Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea

Background@#Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. @*Methods@#An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. @*Results@#During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). @*Conclusion@#This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

A Case of Catheter-Related Bacteremia of Tsukamurella pulmonis / 대한진단검사의학회지

Tsukamurella pulmonis is an aerobic actinomycete. We report a catheter-related bacteremia of T. pulmonis. A 39 yr-old male with ALL was hospitalized to receive bone marrow transplantation (BMT). Although the patient developed a high fever at the 7th hospital day (HD), it subsided with vancomycin treatment, and he received BMT at 9th HD. Fever resurged at 16th HD despite sustained treatment with vancomycin, meropenem, and amphotericin B, but subsided with removal of Hickman catheter (HC) at 19th HD. Three sets of blood cultures comprising one from the HC and two from venipunctures were taken at 7th, 16th, and 19th HD, and the distal tip of the HC was also cultured. The aerobic vials of all 3 HC-withdrawn blood cultures and one peripheral blood culture taken at 19HD and the HC tip culture grew long, straight, thin gram-positive rods that were positive on modified Kinyoun stain. This organism showed tiny, rough, grey colonies after 3-day incubation and grew to large flat colonies when incubation was extended. It was catalase-positive, urease-positive, and alkaline-slant/alkaline-deep on triple sugar iron agar, and hydrolyzed hypoxanthine. The sequence of 1,296 base pairs of 16S rRNA of this organism showed a 100.0% homology with the published sequence of T. pulmonis DSM 44142T. To our knowledge, this is the first report of T. pulmonis bacteremia in Korea.

The usefulness of transient elastography (Fibroscan(R)) for predicting esophageal varices and esophageal variceal hemorrhage in patients with chronic liver diseases / 대한내과학회지

BACKGROUND/AIMS: This study was conducted to evaluate the efficacy of transient elastography (Fibroscan(R)) for predicting esophageal varices and esophageal variceal hemorrhage in patients with chronic liver diseases. METHODS: We studied 245 patients (mean age: 50.1 years, male/female: 181/64) with chronic liver diseases to determine the relation between the clinical or serologic markers associated with liver fibrosis and tissue elastography, and these tests were performed in Feb 2007. The causes of chronic liver diseases were hepatitis B virus in 139 (56.7%), hepatitis C virus in 30 (12.2%), alcohol in 38 (15.5%), nonalcoholic fatty liver disease in 23 (9.4%), autoimmune liver disease in 3 (1.2%), and unknown 12 (4.9%). RESULTS: Transient elastography was correlated with APRI (r=0.712) and the grades of esophageal varices (r=0.635). The AUROC values of transient elastography were 0.916 (95% CI: 0.838-0.954) for the presence of esophageal varices, 0.875 (95% CI: 0.819-0.931) for the esophageal varices grade > or =2, and 0.895 (95% CI: 0.846-0.945) for esophageal variceal hemorrhage. The cutoff values for 90% specificity were 15.3 kPa for esophageal varices, 20.7 kPa for esophageal varices grade > or =2 and 34.8 kPa for esophageal variceal hemorrhage, while the negative predictive values were 90%, 94% and 97%, respectively. CONCLUSIONS: Transient elastography was correlated with the presence of esophageal varices, the grades of esophageal varices and the presence of esophageal variceal hemorrhage. Therefore, this data may help to screen those patients how might undergo upper gastrointestinal endoscopy.

Inverse Tendency between Ex Vivo Expansion Potential of Hematopoietic Progenitors and Time to Engraftment after Hematopoietic Stem Cell Transplantation / 대한진단검사의학회지

BACKGROUND: The CD34+ cell dose and infused number of committed progenitor cells in transplantation are important factors in hematologic engraftment. However, the relationship between expansion potential of progenitor cells and hematologic engraftment remains controversial. We evaluated whether expansion potential of progenitor cells is a predictive factor of post-transplantation hematologic engraftment. METHODS: Mononuclear cells isolated from mobilized peripheral blood and bone marrow were cultured with cytokine cocktail for 7 days. Progenitor cells and committed progenitors were analyzed using stem cell markers (CD34 and CD133) and lineage specific markers. Hematologic engraftment was defined as neutrophil counts over 500/microliter and platelet counts over 20,000/microliter without transfusion. Acute and chronic graft-versus-host disease (GVHD) were investigated. RESULTS: There was inverse tendency between the number and fold expansion of progenitor cells or committed (granulocytic or megakaryocytic) progenitors and time to engraftment. Especially, fold expansion of CD34(+)/CD33(+) cells was significantly correlated with time to neutrophil engraftment in bone marrow transplantation (r=-0.56, P=0.04). The infused number and fold expansion of lymphoid progenitors were not related to the occurrence of acute or chronic GVHD. CONCLUSIONS: We could not prove that expansion potential of progenitor cells and committed progenitor cells is correlated to hematologic engraftment although there is a correlation between CD34(+)/ CD33(+) cells and time to neutrophil engraftment. But, a further study on the value of expansion potential is required because there is an inverse tendency.

A Case of Acute Panmyelosis with Myelofibrosis according to WHO Classification / 대한혈액학회지

A 61-year-old man developed a rapidly progressive disease with anemia, thrombocytopenia and large number of blasts (10%) in the peripheral blood. The bone marrow revealed hypercellular marrow with extensive fibrosis and proliferation of immature cells of trilineage. Immunophenotyping and chromosome study with the bone marrow aspirate showed myeloblasts with aberrant expression of CD19 and complex karyotype including structural abnormalities within chromosome 5 and 7. After induction chemotherapy with Ara-c and daunorubicin, the number of blasts in peripheral blood was increased and the bone marrow showed hypercellular marrow with immature cells of trilineage and fibrosis. Cases like this have been called acute myelofibrosis, acute myelosclerosis or acute myelodysplasia with myelofibrosis. Recently this rare disease with rapidly fatal course was categorized into 'acute panmyelosis with myelofibrosis in acute myelogenous leukemia (AML) not otherwise categorized' by WHO classification.

Two Cases of Neonatal Arrhythmia Observed by Fetal Echocardiography / 대한주산의학회잡지

M-mode, pulsed Doppler and Doppler color flow mapping, in addition to two-dimensional echocardiography, have greatly improved imaging of the fetal heart through identification of abnormal cardiac anatomy and rhythm in utero. The early detection of cardiac disturbance in utero permits alteration in obstetric management such as delivery in a high-risk center for optimal neonatal care and/or decision in optimal delivery time. We report two cases of the neonatal arrhy-thmia which were observed by fetal echocardiography. In the first case, female baby showed neonatal arrhythmias including tachycardia and brady-cardia until 3 days after birth, and then turned to bradyarrhythmia due to non-conducted atrial bigeminy. These events lead us to review the fetal echocardiographs of the patient carefully. Premature atrial contractions were observed in her fetal echocardiography. At 2 months after birth, the patient's electrocardiogram showed normal sinus rhythm. Severe neonatal bradycardia of the second case was due to congenital complete heart block, identified clearly by electrocardiogram after birth. This case also showed complete heart block in her fetal echocardiography. After insertion of the temporary pacemaker, cardiomegaly was improved. Both the neonate and the mother had positive anti-SSA/Ro autoantibody. But any other symptoms and signs of neonatal lupus did not appear in the neonate. Patient's mother also did not show any symptoms and signs of systemic lupus erythematosus. Since the prognosis depends upon the cause of bradyarrhythmia in fetus and neonates, differential diagnosis is important in obstetric management and optimal neonatal treatment.