Treatment outcome of all-trans retinoic acid/anthracycline combination chemotherapy and the prognostic impact of FLT3/ITD mutation in acute promyelocytic leukemia patients

BACKGROUND: All-trans retinoic acid (ATRA)/anthracycline chemotherapy is beneficial in newly diagnosed acute promyelocytic leukemia (APL); however, it is important to identify patients with high-risk disease to increase the cure rate. We investigated the outcome of ATRA/anthracycline chemotherapy and clinicobiological correlations of FLT3/ITD and NPM1 mutations in APL patients. METHODS: Induction therapy included oral ATRA (45 mg/m2/day) and idarubicin (12 mg/m2/day, intravenous, on days 2, 4, and 6). Patients achieving complete remission (CR) received 3 courses of ATRA combined with reinforced consolidation therapy. Mutations were analyzed using GeneScan and polymerasae chain reaction assays of bone marrow samples obtained from patients at diagnosis. RESULTS: Forty-five (84.9%) of 53 eligible patients achieved CR. The overall relapse rate was 8.9%, and the 3-year overall survival (OS) and leukemia-free survival (LFS) were 84.9+/-4.9% and 77.5+/-6.0%, respectively. The NPM1 mutation was not found in any patient, while the FLT3/ITD mutation was found in 10 (20.0%) patients. Of the FLT3/ITD+ patients, 80% belonged to the high-risk group, defined according to the presenting WBC and platelet counts. Among the patients who achieved CR, those who were FLT3/ITD+ had a higher relapse rate than those FLT3/ITD-. FLT3/ITD+ patients also had a significantly lower 3-year LFS than FLT3/ITD- patients. Multivariate analysis of the LFS showed that the FLT3/ITD mutation was independently associated with a shorter overall LFS, after adjusting for pretreatment risk stratification. CONCLUSION: This study investigated the clinical outcome of newly diagnosed APL patients treated with ATRA/anthracycline chemotherapy. Patients carrying the FLT3/ITD mutation had more aggressive clinical features and a poorer clinical outcome.

First Fatal Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Case in an Adult in Korea / 전남의대학술지

It has been suggested that oseltamivir-resistant influenza viruses harboring the H274/275Y mutation are less virulent than are those that are oseltamivir-sensitive, and fatality attributed to infection with an oseltamivir-resistant virus is very rare. Here we report the first fatal adult case of oseltamivir-resistant 2009 pandemic influenza A (H1N1) in Korea. A 60-year-old Korean male who had hypertension, diabetes mellitus, chronic kidney disease, and dilated cardiomyopathy visited Chonnam National University Hospital because of a 7-day history of chest pain and dyspnea. The patient was at another clinic and had been medicated with oseltamivir (75 mg twice daily) beginning 7 days before admission. Empirical antibiotics were started on the first day of hospitalization. Reverse-transcriptase polymerase chain reaction for 2009 pandemic influenza A (H1N1) was reported to be positive, and a double dose of oseltamivir (150 mg twice per day) was started on day four of hospitalization. However, the pneumonia worsened and the patient died, despite 3 days of high-dose antiviral therapy and 6 days of antibacterial therapy. An H275Y mutation was detected in the neuraminidase gene sequence. This case shows that oseltamivir resistance after short-term drug exposure is possible and can be fatal, emphasizing that early use of zanamivir should be considered in suspicious cases.

First Fatal Oseltamivir-Resistant 2009 Pandemic Influenza A (H1N1) Case in an Adult in Korea / 전남의대학술지

It has been suggested that oseltamivir-resistant influenza viruses harboring the H274/275Y mutation are less virulent than are those that are oseltamivir-sensitive, and fatality attributed to infection with an oseltamivir-resistant virus is very rare. Here we report the first fatal adult case of oseltamivir-resistant 2009 pandemic influenza A (H1N1) in Korea. A 60-year-old Korean male who had hypertension, diabetes mellitus, chronic kidney disease, and dilated cardiomyopathy visited Chonnam National University Hospital because of a 7-day history of chest pain and dyspnea. The patient was at another clinic and had been medicated with oseltamivir (75 mg twice daily) beginning 7 days before admission. Empirical antibiotics were started on the first day of hospitalization. Reverse-transcriptase polymerase chain reaction for 2009 pandemic influenza A (H1N1) was reported to be positive, and a double dose of oseltamivir (150 mg twice per day) was started on day four of hospitalization. However, the pneumonia worsened and the patient died, despite 3 days of high-dose antiviral therapy and 6 days of antibacterial therapy. An H275Y mutation was detected in the neuraminidase gene sequence. This case shows that oseltamivir resistance after short-term drug exposure is possible and can be fatal, emphasizing that early use of zanamivir should be considered in suspicious cases.

Two Cases of Neuroendocrine Carcinoma and GIST in a Patient with Neurofibromatosis Type 1 / 대한내과학회지

Patients with neurofibromatosis type 1 (NF1) are at increased risk of developing tumors throughout the gastrointestinal tract, including neuromas, gastrointestinal stromal tumors (GISTs), and periampullary somatostatin-rich carcinoids. The simultaneous occurrence of a GIST and a well-differentiated neuroendocrine carcinoma in a patient with NF1 is very rare. Here, we report two cases of the coexistence of a low-risk GIST in the jejunum with a well-differentiated neuroendocrine carcinoma in the duodenum in patients with NF1. These cases strengthen the known association of GIST with neuroendocrine carcinoma in patients with NF1.

Two Cases of Neuroendocrine Carcinoma and GIST in a Patient with Neurofibromatosis Type 1 / 대한내과학회지

Patients with neurofibromatosis type 1 (NF1) are at increased risk of developing tumors throughout the gastrointestinal tract, including neuromas, gastrointestinal stromal tumors (GISTs), and periampullary somatostatin-rich carcinoids. The simultaneous occurrence of a GIST and a well-differentiated neuroendocrine carcinoma in a patient with NF1 is very rare. Here, we report two cases of the coexistence of a low-risk GIST in the jejunum with a well-differentiated neuroendocrine carcinoma in the duodenum in patients with NF1. These cases strengthen the known association of GIST with neuroendocrine carcinoma in patients with NF1.

Toxic Epidermal Necrolysis after Rituximab Therapy for Immune Thrombocytopenic Purpura

Rituximab is a chimeric monoclonal antibody that specifically targets the CD20 molecule on the B cell surface. Although rituximab was originally introduced for the treatment of lymphoid neoplasms such as non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL), it is now emerging as an effective and relatively safe therapeutic option for the patients with refractory immune thrombocytopenic purpura (ITP). We report here on a case of life-threatening toxic epidermal necrolysis (TEN) that was related with the use of rituximab in a patient with refractory ITP. The patient developed extensive erythematous papules and bullous lesions on his whole body associated with fever and visual disturbance during the second cycle of rituximab. The rituximab was discontinued and high dose intravenous immunoglobuline and steroid were administrated. Four weeks later, he fully recovered without any sequelae. A review of the literature reveals this to be the first reported case of TEN associated with rituximab injection in Korea.