line therapy and immunomodulatory drugs, intensive and conventional chemotherapy regimens as second‐ or next‐line therapy. During follow‐up period fatal outcome was observed in 45 (25.9%) of 174 patients, of them 16 (9.2%) patients with EM. Median early mortality was 4.7 months. The age of patients with EM and patients survived &gt; 1 year was comparable (median age 64.5 vs. 61, respectively). A larger proportion of patients with EM had Durie‐Salmon stage 3 (93.8% vs 79.7%), ISS stage 3 (75.0% vs 55.1%). Fish in situ hybridization analysis was conducted in 126 (72.4%) patients, adverse cytogenetic abnormalities were present in 4/8 (50.0%) patients with EM and 33/118 (27.9%) patients survived &gt;1 year. Risk factors assotiated with EM were ECOG performance status ≥ 3 score (87.5% vs 40.5%, p = 0.0003), C‐reactive protein level &gt; 10 mg/L (62.5% vs 26.6%, p = 0.007), high lactic acid dehydrogenase activity (81.3% vs 46.2%, p = 0.008), platelet count &lt; 150 × 109/L (43.8% vs 18.9%, p = 0.047) (tab.). For the 16 patients with EM, 11 (68.8%) of deaths were related to MM progression, 4 (25.0%) were due to infections and 1 (6.2%) ‐ heart failure.Summary/Conclusion:EM in patients with newly diagnosed MM was 9.2%. Risk factors associated with EM were poor performance status, elevated serum LDH activity, low platelet count, high serum C‐reactive protein.image

The risk of infections in multiple myeloma before and after the advent of novel agents: a 12-year survey.

Infections represent a major cause of morbidity and mortality in multiple myeloma and are linked to both therapy- and disease-related factors. Although it has been suggested that the rate of infections increased since the introduction of novel agents, controversies still exist. To better assess the risk factors associated with infections in the era of novel agents, we conducted a large retrospective analysis of 479 myeloma patients treated at Jena University Hospital over a period of 12years. During their disease history, 65% of patients developed at least one infection, and 37% of therapies were associated with at least one infectious episode. The rate of infections was constant over the years, with no increase in infectious complications after the routine implementation of novel agents. Infections were mainly bacterial and strongly associated with high disease burden, relapsed disease, and treatment with high-dose chemotherapy. Varicella zoster virus (VZV) reactivations occurred late during treatment (median time between high-dose chemotherapy and VZV reactivation 6months, range 0-44months), and fewer patients developed a VZV reactivation after 2009 (p = 0.001). Infections are still one of the major causes of morbidity in myeloma patients, and prophylactic measures are urgently needed to reduce this potentially lethal complication.

Dose-response relationships between internally-deposited uranium and select health outcomes in gaseous diffusion plant workers, 1948-2011.

To examine dose-response relationships between internal uranium exposures and select outcomes among a cohort of uranium enrichment workers. Cox regression was conducted to examine associations between selected health outcomes and cumulative internal uranium with consideration for external ionizing radiation, work-related medical X-rays and contaminant radionuclides technetium (99 Tc) and plutonium (239 Pu) as potential confounders. Elevated and monotonically increasing mortality risks were observed for kidney cancer, chronic renal diseases, and multiple myeloma, and the association with internal uranium absorbed organ dose was statistically significant for multiple myeloma. Adjustment for potential confounders had minimal impact on the risk estimates. Kidney cancer, chronic renal disease, and multiple myeloma mortality risks were elevated with increasing internal uranium absorbed organ dose. The findings add to evidence of an association between internal exposure to uranium and cancer. Future investigation includes a study of cancer incidence in this cohort.

