Rituximab plus multiagent chemotherapy for newly diagnosed CD20-positive acute lymphoblastic leukemia: a prospective phase II study

Background/Aims@#We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). @*Methods@#Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. @*Results@#In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. @*Conclusions@#The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).

Two Clinical Cases of Feline Hemoplasmosis in Korea

Feline hemotropic mycoplasmosis (hemoplasmosis) is an infection of the red blood cells caused by the Mycoplasma haemofelis (Mhf), Candidatus Mycoplasma haemominutum (CMhm), and Candidatus Mycoplasma turicensis (CMt). The existence of Mhf, CMhm, and CMt has been demonstrated in feral cats in Korea using molecular methods, but no clinical cases have yet been reported. This study reports 2 clinical cases of hemotropic mycoplasmosis caused by CMhm and CMt in 2 anemic cats. The first case was a client-owned intact female domestic shorthair cat that presented with fever, pale mucous membranes, and normocytic normochromic non-regenerative anemia. Prior to referral, an immunosuppressive prednisolone dose was administered at the local veterinary clinic for 1 month. The cat was diagnosed with high-grade alimentary lymphoma. Organisms were found on the surface of the red blood cells on blood smear examination. The second case was of a rescued cat that presented with dehydration and fever. The cat had normocytic normochromic non-regenerative anemia. Necropsy revealed concurrent feline infectious peritonitis. Polymerase chain reaction assay targeting 16S rRNA revealed CMhm infection in case 1 and dual infection of CMhm and CMt in case 2. Normocytic normochromic non-regenerative anemia was observed in both cats before and during the management of the systemic inflammation. This is the first clinical case report in Korea to demonstrate CMhm and CMt infections in symptomatic cats.

Management of immune thrombocytopenia: 2022 update of Korean experts recommendations

Despite the availability of therapies to treat patients with immune thrombocytopenia (ITP), there is currently little data from randomized trials to assist clinicians in managing patients. The evidence-based guidelines of the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) are intended to support patients and physicians in the management of ITP. Experts from the KSHAAWP discussed and described this guideline according to the current treatment situation for ITP in Korea and finalized the guidelines. The expert panel recommended the management of ITP in adult and pediatric patients with newly diagnosed, persistent, and chronic disease refractory to first-line therapy with minor bleeding. Management approaches include observation and administration of corticosteroids, intravenous immunoglobulin, anti-D immunoglobulin, and thrombopoietin receptor agonists. Currently, evidence supporting strong recommendations for various management approaches is lacking. Therefore, a large focus was placed on shared decision-making, especially regarding second-line treatment.

Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia

Background/Aims@#We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). @*Methods@#We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. @*Results@#The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. @*Conclusions@#Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Pediatric-inspired regimen with late intensification and increased dose of L-asparaginase for adult acute lymphoblastic leukemia: the KALLA 1406/1407 study

Background/Aims@#The objective of this study was to evaluate the efficacy and feasibility of the pediatric-inspired regimen of the adult acute lymphoblastic leukemia (ALL) Working Party, the Korean Society of Hematology. @*Methods@#Data of 99 patients with newly diagnosed ALL, who were treated with the KALLA 1406/1407 protocol, were retrospectively analyzed. All patients equally received age-adjusted daunorubicin, vincristine, and prednisolone. L-asparaginase was additionally administered to Philadelphia (Ph)-negative patients according to age, whereas Ph-positive patients received 600 mg/day of imatinib. @*Results@#A total of 99 patients were enrolled in this study, of whom 62 (62.6%) were diagnosed with Ph-negative ALL and 37 (37.3%) were diagnosed with Ph-positive ALL. The median age of patients in the Ph-negative ALL group was 46 years, and that of patients in the Ph-positive ALL group was 49 years. In patients with Ph-negative ALL, 57 (92%) patients achieved complete remission (CR) and CR with incomplete hematologic recovery (CRi). Disease-free survival (DFS) and overall survival (OS) rates at 2 years were estimated to be 42% and 63%, respectively. In patients with Ph-positive ALL, 32 (86%) patients achieved CR/CRi, and 2-year DFS and OS were 31.2% and 49.1%, respectively. Patients who were able to proceed to the allogeneic hematopoietic cell transplantation and younger patients showed significantly superior survival in both Ph-negative ALL and Ph-positive ALL. Neutropenic fever and bacterial infection were the most common and severe adverse events. @*Conclusions@#The KALLA 1406/1407 protocol showed tolerable toxicities in adult ALL patients. Especially, younger patients had more survival benefits with KALLA 1406/1407 protocol.

