Prediction of future gastric cancer risk using a machine learning algorithm and comprehensive medical check-up data: A case-control study.

A comprehensive screening method using machine learning and many factors (biological characteristics, Helicobacter pylori infection status, endoscopic findings and blood test results), accumulated daily as data in hospitals, could improve the accuracy of screening to classify patients at high or low risk of developing gastric cancer. We used XGBoost, a classification method known for achieving numerous winning solutions in data analysis competitions, to capture nonlinear relations among many input variables and outcomes using the boosting approach to machine learning. Longitudinal and comprehensive medical check-up data were collected from 25,942 participants who underwent multiple endoscopies from 2006 to 2017 at a single facility in Japan. The participants were classified into a case group (y = 1) or a control group (y = 0) if gastric cancer was or was not detected, respectively, during a 122-month period. Among 1,431 total participants (89 cases and 1,342 controls), 1,144 (80%) were randomly selected for use in training 10 classification models; the remaining 287 (20%) were used to evaluate the models. The results showed that XGBoost outperformed logistic regression and showed the highest area under the curve value (0.899). Accumulating more data in the facility and performing further analyses including other input variables may help expand the clinical utility.

Prediction of Glucose Metabolism Disorder Risk Using a Machine Learning Algorithm: Pilot Study.

BACKGROUND: A 75-g oral glucose tolerance test (OGTT) provides important information about glucose metabolism, although the test is expensive and invasive. Complete OGTT information, such as 1-hour and 2-hour postloading plasma glucose and immunoreactive insulin levels, may be useful for predicting the future risk of diabetes or glucose metabolism disorders (GMD), which includes both diabetes and prediabetes. OBJECTIVE: We trained several classification models for predicting the risk of developing diabetes or GMD using data from thousands of OGTTs and a machine learning technique (XGBoost). The receiver operating characteristic (ROC) curves and their area under the curve (AUC) values for the trained classification models are reported, along with the sensitivity and specificity determined by the cutoff values of the Youden index. We compared the performance of the machine learning techniques with logistic regressions (LR), which are traditionally used in medical research studies. METHODS: Data were collected from subjects who underwent multiple OGTTs during comprehensive check-up medical examinations conducted at a single facility in Tokyo, Japan, from May 2006 to April 2017. For each examination, a subject was diagnosed with diabetes or prediabetes according to the American Diabetes Association guidelines. Given the data, 2 studies were conducted: predicting the risk of developing diabetes (study 1) or GMD (study 2). For each study, to apply supervised machine learning methods, the required label data was prepared. If a subject was diagnosed with diabetes or GMD at least once during the period, then that subject's data obtained in previous trials were classified into the risk group (y=1). After data processing, 13,581 and 6760 OGTTs were analyzed for study 1 and study 2, respectively. For each study, a randomly chosen subset representing 80% of the data was used for training 9 classification models and the remaining 20% was used for evaluating the models. Three classification models, A to C, used XGBoost with various input variables, some including OGTT data. The other 6 classification models, D to I, used LR for comparison. RESULTS: For study 1, the AUC values ranged from 0.78 to 0.93. For study 2, the AUC values ranged from 0.63 to 0.78. The machine learning approach using XGBoost showed better performance compared with traditional LR methods. The AUC values increased when the full OGTT variables were included. In our analysis using a particular setting of input variables, XGBoost showed that the OGTT variables were more important than fasting plasma glucose or glycated hemoglobin. CONCLUSIONS: A machine learning approach, XGBoost, showed better prediction accuracy compared with LR, suggesting that advanced machine learning methods are useful for detecting the early signs of diabetes or GMD. The prediction accuracy increased when all OGTT variables were added. This indicates that complete OGTT information is important for predicting the future risk of diabetes and GMD accurately.

The waist circumference-adjusted associations between hyperuricemia and other lifestyle-related diseases.

