Daratumumab­resistant multiple myeloma with extramedullary disease successfully treated with combination elotuzumab, pomalidomide and dexamethasone: A case report.

Despite the emergence of monoclonal antibodies, the prognosis of patients with multiple myeloma (MM) with extramedullary disease remains poor. The present report describes a rare case of daratumumab-refractory MM that was successfully treated with elotuzumab, pomalidomide and dexamethasone. A 66-year-old male patient diagnosed with MM was treated with bortezomib, lenalidomide and dexamethasone, followed by high-dose chemotherapy and autologous stem cell transplantation. Thereafter, the patient was treated with lenalidomide and dexamethasone as maintenance therapy. This was changed to daratumumab, bortezomib and dexamethasone when new paraskeletal lesions were identified, resulting in marked tumor shrinkage. After 15 months, an increase in serum monoclonal protein levels, development of a skeletal lesion in the right second rib and extramedullary disease of the right thoracic mediastinal lymph nodes were noted. Treatment with elotuzumab, pomalidomide and dexamethasone (EPd) resulted in expeditious symptomatic improvement and regression of the lesions. Notably, during daratumumab, bortezomib and dexamethasone treatment, lymphocyte counts gradually increased to a level at which elotuzumab was sufficiently effective. EPd might be a promising strategy for the treatment of patients with relapsed extramedullary MM while on daratumumab treatment.

Mechanisms of action and resistance in histone methylation-targeted therapy.

Epigenomes enable the rectification of disordered cancer gene expression, thereby providing new targets for pharmacological interventions. The clinical utility of targeting histone H3 lysine trimethylation (H3K27me3) as an epigenetic hallmark has been demonstrated1-7. However, in actual therapeutic settings, the mechanism by which H3K27me3-targeting therapies exert their effects and the response of tumour cells remain unclear. Here we show the potency and mechanisms of action and resistance of the EZH1-EZH2 dual inhibitor valemetostat in clinical trials of patients with adult T cell leukaemia/lymphoma. Administration of valemetostat reduced tumour size and demonstrated durable clinical response in aggressive lymphomas with multiple genetic mutations. Integrative single-cell analyses showed that valemetostat abolishes the highly condensed chromatin structure formed by the plastic H3K27me3 and neutralizes multiple gene loci, including tumour suppressor genes. Nevertheless, subsequent long-term treatment encounters the emergence of resistant clones with reconstructed aggregate chromatin that closely resemble the pre-dose state. Acquired mutations at the PRC2-compound interface result in the propagation of clones with increased H3K27me3 expression. In patients free of PRC2 mutations, TET2 mutation or elevated DNMT3A expression causes similar chromatin recondensation through de novo DNA methylation in the H3K27me3-associated regions. We identified subpopulations with distinct metabolic and gene translation characteristics implicated in primary susceptibility until the acquisition of the heritable (epi)mutations. Targeting epigenetic drivers and chromatin homeostasis may provide opportunities for further sustained epigenetic cancer therapies.

Associations Between Lifestyle Factors and Constipation Among Survivors After the Great East Japan Earthquake: A 9-year Follow-up Study.

BACKGROUND: Disaster survivors experience deterioration in lifestyles and an increase in constipation. After the Great East Japan Earthquake in 2011, some survivors were evacuated for a long term, even after moving to temporary housing and public reconstruction housing. However, annual changes in constipation and the association between lifestyles and constipation among the survivors are still unknown. METHODS: Overall, 9,234 survivors aged 18 years or older participated in this 9-year follow-up survey after the disaster. Information about the prevalence of constipation and lifestyle factors (diet, physical activity, and mental health) was collected using a self-reported questionnaire. Their dietary intake was categorized into the following two dietary patterns: prudent (fish and shellfish, soybean products, vegetables, fruits, and dairy products) and meat (meat and eggs). Odds ratios for constipation according to lifestyle factors were calculated using a generalized linear mixed model. RESULTS: In women, the prevalence of constipation was the highest at baseline (8.7%) and remained around 5% afterward. In both men and women, older age, poor mental health, and poor physical activity were significantly associated with higher odds ratios of constipation. Moreover, a lower frequency of meals and a lower prudent dietary score were significantly associated with women's constipation. CONCLUSION: The prevalence of constipation was the highest at baseline and remained around 5% in women. Lifestyle factors, such as poor mental health, physical inactivity, and low frequency of meals were associated with constipation. Our findings suggest continuous support for the survivors with constipation for medium- to long-term after disasters.

