High Dose Cyclophosphamide, Thiotepa, and Carboplatin followed by Autologous Peripheral Stem Cell Rescue in Patients with Responsive Metastatic or High - Risk Primary Breast Cancer / 대한암학회지

PURPOSE: Positive correlation between dosage of antineoplastic agents and tumor response is well demonstrated in advanced breast cancer. But severe bone marrow depression limit the clinical application of high dose chemotherapy. Autologous peripheral blood stem cell transplantation(PBSCT) after high dose chemotherapy(HDC) was introduced to promote rapid bone marrow recovery. This study was designed to establish the feasibility of combining high dose cyclophosphamide, thiotepa, and carboplatin chemotherapy followed by stem cell rescue in patients with responsive metastatic or high risk primary breast cancer. MATERIALS AND METHOD: Eligibility criteria included the presence of high risk primary breast cancer(10 or more involved axillary lymph node, n=4), recurrent disease after curative resection(n=6) or stage IV disease at the time of diagnosis(n=1). The responses of recurrent disease to initial chemotherapy were 4 complete responses and 1 partial responses. One recurrent case with solitary pulmonary metastasis underwent metastasectomy and got chemotherapy after operation. Colony stimulating factor was administered to mobilize stem cells from bone marrow to peripheral blood. The stem cell collection was performed 4~10 times(median 4) and the number of collected stem cell was 1.95~7.34x10(8)kg(median 4.87x10(8)/kg). High dose chemotherapy with CTCb (cyclophosphamide 1,500 mg/m2/day, thiotepa 125 mg/m2/day, carboplatin 200 mg/m2/ day) was performed from day -7 to day -4 and peripheral stem cell infusion was performed on day 0 as planned. RESULT: Eleven patients were enrolled in this study. Their median age was 39 years old. The median time for bone marrow recovery was 11 days for neutrophil(>500/mm2) and 28 days for platelet(>50,000/mm2). Packed red blood cell and platelet transfusion were performed in 11 patients. The group whose infused mononuclear cell count was less than 4.0 x 10(8)/kg(n=9) needed longer time for bone marrow recovery than those(n=2) who had more than 4.0 x 10(8)/kg( 20 vs 13 day, p < 0.05 ). For non-hematologic toxicity, none have experienced toxicity more than grade III. There were 2 recurrences of 4 cases with high risk breast cancer at the 22 th, and 25 th month but they are still alive at the 28 th, and 29 th month each. The other 2 cases are alive without recurrences at the 18 th, and 20 th months each. In the recurrent disease group, one case who showed partial response to initial chemotherapy recurred at the 4 th month and died at the 13 th month after PBSCT. The other 5 cases are alive without recurrence at the 1st, 3 rd, 3 rd, 5 th, and 31 th month each. One case with stage IV disease(bone metastasis) is alive without evidence of progression at the 3 rd month. CONCLUSION: High dose chemotherapy with PBSCT can be performed safely. Long term survival of patients with advanced breast cancer would be possible by PBSCT after HDC. Further clinical trials based on larger patient population is required to evaluate clinical efficacy of PBSCT after HDC in high risk and recurrent breast cancer.

Clinical Characteristics and Prognostic Factors of Non-Hodgkins Lymphoma / 대한내과학회지