BACKGROUND: Few studies have assessed the associations between hyperuricemia and lifestyle-related diseases after adjusting for waist circumference (WC) and sex. METHODS: This cross-sectional study included 33,498 Japanese individuals, and was conducted at the Center for Preventive Medicine, NTT Kanto Medical Center, Tokyo, from May 2006 to March 2015. Hyperuricemia was defined as a uric acid level of >7 mg/dl in men; >6 mg/dl in women. Metabolic syndrome (Mets) components were defined using the Japanese criteria for Mets. The subjects were stratified into quartiles according to their WC as follows: males: <78.4, 78.4 to <83.5, 83.5 to <89, and ≥89 cm; females: <71.6, 71.6 to <77, 77 to <83.2, and ≥83.2 cm. The relationships between these quartiles and the presence of ≥2 components of Mets or hyperuricemia were then evaluated using Chi square analysis. The presence of ≥2 components of Mets were then determined using multivariate logistic regression analysis adjusting for age, the presence of hyperuricemia, WC, and lifestyle habits. RESULTS: Hyperuricemia was found to be an independent predictor of lifestyle-related diseases after adjusting for age, WC, and lifestyle in both sexes. Males: a uric acid level of >7 mg/dl (odds ratio [OR]: 1.70, 95% confidence interval [CI]: 1.57-1.83), Females: a uric acid level of >6 mg/dl (OR: 2.35, 95% CI 1.83-2.99). CONCLUSION: Hyperuricemia was found to be an independent predictor of several lifestyle-related diseases, even after adjusting for WC which is closely related with insulin resistance. Hyperuricemia might require greater attention during the prevention of lifestyle-related diseases and future cardiovascular disease.

[Successful treatment of large granular lymphocytic leukemia accompanied by refractory anemia with alemtuzumab].

A 39-year-old man with anemia presented at our hospital in November 2011. Peripheral blood analysis revealed lymphocytosis with a large granular lymphocyte (LGL) count of 2,272/µl, with CD3+, CD4-, CD8+, CD56-, TCR-αß+; Southern blotting analysis revealed clonal TCR Cß 1 gene rearrangement, leading to the diagnosis of T-LGL leukemia. In June 2012, the patient was administered with cyclophosphamide as an initial treatment because he developed transfusion-dependent anemia. His anemia improved, and the treatment was discontinued in March 2013. However, anemia recurred in March 2014. The administration of cyclophosphamide was resumed; however, it was subsequently replaced with cyclosporine because of the risk of secondary cancer due to the long-term use of cyclophosphamide. However, his anemia did not improve. Further, the patient was administered with prednisone, methotrexate, and pentostatin; however, the transfusion-dependent state persisted with the cumulative transfusion of 186 RBC units until March 2016. After CD52 expression on the surface of LGL cells was confirmed, treatment with alemtuzumab, which is a monoclonal antibody against CD52, was initiated in April 2016 and the dose was gradually increased from 3 mg to 30 mg thrice per week. The patient's anemia began to improve 1 week after initiating alemtuzumab treatment, and he became transfusion-independent in the second week. Although alemtuzumab treatment was discontinued at the fifth week on the basis of a positive test result for CMV antigenemia, the result consequently became negative after ganciclovir treatment. To date, the patient's hemoglobin level has been maintained at approximately 12 g/dl without any treatment. Herein we reported the case of a patient having LGL leukemia with refractory anemia that was successfully treated using alemtuzumab.

The Relationships between Metabolic Disorders (Hypertension, Dyslipidemia, and Impaired Glucose Tolerance) and Computed Tomography-Based Indices of Hepatic Steatosis or Visceral Fat Accumulation in Middle-Aged Japanese Men.