Korean Multicenter Registry Study of EPIC Stents for the Treatment of Iliac Artery Disease: K-EPIC Registry

Background and Objectives@#The EPIC™ stent is a self-expanding, nitinol stent that has been designed to enhance flexibility and provide expansion within vessels. The aim of the present study was to investigate the clinical efficacy and safety of the EPIC™ stent when used to treat iliac artery diseases in a prospective Korean multicenter registry. @*Methods@#A total of 138 patients with iliac artery diseases who received endovascular treatment with EPIC™ stents at 9 Korean sites were enrolled in a prospective cohort and followed for 1 year. The primary endpoint was the 1-year freedom from target lesion revascularization (TLR). The secondary endpoints were 1-year clinical patency and freedom from major adverse events (MAEs). @*Results@#The mean age of the study subjects was 66.8±8.5 years and most subjects were male (86.2%). The most frequent lesion type was Trans-Atlantic Inter-Society Consensus B (43.5%) and the majority (56.5%) of the target lesions were located in the common iliac artery. Procedural success was obtained in 99.3% of patients. The freedom from TLR and the clinical patency at 1-year follow-up were 94.9% and 92.3%, respectively. The 1-year rate of MAEs was 5.1%. Combined coronary artery disease (hazard ratio [HR], 5.91; 95% confidence interval [CI], 1.13–30.89; p=0.035) and smaller stent diameter (HR, 0.38; 95% CI, 0.17–0.88;p=0.023) were identified as independent risk factors of TLR after EPIC™ stent implantation. @*Conclusions@#The EPIC™ stents demonstrated excellent immediate and 1-year efficacy and safety outcomes in iliac artery lesions in this multicenter, prospective, registry-based study.

Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of defective apoptosis, a disruption of the regulatory pathway that terminates immune and inflammatory responses.Fever, cytopenia, splenomegaly, and/or hemophagocytosis are typical findings of this syndrome. HLH can be induced by genetic disorders (familial) or secondary causes.Familial HLH is rare, while secondary causes in adults include infection, autoimmunity, and malignancy. HLH in adults tends to be confused with or misdiagnosed as sepsis, mainly due to similar clinical manifestations and laboratory findings, which make it difficult to diagnose HLH rapidly and adopt immunosuppressive agents and/or chemotherapy adequately. Treatment of pediatric HLH using HLH-2004 or multi-agent chemotherapy can be applied in adult patients, although the dose and type of drug need to be adjusted.It is highly recommended that allogenic hematopoietic stem cell transplantation should be used in patients who become reactivated or are refractory to the initial treatment as soon as possible to improve survival. Future clinical trials are warranted to determine more suitable treatments for adult patients with HLH.