Trends of incidence, mortality, and survival of multiple myeloma in Switzerland between 1994 and 2013

BackgroundTreatment of multiple myeloma has changed considerably over the last two decades with remarkable reduction in mortality rates in clinical trials and in population-based studies. Since health care systems and patient management differ between countries, population-based data from cancer registries with high coverage may provide further insight into real-life achievements and unmet needs. We report on the first population-based nation-wide study of incidence, mortality and survival of multiple myeloma in Switzerland covering the era of autologous stem cell transplantation and the first proteasome inhibitors and immunomodulatory drugs. MethodsWe performed a retrospective registry study with data from the National Institute for Cancer Epidemiology and Registration (NICER) database in Switzerland from 1994 to 2013. ResultsWe identified 5770 patients with multiple myeloma. Incidence has increased from 419 new cases per year in 1994–1998 to 557 new cases per year in 2009–2013 while the age-adjusted incidence rate remained stable at 4.7–5.0 per 100′000 person-years. Five- and 10-year relative survival increased from 32.6% (95%CI 29.3–36.0) and 17.8% (95%CI 14.9–21.0) in 1994–1998 to 46.4% (95%CI 43.3–49.3) and 25.0% (95%CI 21.9–28.3) in 2009–2013. ConclusionThe increase in incidence can be attributed to demographic changes. There is a trend to longer relative survival in all age groups with substantial increase in myeloma patients aged less than 75 years and only minimal changes in older persons.

Understanding Mortality In Multiple Myeloma (MM): Findings From An Observational Chart Review of Deceased Patients In The UK, France, Germany, Italy And Spain

Understanding Mortality In Multiple Myeloma (MM): Findings From An Observational Chart Review of Deceased Patients In The UK, France, Germany, Italy And Spain

Infectious complications in multiple myeloma receiving autologous stem cell transplantation in the past 10years.

Infection is one of the main causes of early-treatment mortality in multiple myeloma (MM) patients during autologous stem cell transplantation (autoSCT). In the present study, we sought to determine the incidence of, and risk factors for, infection during hospital stays after autoSCT. We retrospectively evaluated 324 autoSCT events that occurred in 285 MM patients between 2006 and 2015, and reviewed the clinical characteristics of patients and history of infections. Sixty-eight infection events occurred, including bacteremia (24), other bacterial infections (7), as well as infections caused by Cytomegalovirus (17), Herpes simplex virus (12), Varicella zoster virus (3), Aspergillus (3) and Pneumocystis jiroveci (2). There was no significant difference in number of infections in the 2006-2010 and 2011-2015 periods (P=0.194). Risk factors for bacteremia included higher beta-2 microglobulin levels at diagnosis [≥3.5mg/L; adjusted odds ratio (aOR) 3.544 (95% CI 1.070-11.736), P=0.038] and previous bortezomib treatment [aOR 4.270 (95% CI 1.389-13.125), P=0.011]. In-hospital mortality occurred in 1.2% of all cases and all were infection-related. In conclusion, infection was the main cause of in-hospital mortality in patients who underwent autoSCT. Bacteremia was the most common type of microbiologically confirmed infection, and was associated with higher beta-2 microglobulin levels and previous bortezomib treatment.

Multiple Myeloma Baseline Immunoglobulin G Level and Pneumococcal Vaccination Antibody Response.

Infections are a major cause of morbidity and mortality in multiple myeloma (MM), a cancer of the immune system. Vaccination clinical efficacy endpoints have not been demonstrated, and there are limited data on surrogate markers of efficacy. This pilot study evaluated sequential immunologic markers after standard pneumococcal vaccination (PV) in patients with MM and non-MM controls. Vaccination was standard for PV (PCV13 or PPV23), with laboratory testing at baseline and at 2, 4, 12 and 24 weeks after vaccination. Immunoglobulin G (IgG) antibodies to pneumococcal antigens were detected by ELISA. Prevaccination total IgG levels and IgG subclass levels were also measured by ELISA. Four of 6 controls responded with at least a 2-fold increase in antibody concentration; only 2 controls had a sustained increase in concentration. Six of 8 patients with MM had at least a 2-fold antibody increase; however, only 2 of these patients showed a sustained increase of antipneumococcal antibody. Response rate differences were not statistically significant in this small pilot, and there was no relationship between responsiveness to PV and initial serum total IgG levels or IgG subclasses at study entry. Future prospective studies are needed to ascertain the immunological and clinical efficacy and effectiveness of various vaccines and vaccination strategies in MM.

The impact of comorbidity on mortality in multiple myeloma: a Danish nationwide population-based study.