OBJECTIVES: The advent of intense combination chemotherapy has transformed aggressive non-Hod-gkins lymphoma from a disease that was once uniformly fatal to one that is now often curable. Remission rates and survival may be improved by using intensive chemotherapy regimens. However, this more aggressive approach is inevitably associated with increased toxicity, and an accurate pretreament prognostic assessment of patients is required to guide the physician in selecting the most appropriate therapeutic regimen. Many studies have reported prognostic factors of non-Hodgkins lymphoma in western countries, but there are few reports on prognostic factors in Koreans and it is suggested that clinical characteristcs of non-Hodgkins lymphoma in Korea differ from those in western countries. The purpose of this study was to illustrate clinical characteristics, prognostic factors and treatment outcome in non-Hodgkins lymphoma in Korea. METHODS: Clinical features of 151patients (age over 15years) with non-Hodgkins lymphoma registered at Asan Medical Center from March 1989 to December 1993 were retrospectively reviewed. Prognostic factors and treatment outcome were evaluated among 121previously untreated patients. Multi variate analysis of potential pretreatment prognostic factors was performed using Coxs proportional hazards model. RESULTS: Of the 151patients evaluated, 55% had diffuse large cell type, while low-grades were encountered in less than 1% of the patients. Extranodal involvement was noted in 76% of the patients. Cental nervous system was the commonest primary extranodal site, followed by stomach. Complete remission was achieved in 73 of 121patients (60%). The median follow-up for 121patients was 24months and the actuarial overall survival was 48% at 3years and 44N at 5years with a median overall survival of 33months. At the median followup of 32months, the actuarial 5year disease-free survival rate among 73patient with complete remission was 65% and median remission duration was not reached. Presence of systemic B symptoms and advanced clinical stages were associated with a low complete remission rate. None turned out to be associated with the remission duration. The Coxs proportional hazards model identified age above 60years, presence of systemic B symptoms and elevated LDH level as significant independent poor prognostic factors influencing overall survival. CONCLUSION: This study reveals a low prevalence rate of the low-grades lymphoma and a higher propensity of diffuse large cell type. These results suggest that clinical characteristics of non-Hodgkins lymphoma in Korea are different from those in the western countries. Our data also show that certain pretreatment clinical factors can help in predicting survival and in planning treatment.

High-Dose Chemotherapy of Cyclophosphamide, Thiotepa, and Carboplatin (CTCb) with Autologous Peripheral Blood Stem Cell Transplantation for High-Risk Primary Breast Cancer and Metastatic Breast Cancer / 대한내과학회지

OBJECTIVES: Recently high dose chemotherapy with autologous peripheral blood stem cell transplantation (APBSCT) has been investigated with the hope of maximizing tumor response and increasing survival. The purpose of this study is to evaluate the effect, feasibility, and toxicity of high-dose cyclophosphamide, thiotepa, and carboplatin (CTCb) with APBSCT in patients with metastatic or high risk primary breast cancer. METHODS: Four cases of high-risk primary breast cancer (with more than 10 involved axillary nodes) and three cases of metastatic disease in complete or partial response were enrolled. Peripheral blood stem cells were mobilized by G-CSF plus chemotherapy, and median number of collected mononuclear cells was 5.44 X 108/kg(range, 1.95-7.08 X 108/kg). High-dose chemotherapy of cyclophosphamide (1,500mg/m2/day), thiotepa (125mg/m2/day) and carboplatin (200mg/m2/day) was administered for 4 days and peripheral blood stem cells were reinfused to the patients 72 hours after the completion of chemotherapy. RESULTS: The median days of recovery for neutrophil (over 500/mm3) and for platelet (over 50,000/mm3) were 10 (range, 8 to 33) and 30 (range, 10 to 40). One patient suffered from seizure attack and grade 3 hepatotoxicity during high dose chemotherapy, There were no treatment-related death. Four patients with high-risk primary breast cancer remained disease-free at 2, 8, 12 and 19 months post-transplant. In one patient with bone metastasis, complete response was induced following APBSCT. All three patients with metastatic disease remained progression-free at 8, 18 and 19 months post-transplant. CONCLUSION: High-dose chemotherapy and autologous peripheral blood stem cell transplantation was feasible and would be a potentially effective treatment modality in high risk and metastatic breast cancer.

Prognostic factors of acute myelocytic leukemia: an analysis of 132 patients in a single institution