Current status of the diagnosis and treatment of hemophagocytic lymphohistiocytosis in adults

Hemophagocytic lymphohistiocytosis (HLH) is a syndrome of defective apoptosis, a disruption of the regulatory pathway that terminates immune and inflammatory responses.Fever, cytopenia, splenomegaly, and/or hemophagocytosis are typical findings of this syndrome. HLH can be induced by genetic disorders (familial) or secondary causes.Familial HLH is rare, while secondary causes in adults include infection, autoimmunity, and malignancy. HLH in adults tends to be confused with or misdiagnosed as sepsis, mainly due to similar clinical manifestations and laboratory findings, which make it difficult to diagnose HLH rapidly and adopt immunosuppressive agents and/or chemotherapy adequately. Treatment of pediatric HLH using HLH-2004 or multi-agent chemotherapy can be applied in adult patients, although the dose and type of drug need to be adjusted.It is highly recommended that allogenic hematopoietic stem cell transplantation should be used in patients who become reactivated or are refractory to the initial treatment as soon as possible to improve survival. Future clinical trials are warranted to determine more suitable treatments for adult patients with HLH.

Korean Multicenter Registry Study of EPIC Stents for the Treatment of Iliac Artery Disease: K-EPIC Registry

Background and Objectives@#The EPIC™ stent is a self-expanding, nitinol stent that has been designed to enhance flexibility and provide expansion within vessels. The aim of the present study was to investigate the clinical efficacy and safety of the EPIC™ stent when used to treat iliac artery diseases in a prospective Korean multicenter registry. @*Methods@#A total of 138 patients with iliac artery diseases who received endovascular treatment with EPIC™ stents at 9 Korean sites were enrolled in a prospective cohort and followed for 1 year. The primary endpoint was the 1-year freedom from target lesion revascularization (TLR). The secondary endpoints were 1-year clinical patency and freedom from major adverse events (MAEs). @*Results@#The mean age of the study subjects was 66.8±8.5 years and most subjects were male (86.2%). The most frequent lesion type was Trans-Atlantic Inter-Society Consensus B (43.5%) and the majority (56.5%) of the target lesions were located in the common iliac artery. Procedural success was obtained in 99.3% of patients. The freedom from TLR and the clinical patency at 1-year follow-up were 94.9% and 92.3%, respectively. The 1-year rate of MAEs was 5.1%. Combined coronary artery disease (hazard ratio [HR], 5.91; 95% confidence interval [CI], 1.13–30.89; p=0.035) and smaller stent diameter (HR, 0.38; 95% CI, 0.17–0.88;p=0.023) were identified as independent risk factors of TLR after EPIC™ stent implantation. @*Conclusions@#The EPIC™ stents demonstrated excellent immediate and 1-year efficacy and safety outcomes in iliac artery lesions in this multicenter, prospective, registry-based study.

Relationship between Obesity and Serum 25-Hydroxyvitamin D Concentrations

BACKGROUND: Vitamin D has been known to play an important role in calcium homeostasis and bone metabolism. It has also been implicated in diabetes mellitus, cardiovascular disease, and immune diseases. Several cross-sectional studies conducted worldwide have found that vitamin D is negatively correlated with obesity. In Korea, however, the results of similar studies were found to be inconsistent.METHODS: The study consisted of 585 adults over 18 years of age, who visited a health promotion center at a university hospital from March, 2015 to February, 2016 and their serum vitamin D levels were recorded. They were divided into two groups according to their sex. The correlation coefficients were calculated using Pearson correlation analysis between obesity and vitamin D. Finally, subjects with vitamin D levels less than <20 ng/mL were classified as deficient. Bivariate logistic regression analysis was used to determine the odds ratio of vitamin D deficiency.RESULTS: We observed a significant negative correlation between obesity and vitamin D (P<0.05) among the women but not in the men. The following are the details of the findings: ≥25 in body mass index (model 3 adjusted odds ratio [OR], 4.11; 95% confidence interval [CI], 1.59–10.67), ≥85 cm in waist circumference (model 3 adjusted OR, 1.81; 95% CI, 1.02–4.01), ≥30% in body fat (model 3 adjusted OR, 2.29; 95% CI, 1.17–4.62).CONCLUSION: Based on the results of this study, we suggest that obesity and vitamin D are negatively correlated and that obesity in women predisposes them to vitamin D deficiency.

