[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.

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.

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.

[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.

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.

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.

[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.

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.

[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 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).

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.

High serum soluble CD44 is correlated with a poor outcome of aggressive non-Hodgkin's lymphoma.

We measured soluble CD44 (sCD44) by enzyme-linked immunosorbent assay in 216 patients with non-Hodgkin's lymphoma (NHL). The sCD44 level was significantly elevated in patients with NHL. A sCD44 level of > or =500 ng/ml showed a significantly decreased overall survival (OS) rate and progression free survival (PFS) rate. In the high-intermediate+high risk group (international prognostic index (IPI)), both the OS rate and the PFS rate were significantly decreased when the sCD44 level was > or =1000 ng/ml. Moreover, the results of a multivariate analysis showed that the five IPI prognostic factors and the sCD44 level were independent prognostic factors, thus suggesting that sCD44 levels could be a useful prognostic marker for aggressive lymphoma

Granulocytic differentiation of leukemic cells with t(9;11)(p22;q23) induced by all-trans-retinoic acid.

Acute leukemia patients with MLL (mixed linage leukemia) rearrangements tend to respond poorly to conventional therapies. We examined differentiation of human myeloid leukemia cells displaying the MLL-AF9 gene, using several differentiation agents. When MOLM-14 cells were treated with all-trans retinoic acid (ATRA) or 1beta,25-dihydroxyvitamin D3, significant induced differentiation was observed. Trichostatin A (TSA), an inhibitor of histone deacetylase, demonstrated enhance effects with ATRA in regard to growth inhibition and differentiation induction in MOLM-14 cells. Pretreatment with TSA before exposure to ATRA displayed increased effect. Based on these findings, combined treatment with ATRA and TSA may be clinically useful in therapy for acute leukemia displaying MLL-AF9 fusion gene.

[Chronic myelogenous leukemia in cessation of therapy after sustained CCR with interferon].

In Ph(+) CML patients who achieved complete cytogenetic response (CCR) with interferon-alpha (IFN) treatment, how long the treatment should be continued has not well been investigated. We report here 2 CML cases who stopped the treatment after CCR had been sustained with IFN for 2-3 years. A 49-year-old male (case 1) achieved CCR 6 months after the initiation of IFN treatment. CCR had been maintained for 3 years, and then the treatment was ceased. CCR has been sustained without any therapy for 4 years. In this case, RT-PCR became negative half a year after achievement of CCR, and since then negative RT-PCR has been maintained. In case 2, a 50-year-old male, CCR was achieved after 8 years of IFN treatment, and maintained for 2 years. One month after cessation of the treatment, CML relapsed cytogenetically. In case 2, negative RT-PCR results were not maintained during the period of CCR. In case 1, the levels of T-cells for PR 1 were undetectable in the peripheral blood.

[Simultaneous occurrence of acute myeloid leukemia with multilineage dysplasia and multiple myeloma].

An 82-year-old woman was admitted to our hospital because of dizziness and petechiae. Peripheral blood examination showed severe anemia and thrombocytopenia. Bone marrow aspiration revealed 42% leukemic blasts positive for peroxidase with multilineage dysplasia, leading to a diagnosis of acute myeloid leukemia with multilineage dysplasia. The levels of the patient's marrow plasma cells increased to 12%, whereas serum levels of IgG, A, and M dropped. lambda type Bence Jones protein was detected on urine immunoelectrophoresis. The total urinary protein was 3, 960 mg/day. Bone scintigraphy detected multifocal uptake in the ribs. The diagnosis was multiple myeloma developing simultaneously with acute myeloid leukemia. Possible mechanisms for the occurrence of acute myeloid leukemia and multiple myeloma were discussed.

[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.

[A family of acute intermittent porphyria].

A 62-year-old man who had twice received laparotomies for abdominal pain of unknown origin was admitted to our hospital with acute abdominal pain. His family history of acute intermittent porphyria (AIP) suggested that it arose from acute porphyria. We treated the patient with 5% glucose solution by i.v. drip infusion and his abdominal pain improved rapidly. Diagnosis of AIP was established by the demonstration of reduced erythrocyte porphobilinogen deaminase (PBGD) activity and a point mutation (CAG --> CGG) in a splicing site in intron 10/exon 11 in the PBGD gene by DNA analysis. For screening of AIP carriers in his family, we measured erythrocyte PBGD activity. Four of his seven children were successfully diagnosed as AIP carriers. This is the ninth AIP family report, in which a mutation in the PBGD gene was revealed by DNA analysis.

[Therapeutic effectiveness of ranimustine chemotherapy for essential thrombocythemia in the elderly].

We studied the therapeutic effectiveness of chemotherapy by ranimustine (MCNU) for essential thrombocythemia (ET) in 14 ET patients over 60 years of age. The median age was 73 years (range: 61-88 years), and the male/female ratio was 6:8. The mean platelet counts before chemotherapy was 1,157 +/- 28.4 x 10(3)/microliter. Five of them had been referred because of thrombotic episodes before admission to our hospital, while one was referred because of nasal bleeding. The platelet counts were maintained at a level below 500 x 10(3)/microliter by intravenous administration of MCNU in 12 patients and below 700 x 10(3)/microliter in two patients. One of the patients suffered cerebral infarction during MCNU therapy. No other patient suffered thrombotic episodes during MCNU therapy. The patient who was referred because of nasal bleeding had no hemorrhagic episode during control of platelet counts by chemotherapy. MCNU chemotherapy appears effective for the prevention of thrombosis and bleeding in ET.