BACKGROUND: Most studies on the relationships between metabolic disorders (hypertension, dyslipidemia, and impaired glucose tolerance) and hepatic steatosis (HS) or visceral fat accumulation (VFA) have been cross-sectional, and thus, these relationships remain unclear. We conducted a retrospective cohort study to clarify the relationships between components of metabolic disorders and HS/VFA. METHODS: The participants were 615 middle-aged men who were free from serious liver disorders, diabetes, and HS/VFA and underwent multiple general health check-ups at our institution between 2009 and 2013. The data from the initial and final check-ups were used. HS and VFA were assessed by computed tomography. HS was defined as a liver to spleen attenuation ratio of ≤1.0. VFA was defined as a visceral fat cross-sectional area of ≥100 cm2 at the level of the navel. Metabolic disorders were defined using Japan's metabolic syndrome diagnostic criteria. The participants were divided into four groups based on the presence (+) or absence (-) of HS/VFA. The onset rates of each metabolic disorder were compared among the four groups. RESULTS: Among the participants, 521, 55, 24, and 15 were classified as HS(-)/VFA(-), HS(-)/VFA(+), HS(+)/VFA(-), and HS(+)/VFA(+), respectively, at the end of the study. Impaired glucose tolerance was more common among the participants that exhibited HS or VFA (p = 0.05). On the other hand, dyslipidemia was more common among the participants that displayed VFA (p = 0.01). CONCLUSIONS: It is likely that VFA is associated with impaired glucose tolerance and dyslipidemia, while HS might be associated with impaired glucose tolerance. Unfortunately, our study failed to detect associations between HS/VFA and metabolic disorders due to the low number of subjects that exhibited fat accumulation. Although our observational study had major limitations, we consider that it obtained some interesting results. HS and VFA might affect different metabolic disorders. Further large-scale longitudinal studies are needed to reveal the relationships between the components of metabolic disorders and HS/VFA.

Utility of 75-g oral glucose tolerance test results and hemoglobin a1c values for predicting the incidence of diabetes mellitus among middle-aged Japanese men -a large-scale retrospective cohort study performed at a single hospital.

OBJECTIVE: The aim of this study was to investigate the associations between the incidence of diabetes and the accumulation of markers of impaired glucose metabolism; i.e., pre-diabetes. METHODS: This retrospective cohort study recruited 1,631 men without diabetes at baseline who attended more than two routine health check-ups at our institution between 2006 and 2012. The participants were divided into four groups based on the number of markers of impaired glucose metabolism exhibited at the initial examination. The following markers of impaired glucose metabolism were defined as risk factors for diabetes: a fasting plasma glucose level of ≥110 mg/dL, 2-hour plasma glucose level of ≥140 mg/dL and glycated hemoglobin (HbA1c) value of ≥6.0% (42 mmol/moL). The risk of developing diabetes was assessed using a multivariate analysis. RESULTS: The median examination interval was 1,092 days. The incidence of diabetes rose in association with the number of markers. The subjects with two markers displayed a multivariate-adjusted odds ratio (OR) for diabetes of 19.43 [95% confidence interval (CI): 9.70-38.97] and the subjects with three markers displayed an OR of 48.30 (95% CI: 20.39-115.85) compared with the subjects with one or no markers. CONCLUSION: The present results demonstrate the impact of accumulating markers of impaired glucose metabolism on the risk of developing diabetes. Anti-diabetes intervention strategies should aim to comprehensively assess an individual's risk of developing diabetes at the pre-diabetes stage.

Associations between healthy lifestyle behaviors and proteinuria and the estimated glomerular filtration rate (eGFR).

AIM: The aim was to investigate the respective associations between lifestyle and proteinuria and the estimated glomerular filtration rate (eGFR). METHODS: The lifestyle habits of 25,493 middle-aged participants were investigated in a cross-sectional study to find habits that are associated with a low eGFR (<60 mL/min/1.73 m(2)) and/or the presence of proteinuria. The lifestyle habits of the participants were evaluated using a questionnaire. Unhealthy lifestyle habits were defined as follows: 1. obesity, 2. being a current/former smoker, 3. eating irregular meals, 4. having less than 5 hours sleep, 5. exercising less than once a week, and 6. drinking more than once a week. The associations among unhealthy habits, eGFR, and proteinuria were evaluated using multivariate analysis. RESULTS: The following lifestyle factors were significantly and independently associated with proteinuria: obesity (odds ratio (OR): 1.18, 95%C.I: 1.04-1.34), being a current/former smoker (OR: 1.26, 95%C.I: 1.11-1.42), eating irregular meals (OR: 1.40, 95%C.I: 1.22-1.61), sleeping less than 5 hours (OR: 1.38, 95%C.I: 1.15-1.65), and exercising less than once a week (OR: 1.18, 95%C.I: 1.05-1.33). In contrast, the following unhealthy lifestyle factors were not clearly associated with a low eGFR: obesity (OR: 1.05, 95%C.I: 0.95-1.17), being a current/former smoker (OR: 0.76, 95%C.I: 0.69-0.84), eating irregular meals (OR: 0.91, 95%C.I: 0.79-1.04), sleeping less than 5 hours (OR: 1.02, 95%C.I: 0.85-1.22), and exercising less than once a week (OR: 0.91, 95%C.I: 0.83-0.99). CONCLUSION: Associations between proteinuria and unhealthy lifestyle habits were observed in our cross-sectional study. Unhealthy lifestyles should be monitored during the management of CKD patients with proteinuria.

