Three Cases of Interstitial Pneumonitis Developed after Anticancer Chemotherapy Containing Cyclophosphamide / 대한내과학회지

Development of diffuse pulmonary infiltrates in patients receiving chemotherapy is a major diagnostic challenge. Diffuse pulmonary infiltrates may be due to infection, pulmonary hemorrhage, pulmonary edema or drug-induced lung injury. Among these, pulmonary toxicity caused by antineoplastic agent is being recognized more frequently. Cyclophosphamide, an alkylating cytotoxic drug, is used widely in the treatment of malignancies including lymphoma. The incidence of pulmonary toxicity is probably less than 1 percent, and its relation with total dosages and schedule of the drug is not yet defined. The typical pictures of cyclophosphamide-induced pulmonary toxicity are non-productive cough, dyspnea, fever, hypoxemia with respiratory alkalosis and interstitial pneumonitis. However, relatively infrequent pulmonary toxicity of cyclophosphamide and frequent development of infectious pulmonary infiltrate in the patients treated with chemotherapy may hamper the early diagnosis of cyclophosphamide toxicity. Interstitial pattern and unresponsiveness to antibiotics of the pneumonitis might be the clues of suspicion. The best ways to treat the patients with cyclophosphamide toxicity are early diagnosis, discontinuation of the drug and early corticosteroid trial, although usefulness of steroid has not been firmly established. Recently, we experienced three cases of interstitial pneumonitis developing during cyclophosphamide-containing chemotherapy for non-Hodgkin's lymphoma in the absence of neutropenia or thrombocytopenia. Early use of corticosteroid in later two cases could resolve the pulmonary complication completely, whereas the pneumonitis failed to improve in spite of the massive use of multiple antibiotics in the first case.

Analysis of Prognostic Factors and Application of International Prognostic Index Model to Determine the High Risk Group for the Treatment of Aggressive Non - Hodgkin's Lymphoma / 대한내과학회지

OBJECTIVE: Although the therapeutic outcome of aggressive non-Hodgkin's lymphoma (NHL) has been considerably improved by the introduction of combination chemotherapy, many patients still fail to achieve complete response(CR) and/or long-term survival. Because the outcome appears to depend on certain prognostic factors, long term prognosis can be predicted by identification of risk group. And also, the patients in high risk group may benefit from new therapeutic modality. In 1993, the international prognostic index model for aggressive NHL as developed far the purpose of predicting outcome and designing of therapeutic trial. Thus, analysis of prognostic factors was performed to identify independent factors for the end points of CR, overall survival, and disease-free survival. METHODS: From 1989 to 1994, total 340 patients were treated with combination chemotherapy and/or radiotherapy for NHL in Korea Cancer Center Hospital. Among 340, informations on eleven prognostic factors(sex, age, performance status, Ann Arbor stage, serum LDH level, tumor size, number of extranodal disease sites, bone marrow involvement, presence of B symptom, sex, time to CR, and histologic grade) were avaliable for 273 patients. Among these, 221 patients with aggressive NHL(NCI clinical schema) were eligible for the prognostic factor analysis for the response and survival. Also, 186 patients were eligible to determine whether International Prognostic Index Model could be applicable for Korean NHL. RESULTS: One hundred fifty patients(68%, 95% CI 62-74%) achieved a complete remission, 43 patients (20%) a partial remission. With a median follow-up of 3,5 years, overall 3 year survival rate was 6396, and 3 year DFS for the 150 CRs was 72%. In a univariate analysis for the CR and survival, Ann Arbor stage, number of extranadal disease, performance status, presence of B symptoms, presence of BM involvement, serum LDH level and histologic grade were found to be statistically significant prognostic factors. Among them, by multivariate analysis, number of extranodal disease(RR 0.2, 95% CI 0.1-0.7), B Symptoms (RR 0.4, 95% CI 0.2-0.9), and histologic grade(RR 0.2, 95% CI 0.08-0.7) showed to be independent adverse prognostic factors for CR. For disease-free survival, Ann Arbor stage(RR 2.6, 95% CI 1.1-6.4) was independent risk factor. For overall survival, number of extranodal involvement(RR 2, 95% CI 1.3-4) and histologic grade(RR 2, 95% CI 1.2-3.7) were independently significant prognostic factors. With these 2 independent prognostic factors for survival, we could establish a prognastic index model which could separate the high risk patients. However, the usefulness of this model should be confirmed in a larger patient population. The dose intensity of cyclophosphamide, during initial 3 months of treatment, was significantly associated with CR rate and overall survival(p=0.01 and 0.03, respectively). When International Prognostic Index Model was applied to our patients, patients in the lower risk groups had significantly better outcome than patients in the higher risk groups(3 year survival and RR: 77% and 1 for low risk group, 61% and 1.9 for low-intermediate risk group, 50% and 2.2 for high-intermediate risk group, and 25% and 6 for high risk group). CONCLUSION: In this study, we confirmed that features other than the Ann Arbor stage were independently associated with CR and survival, and the International Prognostic Index Model would be an useful tool for the selection of high-risk patients who could be benefited from more aggressive chemotherapy.

A Case of Primary Mediastinal Germ Cell Tumor Associated with Klinefelter's Syndrome / 결핵

Klinefelter's syndrome is characterized by small testes, azoospermia, gynecomastia, and elevated levels of plasma gonadotropins in men with two or more X chromosomes. Previous investigators reported that patients with Klinefelter's syndrome are predisposed to the development of a non-seminomatous germ cell tumor in the mediastinum. It is suggested that this linkage may be due to the hormonal imbalance in Klinefelter's syndrome and consequently, the formation of dysgenetic germ cell and/or abnomal migration of germ cell. We report here a case of Klinefelter's syndrome in a 24-years-old man who was presented with anterior mediastinal mass. The clinical and laborarotory findings were compatible with Klinefelter's syndrome and he was found to have 47 XXY karyotype. Pathological findings for mediastinal mass revealed mixed germ cell tumor composed of mature cystic teratoma and endodermal sinus tumor. He was treated with cis-platin containing chemotherapy and followed up in partial remission.

Long Term Survival Rate and Prognostic Factors of Acute Myocardial Infarction

To identify the long-term survival rate and prognostic factors of AMI in Korea, total 404 patients who presented between Jan 1984 and mar 1989 at Seoul National University Hospotal were followed for and average of 24.9+/-18.2 months(range 1 to 69 months). 50 patients(12.4%) died during the in-hospital period and 25 patients(6.2%) died after discharge. Among the survivors reinfarction developled in 11 patients(3.3%). Overall survival rates were 0.87, 0.85, 0.83, 0.81, 0.79, 0.77 and event-free survival rates were 0.87, 0.84, 0.83, 0.79, 0.77, 0.72 at 1, 6, 12, 24, 36, 48 months respectively. During the in-hospital period sex, age, peak creatine kinase level, Killip class, Q wave in ECG, heart failure, and AV block in anterior infarction were of prognostic value. After discharge age, exercise duration on pre-discharge treadmill test, cardiac index, ejection fraction, and presence of heart failure were significant prognostic factors. Pre-discharge coronary angiographies were performed in 217 cases. There was no statistically significant difference in survival rate between multiple vessel disease and single vessel disease. But the more the number of involved vessels was, the higher the incidence of reinfarction was. In the group with jeopardy score less than 8, event-free survival rate was signigicantly higher. Overall survival rate was higher and reinfarction rate was lower in the group, but both were not statistically significant. On discriminant analysis of in-hospital prognostic factors, Killip class, heart failure and age were independent prognostic factors, but other factors had no additional prognostic value.