Clinical impact and characteristics of erythroid dysplasia in adult aplastic anaemia: Results from a multicentre registry.

Morphological dysplasia in haematopoietic cells, defined by a 10% threshold in each lineage, is one of the diagnostic criteria for myelodysplastic neoplasms. Dysplasia limited to the erythroid lineage has also been reported in some cases of aplastic anaemia (AA); however, its significance remains unclear. We herein examined the impact of erythroid dysplasia on immunosuppressive therapy responses and survival in AA patients. The present study included 100 eligible AA patients without ring sideroblasts. Among them, 32 had dysplasia in the erythroid lineage (AA with minimal dysplasia [mini-D]). No significant sex or age differences were observed between AA groups with and without erythroid dysplasia. In severe/very severe AA and non-severe AA patients, a response to anti-thymocyte globulin + ciclosporin within 12 months was observed in 80.0% and 60.0% of AA with mini-D and 42.9% and 90.0% of those without dysplasia, with no significant difference (p = 0.29 and p = 0.24 respectively). Overall survival and leukaemia-free survival did not significantly differ between the groups. Collectively, the present results indicate that the presence of erythroid dysplasia did not significantly affect clinical characteristics or outcomes in AA patients, suggesting that its presence in AA is acceptable. Therefore, erythroid dysplasia should not exclude an AA diagnosis.

Clinical impact of myositis-specific autoantibodies on long-term prognosis of juvenile idiopathic inflammatory myopathies: multicentre study.

OBJECTIVES: This study aimed to investigate the clinical characteristics, treatment and prognosis of juvenile idiopathic inflammatory myopathies (JIIM) in Japan for each myositis-specific autoantibody (MSA) profile. METHODS: A multicentre, retrospective study was conducted using data of patients with JIIM at nine paediatric rheumatology centres in Japan. Patients with MSA profiles, determined by immunoprecipitation using stored serum from the active stage, were included. RESULTS: MSA were detected in 85 of 96 cases eligible for the analyses. Over 90% of the patients in this study had one of the following three MSA types: anti-melanoma differentiation-associated protein 5 (MDA5) (n = 31), anti-transcriptional intermediary factor 1 alpha and/or gamma subunits (TIF1γ) (n = 25) and anti-nuclear matrix protein 2 (NXP2) (n = 25) antibodies. Gottron papules and periungual capillary abnormalities were the most common signs of every MSA group in the initial phase. The presence of interstitial lung disease (ILD) was the highest risk factor for patients with anti-MDA5 antibodies. Most patients were administered multiple drug therapies: glucocorticoids and MTX were administered to patients with anti-TIF1γ or anti-NXP2 antibodies. Half of the patients with anti-MDA5 antibodies received more than three medications including i.v. CYC, especially patients with ILD. Patients with anti-MDA5 antibodies were more likely to achieve drug-free remission (29 vs 21%) and less likely to relapse (26 vs 44%) than others. CONCLUSION: Anti-MDA5 antibodies are the most common MSA type in Japan, and patients with this antibody are characterized by ILD at onset, multiple medications including i.v. CYC, drug-free remission, and a lower frequency of relapse. New therapeutic strategies are required for other MSA types.

External validation of the EULAR/ACR idiopathic inflammatory myopathies classification criteria with a Japanese paediatric cohort.

OBJECTIVES: To assess the performance of the EULAR/ACR idiopathic inflammatory myopathies (IIMs) classification criteria to classify juvenile IIMs (JIIMs) in an Asian paediatric population. METHODS: Sixty-eight JIIM patients and 49 non-JIIM patients diagnosed at seven major paediatric rheumatology centres in Japan between 2008 and 2015 were enrolled. Retrospective data were collected, and each patient's data form was submitted. The expert group reviewed the forms and re-examined the diagnoses. The EULAR/ACR criteria were then applied and the probability of having JIIM was determined for each case. The sensitivity and specificity of the EULAR/ACR criteria were compared with those of other existing criteria. RESULTS: The sensitivity/specificity of the EULAR/ACR classification criteria were 92.1/100% with muscle biopsy data (n = 38); 86.7/100% without muscle biopsy data (n = 30) and 89.7/100% in our total cohort (n = 68). The sensitivity of Bohan and Peter's criteria and Tanimoto's criteria were 80.9 and 64.7% in our total cohort, respectively. Among 68 physician-diagnosed JIIM patients, seven cases (three JDM and four overlap myositis) were not classified as JIIM because the probability did not reach the cut-off point (55%). The three JDM patients all presented with only one of the three skin manifestations that are listed in the criteria: Gottron's sign. CONCLUSION: Our validation study with Japanese JIIM cases indicates that the EULAR/ACR classification criteria for IIM generally perform better than existing diagnostic criteria for myositis.