A cross-sectional study on the risk factors for erosive esophagitis in young adults.

OBJECTIVE: To investigate the impact of metabolic and lifestyle factors on erosive esophagitis in young adults. METHODS: A total of 5,069 people under the age of 40 years old were enrolled in a medical survey at our institute. People with a previous history of upper gastrointestinal tract surgery were excluded, as were individuals taking medication for reflux symptoms, peptic ulcers, or malignancies. Independent and significant predictors affecting the presence of erosive esophagitis were determined by multivariate analysis. RESULTS: A total of 4,990 participants (male/female; 3,871/1,119, age; 33.9±3.9 years) were eligible. A total of 728 participants (14.6%) had erosive esophagitis. Male gender and increasing age were independent predictors for increased prevalence of erosive esophagitis (odds ratio=2.242 and 1.045. 95% confidence interval=1.613-3.117 and 1.019-1.072; p<0.001 and 0.001, respectively). Moderate-to-heavy alcohol consumption, light-to-moderate-to-heavy smoking, hypertension, hyperglycemia, and hiatal hernia each significantly and independently increased the risk for erosive esophagitis (odds ratio=1.499, 1.398, 1.353, 1.570, 1.884, 1.297, 1.562, and 3.213. 95% confidence interval=1.181-1.903, 1.040-1.880, 1.094-1.675, 1.250-1.971, 1.307-2.716, 1.074-1.566, 1.063-2.295, and 2.712-3.807; p=0.001, 0.027, 0.005, <0.001, 0.001, <0.001, 0.007, 0.023, and <0.001 respectively). Helicobacter pylori infection decreased the risk for erosive esophagitis (odds ratio=0.575, 95% confidence interval =0.436-0.759 p<0.001). Neither body mass index nor waist girth conferred increased risk of erosive esophagitis after adjusting for potential confounding factors. CONCLUSION: Risk of erosive esophagitis in Japanese young adults was not increased by obesity, but it was increased by hiatal hernia and metabolic and lifestyle profiles including hypertension, hyperglycemia, alcohol consumption and smoking.

Modest alcohol consumption has an inverse association with liver fat content.

BACKGROUND/AIMS: Modest alcohol consumption has been suggested to be protective against alanine amino-transferase activities and ultrasonography-defined fat-ty liver. We aimed to explore the association between alcohol consumption and liver fat content as quantitative-ly determined by computed tomography (CT). METHODOLOGY: One-thousand two-hundred thirty-one Japanese males, aged over 40 years, voluntarily participated ina health check-up program including CT screening in 2009-2010. Exclusion criteria included positivity for the hepatitis B or C virus, abstinent alcoholics and potential hepatotoxic drug intake. Liver fat content, visceral adipose tissue (VAT) and subcutaneous adipose tis-sue were determined by CT. The association between alcohol consumption (g/week) and liver attenuation values (HU) was investigated by multivariate analysis with metabolic syndrome factors, liver enzyme activities and physical activities as covariates. RESULTS: One-thousand one-hundred thirty-eight subjects were eligible for this cross-sectional survey. VAT, triglyceride, glycated hemoglobin and alanine aminotransferase were significant and independent predictors for a decrease of liver attenuation. Alcohol consumption had a significant and independent association with an increase in liver attenuation (correlation coefficient=0.007, 95%CI=0.004-0.011, p<0.001) after adjusting for potential confounding variables. CONCLUSIONS: Alcohol consumption has an inverse association with CT-determined liv-er fat content independent of metabolic syndrome factors, liver enzyme activities and physical activities.

Alcohol consumption is inversely correlated with insulin resistance, independent of metabolic syndrome factors and fatty liver diseases.

