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.

The First Korean Case of High-Molecular-Weight Kininogen Deficiency, With a Novel Variant, c.488delG, in the KNG1 Gene

No abstract available.

Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab / 대한내과학회지

Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury, which results from uncontrolled complement activation. Delayed diagnosis and treatment of aHUS may result in end-stage renal disease (ESRD) and an associated dependence on dialysis. In extreme cases, it may cause death due to multi-organ failure. Eculizumab, a humanized monoclonal antibody against C5, inhibits the formation of the terminal membrane attack complex and is used to treat aHUS. Here, we report a 46-year-old male patient who suffered from aHUS relapse, despite prior treatment with repeated plasma exchange and hemodialysis. Eculizumab therapy improved his hematologic findings without use of hemodialysis.

Prognostic utility of ADAMTS13 activity for the atypical hemolytic uremic syndrome (aHUS) and comparison of complement serology between aHUS and thrombotic thrombocytopenic purpura

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) involves dysregulation of the complement system, but whether this also occurs in thrombotic thrombocytopenic purpura (TTP) remains unclear. Although these conditions are difficult to differentiate clinically, TTP can be distinguished by low (<10%) ADAMTS13 activity. The aim was to identify the differences in complement activation products between TTP and aHUS and investigate ADAMTS13 activity as a prognostic factor in aHUS. METHODS: We analyzed patients with thrombotic microangiopathy diagnosed as TTP (N=48) or aHUS (N=50), selected from a Korean registry (N=551). Complement activation products in the plasma samples collected from the patients prior to treatment and in 40 healthy controls were measured by ELISA. RESULTS: The levels of generalized (C3a), alternate (factor Bb), and terminal (C5a and C5b-9) markers were significantly higher (all P<0.01) in the patients than in the healthy controls. Only the factor Bb levels significantly differed (P=0.008) between the two disease groups. In aHUS patients, high normal ADAMTS13 activity (≥77%) was associated with improved treatment response (OR, 6.769; 95% CI, 1.605–28.542; P=0.005), remission (OR, 6.000; 95% CI, 1.693–21.262; P=0.004), exacerbation (OR, 0.242; 95% CI, 0.064–0.916; P=0.031), and disease-associated mortality rates (OR, 0.155; 95% CI, 0.029–0.813; P=0.017). CONCLUSION: These data suggest that complement biomarkers, except factor Bb, are similarly activated in TTP and aHUS patients, and ADAMTS13 activity can predict the treatment response and outcome in aHUS patients.

Multicenter Retrospective Analysis of Clinical Characteristics, Treatment Patterns, and Outcomes in Very Elderly Patients with Diffuse Large B-Cell Lymphoma: The Korean Cancer Study Group LY16-01 / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The treatment strategy for elderly patients older than 80 years with diffuse large B-cell lymphoma (DLBCL) has not been established because of poor treatment tolerability and lack of data. MATERIALS AND METHODS: This multicenter retrospective study was conducted to investigate clinical characteristics, treatment patterns and outcomes of patients older than 80 years who were diagnosed with DLBCL at 19 institutions in Korea between 2005 and 2016. RESULTS: A total of 194 patients were identified (median age, 83.3 years). Of these, 114 patients had an age-adjusted International Prognostic Index (aaIPI) score of 2-3 and 48 had a Charlson index score of 4 or more. R-CHOP was given in 124 cases, R-CVP in 13 cases, other chemotherapy in 17 cases, radiation alone in nine cases, and surgery alone in two cases. Twenty-nine patients did not undergo any treatment. The median number of chemotherapy cycles was three. Only 37 patients completed the planned treatment cycles. The overall response rate from 105 evaluable patients was 90.5% (complete response, 41.9%). Twentynine patients died due to treatment-related toxicities (TRT). Thirteen patients died due to TRT after the first cycle. Median overall survival was 14.0 months. The main causes of death were disease progression (30.8%) and TRT (27.1%). In multivariate analysis, overall survival was affected by aaIPI, hypoalbuminemia, elevated creatinine, and treatment. CONCLUSION: Age itself should not be a contraindication to treatment. However, since elderly patients show higher rates of TRT due to infection, careful monitoring and dose modification of chemotherapeutic agents is needed.

A Case of Myeloid Neoplasm with a PDGFRB Rearrangement and Eosinophilia / 대한내과학회지

Myeloid neoplasia with eosinophilia and platelet-derived growth factor receptor beta (PDGFRB) rearrangements is an uncommon Philadelphia-negative myeloproliferative neoplasm. Their most common morphological diagnosis is chronic myelomonocytic leukemia with eosinophilia, which is associated with t(5;12)(q33;p13) and results in the formation of the ETV6-PDGFRB fusion gene. Here, we report a 49-year-old man with a myeloid neoplasm with a PDGFRB rearrangement, who was incidentally diagnosed with hyperleukocytosis and eosinophilia during a health screening. A chromosome analysis of a bone marrow sample revealed 46, XY, t(5;12)(q33;p13), and fluorescence in situ hybridization analysis revealed the PDGFRB gene rearrangement. The patient was treated with imatinib and subsequently achieved complete hematological and molecular remission.