[Acquired thrombotic thrombocytopenic purpura following COVID-19].

COVID-19 often contributes to thrombus formation in microvessels, resulting in damaged vital organs. In this study, we report a case of COVID-19 associated with acquired thrombotic thrombocytopenic purpura (TTP). A 44-year-old man with a history of systemic lupus erythematosus presented with COVID-19 and concomitant hemolytic anemia and a marked thrombocytopenia. The patient was diagnosed with acquired TTP because ADAMTS13 inhibitor was detected and ADAMTS13 activity below the sensitivity level. The patient developed agitated neuropsychiatric symptoms, such as aphasia, disorientation, and delirium, which improved after a plasma exchange, prednisolone, and rituximab administration. Only a few reports have revealed COVID-19 with TTP, and this is the first case in Japan. Although acquired TTP rarely develops, it is an important complication of COVID-19, and thus, it should be promptly diagnosed and treated as soon as possible.

Psychological distress in children and adolescent disaster survivors.

BACKGROUND: This study aimed to clarify the association between mental and behavioral changes and subsequent psychological distress among children and adolescents living in areas affected by the 2011 Great East Japan Earthquake. METHODS: We conducted a two-wave study, with waves 1 and 2 occurring in 2011 and 2014, respectively. Data of 462 respondents aged 9-14 years during wave 1 and who participated in both surveys were used in the present analysis. A factor analysis was performed using the mental and behavioral changes reported by respondents in wave 1. Psychological distress was defined as a score of ≥5 on the six-item Kessler Psychological Distress Scale, as measured in wave 2. With the factors generated in this analysis set as independent variables, the odds ratios (OR) (95% confidence intervals, 95% CIs) for psychological distress were calculated using logistic regression, adjusting for age, sex, house damage, living environment, and loss of family or friends. RESULTS: Psychological distress was present in 108 (23.4%) of the respondents. The factor analysis yielded three factors describing mental and behavioral changes: interpersonal issues, brain fog, and anxiety and panic. Of these, interpersonal issues were significantly associated with subsequent psychological distress, with an OR of 2.59 (95% CI 1.58-4.25). This association did not change even when stratified by age and sex. CONCLUSIONS: This study suggests that interpersonal issues are a significant predictor of psychological distress in children and adolescents living in areas affected by a large-scale disaster.

Anti-inflammatory effects of ruxolitinib on chronic neutrophilic leukemia harboring CSF3R-T618I mutation with bilateral renal abscesses.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by sustained mature neutrophilic leukocytosis. Recently, presence of colony-stimulating factor 3 receptor (CSF3R) mutations has been added to the diagnostic criteria for CNL. Anti-inflammatory effects of the JAK1/2 inhibitor ruxolitinib relieve constitutional symptoms associated with MPN, such as fatigue, night sweats, and fever. We present a case of CNL harboring CSF3R-T618I mutation exacerbated by concomitant bilateral renal abscesses, which was refractory to antibiotics, at the time of initial diagnosis. In this case, ruxolitinib rapidly improved not only CNL but the infection, due to its anti-inflammatory potency.

Seven-year incidence of new-onset hypertension by frequency of dairy intake among survivors of the Great East Japan Earthquake.

Survivors of natural disasters are at a high risk of cardiovascular disease. Behavioral risk factors, including modifiable diet, need to be identified. Thus far, the association between dairy intake and new-onset hypertension among these survivors is unknown. Therefore, we investigated this relationship. We conducted a longitudinal cohort study of 4475 survivors of the Great East Japan Earthquake in 2011 who participated in a 7-year follow-up survey. New-onset hypertension was assessed using annual health checkup data. Information on the frequency of dairy intake was obtained using a self-report questionnaire. The hazard ratio for developing hypertension according to the frequency of dairy intake was calculated using Cox proportional hazards regression models. The total number of person-years observed was 20,042, with a median follow-up of 5.4 years. During the observation period, 1554 individuals developed hypertension. The multivariable-adjusted hazard ratios of new-onset hypertension were significantly lower in those who consumed dairy products once per day (0.82, 95% confidence interval 0.71-0.94) and twice or more times per day (0.84, 95% confidence interval 0.71-0.99) than in nonconsumers; the inverse linear trend was marginally significant (P = 0.083). This association was not affected by lipid metabolism and was consistent across subgroups by sex, age, behavioral factors, cardiometabolic factors, and housing type due to the disaster. A higher frequency of dairy intake was associated with a lower risk of new-onset hypertension in community-dwelling survivors of earthquakes and tsunamis. Dietary guidance involving dairy intake could reduce the risk of developing hypertension among these survivors.