BACKGROUND AND AIM: The role of alcohol consumption in insulin resistance remains unclear. The aim of this study was to examine the association between alcohol consumption and insulin resistance in a large asymptomatic population. METHODS: A total of 2463 asymptomatic Japanese men aged 28 years or above undergoing a comprehensive health checkup including an oral glucose tolerance test between May 2007 and April 2010 were recruited. Participants positive for hepatitis B or C virus, abstinent alcoholics, those taking hepatotoxic drugs, those with chronic renal or hepatic failure, and those under treatment for metabolic disorders were excluded. Fatty liver was defined ultrasonographically. Visceral and subcutaneous adipose tissues were measured with computed tomography. The homeostasis model assessment of insulin resistance (HOMA-IR) score was determined to estimate insulin resistance. The association between alcohol consumption and HOMA-IR score was investigated with multivariate regression analysis. RESULTS: A total of 1902 participants were eligible for this cross-sectional survey. A significant difference in distribution of each drinking category was noted between 249 participants with insulin resistance (HOMA-IR ≥2.5) and 1653 participants without insulin resistance (HOMA-IR <2.5; P=0.001). Light (40 to 140 g/wk), moderate (140 to 280 g/wk), and heavy alcohol consumption was inversely associated with HOMA-IR scores (coefficients=-0.125, -0.127, and -0.162; P=0.007, 0.011, and 0.006, respectively) with multivariate analysis after adjusting for potential confounding variables, including visceral and subcutaneous adipose tissues, metabolic profiles, fatty liver, and liver enzyme activities. CONCLUSIONS: Alcohol consumption was inversely associated with insulin resistance, independent of central obesity, metabolic profiles, and fatty liver diseases.

Risk factors for erosive esophagitis: a cross-sectional study of a large number of Japanese males.

BACKGROUND: The impact of obesity on gastroesophageal reflux disease remains controversial. We undertook this study, with a large sample size, to investigate risk factors for endoscopic erosive esophagitis by multivariate analysis, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) as covariates. METHODS: Japanese males who visited our institute for a comprehensive medical survey between 2007 and 2010 were enrolled. All subjects voluntarily participated in a self-paid health check-up program including blood test screening, physical examinations, and esophagogastroduodenoscopy. VAT and SAT were measured by computed tomography at the navel level. Independent and significant predictors of erosive esophagitis were determined by multivariate analysis. RESULTS: Of 9840 eligible subjects, 1831 (18.6%) were diagnosed with erosive esophagitis. Body mass index and triglyceride were predictors of an increased prevalence of erosive esophagitis (odds ratios [ORs] = 1.063 and 1.001; 95% confidence intervals [CIs] = 1.020-1.108 and 1.001-1.002; p = 0.004 and <0.001, respectively). Heavy alcohol consumption, heavy smoking, and hiatal hernia were also associated with an increased prevalence of erosive esophagitis (ORs = 1.276, 1.399, and 2.758; 95% CIs = 1.085-1.501, 1.220-1.605, and 2.474-3.075; p < 0.001 for all). Helicobacter pylori infection significantly and independently decreased the prevalence of erosive esophagitis (OR = 0.346, 95% CI = 0.299-0.401, p < 0.001). Central obesity, as determined by VAT and waist girth, did not confer an increased risk of erosive esophagitis after adjusting for confounders. CONCLUSIONS: Lifestyle factors including heavy alcohol consumption, heavy smoking, metabolic disorders, and hiatal hernia increased the risk of erosive esophagitis, but central obesity did not.

Risk factors for serum alanine aminotransferase elevation: A cross-sectional study of healthy adult males in Tokyo, Japan.

BACKGROUND: Liver-protective effects of light-to-moderate alcohol consumption have been suggested. AIMS: To determine predictors of ALT elevation in asymptomatic subjects with and without ultrasonographical evidence of fatty liver. METHODS: Cross-sectional survey of 9703 healthy males. Exclusion criteria were HBV or HCV infection, any use of hepatotoxic medication, history of alcohol abuse, chronic renal or hepatic failure, or treatment for metabolic disorders. Presence of fatty liver was evaluated by ultrasonography; visceral adipose tissue (VAT) was measured by computed tomography (CT). RESULTS: 7148 males (mean age, 50.3±7.8 years) were included; 2406 (33.7%) had fatty liver at ultrasonography. ALT was elevated in 163 (3.4%) and 554 subjects (23.0%) of fatty liver-negative and fatty liver-positive subgroups, respectively. Light (40-140g/week) alcohol consumption was significantly and independently associated with reduced prevalence of ALT elevation in the fatty liver-negative subgroup (OR=0.568, 95% CI=0.342-0.943, P=0.029). ALT elevation was significantly related to age, VAT, high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) in the fatty liver-negative subgroup. CONCLUSION: Light alcohol consumption is not associated with serum ALT elevation in the Japanese male population. Metabolic syndrome factors are significantly associated with prevalence of ALT elevation, irrespective of the presence of fatty liver.

