BACKGROUND: Most of adult patients with chronic immune thrombocytopenic purpura (ITP) that was refractory or relapsed to high-dose corticosteroid have been treated with splenectomy as a 2nd line treatment. However, these patients may have increased morbidity and mortality according to the operation and the increased risk of infection for a lifetime after splenectomy. Despite of the above risks, 30~40% of these patients can't maintain remission. Furthermore, the remission rate after splenectomy is relatively lower in patients with corticosteroid-refractory chronic ITP than that in those patients with corticosteroid-responsiveness. We studied whether danazol, an attenuated androgen, is useful or safe as 2nd line treatment for chronic ITP instead of splenectomy and which factors are associated with the response to danazol. METHODS: Among the patients with chronic ITP who failed corticosteroid therapy in our hospital, 28 patients who received danazol as the 2nd line treatment were analyzed retrospectively. A complete response was defined that the platelet count was increased to 150 x 10(3)/microL, and a partial response was defined that the platelet count was increased above 50 x 10(3)/microL or there was an increased platelet count of more than 20 x 10(3)/microL from the pre-treatment platelet count when the platelet count was above 50 x 10(3)/microL at the time of danazol therapy. RESULTS: The median age of patients was 44 years (range: 19~67) and the number of male patients was 9 (32.1%) and the number of females was 19 (67.9%). The starting daily doses of danazol were variable from 200 to 600mg, though most of the patients were treated with 400mg daily (18 cases, 64.3%). The median duration of danazol therapy was 201.5 days (range: 13~973) and the median duration from ITP diagnosis to danazol treatment was 56 days (range: 20~2,430). Among the accrued 28 patients, 22 patients showed a response to danazol (78.5%); there were 6 patients (21.4%) with a complete response and 16 patients (57.1%) with a partial response. The median duration from danazol treatment to response was 30 days (range: 0~180). The median response duration of danazol treatment was 330 days (95% CI: 182~478) by the Kaplan-Meiyer method. For the danazol-responsive patients, 9 patients (40.9%) remained in remission and 13 patients (59.1%) relapsed. Grade 3~4 toxicity was observed in two patients and three patients stopped danazol because of adverse effects. Hepatotoxicity was the most common toxicity. CONCLUSION: Our findings suggest that danazol is a beneficial, safe choice as the 2nd line treatment for patients with chronic ITP that was refractory or relapsed to corticosteroid.
Adult ; Danazol* ; Diagnosis ; Female ; Humans ; Male ; Mortality ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic* ; Retrospective Studies ; Splenectomy

A 60-year-old man presented with cough, sputum, and dyspnea. He had a history of acute myeloid leukemia and hematopoietic stem cell transplantation with chronic renal failure. Chest CT scans showed miliary nodules and patchy consolidations. Histological examination revealed numerous fibrin balls within the alveoli and thickening of the alveolar septum, both of which are typical pathological features of acute fibrinous and organizing pneumonia (AFOP). We report the first case of AFOP following allogeneic hematopoietic stem cell transplantation.
Acute Disease ; Anti-Bacterial Agents/therapeutic use ; Biopsy ; Cryptogenic Organizing Pneumonia/etiology/pathology ; Fatal Outcome ; Glucocorticoids/administration & dosage ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Hemoptysis/etiology ; Humans ; Leukemia, Myeloid, Acute/*surgery ; Lung Diseases/*etiology/pathology ; Male ; Middle Aged ; Pleural Effusion/etiology ; Pulse Therapy, Drug ; Radiography, Thoracic ; Respiratory Insufficiency/etiology ; Tomography, X-Ray Computed