Metastatic Thyroid Gland Tumor Presenting as an Initial Manifestation of Recurrent Uterine Cervical Cancer / 대한내과학회지

Most patients with recurrent uterine cervical cancer have intra-pelvis metastasis with adjacent lymph node involvement, while a lone, distant metastasis is extremely rare. We report a 79-year-old woman with recurrent uterine cervical cancer that presented as thyroid mass with no intra-pelvic recurrence. Four years earlier, the patient had been diagnosed with uterine cervical cancer. She had undergone a course of concurrent chemoradiotherapy to the pelvis and had no subsequent evidence of recurrence. Several weeks before presenting, she had noticed a foreign body sensation in her throat and a palpable mass in the left side of her neck. Clinically, this was metastatic squamous cell carcinoma from the uterine cervix. Patients who present with swelling or palpable nodules in the neck with a previously diagnosed malignancy must be evaluated for metastatic disease, although metastasis from uterine cervical carcinoma to the thyroid gland is rare.

Mass-forming Eosinophilic Infiltration Involving the Central Airway: A Case Report of Endobronchial Involvement of Eosinophilic Inflammation Mimicking Bronchogenic Malignancy / 대한내과학회지

We report a very unusual case of endobronchial involvement of eosinophilic inflammation. A 58-year-old woman visited our clinic complaining of cough. A chest computed tomography scan showed a poorly enhancing mass compressing both main bronchi in the subcarinal area. Bronchoscopy also showed stenosis of the two main bronchi with irregular mucosal thickening. A bronchoscopic endobronchial mucosal biopsy revealed eosinophilic inflammation without evidence of malignancy. The subcarinal mass disappeared after systemic steroid treatment. This is the first report of mass-forming eosinophilic infiltration involving the central airway mimicking primary lung cancer.

A case of oxaliplatin-induced immune-mediated thrombocytopenia

Oxaliplatin is a platinum compound used in patients with gastrointestinal malignancies. It is known to evoke a drug-induced immune-mediated thrombocytopenia, which has not been reported in Korea. We describe a 53-year-old man who developed oxaliplatin-induced immune-mediated thrombocytopenia during chemotherapy for colon cancer. Oxaliplatin-dependent IgG platelet antibodies were detected in his serum on flow cytometry. He was treated with immunoglobulin and corticosteroids without any complications. Physicians should consider oxaliplatin-induced immune-mediated thrombocytopenia, when a sudden, isolated thrombocytopenia develops during chemotherapy with oxaliplatin.

Two Cases of Hodgkin's Lymphoma after Allogeneic Hematopoietic Cell Transplantation / 대한내과학회지

Hematopoietic cell transplantation recipients have a high risk of subsequent malignant neoplasms. Among post-transplantation lymphoproliferative disorders (PTLDs) after hematopoietic cell transplantation, Hodgkin's lymphoma is rare and distinct from the majority of other PTLDs because of its later onset and relatively good prognosis. It is known to be associated with exposure to the Epstein-Barr virus, and the mixed cellularity subtype is the most common. We herein describe two cases of Hodgkin's lymphoma that developed after allogeneic hematopoietic cell transplantation.

Precursor B-Cell Acute Lymphoblastic Leukemia in Two Patients with a History of Cytotoxic Therapy / 대한내과학회지

Therapy-related myeloid neoplasms have been well characterized. However, precursor B-cell acute lymphoblastic leukemia in patients with prior malignancies is uncommon, and the effect of prior cytotoxic therapy on development of precursor B-cell acute lymphoblastic leukemia is controversial. Therapy-related precursor B-cell acute lymphoblastic leukemia has been reported occasionally. However, cytotoxic therapy-related precursor B-cell acute lymphoblastic leukemia has been reported in Korea only rarely. We herein describe two cases of therapy-related precursor B-cell acute lymphoblastic leukemia.