To describe the prevalence of comorbidity and its impact on survival in newly diagnosed multiple myeloma patients compared with population controls. Cases of newly diagnosed symptomatic multiple myeloma during the 2005–2012 period were identified in the Danish National Multiple Myeloma Registry. For each myeloma patient, 10 members of the general population matched by age and sex were chosen from the national Civil Registration System. Data on comorbidity in the myeloma patients and the general population comparison cohort were collected by linkage to the Danish National Patient Registry (DNPR). Cox proportional hazards regression models were used to evaluate the prognostic significance of comorbidity. The study included 2190 cases of multiple myeloma and 21,900 population controls. The comorbidity was increased in multiple myeloma patients compared with population controls, odds ratio (OR) 1.4 (1.1–1.7). The registration of comorbidity was highly increased within the year preceding diagnosis of multiple myeloma (OR 3.0 [2.5–3.5]), which was attributable to an increased registration of various diseases, in particular, renal disease with OR 11.0 (8.1–14.9). The median follow‐up time from diagnosis of multiple myeloma for patients alive was 4.3 years (interquartile range 2.4–6.3). Patients with registered comorbidity had increased mortality compared with patients without comorbidity, hazard ratio 1.6 (1.5–1.8). Multiple myeloma patients have increased comorbidity compared with the background population, in particular during the year preceding the diagnosis of myeloma.

Statins Are Associated With Reduced Mortality in Multiple Myeloma.

Purpose The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have activity in one of the pathways influenced by nitrogen-containing bisphosphonates, which are associated with improved survival in multiple myeloma (MM). To understand the benefit of statins in MM, we evaluated the association between statin use and mortality in a large cohort of patients with MM. Patients and Methods From the Veterans Administration Central Cancer Registry, we identified patients diagnosed with MM between 1999 and 2013. We defined statin use as the presence of any prescription for a statin within 3 months before or any time after MM diagnosis. Cox proportional hazards regression assessed the association of statin use with mortality, while controlling for known MM prognostic factors. Results We identified a cohort of 4,957 patients, of whom 2,294 received statin therapy. Statin use was associated with a 21% decrease in all-cause mortality (adjusted hazard ratio, 0.79; 95% CI, 0.73 to 0.86; P < .001) as well as a 24% decrease in MM-specific mortality (adjusted hazard ratio, 0.76; 95% CI, 0.67 to 0.86; P < .001). This association remained significant across all sensitivity analyses. In addition to reductions in mortality, statin use was associated with a 31% decreased risk of developing a skeletal-related event. Conclusion In this cohort study of US veterans with MM, statin therapy was associated with a reduced risk of both all-cause and MM-specific mortality. Our findings suggest a potential role for statin therapy in patients with MM. The putative benefit of statin therapy in MM should be corroborated in prospective studies.

Secondary immunodeficiency in lymphoproliferative malignancies

Secondary immunodeficiencies occur as a consequence of various diseases, including hematological malignancies, and the use of pharmacological therapies, such as immunosuppressive, anti-inflammatory, and biological drugs. Infections are the main cause of morbidity and mortality in multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients. Recent advances in treatment have prolonged the duration of remission and the time between relapse phases in MM and CLL patients. However, managing multiple relapses and the use of salvage therapies can lead to cumulative immunosuppression and a higher risk of infections. The pathogenesis of immune deficiency secondary to lymphoproliferative malignancy is multifactorial including disease- and treatment-related factors. Supportive treatment, including early vaccination, anti-infective prophylaxis, and replacement immunoglobulin, plays a key role in preventing infections in MM and CLL. This article provides an overview of the basic immunology necessary to understand the pathogenesis of secondary immunodeficiency and the infectious complications in MM and CLL. We also discuss the evidence supporting the role of prophylactic replacement immunoglobulin treatment in patients with antibody failure secondary to MM and CLL and the indications for its use. Copyright © 2016 John Wiley & Sons, Ltd.

Multiple Myeloma Mortality in Relation to Obesity Among African Americans.

Multiple myeloma (MM) incidence and mortality are higher among African Americans (AAs) than among other population groups. The prevalence of obesity is also elevated among AAs, but few studies have examined risk of this cancer in relation to body size among AAs. We combined data from seven prospective cohorts tracking mortality among 239 597 AA adults and used Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for death because of MM according to body mass index (BMI) at cohort entry, adjusted for age (as time-scale) and sex. Relative to those with normal BMIs (18.5-25 kg/m(2)), mortality increased monotonically as BMI increased, with hazard ratios reaching 1.43 (95% CI = 1.03 to 1.97) for BMIs of 35 kg/m(2) or greater. The findings suggest that obesity is a risk factor for MM and a contributor to the elevated rates and rising incidence trends of MM among AAs in the United States.