First external validation of sensitivity and specificity of the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for idiopathic inflammatory myopathies with a Japanese cohort.

OBJECTIVE: To externally validate the performance of the new European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria set for idiopathic inflammatory myopathies (IIM) with a Japanese cohort. METHODS: This study included 420 IIM and 402 non-IIM cases. Probability of having IIM in each patient was calculated using the collected data set. The cut-off probability was set at 55%, as recommended by EULAR/ACR. Patients classified as IIM by the criteria were further subclassified with classification trees. RESULTS: When the probability cut-off was set at 55%, the sensitivity/specificity of the new criteria to diagnose IIM were 89.3%/91.0% in the total cohort, 88.1%/95.1% without muscle biopsy data and 90.4%/65.5% with biopsy data. The cohort included 12 overlap syndrome patients with biopsy data, who were included as non-IIM cases in accordance with traditional Japanese methods. When they were included in the IIM cases, the specificity in patients with biopsy increased to 74.4%. The sensitivity/specificity of the new criteria to diagnose polymyositis/dermatomyositis (PM/DM) plus juvenile and amyopathic DM in the Japanese cohort was 87.4%/92.4%, which were greater than those of the Tanimoto's criteria revised to enable classification of amyopathic DM (ADM) (71.2%/87.8%) and were comparable with those of Bohan & Peter's criteria to diagnose those diseases except for ADM (88.4%/88.3%). CONCLUSIONS: Our study externally validated high specificity of the new criteria for the first time, although with several limitations, including low percentage of child patients. The new criteria have higher sensitivity and/or specificity in classification of PM/DM than the previously reported criteria, demonstrating its usefulness for interethnic patients.

Estimating nationwide cases of sexually transmitted diseases in 2015 from sentinel surveillance data in Japan.

BACKGROUND: The rates of newly diagnosed cases of sexually transmitted diseases, including genital chlamydial infection and gonorrhea, are important for prevention and control of these diseases. However, nationwide rates are not reported in Japan. METHODS: We used the number of cases of sexually transmitted diseases reported by nationwide sentinel surveillance in 2015, together with the number of all disease outpatients in September 2014 at all medical institutions, drawn from the Survey of Medical Institutions of Japan. The number of cases of sexually transmitted diseases in the total population was estimated using the ratio estimation method with the number of all disease outpatients as auxiliary information. This method is currently used for estimating influenza cases from sentinel surveillance data in Japan. RESULTS: The estimated number of newly diagnosed cases per 100,000 population in 2015 in Japan was 244 (95% confidence interval 211-277) for genital chlamydial infection, 87 (95% confidence interval 74-100) for genital herpes, 61 (95% confidence interval 29-93) for condyloma acuminatum, and 89 (95% confidence interval 64-113) for gonorrhea. CONCLUSION: We estimated the nationwide number of newly diagnosed cases of sexually transmitted diseases in Japan from sentinel surveillance data. This provides useful information for public health policy-making.

Treatment consensus for management of polymyositis and dermatomyositis among rheumatologists, neurologists and dermatologists.

Although rheumatologists, neurologists and dermatologists see patients with polymyositis (PM) and dermatomyositis (DM), their management appears to vary depending on the physician's specialty. The aim of the present study was to establish the treatment consensus among specialists of the three fields to standardize the patient care. We formed a research team supported by a grant from the Ministry of Health, Labor and Welfare, Japan. Clinical questions (CQ) on the management of PM and DM were raised. A published work search on CQ was performed primarily using PubMed. Using the nominal group technique, qualified studies and results in the published work were evaluated and discussed to reach consensus recommendations. They were sent out to the Japan College of Rheumatology, Japanese Society of Neurology and Japanese Dermatological Association for their approval. We reached a consensus in 23 CQ and made recommendations and a decision tree for management was proposed. They were officially approved by the three scientific societies. In conclusion, a multidisciplinary treatment consensus for the management of PM and DM was established for the first time.

Clinical practice guideline for Sjögren's syndrome 2017.