A Trp33Arg Mutation at Exon 1 of the MYH9 Gene in a Korean Patient with May-Hegglin Anomaly

In this report, we describe a Korean patient with May-Hegglin anomaly from a mutation of the MYH9 gene. The proband was a 21-year-old man with thrombocytopenia. He did not have a bleeding tendency. His neutrophil count was normal at 7490/mm3; however, the neutrophils contained abnormal basophilic inclusions in their cytoplasm. The platelet count was decreased at 15000/mm3 with giant platelets. Coagulation test results were not remarkable. Direct sequencing of MYH9 revealed that he was heterozygous for a mutation in exon 1, which was a 97T>A substitution mutation affecting codon 33, substituting tryptophan with arginine (Trp33Arg). Family study showed that both of his parents had normal phenotype and genotypes, indicating a de novo occurrence of the mutation in the proband.

Asymptomatic pneumatosis intestinalis following chemotherapy for B lymphoblastic leukemia with recurrent genetic abnormalities in an adolescent patient

Pneumatosis intestinalis (PI) is a rare condition characterized by multiple pneumocysts in the submucosa or subserosa of the bowel. Here, we report a rare case of asymptomatic PI after chemotherapy induction in an 18-yr-old man with B lymphoblastic leukemia with recurrent genetic abnormalities. The patient was treated conservatively and recovered without complications. The possibility of PI should be considered as a complication during or after chemotherapy for hematologic malignancies. Conservative treatment should be considered unless there are complications, including peritonitis, bowel perforation, and severe sepsis.

Intravesical Cidofovir in the Treatment of Hemorrhagic Cystitis after Unrelated Cord Blood Transplantation / 대한내과학회지

Hemorrhagic cystitis is a common complication in hematopoietic stem cell transplant recipients. We report a case of hemorrhagic cystitis after unrelated cord blood transplantation associated with adenovirus infection. Despite hydration, hematuria and large clots persisted. We instilled cidofovir into the bladder, which resulted in clearance of the adenovirus and significant clinical improvement. Our case emphasizes the effectiveness of intravesical cidofovir treatment for viral hemorrhagic cystitis.

Limbic Encephalitis Caused by Human Herpesvirus-6 Infection in Allogenic Hematopoietic Stem Cell Transplantation Patient

No abstract available.

Partial Duodenal Obstruction Caused by an Impacted Gastritis Cystica Polyposa / 대한소화기내시경학회지

Gastritis cystica polyposa is an uncommon lesion that usually occurs at the gastroenterostomy site, but it may also develop in the non-operated stomach. This malady is characterized by polypoid mucosal changes with hyperplasia and cystic dilatation of glands that infiltrate into the submucosal layer. We report here on a case of gastritis cystica polyposa that presented as a mass impacted in the duodenum in a 63-year-old male, and this patient had been admitted for evaluation of progressive epigastric fullness and dyspepsia. Esophagogastroduodenoscopy revealed that the partial duodenal obstruction was caused by impaction of a huge polypoid mass with a stalk that originated from the lower body of the stomach. We fished out the impacted mass with a forceps catheter while holding the neck with a snare catheter. Thereafter, an endoloop was applied to the stalk of mass, and this was followed by polypectomy using a snare catheter.

Frequency of Pro475Ser Polymorphism of ADAMTS13 Gene and Its Association with ADAMTS-13 Activity in the Korean Population

PURPOSE: The in vitro study suggested that proline to serine polymorphism in codon 475 (C1423T) of the A Disintegrin and Metalloprotease with ThromboSpondin type 1 repeats-13 (ADAMTS-13) gene is related to reduced activity of ADAMTS- 13. In this study, the frequency of the Pro475Ser polymorphism in Koreans was studied and plasma ADAMTS-13 activity was measured to find out whether this polymorphism contributes to decreased ADAMTS-13 activity in Koreans. PATIENTS AND METHODS: The frequency of the C1423T allele of the ADAMTS13 gene was studied along with measuring plasma ADAMTS-13 activity in 250 healthy Korean individuals. RESULTS: The allele frequency of C1423T polymorphism was 4%, and the median activity of CT type was 107 (69-143)%, which was lower than in controls with the CC genotype [118 (48-197)%, (p=0.021)]. CONCLUSION: Therefore, the Pro475Ser polymorphism seems to be popular in the Korean population, and attenuates ADAMTS-13 plasma activity.