[Extranodal NK/T cell lymphoma, nasal type with local recurrence in the contralateral nasal cavity 15 years after initial sequential chemoradiotherapy].

A 72-year-old woman was diagnosed with extranodal NK/T cell lymphoma of the right nasal cavity and received sequential radiochemotherapy comprising focal radiotherapy and THP-COP chemotherapy. Showed a complete tumor response to the treatment; however, the tumor recurred in the contralateral right nasal cavity 15 years after the initial treatment. This was judged to be a marginal recurrence in the radiation field. After four cycles of dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy, a second complete response was achieved. It is possible that another recurrence occurs in the future, and if the lesion is localized at the time of recurrence, it may be possible to control the disease again. Careful follow-up is considered necessary.

[Listeria meningitis during daratumumab/bortezomib/dexamethasone therapy in a patient with multiple myeloma].

An 88-year-old woman was diagnosed with multiple myeloma received third-line chemotherapy, including DBd (daratumumab [DARA], bortezomib, and dexamethasone [Dex]), and the myeloma was in remission. Sulfamethoxazole/trimethoprim (ST) prophylaxis was discontinued because the dose of Dex was reduced to 20 mg every 4 weeks after 21 cycles of DBd. After 28 cycles of DBd, altered consciousness with fever ensued, and she was referred to the emergency department where Listeria monocytogenes (LM) meningitis was diagnosed. CD38 inactivation is associated with increased LM susceptibility. In patients on Dara-based chemotherapy, antibiotic prophylaxis should be considered using ST, which has activity against Listeria.

Association between the prevalence of hypertension and dairy consumption by housing type among survivors of the Great East Japan Earthquake.

Survivors of the Great East Japan Earthquake in 2011 had higher risks of cardiovascular diseases and hypertension, particularly residents of heavy flooding areas and evacuees. Thus far, the association between the prevalence of hypertension and dairy consumption remains unknown among these evacuees. We investigated this association by housing type after the Great East Japan Earthquake. In this cross-sectional study, we conducted a baseline survey among 9569 survivors of the earthquake, aged ≥18 years, between September 2011 and February 2012. Hypertension was defined as a systolic/diastolic blood pressure ≥140/90 mmHg or as persons undergoing treatment for high blood pressure. The frequency of dairy consumption was determined using a questionnaire. Participants living in prefabricated housing and emergency shelters were regarded as residents of temporary housing. Hypertension was prevalent among 43.8% and 44.7% of the participants in temporary and non-temporary housing, respectively. A logistic regression analysis of the prevalence of hypertension by daily dairy consumption showed that the magnitude of multivariable-adjusted odds ratios differed according to housing type (odds ratio, 0.64; 95% confidence interval, 0.51-0.80 in temporary housing; odds ratio, 0.85; 95% confidence interval, 0.73-0.995 in non-temporary housing; P for interaction = 0.0501). These associations were consistent across subgroups according to sex, age, behavioral factors, obesity, disorders of lipid metabolism, and economic status. A higher frequency of dairy consumption was associated with a lower prevalence of hypertension among community-dwelling survivors of earthquakes and tsunamis, particularly those living in temporary housing. Therefore, dietary therapy involving dairy consumption could help prevent hypertension among evacuees.

Psychological Distress in Responders and Nonresponders in a 5-year Follow-up Health Survey: The RIAS Study.

BACKGROUND: People with poor health or mental conditions are generally unwilling to participate in the health examinations, and no studies have directly examined the relationship of psychological distress among disaster survivors with participation status to date. The present study thus examined psychosocial differences according to the respondent status in a 5-year follow-up survey among participants in the prospective health surveys on survivors of the Great East Japan Earthquake and Tsunami Disaster study in Iwate Prefecture, Japan. METHODS: We analyzed data from 10,203 Japanese survivors aged ≥18 years (mean age, 65.6 years; 38.0% men) and who underwent health examinations at baseline in 2011. Participants were classified into responders and nonresponders according to their 2015 health examination participation status. Psychological distress was evaluated using the Kessler 6 scale and categorized as none, mild, and severe. Multinominal logistic regression was used to examine the risk of psychological distress in relation to participation status. RESULTS: In the 2015 survey, 6,334 of 6,492 responders and 1,686 of 3,356 nonresponders were analyzed. The most common reasons for nonparticipation in the survey were participated in other health examinations, examined at a hospital, and did not have time to participate. Nonresponse in males was associated only with mild psychological stress, whereas nonresponse in females was associated with mild and severe psychological distress. CONCLUSION: Nonresponders in the follow-up survey had a higher risk of psychological distress than responders. Continuous monitoring of the health of nonresponders and responders may help to prevent future health deterioration.