OBJECTIVES: The objective of this study is to develop clinical practice guideline (CPG) for Sjögren's syndrome (SS) based on recently available clinical and therapeutic evidences. METHODS: The CPG committee for SS was organized by the Research Team for Autoimmune Diseases, Research Program for Intractable Disease of the Ministry of Health, Labor and Welfare (MHLW), Japan. The committee completed a systematic review of evidences for several clinical questions and developed CPG for SS 2017 according to the procedure proposed by the Medical Information Network Distribution Service (Minds). The recommendations and their strength were checked by the modified Delphi method. The CPG for SS 2017 has been officially approved by both Japan College of Rheumatology and the Japanese Society for SS. RESULTS: The CPG committee set 38 clinical questions for clinical symptoms, signs, treatment, and management of SS in pediatric, adult and pregnant patients, using the PICO (P: patients, problem, population, I: interventions, C: comparisons, controls, comparators, O: outcomes) format. A summary of evidence, development of recommendation, recommendation, and strength for these 38 clinical questions are presented in the CPG. CONCLUSION: The CPG for SS 2017 should contribute to improvement and standardization of diagnosis and treatment of SS.

Epidemiologic analysis of the clinical features of Japanese patients with polymyositis and dermatomyositis.

OBJECTIVES: This study aimed to investigate the clinical characteristics of polymyositis/dermatomyositis (PM/DM) in Japan by analyzing data from the nationwide registration system. METHODS: The data of the registration system in 2009 were analyzed to investigate patient numbers, sex, clinical symptoms, therapies, complications, and prognosis of PM/DM. RESULTS: The total number of PM/DM cases was approximately 17,000, and the female/male sex ratio was 2.7:1. Almost all patients improved as a result of therapy, but many suffered from sequelae such as muscle weakness. CONCLUSIONS: The results characterize significant aspects of Japanese PM/DM patients. However, a further prospective survey is required to clarify the true epidemiology and natural history of PM/DM.

Extracellular adenosine controls NKT-cell-dependent hepatitis induction.

Extracellular adenosine regulates inflammatory responses via the A2A adenosine receptor (A2AR). A2AR deficiency results in much exaggerated acute hepatitis, indicating nonredundancy of adenosine-A2AR pathway in inhibiting immune activation. To identify a critical target of immunoregulatory effect of extracellular adenosine, we focused on NKT cells, which play an indispensable role in hepatitis. An A2AR agonist abolished NKT-cell-dependent induction of acute hepatitis by concanavalin A (Con A) or α-galactosylceramide in mice, corresponding to downregulation of activation markers and cytokines in NKT cells and of NK-cell co-activation. These results show that A2AR signaling can downregulate NKT-cell activation and suppress NKT-cell-triggered inflammatory responses. Next, we hypothesized that NKT cells might be under physiological control of the adenosine-A2AR pathway. Indeed, both Con A and α-galactosylceramide induced more severe hepatitis in A2AR-deficient mice than in WT controls. Transfer of A2AR-deficient NKT cells into A2AR-expressing recipients resulted in exaggeration of Con A-induced liver damage, suggesting that NKT-cell activation is controlled by endogenous adenosine via A2AR, and this physiological regulatory mechanism of NKT cells is critical in the control of tissue-damaging inflammation. The current study suggests the possibility to manipulate NKT-cell activity in inflammatory disorders through intervention to the adenosine-A2AR pathway.

Hypoxia-induced and A2A adenosine receptor-independent T-cell suppression is short lived and easily reversible.

Tissue hypoxia plays a key role in establishing an immunosuppressive environment in vivo by, among other effects, increasing the level of extracellular adenosine, which then signals through A2A adenosine receptor (A2AR) to elicit its immunosuppressive effect. Although the important role of the adenosine--A2AR interaction in limiting inflammation has been established, the current study revisited this issue by asking whether hypoxia can also exert its T-cell inhibitory effects even without A2AR. A similar degree of hypoxia-triggered inhibition was observed in wild-type and A2AR-deficient T cells both in vitro and, after exposure of mice to a hypoxic atmosphere, in vivo. This A2AR-independent hypoxic T-cell suppression was qualitatively and mechanistically different from immunosuppression by A2AR stimulation. The A2AR-independent hypoxic immunosuppression strongly reduced T-cell proliferation, while IFN-γ-producing activity was more susceptible to the A2AR-dependent inhibition. In contrast to the sustained functional impairment after A2AR-mediated T-cell inhibition, the A2AR-independent inhibition under hypoxia was short lived, as evidenced by the quick recovery of IFN-γ-producing activity upon re-stimulation. These data support the view that T-cell inhibition by hypoxia can be mediated by multiple mechanisms and that both A2AR and key molecules in the A2AR-independent T-cell inhibition should be targeted to overcome the hypoxia-related immunosuppression in infected tissues and tumors.