Hereditary Hemolytic Anemia in Korea: a Retrospective Study from 1997 to 2006

BACKGROUND: The aim of this study was to investigate the prevalence, clinical and laboratory findings of hereditary hemolytic anemia (HHA) in Korea from 1997 to 2006 and to develop the appropriate diagnostic approach for HHA. METHODS: By the use of questionnaires, information on the clinical and laboratory findings ofHHA diagnosed from 1997 to 2006 in Korea was collected and analyzed retrospectively. A total of 431 cases were enrolled in this study from 46 departments of 35 hospitals. RESULTS: The overall frequency of HHA did not change through the 10-year period for pediatrics but did show an increasing tendency for internal medicine. The overall male to female sex ratio did not show sex predominance (1.17:1), but a significant male predominance with a ratio of 1.49:1 was seen for pediatrics while a significant female predominance with a ratio of 1:1.97 was seen forinternal medicine. Of the total cases, 74.2% (282/431) were diagnosed before the age of 15 years. The etiologies of HHA were classified as red cell membrane defects, hemoglobinopathies, red cell enzyme deficiencies and unknown causes. There were 382 cases (88.6%) of red cell membrane defects with 376 cases (87.2%) of hereditary spherocytosis and 6 cases (1.4%) of hereditary elliptocytosis, 20 cases (4.6%) of hemoglobinopathies with 18 cases (4.2%) of beta-thalassemia, a case (0.2%) of alpha-thalassemia and a case (0.2%) of Hemoglobin Madrid, 7 cases (1.6%) of red cell enzyme deficiencies with 5 cases (1.2%) of glucose-6- phosphate dehydrogenase (G-6-PD) deficiency, a case (0.2%) of pyruvate kinase (PK) deficiency and a case (0.2%) of enolase deficiency, and 22 cases (5.1%) of unknown causes. The most common chief complaint in pediatric patients was pallor and that in adult patients was jaundice. In the red cell membrane defect group of patients, the level of hemoglobin was significantly higher than in adult patients. The mean corpuscular volume, mean corpuscular hemoglobin, corrected reticulocyte count, total and indirect bilirubin level and lactate dehydrogenase levels in the hemoglobinopathy group of patients were significantly lower than the values in the red cell membrane defect group of patients. The mean concentration of G-6-PD was 0.8+/-0.7U/1012RBC in the G-6-PD deficient patients, PK was 1.7U/1010 RBC in the PK deficient patient, and the level of enolase was 0.04U/g of Hb in the enolase deficient patient. CONCLUSION: The most prevalent cause of HHA in Korea during 1997 to 2006 was hereditary spherocytosis, but HHA by other causes such as hemoglobinopathy and red cell enzyme deficiency gradually increased with the development of molecular diagnostic methods and increasing general interest. However, the etiologies of HHA need to be pursued further in 5.1% of the patients. An systematic standard diagnostic approach is needed in a nationwide prospective study for correct diagnoses and appropriate management of HHA.

Clinical Features of Pregnancy and Delivery in Patients with Idiopathic Thrombocytopenic Purpura

BACKGROUND: Patients with the condition of idiopathic thrombocytopenic purpura (ITP) may present with, maternal and fetal hemorrhagic complications. Appropriate monitoring and treatment may be important in obstetric management. METHODS: A retrospective chart review was performed for obstetric patients with ITP at Bundang CHA hospital from March 1996 to March 2005. RESULTS: Nineteen women with ITP delivered 22 children in 22 pregnancies. The median age at delivery was 30 years (range, 21~37 years). The median platelet counts before pregnancy, during pregnancy, and at delivery were 44,000/microliter (range, 20,000~225,000/microliter), 40,500/microliter (range, 13,000~335,000/microliter), and 73,500/microliter (range, 40,000~308,000/microliter. Treatment for ITP was done in 14 cases (63.6%) during pregnancy and in 18 cases (81.8%) at delivery. Platelet transfusion was done for one case during pregnancy but, was performed in 17 cases (77.3%) at delivery. Vaginal delivery was done in 10 cases (45%) and a Cesarean section was done in 12 cases (55%). No obstetric complications were observed. The median platelet count of 17 infants was 220,000/microliter (range, 59,000~315,000/microliter). Four neonates were born with platelet counts below 150,000/microliter. No infant showed any clinical signs of hemorrhage and there were not any neonatal complications. CONCLUSION: In our study, obstetric patients with ITP and their neonates were safe with no hemorrhagic complication. However, when compared to the current guidelines, the treatment strategy used in the present study was excessive. Appropriate treatment according to the guidelines is necessary during the obstetric management of patients with ITP.

A Case of Mantle Cell Lymphoma Treated with Autologous Stem Cell Transplantation and Rituximab

Mantle cell lymphoma is a subtype of aggressive non-Hodgkin's lymphoma and usually presents in advanced stages. When treated with a regimen such as CHOP, the median survival is about three years. More aggressive front-line therapy with the hyper-CVAD regimen or high-dose therapy with stem cell support has shown encouraging results in several trials. The addition of rituximab to the chemotherapy regimens, or high-dose therapy, increased the response and survival rates in patients with mantle cell lymphoma. We report a case of mantle cell lymphoma that was successfully treated with aggressive front-line treatment strategies. The patient achieved complete remission with initial hyper-CVAD regimen, and was consolidated with autologous stem cell transplantation and subsequent rituximab.