BACKGROUND: There has been contradictory reports regarding the homing potential of hematopoietic cells briefly exposed to hematopoietic growth factors in vitro. To get a resolution to this controversy, we investigated the effects of short-term growth factor treatment of hematopoietic cells on the expression of CXCR4 and adhesion molecules, and the chemotaxis in response to stromal cell-derived factor-1 (SDF-1), which is widely accepted to play a critical role in bone marrow (BM) homing of hematopoietic stem cells. METHODS: BM and cord blood(CB) CD34+ cells were incubated with various hematopoietic growth factors including IL-1beta, IL-3, IL-6, G-CSF, GM-CSF, stem cell factor (SCF), flk-2 ligand, and thrombopoietin, alone or in combination for up to 48 hours. Before and after the incubation, the expression of CXCR4 and adhesion molecules of CD34+ cells was analyzed using flow cytometry. SDF-1-mediated transmembrane or transendothelial migration of CD34+ cells, cobblestone area-forming cells (CAFCs), and/or long-term culture-initiating cells (LTC-ICs) was measured using Transwell(TM) system. RESULTS: VLA-4 was moderately up-regulated by the incubation of the cells with IL-3 and SCF, and ICAM-1 was slightly up-regulated by IL-1 and IL-3. The expression of L-selectin, PECAM-1 or LFA-1 was not altered by any growth factors. With the incubation of the cells in the absence of growth factors or SDF-1, CXCR4 expression of CD34+ cells was rapidly increased, reaching a plateau at 24 hours. The spontaneous up-regulation was abrogated with the addition of SDF-1. In agreement with the up-regulation of CXCR4, CD34+ cells incubated for 40 hours showed much enhanced chemotaxis in response to SDF-1 compared to non-incubated cells (24.7 3.5% vs. 7.0 1.6%, P=0.01). Any growth factors examined in this study did not alter the CXCR4 expression of CD34+ cells. Neither did growth factors affect the transendothelial migration of LTC-ICs toward bone marrow stromal cells as well as the SDF-1-induced transmembrane chemotaxis of CD34+ cells and CAFCs. CONCLUSION: Short-term treatment of hemo-topoietic cells with hematopoietic growth factors does not alter the expression of CXCR4 or SDF-1-mediated transendothelial chemotaxis.
Antigens, CD31 ; Bone Marrow ; Chemotaxis ; Flow Cytometry ; Granulocyte Colony-Stimulating Factor ; Granulocyte-Macrophage Colony-Stimulating Factor ; Hematopoietic Stem Cells ; Integrin alpha4beta1 ; Intercellular Adhesion Molecule-1 ; Intercellular Signaling Peptides and Proteins* ; Interleukin-1 ; Interleukin-3 ; Interleukin-6 ; L-Selectin ; Lymphocyte Function-Associated Antigen-1 ; Mesenchymal Stromal Cells ; Stem Cell Factor ; Thrombopoietin ; Transendothelial and Transepithelial Migration* ; Up-Regulation

Primary gastric choriocarcinomas are very rare, and their prognosis is extremely poor. A 37-year-old woman presented with amenorrhea, vaginal spotting and severe nausea, which mimicked a pregnancy and gestational trophoblastic disease. The serum level of the beta-subunit of human chorionic gonadotrophin (beta-hCG) was significantly increased. An endoscopic biopsy of the stomach mass showed the features of a choriocarcinoma, with marked anaplasia and necrosis. Immunohistochemical staining for beta-hCG showed positive results in the choriocarcinoma. Chemotherapy for the choriocarcinoma was administered, but she died 8 months following diagnosis.
Adult ; Amenorrhea* ; Anaplasia ; Biopsy ; Choriocarcinoma* ; Chorion ; Diagnosis ; Drug Therapy ; Female ; Gestational Trophoblastic Disease ; Humans ; Metrorrhagia ; Nausea ; Necrosis ; Pregnancy ; Prognosis ; Stomach

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.
Acute Disease ; Antimetabolites, Antineoplastic/*adverse effects ; Female ; Fluorouracil/*adverse effects ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Nasopharyngeal Neoplasms/drug therapy/radiotherapy ; Thiamine/therapeutic use ; Thiamine Deficiency/*complications/diagnosis ; Wernicke Encephalopathy/*chemically induced/diagnosis

BACKGROUND: There are few therapeutic options for patients with multiple myeloma who relapse after autologous or allogeneic stem cell transplantation, or for patients who are refractory to conventional chemotherapy and not eligible for salvage high-dose therapy. Thalidomide, a potent antiangiogenic agent, has been suggested as an effective salvage therapy in refractory multiple myeloma. The aim of this study was to evaluate the efficacy and tolerance of thalidomide as a single agent as multicenter trial in Korea. METHOD: From February 2001 to September 2002, 28 patients from 4 institutions were included. At start of treatment, all patients had active disease and 17 (61%) had received at least one autologous transplantation. RESULTS: The serum or urine levels of paraprotein were reduced by at least 90 percent in two patients, at least 50 percent in three patients, and at least 25 percent in two patients; for a total response rate of 25 percent. 13 patients had stable disease and 8 patients had progressed. At least half of the patients had mild or moderate constipation and fatigue. More severe adverse effects were infrequent. CONCLUSION: This study confirms that thalidomide is an effective and safe agent in patients with relapsed or refractory multiple myeloma.
Autografts ; Constipation ; Drug Therapy ; Fatigue ; Humans ; Korea ; Multiple Myeloma* ; Recurrence ; Salvage Therapy* ; Stem Cell Transplantation ; Thalidomide* ; Transplantation, Autologous

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.