High-dose Versus Low-dose Cyclophosphamide in Combination with G-CSF for Peripheral Blood Progenitor Cell Mobilization

BACKGROUND: To compare the mobilizing effects and toxicities of two different doses of cyclophosphamide (CY) plus lenograstim (glycosylated G-CSF), we performed a prospective randomized study by enrolling patients suffering with either high-risk Non-Hodgkin's lymphoma (NHL) or breast cancer undergoing ablative chemotherapy. METHODS: The NHL patients received 4 cycles of CHOP and the breast cancer patients received 2-3 cycles of FAC (FEC) adjuvant chemotherapy. Then, the patients were randomly allocated to receive CY 4 g/m2 (arm A) or 1.5 g/m2 (arm B) in combination with lenograstim. Large volume leukapheresis was carried out and it was continued daily until the target cell dose of 2x10 (6) CD34+ cell/kg was reached. RESULTS: Twenty-seven patients were enrolled in the study. The median number of leukaphereis sessions actually performed was 2.5 sessions in arm A and 3 sessions in arm B. The target cell dose was obtained with the median number of one leukapheresis session in both arms of the study (p=0.09). The collected number of CD34+ cells in the leukapheresis products was higher in arm A than arm B (22.4 vs. 9.9x10 (6) /kg, respectively, p=0.05). Grade III or IV leukopenia was present in 14/15 patients (94%) in arm A and in 1/12 patients (8%) in arm B (p< 0.0001). Grade III or IV thrombocytopenia was present in 8/15 patients (54%) in arm A, but this was not present in any patients of arm B (p=0.0004). Neutropenic fever occurred in 6/15 patients (40%) in arm A, and in 1/12 patients (8%) in arm B (p=0.09). The hematological recovery of the leukocytes and platelets after transplantation was not statistically different between the two doses. CONCLUSION: Low-dose CY plus lenograstim is a safe and effective mobilizing regimen.

High Dose Therapy Followed by Autologous Peripheral Blood Stem Cell Transplantation as a First Line Treatment for Multiple Myeloma: a Korean Multicenter Study

We conducted a phase II multicenter trial to estimate the response and survival of patients with newly diagnosed multiple myeloma to high dose melphalan therapy followed by autologous peripheral blood stem cell transplantation. Eligible patients who had undergone induction with vincristine, adriamycin and dexamethasone (VAD) should have adequate cardiac, pulmonary and renal function (creatinine <2 mg/dL). Melphalan at 200 mg/m2 was used as a conditioning regimen. Eighty patients were enrolled from 13 centers. The median age of the patients was 53 yr (range; 20 to 68 yr). The initial stage was IA/IIA/IIB/IIIA/IIIB in 3/8/1/54/14 patients, respectively. Beta2-microglobulin, CRP and LDH were increased in 74, 42 and 34% of the patients examined. Cytogenetic data were available in 30 patients, and 6 patients showed numeric or structural abnormalities. Two therapy-related mortalities occurred from infection. Among the 78 evaluable patients, CR/PR/MR/NC/PD were achieved in 48/26/2/1/1patients, respectively. After a median follow-up of 30 months, the median overall and event-free survivals were 66 months (95% CI: 20-112) and 24 months (95% CI: 18-29), respectively. This study verifies the efficacy and feasibility of high dose melphalan therapy with autologous stem cell transplantation in newly diagnosed multiple myeloma.

Gemcitabine and Infusional 5-Fluorouracil in Advanced Pancreatic Cancer: A Clinical Benefit Response-Oriented Phase II Study / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Gemcitabine and 5-fluorouracil (5-FU) are two compounds with reproducible activity against advanced pancreatic carcinomas. To evaluate the activity and feasibility of this combination chemotherapy, a multi-institutional phase II study was performed. MATERIALS AND METHODS: Twenty patients (male: female 15: 5, median age: 60.5 years), with histologically verified locally advanced or metastatic pancreatic carcinomas, were enrolled between April 2000 and March 2002. Gemcitabine was administered by intravenous injection at the doses of 1, 000 mg/m2 on days 1, 8 and 15, and 5-FU 800 mg/m2/day, was given by continuous intravenous infusion on days 1~5. The treatment was repeated every 4 weeks. The clinical benefit response (CBR) was a composite of the pain, Karnofsky performance status and body weight change measurement. RESULTS: Nineteen of the twenty patients were assessable for response. The median follow-up duration was 4.6 months (0.4~15.2 months). Five patients achieved a partial response and eight a stable disease. The overall response rate was 25.0%. The CBR was assessable in 12 patients. The overall CBR was 41.7% (5/12). The median survival of all the patients was 8.0 months. Grade 3~4 toxicities included neutropenia (9.3%) and thrombocytopenia (5.3%). CONCLUSION: This study suggested that gemcitabine, combined with infusional 5-FU, was well tolerated, and produced modest antitumor activity and symptomatic relief in advanced pancreatic cancer patients.

A Case of Ovarian-Relapse Sparing of the Marrow in a Patient with Acute T Cell Lymphoblastic Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation / 대한진단검사의학회지

Isolated extramedullary relapse of acute lymphoblastic leukemia (ALL) with sparing of the marrow after allogeneic stem cell transplantation is not common. We report a 32-year-old female patient with isolated ovarian relapse of T-cell ALL 18 months after allogeneic stem cell transplantation. She had no evidence of concomitant relapse in the bone marrow.