Patients with acute myelocytic leukemia (AML) have varied outlooks for survival after the diagnosis. To identify pretreatment prognostic indicators in AML, we analyzed 132 cases of AML seen at our hospital between June, 1989 and December, 1994. The median age of the patients was 40 years (range, 15-81). There were 63 male and 69 female patients. One hundred eight patients (82%) received induction chemotherapy which was based on cytarabine plus anthracyclines. Sixty six patients achieved complete remission (CR) and the CR rate among the patients given induction chemotherapy was 61%. The median duration of CR was 11.2 months. After median follow up of 6.6 months (range 0.5-51.4), 26 patients (39%) remain in continuous CR. The median duration of overall survival of the patients was 6.7 months. After median follow up of 10.6 months (range, 0.1-52.7), 41 patients (31%) are alive. Variables affecting duration of CR included the age of the patients, performance status of the patients, percentage of blast in the peripheral blood, hemoglobin level, percentage of blast in the bone marrow, FAB subtype, and CD7 marker positivity. Variables affecting survival duration included age of the patients, performance status of the patients, absolute blast count (ABC) in the peripheral blood, bone marrow cellularity, the percentage of blast in the bone marrow, and CD5 marker positivity. Multivariate analysis showed that the age of the patients and percentage of blast in the bone marrow were significant independent indicators for overall survival of the patients. Further studies utilizing cytogenetics and molecular characteristics of leukemic cell are warranted to better define the prognostic factors of patients with AML.

Veno-occlusive disease (VOD) of the liver in Korean patients following allogeneic bone marrow transplantation (BMT): efficacy of recombinant human tissue plasminogen activator (rt-PA) treatment

Veno-occlusive disease (VOD) of the liver is a clinical syndrome characterized by hyperbilirubinemia, painful hepatomegaly, and fluid retention. In the bone marrow transplantation (BMT) setting, VOD is caused by dose-intensive chemotherapy and/or radiotherapy used to prepare patients for transplant. VOD occurs in up to 50% of the patients who undergo BMT and is usually associated with a high mortality rate. Until recently, there was no proven effective medical therapy for this condition once it was clinically apparent. We report here on the frequency and treatment result of VOD with rt-PA in our allogeneic BMT patients. Eight patients (median age 28.5 years) underwent allogeneic BMT from December, 1993 to June, 1995 in Asan Medical Center. Six leukemia patients were prepared for BMT with busulfan and cyclophosphmide, while two aplastic anemia patients received cyclophosphamide and antithymocyte globulin. VOD was defined as having two of the following features before day 20 posttransplant: jaundice (bilirubin > or = 2 mg/dL), tender hepatomegaly and/or right upper quadrant pain, ascites and/or unexplained weight gain (> 2% from baseline). All patients who were diagnosed with VOD received rt-PA (10-20 mg/day) and heparin (10,000 U/day). Three (37.5%) of the eight patients developed VOD that occurred between 6 and 10 days posttransplant. All three patients developed jaundice, weight gain, and tender hepatomegaly. Ascites and renal insufficiency occurred in two patients and pleural effusion in one patient. rt-PA and heparin were begun 6 to 26 days posttransplant and rt-PA was administered for 7 to 14 days. All three patients responded to the therapy; bilirubin levels began to decrease at 4 to 13 days from the start of therapy. They are all alive at day 111, 316, and 548 days posttransplant. None of the patients had significant hemorrhagic complications after rt-PA treatment. Prolonged administration of rt-PA was feasible without bleeding episode and it seems that rt-PA may alter the natural course of VOD.

Thromboembolism of Left Anterior Descending Artery Complicated during Angioplasty of Left Circumflex Artery: Report of 1 Case

Percutaneous transluminal coronary angioplasty(PTCA) has been widely applied in patients with coronary artery disease since 1977. Although coronary angioplasty has beeb shown to be safe and effective treatment strategy, acute closure & restenosis remain as major limitations of PTCA. Acute occlusion due to intracoronary thrombus accumulation during or immediately after coronary angioplasty is serious complication of PTCA, also, Intracoronary urokinase has been used to treat acute occlusion by intracoronary thrombus that complicated in PTCA and proved to be effective in restoring vessel preventing acute myocardial infarction. We report a case in which embolism of left anterior descending artery was complicated during angioplasty of left circumflex artery and managed with intracoronary infusion of urokinas.

Intravitary cardiac metastasis in primary hepatoma

Intracavitary metastasis is an uncommon secondary cardiac malignancy and metastasis to the right atrium and ventricle is even less common. Prior reports have demonstrated an association of this disease entity with sudden death. We report a recent experience of intracavitary cardiac metastasis of a primary hepatoma in a 24-year-old woman who presented with a exertional dyspnea and a syncopal episode.