[Successful treatment with imatinib for a patient with myeloid neoplasms with eosinophilia and abnormalities of PDGFRB due to t (5;14)(q33;q22)].

A 50-year old man with a 1-year history of eosinophilia presented with an eosinophil count exceeding 13,800/mm3 in the peripheral blood at the first visit. Bone marrow examination revealed that eosinophils accounted for 30% of the nucleated cell count, and G-band karyotyping analysis detected t (5;14)(q33;q22). Using peripheral blood FISH test, he was found to have platelet-derived growth factor receptor ß (PDGFRB) locus rearrangement at 5q32-33. The level of eosinophils in the peripheral blood reduced markedly 3 days after the initiation of Imatinib mesylate, 400 mg daily. This treatment was administered for 2 years, after which the peripheral blood FISH test was negative for PDGFRB. In this disease, although most cases are with t (5;12), those with t (5;14) are relatively rare, and the long-term course of this translocation is unknown.

Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma.

Subclonal genetic heterogeneity and their diverse gene expression impose serious problems in understanding the behavior of cancers and contemplating therapeutic strategies. Here we develop and utilize a capture-based sequencing panel, which covers host hotspot genes and the full-length genome of human T-cell leukemia virus type-1 (HTLV-1), to investigate the clonal architecture of adult T-cell leukemia-lymphoma (ATL). For chronologically collected specimens from patients with ATL or pre-onset individuals, we integrate deep DNA sequencing and single-cell RNA sequencing to detect the somatic mutations and virus directly and characterize the transcriptional readouts in respective subclones. Characteristic genomic and transcriptomic patterns are associated with subclonal expansion and switches during the clinical timeline. Multistep mutations in the T-cell receptor (TCR), STAT3, and NOTCH pathways establish clone-specific transcriptomic abnormalities and further accelerate their proliferative potential to develop highly malignant clones, leading to disease onset and progression. Early detection and characterization of newly expanded subclones through the integrative analytical platform will be valuable for the development of an in-depth understanding of this disease.

The differences of poor SRH among municipalities in Iwate after the Great East Japan Earthquake.

The health of communities has been observed to recover at differential rates in the wake of disasters. In the present study, the 5-year trends in poor self-rated health (SRH) in three municipalities of Iwate Prefecture following the 2011 Great East Japan Earthquake and Tsunami were compared. Annual surveys were conducted from 2011 to 2015 in three municipalities (Otsuchi, Rikuzentakata, and Yamada) that were heavily damaged by the tsunami. We tracked the prevalence of poor SRH in 10,052 participants (mean age, 61.0 years; 39.0% men). Trends in the prevalence of poor SRH were analyzed using generalized linear mixed effect models with control for covariates. Immediately after the disaster (2011), all three municipalities reported similar prevalences of poor SRH (around 15%). Among people under the age of 65 years, there was a gradual improvement in health for residents of Rikuzentakata and Yamada, but the prevalence of poor SRH remained persistently high in Otsuchi. Among people over the age of 65 years, the prevalence of poor SRH remained constant in Rikuzentakata and Yamada but increased over a 5-year follow-up period in Otsuchi. The delayed health recovery in Otsuchi may be due to the characteristics of the local health system. Examination of the variations in health recovery may provide clues about the sources of disaster resilience.

[Falls and associated risk factors among elderly survivors of the Great East Japan Earthquake: RIAS Study].