[Immunosuppressive therapy with antithymocyte globulin and cyclosporine for paroxysmal nocturnal hemoglobinuria].

Immunosuppressive therapy (IST) for paroxysmal nocturnal hemoglobinuria (PNH) has been infrequently reported. Four PNH cases were treated with antithymocyte globulin (ATG) at our center. We assessed and reviewed the efficacy and safety of IST for PNH. ATG therapy was performed for progression of cytopenia in 3 classical-type and 1 marrow failure-type PNH cases. ATG was administered at a dose of 15 mg/kg for 5 consecutive days. Hydration and anticoagulant therapy were given as prophylaxis for thrombosis during ATG therapy. Cyclosporine was also given to the 3 classical-type PNH patients. Three patients showed hemolytic exacerbation and thrombocytopenia during ATG administration, and all needed to receive transfusions of red blood cells and platelets; however, renal failure and thrombosis did not occur. Anemia improved in all cases within 1 year, but thereafter, recurred in 2 cases. ATG therapy is a choice of treatment for PNH, although its mechanism remains unknown.

Stable response after administration of stem cell factor combined with granulocyte colony-stimulating factor in aplastic anemia.

We report successful treatment with 25 microg/kg of recombinant methionyl human stem cell factor (SCF) combined with 400 microg/m2 of recombinant human granulocyte colony-stimulating factor (G-CSF) in 2 patients with aplastic anemia refractory to immunosuppressive therapy. In one patient, hemoglobin levels increased from 6.4 g/dL to 11.3 g/dL after 36 weeks of SCF/G-CSF treatment. Thereafter, the platelet count (24.0 x 10(9)/L) began to improve without the therapy, and as of week 272, the platelet count was 125.0 x 10(9)/L with a leukocyte count of 8.4 x 10(9)/L and a hemoglobin level of 12.9 g/dL. In the other patient, more than 3 years of SCF/G-CSF treatment ameliorated hemoglobin levels and platelet counts from 5.8 g/dL to 15.9 g/dL and 8.0 x 10(9)/L to 50.0 x 10(9)/L, respectively. After cessation of SCF/G-CSF treatment, the positive response was sustained, and the platelet count improved further to 71.0 x 10(9)/L as of week 242. These observations suggest the clinical benefit of SCF/G-CSF administration to patients with refractory aplastic anemia.

A randomized controlled trial to compare once- versus twice-daily filgrastim for mobilization of peripheral blood stem cells from healthy donors.

Although the mobilization of peripheral blood stem cells from normal donors using granulocyte colony-stimulating factor is widely used, the ideal method for the administration of filgrastim has not been determined. Therefore, we compared the efficacy of peripheral blood stem cell mobilization on day 4 of filgrastim between once-daily (group O) and twice-daily (group T) administration of filgrastim at 400 microg/m(2)/d. In all, 38 and 34 donors were randomly assigned to groups O and T, respectively. The number of CD34(+) cells collected on day 4 was not significantly different (1.74 x 10(6) cells/kg in group O and 2.08 x 10(6) cells/kg in group T, P = .37). The incidence and severity of adverse events were similar in the two groups. The baseline white blood cell count was the strongest predictor of poor mobilization. Donor age, sex, and serum concentrations of several cytokines did not significantly affect the CD34(+) cell yield. In conclusion, once-daily administration of filgrastim at 400 microg/m(2)/d appeared to be appropriate for the mobilization of CD34(+) cells in normal donors when apheresis is planned on day 4 of filgrastim. Selection of a donor with a steady-state white blood cell count of 5.0 x 10(9)/L or more may lead to a lower incidence of poor mobilization.