Number of sentinel medical institutions needed for estimating prefectural incidence in influenza surveillance in Japan.

BACKGROUND: The sentinel surveillance system in Japan provides estimates of nationwide influenza incidence. Although prefectural influenza incidences can be estimated using data from the current surveillance system, such estimates may be imprecise. METHODS: We calculated the numbers of sentinel medical institutions (SMIs) needed in the surveillance system to estimate influenza incidences in prefectures, under the assumption that the standard error rates in 75% of influenza epidemic cases are less than 10%. Epidemic cases observed in 47 prefectures during the 2007/2008, 2008/2009, and 2009/2010 seasons, respectively, were used. RESULTS: The present total number of SMIs was 6669. With respect to current standards, the increases required in prefectures ranged from 0 to 59, and the total increase required in the number of SMIs was 1668. CONCLUSIONS: We used sentinel surveillance data for Japan to calculate the number of SMIs required to estimate influenza incidence in each prefecture.

Prevalence and incidence of polymyositis and dermatomyositis in Japan.

OBJECTIVES: To estimate the number of patients with polymyositis/dermatomyositis (PM/DM) in Japan and the prevalence rate and incidence rate of the disease. METHODS: The electronic database in the nationwide registration system on intractable diseases from 2003 to 2010 was utilized to identify the number of prevalent and incident cases of PM/DM. The electronic data entry rate was used to establish the total number of registered cases. RESULTS: The estimated total number of patients with PM/DM and the prevalence rate in Japan in 2010 were 17,000 and 13.2 per 100,000 population, respectively. The prevalence of PM/DM ranged from 10 to 13 per 100,000 population with a trend toward increasing over time. The incidence of PM/DM was estimated within the range 10-13 per 1,000,000 person-years, except for 2003. CONCLUSIONS: We report the prevalence and incidence of PM/DM recently in Japan for the first time at the nationwide population level. Because the prevalence seems to be increasing recently, continued monitoring of these epidemiologic features is required.

Primary and secondary surveys on epidemiology of Sjögren's syndrome in Japan.

OBJECTIVE: To characterize the epidemiology of Sjögren's syndrome (SS), including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatment used in Japan. METHODS: The Research Team for Autoimmune Diseases, the Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare conducted primary and secondary surveys on epidemiology of SS in 2011. The primary survey covered 4,729 out of 14,095 Japan-wide Hospital Departments to investigate the prevalence of SS. The secondary survey encompassed 214 Hospital Departments that agreed to the survey, to characterize disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets, and treatments. RESULTS: The number of patients with SS in Japan estimated by the primary survey was 68,483. The secondary survey involving data collected from 2,195 SS patients from 98 Hospital Departments showed that the mean age of patients was 60.8 ± 15.2 years, male/female ratio was 1/17.4, primary/secondary SS was about 60%/40% and glandular/extra-glandular form in primary SS was about 70%/25%. The satisfaction rate was 53.8% for the 1999 revised Japanese Ministry of Health criteria for the diagnosis of SS, 47.7% for the 2002 American-European Consensus Group classification criteria for SS and 49.6% for 2012 American College of Rheumatology classification criteria for SS. Corticosteroids were used by 752 of 2,195 patients (34%), immunosuppressants by 358 patients (16%), biologics by 68 patients (3%) and secretagogues by 695 patients (32%). CONCLUSION: The surveys provided valuable information on the epidemiology of SS including prevalence, disease type, extra-glandular involvement, satisfaction of diagnostic criteria sets and treatments used today in Japan.

[The effect of determining birthdays by social factors such as maternal preference on the distribution in the number of daily live births].

