Myelodysplastic syndrome (MDS) refers to a group of clonal disorders affect both hematopoietic stem cells and progenitor cells within the erythrocytic, granulocytic, and megakaryocytic lineages. Ineffective hematopoiesis, the major manifestation of MDS, arises from a complex interaction between hematopoietic progenitors and the microenvironment, resulting in premature apoptotic death of progenitors and their maturing progeny. Development and progression of MDS is suggested to be a multistep alteration to hematopoietic stem cells. Although the molecular pathogenesis of MDS has not been clearly elucidated, a model of MDS pathogenesis has been proposed whereby a normal hematopoietic stem cell acquires successive genetic abnormalities that ultimately lead to malignant transformation and clonal expansion. Early mutations in stem cells may cause differentiation arrest and apoptosis leading to dysplasia and cytopenia, wherease subsequent defects affecting myeloid cell proliferation may cause the clonal expansion of aberrant cells and leukemic transformation. The heterogeneity in the clinical and morphologic features in MDS reflects the diversity and complexity of the underlying genetic defects. Some of these different molecular alterations have been described. However, since the developing targeted therapeutic advances in MDS will likely depend on a full comprehension of underlying molecular mechanisms, it may be required to make further progress in understanding the exact pathomechanisms of this disease.
Apoptosis ; Comprehension ; Diagnosis, Differential ; Hematopoiesis ; Hematopoietic Stem Cells ; Myelodysplastic Syndromes ; Myeloid Cells ; Population Characteristics ; Stem Cells

In case of unresectable or metastatic gastric cancer, though many trials have been going, treatment results are poor yet. We report a patient with peritoneal metastasis from gastric cancer effectively treated with docetaxel and cisplatin chemotherapy. The patient was a 33 year-old man who was confirmed poorly differenciated adenocarcinoma of stomach 5 years ago. At the diagnosis, the stage of gastric cancer was T2N3M0. He underwent subtotal gastrectomy with Billoth II anastomosis and 6th cycles of postoperative adjuvant chemotherapy consisting of FAMTX. After that, there was no evidence of recurrence. Three years later, he was admitted to our hospital complaining of abdominal pain and distension. Abdominal CT revealed that recurred gastric cancer in anastomotic site with carcinomatous peritonei and multiple lymphadenopathy. He was performed chemotherapy combined with docetaxel (75 mg/m2) and cisplatin (75 mg/m2). After 3rd chemotherapy, follow up abdominal CT showed nearly complete regression of bowel loops, lymph node and ascites. After completion of 7th cycles of chemotherapy, it remained as complete response for recurred gastric cancer and he has no evidence of recurrence for over 2 years.
Abdominal Pain ; Adenocarcinoma ; Adult ; Ascites ; Chemotherapy, Adjuvant ; Cisplatin* ; Diagnosis ; Drug Therapy* ; Follow-Up Studies ; Gastrectomy ; Humans ; Lymph Nodes ; Lymphatic Diseases ; Neoplasm Metastasis* ; Peritoneal Neoplasms ; Recurrence ; Stomach ; Stomach Neoplasms* ; Tomography, X-Ray Computed

Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are collectively known as 'Philadelphia-negative classical myeloproliferative neoplasms (MPNs).' The discovery of new genetic aberrations such as Janus kinase 2 (JAK2) have enhanced our understanding of the pathophysiology of MPNs. Currently, the JAK2 mutation is not only a standard criterion for diagnosis but is also a new target for drug development. The JAK1/2 inhibitor, ruxolitinib, was the first JAK inhibitor approved for patients with intermediate- to high-risk myelofibrosis and its effects in improving symptoms and survival benefits were demonstrated by randomized controlled trials. In 2011, the Korean Society of Hematology MPN Working Party devised diagnostic and therapeutic guidelines for Korean MPN patients. Subsequently, other genetic mutations have been discovered and many kinds of new drugs are now under clinical investigation. In view of recent developments, we have revised the guidelines for the diagnosis and management of MPN based on published evidence and the experiences of the expert panel. Here we describe the epidemiology, new genetic mutations, and novel therapeutic options as well as diagnostic criteria and standard treatment strategies for MPN patients in Korea.
Antineoplastic Agents/*therapeutic use ; Asian Continental Ancestry Group/genetics ; Humans ; Janus Kinase 2/*antagonists & inhibitors/genetics/metabolism ; Molecular Targeted Therapy ; Mutation ; Myeloproliferative Disorders/diagnosis/drug therapy/enzymology/ethnology/genetics ; Protein Kinase Inhibitors/*therapeutic use ; Republic of Korea/epidemiology ; Risk Factors ; Signal Transduction/drug effects ; Treatment Outcome