Early mortality in multiple myeloma: the time-dependent impact of comorbidity: A population-based study in 621 real-life patients.

Multiple myeloma is a heterogeneous disease with variable survival; this variability cannot be fully explained by the current systems of risk stratification. Early mortality remains a serious obstacle to further improve the trend toward increased survival demonstrated in recent years. However, the definition of early mortality is not standardized yet. Importantly, no study has focused on the impact of comorbidity on early mortality in multiple myeloma to date. Therefore, we analyzed the role of baseline comorbidity in a large population-based cohort of 621 real-life myeloma patients over a 31-year period. To evaluate early mortality, a sequential multivariate regression model at 2, 6, and 12 months from diagnosis was performed. It was demonstrated that comorbidity had an independent impact on early mortality, which is differential and time-dependent. Besides renal failure, respiratory disease at 2 months, liver disease at 6 months, and hepatitis virus C infection at 12 months, were, respectively, associated with early mortality, adjusting for other well-established prognostic factors. On the other hand, the long-term monitoring in our study points out a modest downward trend in early mortality over time. This is the first single institution population-based study aiming to assess the impact of comorbidity on early mortality in multiple myeloma. It is suggested that early mortality should be analyzed at three key time points (2, 6, and 12 months), in order to allow comparisons between studies. Comorbidity plays a critical role in the outcome of myeloma patients in terms of early mortality. Am. J. Hematol. 91:700-704, 2016. © 2016 Wiley Periodicals, Inc.

Early mortality in multiple myeloma: Experiences from a single institution

Objective: Multiple myeloma (MM) is a hematological malignancy that presents with infection, anemia, bone lesions, renal function impairment, and hypercalcemia. The survival of MM patients has improved in recent decades; however, early mortality remains a critical problem. The aim of this study was to identify the etiologies and clinical variables associated with early mortality in MM. In addition, the effects of bortezomib on reducing early mortality incidence were investigated.Method and materials: Medical records from 122 MM patients diagnosed between November 2007 and December 2013 were retrospectively reviewed. Early mortality was defined as death by any cause within the first 180 days after pathological diagnosis.Results: In newly diagnosed MM patients, early mortality occurred in 22.95% of patients. Infection accounted for 67.86% of early deaths. Multivariate analyses by Cox proportional-hazards regression showed that higher β2-microglobulin (P < 0.001) and serum lactate dehydrogenase (P < 0.001) levels, and lower serum albumin levels (P < 0.001) were associated with early mortality. Both first-line and greater than or equal to second-line bortezomib treatments were not associated with superior 180-day overall survival (P = 0.546 for first-line bortezomib treatment; P = 0.066 for greater than or equal to second-line bortezomib treatment).Conclusion: Our results suggest that infection is the leading cause of early death in MM. High β2-microglobulin, high serum lactate dehydrogenase, and low serum albumin levels are poor prognostic factors for early mortality. Bortezomib therapy does not appear to reduce the incidence of early mortality in MM patients.