OBJECTIVES: To investigate the effect of determining birthdays by social factors on the distribution of daily live births. METHODS: We obtained data on live births tabulated by date and birthplace (hospitals, clinics, and maternity homes) between 1981 and 2010 in Japan from the National Vital Statistics System. This study analyzed the variations in live births for each day of the week, as well as for several specific days observed to have a systematic variation in the number of live births. We determined the ratio of the mean daily live births on those specific days to the overall daily average each month (the birth number ratio). The standardized deviation (the ratio of the deviation to the standard deviation for the day of week) regarding the birth number ratio of each specific day was also determined. RESULTS: The birth number ratio in hospitals and clinics was highest on Tuesdays and lowest on Sundays. Hospitals showed a large difference in the birth number ratio between weekdays and weekends, although the difference in the birth number ratio between weekdays and Saturdays was smaller in clinics than in hospitals. The birth number ratio during the first three days of the New Year was lower than that on Sundays. Until approximately 1995, the standardized deviation on February 29th and April 1st (the end of the Japanese school year) showed abnormally low values, while those on March 1st and April 2nd showed significantly high values. Following that time period, the significant variations on February 29th (only on Sundays), April 1st (only on Sundays), March 1st, and April 2nd almost completely disappeared. Maternity homes showed equivalent results until the 1980s or the middle of the 1990s. CONCLUSION: The variations in the days of the week were inconsistent with nationwide policies for consultation in each setting. These results indicate that some birth dates were set for institutional reasons or maternal preferences (i.e., the day after the leap day or the next school year) by using or avoiding obstetric intervention. The abnormal variation on leap days and on April 1st might be related to fictitious reporting. More recent variations in the birth number ratio on specific days suggest that some individuals may avoid obstetric intervention. The results of this study indicate that determining birthdays by social factors may have been practiced in maternity homes until approximately 1990.

Homebound older adults who live independently in rural Japan: Prevalence and contributing factors during the COVID-19 pandemic.

Being homebound is a phenomenon of confining older adults to their homes owing to health, social, and psychological factors. During the COVID-19 pandemic, people were requested to refrain from going out to prevent infection. Consequently, the homebound status of older adults was influenced by social and environmental factors, resulting in an increase in the number of homebound older adults during the pandemic. This study aimed to determine the homebound prevalence and related factors among homebound older adults during the COVID-19 pandemic. In 2021, a cross-sectional study conducted in rural Saitama, Japan, included 1,020 participants aged 65 years and above who did not have long-term care insurance certification and were independent in instrumental activities of daily living. Herein, homebound individuals were defined as those who went out once a week or less. The relationships of homebound status with demographic, health, social, and psychological factors in older adults were examined. The prevalence of homebound independent older adults was estimated as 10.4 % (6.6 % males, 13.8 % females). Homebound status was significantly associated with one or more medical histories (odds ratio [OR] = 1.98, 95 % confidence interval [CI] = 1.00-3.90), no social or family roles (OR = 1.95, 95 % CI = 1.09-3.48), and no hobbies (OR = 1.84, 95 % CI = 1.02-3.34). Establishing social or family roles and promoting participation in hobbies may prevent older adults from being homebound. The social environment, which changed during the pandemic, should be improved to encourage older adults to go out.

Age at onset and gender distribution of systemic lupus erythematosus, polymyositis/dermatomyositis, and systemic sclerosis in Japan.

OBJECTIVES: The aim of this study was to describe age, gender distribution, and age at onset of systemic lupus erythematosus (SLE), polymyositis/dermatomyositis (PM/DM), and systemic sclerosis (SSc) in Japan. METHODS: We used epidemiological information on 21,405, 6,327, and 10,058 patients with SLE, PM/DM, and SSc, respectively, in a Japanese nationwide registration database of patients with intractable diseases. RESULTS: All three diseases occur predominantly in women, with the female-to-male ratio being 8.2:1, 2.6:1, and 7.7:1 for SLE, PM/DM, and SSc, respectively. The most susceptible age for SLE is 15-44 and 20-39 years for males and females, respectively. For PM/DM it is 45-64 and 40-64 years and for SSc, 50-69 and 40-59 for men and women, respectively. CONCLUSIONS: The basic descriptive epidemiological characteristics of SLE, PM/DM, and SSc in Japan, such as gender distribution, present age, and age at onset, were surveyed nationwide for fiscal 2007. It was found that these characteristics were similar to those in Western populations. Our finding provides new information on the natural history of disease development.

Clinical value of therapeutic drug monitoring for levetiracetam in pediatric patients with epilepsy.