Generalized vitiligo associated with allogeneic bone marrow or stem cell transplantation has rarely been reported. We experienced two cases of generalized vitiligo after allogeneic bone marrow and stem cell transplantation. The first patient was received an allogeneic bone marrow transplantation and subsequent allogeneic peripheral blood stem cell transplantation for severe aplastic anemia from his sister. The second patient underwent allogeneic bone marrow transplantation for acute myelogeneous leukemia from his sister. Generalized vitiligo developed after transplantation. Neither vitiligo nor evidences of autoimmune diseases were found in their stem cell donors. Vitiligo was effectively treated with narrow band UVB irradiation.
Anemia, Aplastic ; Autoimmune Diseases ; Bone Marrow ; Bone Marrow Transplantation ; Humans ; Leukemia ; Peripheral Blood Stem Cell Transplantation ; Siblings ; Stem Cell Transplantation* ; Stem Cells* ; Tissue Donors ; Vitiligo*

This guideline focuses on the primary prevention of venous thromboembolism (VTE) in Korea. The guidelines should be individualized and aim at patients scheduled for major surgery, as well as patients with a history of trauma, high-risk pregnancy, cancer, or other severe medical illnesses. Currently, no nation-wide data on the incidence of VTE exist, and randomized controlled trials aiming at the prevention of VTE in Korea have yielded few results. Therefore, these guidelines were based on the second edition of the Japanese Guidelines for the Prevention of VTE and the eighth edition of the American College of Chest Physicians (ACCP) Evidenced-Based Clinical Practice Guidelines. These guidelines establish low-, moderate-, and high-risk groups, and recommend appropriate thromboprophylaxis for each group.
Heparin, Low-Molecular-Weight/therapeutic use ; Humans ; Polysaccharides/therapeutic use ; Republic of Korea ; Risk Factors ; Venous Thromboembolism/*prevention & control/surgery/therapy ; Warfarin/therapeutic use

DNA methyltransferase inhibitor, 5-azacitidine (AC) is effective in myelodysplastic syndromes (MDS) and can induce re-expression in cancer. We analyzed the methylation of 25 tumor suppressor genes in AC-treated MDS. Hypermethylation of CDKN2B, FHIT, ESR1, and IGSF4 gene was detected in 9/44 patients. In concordance with the clinical response, a lack of or decreased methylation in 4 patients with hematologic improvements and persistent methylation in 4 others with no response was observed. The mRNA expression of CDKN2B, IGSF4, and ESR1 was significantly reduced in MDS. Our results suggest that methylation changes contribute to disease pathogenesis and may serve as marker to monitor the efficacy of treatments.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Azacitidine/*pharmacology/*therapeutic use ; DNA Methylation/*drug effects ; DNA Modification Methylases/antagonists & inhibitors/metabolism ; Enzyme Inhibitors/*pharmacology/*therapeutic use ; Female ; Genes, Tumor Suppressor ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes/*drug therapy/*genetics ; Young Adult

BACKGROUND: A change in urine output has been recently recognized as a valuable biomarker of acute kidney injury that is associated with mortality in critically ill patients. We investigated the prognostic impact of oliguria for survival outcomes in multiple myeloma (MM) patients presenting with renal impairment (RI). METHODS: Retrospective data on 98 patients with MM and RI, who received initial treatment with novel therapies, were analyzed. Oliguria was defined as a urine output of <0.5 mL/kg/h. RESULTS: The baseline median eGFR was 39.7 mL/min (range, 5.1-59.8). Achievement of renal complete response (CR) was observed in 39.8% of patients. Nine patients (9.2%) presented with oliguria at initial diagnosis, and 4 initially required dialysis. Over a median follow-up period of 17.1 months (range, 1.7-100.0), the median overall survival (OS) was 38.7 months (95% CI 25.0-52.5). Multivariate analyses indicated that oliguria at diagnosis [hazard ratio (HR) 3.628, 95% CI 1.366-9.849, P=0.011], and thrombocytopenia <100x10(9)/L at diagnosis (HR 2.534, 95% CI 1.068-6.015, P=0.035), were significantly associated with overall survival. CONCLUSION: Oliguria was significantly associated with higher mortality in MM patients with RI. Therefore, close monitoring of urine output could be important for these patients.
Acute Kidney Injury ; Critical Illness ; Diagnosis ; Dialysis ; Follow-Up Studies ; Humans ; Mortality* ; Multiple Myeloma* ; Multivariate Analysis ; Oliguria* ; Renal Insufficiency ; Retrospective Studies ; Thrombocytopenia