Objective　An increasing incidence of disuse syndrome is commonly observed in areas affected by large-scale natural disasters. Consequently, the fall risk is high in such populations, necessitating adequate attention to fall prevention measures. It is important to identify factors associated with falls to prevent deterioration in functional ability. We investigated the risk factors associated with falls among elderly survivors in disaster-stricken areas using longitudinal data from the Research project for the prospective Investigation of health problems Among Survivors of the Great East Japan Earthquake (RIAS) Study.Methods　Of all data obtained from the RIAS Study, we used the data of 1,380 survivors who were aged ≥65 years, were not diagnosed with cancer or cardiovascular disease, did not need supportive care, and could participate in the annual survey between 2011 and 2016. Self-administered questionnaires were distributed, and anthropometric and grip tests were performed during the 2011 survey to obtain information regarding housing damage, the fear of falls, arthralgia, cognitive function psychological distress, insomnia, frequency of leaving the house, a history of hypertension, dyslipidemia, diabetes, alcohol consumption status, smoking status, and/or body mass index, and grip strength. Based on the responses obtained from each annual survey, a fall was defined as an event during which an individual had fallen at least once. Multivariate-adjusted odds ratio(OR) and 95% confidence interval(CI) for all variables related to falls were calculated using logistic regression with adjustment for sex and residential area. Similar analyses were performed based on age groups (65-74 years and ≥75 years).Results　The 5-year fall incidence rate was 35.5% (31.9% [men], 37.9% [women]). In men, cognitive dysfunction was significantly associated with falls (OR 1.50, 95%CI 1.01-2.22). In women, cognitive dysfunction (OR 1.82, 95%CI 1.34-2.47), insomnia (OR 1.41, 95%CI 1.02-1.94), dyslipidemia (OR 1.58, 95% 95% CI 1.11-2.25), and a history of smoking (OR 4.30, 95%CI 1.08-17.14) were significantly associated with falls. In women aged ≥75 years, partial housing damage (OR 7.93, 95%CI 1.85-33.91) and psychological distress (OR 2.83, 95%CI 1.09-.7.37) were also significantly associated with falls.Conclusion　This study suggests that cognitive dysfunction in both sexes and insomnia, dyslipidemia, and a history of smoking in women were significantly associated with falls, and partial housing damage and psychological distress were risk factors for falls in women aged ≥75 years. Fall prevention after large-scale natural disasters warrants close attention to known risk factors and environmental and mental health changes.

Overexpression of aberrant Wnt5a and its effect on acquisition of malignant phenotypes in adult T-cell leukemia/lymphoma (ATL) cells.

Wnt5a is a ligand of the non-canonical Wnt signaling pathway involved in cell differentiation, motility, and inflammatory response. Adult T-cell leukemia/lymphoma (ATL) is one of the most aggressive T-cell malignancies caused by infection of human T-cell leukemia virus type1 (HTLV-1). Among subtypes of ATL, acute-type ATL cells are particularly resistant to current multidrug chemotherapies and show remarkably high cell-proliferative and invasive phenotypes. Here we show a dramatic increase of WNT5A gene expression in acute-type ATL cells compared with those of indolent-type ATL cells. Treatment with IWP-2 or Wnt5a-specific knockdown significantly suppressed cell growth of ATL-derived T-cell lines. We demonstrated that the overexpression of c-Myb and FoxM1 was responsible for the synergistic activation of the WNT5A promoter. Also, a WNT5A transcript variant without the exon4 (the ΔE4-WNT5A mRNA), encoding ΔC-Wnt5 (1-136aa of 380aa), is overexpressed in acute-type ATL cells. The ΔC-Wnt5a is secreted extracellularly and enhances cellular migration/invasion to a greater extent compared with wildtype (WT)-Wnt5a. Moreover, the ΔC-Wnt5a secretion was not suppressed by IWP-2, indicating that this mutant Wnt5a is secreted via a different pathway from the WT-Wnt5a. Taken together, synergistic overexpression of the ΔC-Wnt5a by c-Myb and FoxM1 may be responsible for the malignant phenotype of acute-type ATL cells.

Five-year blood pressure trajectories of survivors of the tsunami following the Great East Japan Earthquake in Iwate.

Whether tsunami survivors who suffered substantial damage experienced increases in blood pressure (BP) immediately after the disaster and in the medium to long term is unclear. We divided tsunami survivors into groups, those who relocated (substantial damage) and those who did not (little damage) and compared the BP trajectories between the groups over the first 5 years after the disaster. Of the 42,831 residents, 3914 were assessed from 2010 to 2015. Subgroup analysis was performed among the 2037 subjects with no information on antihypertensive medications between 2010 and 2015 (no antihypertensive medication group). The BP trajectories in the relocation and no relocation groups were compared using linear mixed models. The multivariate-adjusted mean systolic BP (SBP) values for all subjects significantly decreased after the disaster in both the group who relocated (2010: 130.6 mmHg, 2015: 124.8 mmHg) and the group who did not relocate (2010: 130.7 mmHg, 2015: 126.7 mmHg). The interaction between relocation and time points on SBP was significant (P = 0.017). In the no antihypertensive medication group, the SBP values in the subgroup who relocated were significantly lower in the second, third, and fifth years after the disaster than those in the subgroup who did not relocate. It was concluded that the SBP values of survivors of the tsunami caused by Great East Japan Earthquake decreased in the medium to long term after the disaster, and the group who relocated had a larger decrease in SBP than the group who did not relocate.