Association between Benign Prostate Hyperplasia and Occupational Group

BACKGROUND: Insufficient physical activity is well known to increase benign prostate hyperplasia (BPH). However, only few studies have been conducted on the relationship between occupational physical activity and BPH. This study aimed to investigate the relationship between occupational physical activities and BPH in South Korea.METHODS: The study subjects included 4,102 workers who visited the health promotion center at Ulsan University Hospital and underwent transrectal ultrasonography between January 2016 and December 2017. The subjects were divided into two groups according to occupational physical activity (manual or non-manual workers). BPH was defined as a prostate volume of >25 mL. We performed a multivariate regression analysis to investigate the associations between the occupational groups and BPH. In addition, we divided the subgroups according to age and body mass index and analyzed the relationship between occupational physical activities and BPH in each subgroup.RESULTS: The risk of BPH was significantly higher in the non-manual workers than in the manual workers. This result was consistent after adjusting for other risk factors of BPH (odds ratio, 1.26; 95% confidence interval, 1.05–1.51). Likewise, in the subgroup analysis according to age and body mass index, the non-manual workers had higher BPH risk than the manual workers.CONCLUSION: The risk of BPH was significantly higher in the non-manual workers than in the manual workers. To prevent BPH, more attention should be paid to the physical activities and education of non-manual workers.

PI3K-Akt-Wnt Pathway Is Implicated in Exercise-Induced Improvement of Short-term Memory in Cerebral Palsy Rats / 대한배뇨장애요실금학회지

PURPOSE: Maternal lipopolysaccharide (LPS) injection induces neurodevelopmental disorders, such as cerebral palsy. Exercise activates phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway that enhances neurogenesis. Wnt ligands are also implicated in the hippocampal neurogenesis and synaptic plasticity. Glycogen synthase kinase-3β (GSK-3β) is a downstream molecule of Akt, and GSK-3β is known to modulate hippocampal neurogenesis negatively. METHODS: Cerebral palsy was made by maternal LPS-injection. On the 5 weeks after birth, treadmill running was applied to the rat pups of the exercise groups, for 30 minutes, 5 times a week during 6 weeks. RESULTS: Treadmill running alleviated short-term memory impairments of the cerebral palsy rat pups. Hippocampal cell proliferation was increased and hippocampal apoptosis was suppressed by treadmill running in the cerebral palsy rat pups. Hippocampal phosphorylated-PI3K/PI3K ratio, phosphorylated-Akt/Akt ratio, and Wnt expression were enhanced by treadmill running in the cerebral palsy rat pups. In contrast, hippocampal phosphorylated-GSK-3β/GSK-3β ratio and β-catenin expression were suppressed by treadmill running in the cerebral palsy rat pups. CONCLUSIONS: The results of this study showed that short-term memory improvement due to treadmill running in cerebral palsy occurs via activation of the PI3K-Akt-Wnt pathway.

Unusual Case of Posterior Reversible Encephalopathy Syndrome in a Patient with Anti-glomerular Basement Membrane Antibody Glomerulonephritis: A Case Report and Review of the Literature

Posterior reversible encephalopathy syndrome (PRES) is characterized by a clinical and radiological entity with the sudden onset of seizures, headache, altered consciousness, and visual disturbances in patients with the findings of reversible vasogenic subcortical edema without infarction. Hypertension, renal disease, and autoimmune disease are co-morbid conditions of PRES. Nevertheless, there have only been a few case reports of PRES in a patient with anti-glomerular basement membrane antibody glomerulonephritis (anti-GBM GN). This paper presents the possible first Korean case of a 36-year-old woman with the striking features of PRES. She presented with a sudden onset of visual blindness, headache, and seizure. The brain MRI images revealed hyperintense lesions in both the occipital and parietal lobes, which suggested vasogenic edema. Three months before this presentation, she was diagnosed with anti-GBM GN. Since then, she underwent immunosuppression with cyclophosphamide and steroid, and hemodialysis for renal failure with a treatment of anti-GBM GN.