Although various combinations of chemotherapy regimens have been tried for patients with esophageal cancer, their duration of survival is extremely poor. In this study, we investigated the safety and clinical efficacy of paclitaxel and cisplatin chemotherapy in metastatic or recurrent esophageal cancer. 32 patients enrolled in this study and the median age was 60 yr. Of all the 32, 28 patients (88%) had been treated previously, 22 of them with chemotherapy or radiation therapy. All patients in the study received biweekly paclitaxel (90 mg/m2) followed by cisplatin (50 mg/m2). One patient (3%) responded completely, and 12 patients (38%) showed a partial response; in 9 patients (28%) the disease remained stable, and in 10 patients (31%) it progressed. The objective response rate was 41%. The median duration of response was 4.8 months, and the median overall survival in all patients was 7 months. The 1-yr and 2-yr survival rates were 28.1% and 7.1%, respectively. Grade 3 or 4 of neutropenia and anemia were observed in 6 (19%) and 5 (16%) patients, respectively. The major non-hematologic toxicity was fatigue, but most of them could manageable. In conclusion, biweekly paclitaxel and cisplatin is effective in patients with metastatic or recurrent esophageal cancer.
Aged ; Anemia/chemically induced ; Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Bone Neoplasms/drug therapy/secondary ; Cisplatin/administration & dosage/adverse effects ; Diarrhea/chemically induced ; Esophageal Neoplasms/*drug therapy/pathology ; Fatigue/chemically induced ; Humans ; Liver Neoplasms/drug therapy/secondary ; Lung Neoplasms/drug therapy/secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea/chemically induced ; Neoplasm Recurrence, Local ; Paclitaxel/administration & dosage/adverse effects ; Survival Analysis ; Thrombocytopenia/chemically induced ; Time Factors ; Treatment Outcome ; Vomiting/chemically induced

BACKGROUND: Eltrombopag is a thrombopoietin receptor agonist with excellent treatment outcomes in immune thrombocytopenia (ITP). Here, we analyzed the dose of eltrombopag required to achieve and maintain safe platelet counts in Korean ITP patients. METHODS: Adult refractory ITP patients (<30,000 platelets/microL) were enrolled. Eltrombopag doses were increased to achieve a target platelet count (> or =50,000 cells/microL). After achieving the target platelet count, the dose of concomitant ITP medications and eltrombopag was reduced to identify the lowest effective dose required to maintain the platelet count. RESULTS: Among 18 patients, 66.7% achieved complete response, 5.6% achieved platelet counts between 50,000 and 100,000 cells/microL, and 27.8% failed to achieve the target platelet count. The median ITP duration was significantly shorter in patients who achieved the target platelet count. The initial dose required to achieve the target platelet count was 25 mg/d. The adjusted maintenance doses were 25 mg twice per week or 25 mg/d. After discontinuation, 83.3% relapsed, and the median relapse-free survival was 15 days. Two relapsed and 1 failed patient switched to romiplostim. The response to romiplostim was similar to eltrombopag. During eltrombopag treatment, 38.9% showed hepatobiliary laboratory anomalies. Among 9 follow-up bone marrow examinations, 1 revealed fibrosis after 1 year of treatment. CONCLUSION: Eltrombopag was well tolerated with excellent treatment outcomes in refractory adult ITP patients. Low-dose eltrombopag effectively maintained the target platelet count. However, some patients required longer or higher-dose treatment to maintain the target platelet count, especially in heavily pretreated or longer ITP cases.
Adult* ; Bone Marrow Examination ; Fibrosis ; Follow-Up Studies ; Humans ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Receptors, Thrombopoietin ; Thrombocytopenia*

Paroxysmal nocturnal hemoglobinuria (PNH) is a progressive, systemic, life-threatening disease, characterized by chronic uncontrolled complement activation. A retrospective analysis of 301 Korean PNH patients who had not received eculizumab was performed to systematically identify the clinical symptoms and signs predictive of mortality. PNH patients with hemolysis (lactate dehydrogenase [LDH] > or = 1.5 x the upper limit of normal [ULN]) have a 4.8-fold higher mortality rate compared with the age- and sex-matched general population (P < 0.001). In contrast, patients with LDH < 1.5 x ULN have a similar mortality rate as the general population (P = 0.824). Thromboembolism (TE) (odds ratio [OR] 7.11; 95% confidence interval [CI] (3.052-16.562), renal impairment (OR, 2.953; 95% CI, 1.116-7.818) and PNH-cytopenia (OR, 2.547; 95% CI, 1.159-5.597) are independent risk factors for mortality, with mortality rates 14-fold (P < 0.001), 8-fold (P < 0.001), and 6.2-fold (P < 0.001) greater than that of the age- and sex-matched general population, respectively. The combination of hemolysis and 1 or more of the clinical symptoms such as abdominal pain, chest pain, or dyspnea, resulted in a much greater increased mortality rate when compared with patients with just the individual symptom alone or just hemolysis. Early identification of risk factors related to mortality is crucial for the management of PNH. This trial was registered at www.clinicaltrials.gov as NCT01224483.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/therapeutic use ; Antibodies, Monoclonal, Humanized/therapeutic use ; Area Under Curve ; Child ; Dyspnea/etiology ; Female ; Hemoglobinuria, Paroxysmal/*diagnosis/drug therapy/mortality ; Hemolysis ; Humans ; Kaplan-Meier Estimate ; Kidney Diseases/complications/diagnosis ; L-Lactate Dehydrogenase/metabolism ; Male ; Middle Aged ; Odds Ratio ; ROC Curve ; Registries ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Thromboembolism/complications/diagnosis ; Young Adult