Increase in Body Weight Following Residential Displacement: 5-year Follow-up After the 2011 Great East Japan Earthquake and Tsunami.

BACKGROUND: Previous studies have linked residential displacement as a result of the 2011 East Japan Earthquake to increases in body weight. However, no study has examined longer-term trajectories of body weight among displaced survivors. We compared body weight change between survivors relocated to temporary housing (TH) group versus other types of accommodation for up to 5 years after the Great East Japan Earthquake. METHODS: Longitudinal follow-up was conducted from 2011 to 2015 in a cohort of 9,909 residents of 42,831. We compared trends in body weight in the TH group (n = 3,169) and the non-TH group (n = 6,740) using a mixed linear regression model stratified by sex (mean age, 61.0 years old; male, 38.9%). RESULTS: In age-adjusted analysis, the body weight in the 2011 survey was not significantly different between two groups for either sex. In men, the TH group significantly increased body weight compared to the non-TH group since 2012. In women, body weight sharply increased in the TH group while body weight did not change in the non-TH group during survey time points. The interaction of living conditions and survey years was statistically significant in both sexes (men; F-value, 6.958; P < 0.001: women; F-value, 19.127; P < 0.001). CONCLUSION: Survivors relocated to temporary housing had an increased risk of weight gain. The weight gain in this group is a potential risk factor for metabolic syndrome in the post-disaster period.

Effect of temporary housing on incidence of diabetes mellitus in survivors of a tsunami-stricken area in 2011 Japan disaster: a serial cross-sectional RIAS study.

The association between incidence of diabetes mellitus (DM) and living conditions has not been studied after natural disasters. We compared the incidence of DM between individuals living in temporary housing (TH) and those living in other types of accommodation (non-TH) five years after the 2011 Great East Japan Earthquake. Longitudinal follow-up was conducted from 2011 to 2015 in a cohort of 7,491 residents of coastal communities in Iwate Prefecture directly impacted by the 2011 disaster (mean age, 61.6 years; men, 36.0%). We calculated the odds ratio of new onset of DM in the TH group (n = 2,372) compared with the non-TH group (n = 5,119) using discrete-time logit models stratified by sex and age classes (64 years or younger and older than 65 years). The TH group showed a significantly higher odds ratio (OR) for DM in men aged 64 years or younger (OR [95% confidence interval (CI)], 1.71 [1.03-2.85]; P-value = 0.040). In women, living conditions were not significantly associated DM. Survivors relocated to TH appeared to be at an increased risk of new onset DM.

Increased incidence of metabolic syndrome among older survivors relocated to temporary housing after the 2011 Great East Japan earthquake & tsunami.

BACKGROUND: Beyond the immediate toll of injuries and deaths, major disasters are often associated with long-term increased risks of chronic disease. We sought to investigate the incidence of metabolic syndrome (MetS) among survivors of the 2011 Great East Japan Earthquake and tsunami. METHODS: Subjects aged ≥18 years from the tsunami-stricken area participated in a prospective cohort study of disaster survivors (the RIAS Study) from 2011 to 2015. After excluding subjects who were previously diagnosed with MetS, we observed the cumulative incidence of MetS across four annual examinations among 7318 subjects (mean age, 59.8 years; 43.5% men). We defined MetS using the International Diabetes Foundation criteria. RESULTS: The 4-year cumulative incidence of MetS was 18.0% in the overall sample. The incidence was significantly higher among older women survivors relocated to prefabricated temporary housing (40.9%, 95% confidence interval, 36.4-44.6), and other types of housing (36.2%, 95% CI: 32.3-40.6) compared to those who were not relocated (34.1%, 95% CI: 30.9-37.4). An increase in incidence of MetS was not observed for older men, or younger survivors aged ≤64 years. CONCLUSION: Relocation to prefabricated temporary housing was a risk factor for increased incidence of MetS in older women.