The Role of County-Level Contextual Predictors in Multiple Myeloma Mortality

Background: Myeloma is the second most common hematologic malignancy in the US.. Prior studies elucidate that lower socio economic status (SES) and other social predictors such as education, poverty-line, income inequality and unemployment influence all-cause mortality and survival outcomes. We have explored the independent association of county-level contextual predictors on mortality among myeloma patients.Methods: Using SEER data from 18 registries across the US, with ICD-O-3 and morphologic (9732/3) codes, mortality data was examined from 1973-2012. Analysis was done on individual (race, sex and age of diagnosis) and county-level (SES, high school education, poverty level and unemployment). Differences in baseline characteristics at diagnosis across racial groups were analyzed using two-sided t-tests and ANOVA tests. Crude incidence and mortality rates and regression models were used for analysis. Statistics were computed using the National Cancer Institute SEER*Stat software, version 8.2.0. and SAS software, version 9.4 (SAS Institute Inc, Cary, NC).Results: The study population consisted of 89, 867 cases (68701 white, 16364 black and 4,802 other patients). Median age at diagnosis was lower for blacks vs. whites (66 vs. 71 years, P<0.01) and lower for females vs. males (69 vs. 71 years, P<0.01). The age-adjusted incidence rates and mortality rates per 100,000 populations were: blacks- 11.9 (95% CI 11.6, 12.1, P-value<0.05) and 10.2 (95% CI 9.9, 10.4, p<0.05); whites- 5.1 (95% CI 5.0, 5.2) and 4.3 (95% CI 4.3, 4.4); others- 3.7 (95% CI 3.6, 3.9) and 3.0 (95% CI 2.9, 3.1), respectively. ANOVA tests show black and other race are less likely to have received high school education compared to whites (P<0.0001). Similarly, black and other race was significantly associated with living below poverty line and unemployment when compared to whites (P<0.0001). A multivariate model showed gender, race, county-level SES and year of diagnosis to be independently associated with survival outcomes. Blacks showed reduced mortality (HR = 0.851, P<0.0001) as compared to whites. Conversely, middle and low SES were significantly associated with higher mortality compared to high SES (HR = 1.096 and 1.191; P <0.0001, respectively).Conclusions: To our knowledge, no previous studies have analyzed the independent association of county-level contextual predictors on mortality. Black patients have higher crude mortality rates compared to whites and other myeloma patients. After controlling for county-level contextual variables; blacks had comparatively lower mortality rates signifying the role of confounders between race and myeloma mortality. Lower SES is an independent risk factor for increased mortality. Further studies examining both, the racial biological disease variants in conjunction with contextual factors, are needed to bridge the gap. DisclosuresLonial:Novartis: Consultancy, Research Funding; Millennium: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Onyx: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Nooka:Onyx Pharmaceuticals: Consultancy; Spectrum Pharmaceuticals: Consultancy.

Ionising radiation and risk of death from leukaemia and lymphoma in radiation-monitored workers (INWORKS): an international cohort study

SummaryBackgroundThere is much uncertainty about the risks of leukaemia and lymphoma after repeated or protracted low-dose radiation exposure typical of occupational, environmental, and diagnostic medical settings. We quantified associations between protracted low-dose radiation exposures and leukaemia, lymphoma, and multiple myeloma mortality among radiation-monitored adults employed in France, the UK, and the USA.MethodsWe assembled a cohort of 308 297 radiation-monitored workers employed for at least 1 year by the Atomic Energy Commission, AREVA Nuclear Cycle, or the National Electricity Company in France, the Departments of Energy and Defence in the USA, and nuclear industry employers included in the National Registry for Radiation Workers in the UK. The cohort was followed up for a total of 8·22 million person-years. We ascertained deaths caused by leukaemia, lymphoma, and multiple myeloma. We used Poisson regression to quantify associations between estimated red bone marrow absorbed dose and leukaemia and lymphoma mortality.FindingsDoses were accrued at very low rates (mean 1·1 mGy per year, SD 2·6). The excess relative risk of leukaemia mortality (excluding chronic lymphocytic leukaemia) was 2·96 per Gy (90% CI 1·17–5·21; lagged 2 years), most notably because of an association between radiation dose and mortality from chronic myeloid leukaemia (excess relative risk per Gy 10·45, 90% CI 4·48–19·65).InterpretationThis study provides strong evidence of positive associations between protracted low-dose radiation exposure and leukaemia.FundingCenters for Disease Control and Prevention, Ministry of Health, Labour and Welfare of Japan, Institut de Radioprotection et de Sûreté Nucléaire, AREVA, Electricité de France, National Institute for Occupational Safety and Health, US Department of Energy, US Department of Health and Human Services, University of North Carolina, Public Health England.

Early mortality in multiple myeloma

The life expectancy of patients diagnosed with multiple myeloma (MM) in the US has improved substantially over the last two decades, a phenomenon affecting predominantly, but not exclusively, younger patients.1 This improvement in survival has been attributed to the broader use of autologous hematopoietic progenitor cell transplantation (AHPCT)2 and increasing availability of novel drugs both in the newly diagnosed and relapsed setting,1 as well as improved supportive care. The impact of these interventions in early mortality (EM, henceforth defined as death in the first year after the diagnosis) is less well known.