An isolated cardiac relapse after allogeneic hematopoietic stem cell transplantation for acute lymphoblastic leukemia

No abstract available.

Vestibular Neuritis With Minimal Canal Paresis: Characteristics and Clinical Implication

OBJECTIVES: To analyze the clinical characteristics of vestibular neuritis patients with minimal canal paresis (canal paresis <25%). METHODS: Patients clinically diagnosed with vestibular neuritis and treated at our institute (n=201) underwent otoneurological examination and vestibular function tests. Patients were categorized in terms of the results of caloric testing (canal paresis<25%, n=58; canal paresis≥25%, n=143). Clinical characteristics and laboratory outcomes were compared between two groups. RESULTS: Existence of underlying diseases, preceding symptoms, and direction of spontaneous nystagmus were not different between the groups. The mean duration of spontaneous nystagmus was shortest in the minimal canal paresis group (P<0.001) and the direction of spontaneous nystagmus changed more frequently in this group (P<0.001) during recovery. Among the subgroup with minimal canal paresis, only 29.5% had an abnormal finding on the rotatory chair test, as compared to 81.5% of the canal paresis group. The minimal canal paresis group showed higher sensory organization test scores in computerized dynamic posturography. CONCLUSION: Patients with minimal canal paresis (canal paresis <25%) show similar clinical manifestations as conventional vestibular neuritis patients, but have faster recovery of symptoms and a higher incidence of recovery nystagmus. This finding support that the minimal canal paresis could be considered as a milder type of vestibular neuritis.

Usefulness Assessment of Cochlear Hydrops Analysis Masking Procedure Test in Progress of Ménière's Disease / 대한평형의학회지

OBJECTIVE: There were few recent study concern about usefulness of cochlear hydrops analysis masking procedure (CHAMP) in progression of Ménière's disease. The purpose of this study is to analyze changes in the CHAMP as advancement of Ménière's disease. METHODS: We studied 19 cases of ‘ Definite’ group of Ménière's disease. We assumed progression of Ménière's disease would be checked by pure tone threshold by four tone average (4PTA), low tone average (LPTA). We also compared electrocochleography (ECoG), dizziness handicap inventory (DHI), tinnitus handicap inventory (THI) as parameters for progression of Ménière's disease to CHAMP latency delay and amplitude ratio. Chi-square test was used as a statistical method. RESULTS: In the group of patients had abnormal amplitude ratio, ECoG value were not improved, but there was not statistically significant (odds ratio [OR]=5.727, p>0.05). Better DHI and THI score were not necessarily construed as the improvement value in the CHAMP (p>0.05). In amplitude ratio abnormal group, 4PTA was aggravated, but not statistically significant (OR=1.5, p>0.05). In the group of patient had abnormality in both latency delay and amplitude ratio, LPTA was relatively aggravated (OR in latency delay: 2, OR in amplitude ratio: 10); however, reveals no statistically significance between them (p>0.05). Change of ECoG, hearing threshold including 4PTA and LPTA with progression of Ménière's disease were not correlated significantly with latency delay or amplitude ratio of CHAMP. CONCLUSION: We conclude that CHAMP does not reflect clinical features with progression of Ménière's disease.

Causes of False Negative Bedside Head Impulse Test / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The bedside head impulse test (bHIT) in bare eyes often overlooks possible vestibular losses by missing the corrective saccade. This is why it is necessary to compare bHIT against video head impulse test (vHIT), which is more accurate in identifying vestibular losses than the bedside test. SUBJECTS AND METHOD: A total of 51 vHIT positive ears underwent the study, and out of those, 47 were diagnosed with dizziness. bHIT and vHIT were performed for patients, and the occurrence rate of overt saccade (OS) was calculated. RESULTS: Among the 51 vHIT positive ears, 33 (64.7%) were bHIT positive ears and 18 ears (35.3%) were bHIT negative. Patterns of positive vHIT were classified as A: no corrective saccade, B: covert saccade (CS) only, C: OS only, and D: CS with OS (CS+OS), which were 45 out of 51 ears (88%). The occurrence rate of OS was higher in the bHIT positive group than in the bHIT negative group (p=0.05), and higher in the CS negative group (CS-) than in the CS positive group (CS+) (p<0.001). CONCLUSION: Possible causes of false negative results of bHIT are seen as following: the absence of corrective (covert and overt) saccade, the occurrence of CS only, and missing the OS during the bHIT (probably due to low occurrence rate of OS). The occurrence of CS should be considered as an important factor in false negative bHIT when lowering the occurrence rate of OS.