PURPOSE: To identify pediatric patients who require therapeutic drug monitoring (TDM) of levetiracetam (LEV). METHODS: We retrospectively investigated 2413 routine therapeutic drug monitoring data on serum LEV concentration from 1398 pediatric patients (age, 0-15 years). Samples were grouped by age (infants, < 1 year; preschool children, 1-5 years; primary school children, 6-11 years; and adolescents, 12-15 years), and the LEV concentration-to-dose (CD) ratio was calculated. RESULTS: The mean CD ratio was highest in adolescents (analysis of variance, p < 0.001); 22.5 % and 15.7 % higher in adolescents than in preschool children and school children, respectively (Scheffé test, p < 0.001); and higher in infants than in preschool children. Preschool children had the lowest ratio and tended to show an increase in the ratio from age 2 to 5 years. Use of enzyme-inducing antiseizure medication reduced the CD ratio by 6.1 % in infants, 12.2 % in preschool children, 5.9 % in primary school children, and 9.4 % in adolescents. The mean CD ratio was 2.7 %, 26.9 %, and 39.3 % higher in preschool children, primary school children, and adolescents with defined chronic kidney disease (CKD) than in the respective age group of patients without CKD. The therapeutic concentration range for a long-term LEV therapy was 11 to 32 µg/mL. CONCLUSIONS: LEV pharmacokinetics are significantly different between infant and preschool children, so TDM of LEV is clinically useful in these patients. In pediatric patients at higher risk for CKD, glomerular filtration rate and LEV levels should be carefully monitored.

Incidence trends and risk factors for hyponatremia in epilepsy patients: A large-scale real-world data study.

Objective: This study aimed to evaluate the annual incidence and risk factors of hyponatremia in pediatric, adult, and older adult patients with epilepsy. Methods: We enrolled 26,179 patients: 8598 pediatric patients (aged 0-15 years), 16,476 adults (aged 16-64 years), and 1105 older adults (aged ≥65 years). Patients were included if their serum sodium levels were measured between January 2006 and December 2020. Moderate-severe hyponatremia was defined as a serum sodium level of less than 130 mEq/L. Results: From 2006 to 2020, 677 patients (2.6%) developed moderate-severe hyponatremia. The incidence of hyponatremia per 1000 person-years was 3.1 in the pediatric group, 19.8 in the adult group, and 50.4 in the older adult group. The incidence increased markedly from 36.8 in 2007 to 58.5 in 2020 in the older adult group but remained unchanged in the adult group and tended to decrease in the pediatric group. In the multiple logistic regression model, use of carbamazepine, valproate, phenytoin, phenobarbital, benzodiazepines, and antipsychotics was found to be a significant risk factor for hyponatremia. In adult patients, carbamazepine, benzodiazepine, and antipsychotics induced hyponatremia in a dose-dependent manner. Concomitant use of zonisamide reduced the risk of hyponatremia. Significance: Hyponatremia will become an increasingly important concern in clinical settings because the population of epilepsy patients is aging. Serum sodium levels should be monitored carefully when patients are receiving first-generation antiseizure medications or antipsychotics or combinations of these drugs. Our findings may help to minimize the risk of hyponatremia in epilepsy patients.

Decision analysis of allogeneic bone marrow transplantation versus immunosuppressive therapy for young adult patients with aplastic anemia.

BACKGROUND: Allogeneic bone marrow transplantation (BMT) from an HLA-matched sibling donor is recommended as an initial treatment for young patients. However, immunosuppressive therapy (IST) with cyclosporine and anti-thymocyte globulin may be a viable option even when an HLA-identical sibling donor is available. METHODS: We constructed a Markov model to simulate the 10-year clinical course of patients aged 21-40 years with newly diagnosed severe aplastic anemia. Immediate BMT and IST were compared as an initial treatment assuming the availability of an HLA-identical sibling donor. Transition probabilities after treatment were determined based on a registry data analysis for BMT and a long-term prospective study for IST. RESULTS: Quality-adjusted life years (QALYs) after treatment selection were 6.77 for BMT and 6.74 for IST. One-way sensitivity analysis revealed that the utility for being alive without GVHD after BMT, that for being alive with partial response after IST, and the response rate after initial IST strongly affected the results. CONCLUSIONS: BMT and IST produced similar QALY for young patients with severe aplastic anemia. An estimation of the response rate to the initial IST may enable an individualized comparison between BMT and IST.