Quantitative Assessment of Philadelphia Chromosome Using Interphase/Hypermetaphase FISH and Toxicity after STI571 Treatment in Chronic Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: Chronic Myelogenous Leukemia (CML) is the first proven disease in which gene abnormality, t(9;22)(q34;q11) can cause the disease to occur in humans. Recently, targeted therapy with STI571 (GleevecTM), signal transduction inhibitor for BCR-ABL kinase was developed and can induce cytogenetic remission in patients with CML. Hypermetaphase-FISH (HMF)/Interphase-FISH (I-FISH, Fluorescence in situ hybridization) aiming specific chromosomal abnormalities are unambiguous quantitative molecular genetic methods for individual Philadelphia (Ph1) chromosome positive cells. We evaluated the change of Ph1 chromosome in CML patients during STI571 therapy using HMF/I- FISH. METHODS: Twenty one patients with CML were treated with STI571 which was provided from Norvatis pharmaceutical company as Expanded Access Program for Compassionate Use from May 2001 at the doses of 200-600 mg/day orally. Median age of this cohort was 37 years old and median follow up duration was 113 days (48~165 days). HMF or I-FISH using bone marrow or peripheral blood were performed on the sample at baseline, day 14, day 28 and then monthly. RESULTS: Complete cytogenetic responses which were assessed by HMF/I-FISH counting several hundreds cells were found in 8 of 21 patients. Among them, 4 of 10 chronic phase, 2 of 2 accelerate phase and 2 of 8 blastic crisis patients achieved cytogenetic complete response. One patient with blastic crisis was relapsed after achieving cytogenetic complete response. Grade III-IV thrombocytopenia and neutropenia were noticed in 8 and in 7 patients respectively, but there were no major bleeding episodes nor neutropenic fever. CONCLUSION: BCR-ABL tyrosine kinase inhibitor, STI571 was tolerable for patients with CML. The majority of patients achieved hematologic remission and 8 out of 21 patients achieved complete cytogenetic response regardless of their disease stage. Cytogenetic response of Ph1 chromosome can be quantified accurately with HMF/I-FISH.

Clinical Features and Prognosis of Lung Cancer with Brain Metastasis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Brain metastasis is estimated to occur in 20~40% of solid tumor patients and the most common primary tumor is lung cancer. Even though the prognosis of brain metastasis is grave and the 1-year survival rate is only 15%, symptom palliations are made with whole brain radiation therapy. We retrospectively evaluated the clinical features and prognostic factors of lung cancer with brain metastasis. MATERIALS AND METHODS: From January 1987 to October 1999, 50 lung cancer patients with brain metastasis underwent whole brain radiation therapy. We reviewed the improvement in neurologic symptoms and survival according to the following parameters; performance status, histological type, presence of brain metastasis at the initial diagnosis of lung cancer, presence of extracranial metastasis, multiplicity of brain lesion, presence of primary lung symptom and treatment modalities. RESULTS: The most frequent symptom with brain metastasis was a headache (50%). Palliation of the headache and other symptoms was achieved in 81% of the patients. Median overall survival after brain metastasis was 21 weeks and the 1 year survival rate was 15%. Patients without extracranial metastasis had a longer median survival than those with, 38 weeks versus 15 weeks, respectively (p=0.01). CONCLUSION: In lung cancer with brain metastasis, neurologic symptoms can be palliated with whole brain radiation therapy, and in this study among such patients, absence of extracranial metastasis can be a good prognostic factor.

The Significance of Vascular Endothelial Growth Factor Expression and Angiogenesis in Acute Myelogenous Leukemia / 대한혈액학회지

BACKGROUND: Angiogenesis plays a key role in the growth and metastasis of solid tumor. But it is not known whether the hematopoietic tumor depends on angiogenesis. To evaluate the prognostic roles of vascular endothelial growth factor (VEGF) expression and angiogenesis in patients with acute myelogenous leukemia, we analyzed the relationships between the level of VEGF expression, microvessel counts (MVC) in the bone marrow specimen of acute myelogenous leukemia patient and remission, relapse, and overall survival. METHODS: We evaluated bone marrow biopsy from 32 adult patients with newly diagnosed acute myelogenous leukemia and 16 controls with normal bone marrow. VEGF expression and MVC were assessed by immunohistochemical stain with monoclonal antibody to VEGF and polyclonal antibody to factor VIIIRAg, respectively. RESULTS: VEGF expression was higher in acute myelogenous leukemia than that of control (56.4+/-32.8% vs 19.0+/-25.9%, P=0.004). MVC was also higher in acute myelogenousleukemia than that of control (14.7+/-10.3 vs 6.2+/-3.8, P<0.001). Between high VEGF expression group and low VEGF expression group, there were no significant differences in the complete remission (CR), relapse and overall survival. There was no significant difference of MVC between CR group and non- CR group. Relapse group tends to have higher MVC than non-relapse group without statistical significance (P=0.06). There were no significant differences of MVC between hypervascular group and hypovascular group in remission, relapse and overall survival. CONCLUSION: In patients with acute myelogenous leukemia, VEGF expression and MVC were significantly higher than those of control. These findings suggest angiogenesis may play an important role in the pathogenesis of acute myelogenous leukemia. But there was no clinical correlation between the level of VEGF expression, MVC and remission, relapse and overall survival in this study. Further study willbe necessary for the establishment of prognostic role of VEGF expression and angioge-nesis and clinical efficacy of angiogenic inhibitors in acute myelogenous leukemia.