[Superior sagittal sinus thrombosis during remission induction therapy for acute lymphoblastic leukemia].

Superior sagittal sinus thrombosis (SSST) has been reported to be caused by coagulopathy following oral contraceptive therapy, DIC, infection around the sinus, compression from a tumor, infiltration of tumor, and an inherited deficiency of proteins C and S, but SSST associated with hematological malignancies and L-asparaginase (L-Asp) therapy is rare. We report a case of an adult patient with acute lymphoblastic leukemia (ALL) who developed SSST during the remission induction therapy. A 25-year-old man was admitted with left facial nerve palsy and, following bone marrow aspiration and lumbar puncture, he was diagnosed as having T-ALL with CNS involvement. He received a 1-AdVP regimen as remission induction therapy and intrathecal administration of methotrexate and cytarabine. On day 29, he had a generalized convulsion and SSST was demonstrated by imaging tests. Lymphoid malignancy (ALL in particular), the use of L-Asp, CNS involvement, and intrathecal chemotherapy might be risk factors for the occurrence SSST. When a patient with those factors develops any neurological symptoms, we should pay attention to the occurrence of SSST, as well as stroke or CNS involvement, though SSST is rare.

[Effective treatment with rituximab in two patients with Waldenström macroglobulinemia].

CD20 is usually expressed on tumor cells in Waldenström's macroglobulinemia (WM). We report on two patients who achieved good responses with rituximab treatment. A 78-year-old man had anemia and was referred to our hospital in 1997. On admission, IgM-kappa monoclonal protein was detected in the serum and the IgM level was 4850 mg/dl, leading to the diagnosis of WM. In 2002, he developed heart failure due to anemia, and was treated with rituximab. The IgM level decreased to about 200 mg/dl and remained unelevated for 2.5 years. The anemia also improved. < Case 2 > A 59-year-old man was found to have elevated serum IgM (4850 mg/dl) and came to our hospital in 1998. IgM-kappa monoclonal protein was detected in the serum and he was diagnosed as having WM. His IgM level had been controlled with cyclophosphamide administration, but elevated levels were noted again in 2004. He was given rituximab, and a partial response was obtained (IgM 995 mg/dl).

[Immunosuppressive therapy for adult aplastic anemia in a single institution study].

We evaluated the efficacy and long-term outcomes of immunosuppressive therapy (IST) in 50 adult patients with aplastic anemia at a single institution. Twenty-one patients who had not responded to the first course of IST or relapsed after the initial response to IST were retreated with the second course of IST with antithymocyte globulin. The response and relapse rate of the initial IST were 76.7% and 23.3%, respectively. The response rate of salvage IST was 61.9%. Overall survival at 10 years was 84.0%. Failure-free survival at 10 years was 62.0%. Clonal or malignant diseases developed in 2 patients. Early deaths due to bleeding or infection were observed only in elderly patients. We conclude that most patients with aplastic anemia treated with IST show hematologic improvement and excellent long-term survival.

[Effective treatment with rituximab in a patient with refractory idiopathic thrombocytopenic purpura].

A 75-year-old woman had an episode of sudden nasal and oral bleeding. After that, petechiae appeared on her entire body. She received a platelet transfusion, and was referred to our hospital. On admission, the platelet count was as low as 1.2 X 10(4)/microl, and the PAIgG level was slightly elevated. Bone marrow cellularity was low, with a normal count of megakaryocytes. Anti-glycoprotein IIb/IIIa antibody-secreting B cells in the peripheral blood and platelet-associated anti-glycoprotein IIb/ IIIa antibodies were significantly high, and the patient was diagnosed as having idiopathic thrombocytopenic purpura (ITP). She failed to respond to corticosteroids, splenectomy and other therapies, so we administered rituximab, anti-CD20 monoclonal antibody, 375 mg/m2 weekly for four weeks. After the second infusion of rituximab, the platelet count began to increase. The platelet count continued to rise until a peak count (15.0 x 10(4)/microl) observed after 2 weeks from the fourth infusion, and the response was maintained for 8 more weeks. The levels of anti-glycoprotein IIb/IIIa antibody-secreting B cells and platelet-associated anti-glycoprotein IIb/IIIa antibodies decreased after the administration of rituximab. Rituximab was effective in this case of refractory ITP.