Cold Dry Air Provocation and Immunoglobulin E in Nasal Fluid for Diagnosing Nonspecific Hyper-Reactivity / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: We aimed to evaluate the usefulness of cold dry air (CDA) provocation test in patients with non-allergic or allergic rhinitis. SUBJECTS AND METHOD: Twenty-one patients (13 males and 8 females, mean age 36.9±17.6 years) with symptoms of rhinitis were enrolled. We classified patients into groups A (control group, n=9) and B (allergic group, n=12) according to their skin prick test results. Before and after CDA provocation (0℃, relative humidity<10%, total 400 liters during 6 minutes), we evaluated changes in nasal symptoms. We collected serum, and nasal fluid before and after CDA provocation using the filter paper method. We measured serum and nasal fluid IgE levels, compared them between the groups, and evaluated the correlation between serum and nasal fluid IgE. RESULTS: After the CDA provocation, group B had more aggravation of symptoms than group A, with a statistical significance (for nasal obstruction, group A: 3.0±2.4, group B: 5.8±3.4, p=0.049; for itching, group A: 1.0±1.6, group B: 3.8±3.4, p=0.045). The level of serum total IgE was significantly higher in group B (group A: 152.7±67.3 ng/mL, group B: 612.1±291.4 ng/mL, p=0.001). The titer of nasal fluid IgE was higher in group B, before and after the CDA challenge (before CDA, group A: 91.7±52.6 ng/mL, group B: 810.0±1042.3 ng/mL, p=0.029, after CDA, group A: 55.8±43.8 ng/mL, group B: 354.9±236.7 ng/mL, p=0.003). There was a significant correlation between the serum IgE and nasal fluid IgE levels after the CDA provocation test (R2=0.749, p<0.001). CONCLUSION: The CDA provocation test and measurement of nasal fluid IgE level could be useful for the evaluation of nonspecific hyper-reactivity.

A Case of Fibrous Mass Diagnosed as Spidle Cell Rhabdomyosarcoma in the Vocal Fold

Rhabdomyosarcoma is an uncommon type of soft tissue malignant neoplasm characterized by undifferentiated mesodermal tissue. Sarcomas account for approximately 1% of all laryngeal neoplasm and rhabdomyosarcomas are the rarest sarcoma found in the larynx. When the sarcoma involves the larynx, radical surgery such as laryngectomy has been considered. With recent advances of combined therapy, however, it can be treated by conservative surgeries followed by postoperative radiotherapy and/or pulse chemotherapy. With reviews of literature, we report a 47-year-old patient complaining of husky voice and throat discomfort who was finally diagnosed as rhabdomyosarcoma of the vocal fold and successfully treated by laser cordectomy followed by adjuvant chemoradiotherapy.

Prospective validation of a novel dosing scheme for intravenous busulfan in adult patients undergoing hematopoietic stem cell transplantation

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) (23×ABW(0.5) mg daily) targeting an area under the concentration-time curve (AUC) of 5924 µM·min. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC (AUC(PRED)). The accuracy and precision of the AUC(PRED) values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of 5924 µM·min. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of AUCPRED were -5.8% and 20.6%, respectively, in the conventional dosing group and −2.1% and 14.0%, respectively, in the new dosing scheme group. These fi ndings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.